Phosphate Institute – IMPHOS http://imphos.org/ Wed, 23 Nov 2022 09:29:13 +0000 en-US hourly 1 https://wordpress.org/?v=5.9.3 https://imphos.org/wp-content/uploads/2021/08/IMPHOS-icon-150x150.jpg Phosphate Institute – IMPHOS http://imphos.org/ 32 32 Research reveals how chickens fight Marek’s disease https://imphos.org/research-reveals-how-chickens-fight-mareks-disease/ Wed, 23 Nov 2022 09:29:13 +0000 https://imphos.org/research-reveals-how-chickens-fight-mareks-disease/ The research undertaken at The Pirbright Institute in Surrey could pave the way for the development of more effective vaccines against the disease. In a recent paper Posted in Frontiers in immunology, the researchers found that immune cells, known as T cells, had distinct functions depending on the birds’ susceptibility to disease. T cells play […]]]>

The research undertaken at The Pirbright Institute in Surrey could pave the way for the development of more effective vaccines against the disease.

In a recent paper Posted in Frontiers in immunology, the researchers found that immune cells, known as T cells, had distinct functions depending on the birds’ susceptibility to disease. T cells play an important role in the adaptive immune response, which helps protect against invading pathogens such as viruses and bacteria. The adaptive immune system has memory cells that can protect when the body detects the pathogen again.

The role of cytokines

Researchers found that T cells from chickens resistant to Mark’s disease produce more IL-2 and IL-4 in response to the virus than those susceptible to the disease. IL-2 and IL-4 are chemicals, called cytokines, released by the immune system to help it eliminate pathogens. This research shows that these cytokines play an important role in protecting poultry against Marek’s disease.

In addition to cytokine responses, the researchers found that T cells from Marek’s disease-resistant chickens produce more granzyme B and perforin – proteins associated with the destruction of infected cells, suggesting a link between the production of these 2 proteins and resistance to Marek’s disease.

Impaired cytotoxic T cell function

The study is also the first to report that Marek’s disease impairs cytotoxic T cell function in naïve chickens (those never infected with Marek’s disease) regardless of their genetic resistance or susceptibility to disease. Further research is needed to explore this phenomenon as it may explain why current vaccines fail to prevent the spread of Marek’s disease virus.

Commenting on the research, Dr Shahriar Behboudi, Head of the Avian Immunology Group at Pirbright, said: “Understanding the different functions of T cell responses in chickens with different susceptibility to Marek’s disease may lead to the development of new effective vaccines that can inhibit the virus. replication and excretion. This would be an important step in controlling this disease, protecting poultry health and improving food safety.

The work was supported by a grant from the Biotechnology and Biological Sciences Research Council (BBSRC), which is part of Research and innovation in the UK(UKRI). The study is located here.

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FDA panel approves kidney disease drug for serum phosphorus control https://imphos.org/fda-panel-approves-kidney-disease-drug-for-serum-phosphorus-control/ Thu, 17 Nov 2022 14:36:07 +0000 https://imphos.org/fda-panel-approves-kidney-disease-drug-for-serum-phosphorus-control/ A group of FDA advisors has recommended approval of tenapanor (Ibsrela) for the control of serum phosphorus levels in adults with chronic kidney disease (CKD) on dialysis, both as a single agent and in combination with phosphate binder treatment. By a vote of 9 to 4, the Cardiovascular and Kidney Drugs Advisory Committee said on […]]]>

A group of FDA advisors has recommended approval of tenapanor (Ibsrela) for the control of serum phosphorus levels in adults with chronic kidney disease (CKD) on dialysis, both as a single agent and in combination with phosphate binder treatment.

By a vote of 9 to 4, the Cardiovascular and Kidney Drugs Advisory Committee said on Wednesday that the benefits of monotherapy treatment with the sodium/hydrogen exchanger 3 (NHE3) inhibitor outweigh its risks, primarily diarrhea, with panelists emphasizing the importance of having another option for patients who cannot tolerate agents currently approved for this indication.

And by a vote of 10 to 2 (with one abstention), the committee determined that the positive risk-benefit profile extended to its use in combination with phosphate binders, as a significant proportion of patients do not get adequate control of phosphorus levels on their skin. current therapies.

The somewhat surprising recommendation comes just over a year after the FDA tenapanor rejected for this indicationciting uncertainty about the clinical significance of the treatment effect.

“Usually more choice is better,” said C. Noel Bairey Merz, MD, of Cedars-Sinai Medical Center in Los Angeles, who voted “yes” on both questions and called for the use shared decision-making when the data is not ironclad. . “I would favor this as a complementary therapy and as an alternative for people who just can’t keep up with existing therapy.”

Patrick Nachman, MD, of the University of Minnesota in Minneapolis, voted “no” for using tenapanor as monotherapy but “yes” as an add-on therapy.

“Acknowledging all the limitations of our data, if there is one patient population that could benefit from a substantial reduction in serum phosphorus, it would be those with very severe hyperphosphatemia or complications thereof,” said Nachman. “These patients are not likely to achieve control with monotherapy; they will likely need multiple agents and if tenapanor can get them to the finish line, in addition to other agents, I think it is worth it. to have that option on the table.”

In its full response letter, the FDA had stated that although tenapanor reduces serum phosphorus in CKD patients on dialysis, “the magnitude of the treatment effect is small and of uncertain clinical significance.” . Wednesday’s advisory board meeting was called in response to a call from Ardelyx, the maker of tenapanor. (Tenapanor is currently approved for irritable bowel syndrome with constipation.)

Panelist Ian de Boer, MD, of the University of Washington in Seattle, sided with the FDA’s assessment and voted “no” to both questions.

“I think there is not enough data to support the clinical benefit of this intervention,” de Boer said. “I certainly understand the need and desire for new tools, but I think we need tools that work for results that matter.”

A lower pill burden is an advantage of tenapanor over phosphate binders, and taking fewer smaller pills “is important for almost all of our patients,” said committee chair Julia Lewis, MD, of Vanderbilt Medical Center. in Nashville, which voted in favor of the drug.

She noted, however, that monotherapy treatment with tenapanor is problematic due to an effect size that is smaller than that of existing therapies.

“I agree that there is a small subset that will respond to monotherapy, but let’s make this available to them,” Lewis said.

Intent-to-treat analyzes of randomized trials supporting the drug’s application for approval showed a mean reduction in serum phosphorus of approximately 0.7 mg/dL with treatment as monotherapy compared to approximately 1. 5 to 2.2 mg/dL with existing approved therapies.

Linda Fried, MD, MPH, of the University of Pittsburgh, said, “I see this drug [as monotherapy] would only be reserved for those who are intolerant of phosphate binders, which is unfortunately a reasonable number. I see its usefulness more as a complementary therapy, reflecting the difficulty in lowering phosphorus.”

According to Scott Emerson, MD, PhD, of the University of Washington Seattle, although he cautioned against relying on observational data in the absence of clinical trial data linking therapeutic reductions in phosphorus levels to the improved results. Emerson voted to recommend approval of tenapanor as both monotherapy and combination therapy.

Is a reduction of 0.7 mg/dL “enough when talking about a surrogate endpoint that has not been validated?” asked Christopher O’Connor, MD, of the Inova Heart and Vascular Institute in Falls Church, Va., who ultimately voted “no” on both questions. “We envision an effect size that is, at best, 40% lower than current therapies.”

As an add-on therapy, Emerson cited data showing that with tenapanor titration, an additional 20% of patients could achieve a target phosphorus level of <5.5 mg/dL. "I think that's the way to use it, [and] is an important tool to have,” he said.

At the meeting, Ardelyx showed data that responders can be identified early in treatment and that 79% who achieve an early response remain responsive at later times.

“Given that I don’t see a compelling safety issue, I would say…approving this would allow treating physicians to put this in their arsenal, [and] identify people who seem to respond,” said Thomas Cook, PhD, of the University of Wisconsin-Madison, who voted tenapanor for both questions.

The risk imposed by diarrhea with tenapanor is minimal in a closely monitored population such as those with CKD on dialysis, several committee members said. Diarrhea is a known side effect of tenapanor since the agent is already approved for the treatment of irritable bowel syndrome with constipation, Bairey Merz recalled.

Although the FDA is not required to follow the recommendations of its advisory committees, it generally does.

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Researchers are planning a new way to remove microplastics from water https://imphos.org/researchers-are-planning-a-new-way-to-remove-microplastics-from-water/ Mon, 14 Nov 2022 17:49:56 +0000 https://imphos.org/researchers-are-planning-a-new-way-to-remove-microplastics-from-water/ Researchers at Princeton Engineering have found a way to turn your breakfast foods into a new material that can cost-effectively remove salt and microplastics from seawater. Researchers used egg whites to create airgel, a lightweight, porous material that can be used in many types of applications, including water filtration, energy storage, and sound insulation and […]]]>

Researchers at Princeton Engineering have found a way to turn your breakfast foods into a new material that can cost-effectively remove salt and microplastics from seawater.

Researchers used egg whites to create airgel, a lightweight, porous material that can be used in many types of applications, including water filtration, energy storage, and sound insulation and thermal. Craig Arnold, Susan Dod Brown Professor of Mechanical and Aerospace Engineering and Vice Dean of Innovation at Princeton, works with his lab to create new materials, including aerogels, for engineering applications.

One day, sitting in a faculty meeting, he had an idea.

“I was sitting there looking at the bread in my sandwich,” Arnold said. “And I thought to myself, this is exactly the kind of structure that we need.” So he asked his lab group to make different carbon-mixed bread recipes to see if they could recreate the airgel structure he was looking for. None of them worked properly at first, so the team continued to weed out ingredients as they tested, until eventually only egg whites remained.

“We started with a more complex system,” Arnold said, “and we kept cutting, cutting, cutting, until we got to the core of what it was. These are the proteins in the egg whites that created the structures we needed.

Egg whites are a complex system of nearly pure proteins which, when freeze-dried and heated to 900 degrees Celsius in an oxygen-free environment, create a structure of interconnected strands of carbon fibers and graphene sheets. In an article published in Materials today Arnold and his co-authors showed that the resulting material can remove salt and microplastics from seawater with 98% and 99% efficiency, respectively.

“Egg whites worked even if fried on the stove top or whipped first,” said Sehmus Ozden, the paper’s first author. Ozden is a former postdoctoral research associate at the Princeton Center for Complex Materials and now a scientist at the Aramco Research Center. While store-bought egg whites were used in the initial tests, Ozden said, other similar commercially available proteins produced the same results.

“Eggs are cool because we can all connect to them and they’re easy to get, but you have to be careful not to compete with the food cycle,” Arnold said. Because other proteins have also worked, the material can potentially be produced in large quantities relatively inexpensively and without impacting the food supply. A next step for the researchers, Ozden noted, is to refine the manufacturing process so it can be used in water purification on a larger scale.

If this challenge can be solved, the material has significant advantages as it is inexpensive to produce, energy efficient to use, and highly efficient. “Activated carbon is one of the cheapest materials used for water purification. We compared our results with activated charcoal, and it’s much better,” Ozden said. Compared to reverse osmosis, which requires a large energy input and excess water to operate, this filtration process only requires gravity to operate and wastes no water.

Although Arnold sees water purity as a “great big challenge”, that’s not the only potential application for this material. It also explores other uses related to energy storage and insulation.

The research included contributions from the chemical and biological engineering and geoscience departments at Princeton and elsewhere. “It’s one thing to make something in the lab,” Arnold said, “and it’s another to figure out why and how.” Collaborators who helped answer the why and how questions included Professors Rodney Priestley and A. James Link of Chemical and Biological Engineering, who helped identify the mechanism of egg white protein transformation at the molecular level. Princeton colleagues in geosciences participated in the water filtration measurements.

Susanna Monti from the Institute of Chemistry of Organometallic Compounds and Valentina Tozzi from Instituto Nanoscienze and NEST-Scuola Normale Superiore created the theoretical simulations that revealed the transformation of egg white proteins into airgel.

The article, “Ultralight Hybrid Monolithic Airgel Derived from Egg Protein for Water Purification“, was published in the journal materials today. Besides Arnold, Monti, Ozden, Priestley, Link, and Tozzi, the authors include Nikita Dutta, a former graduate student in mechanical and aerospace engineering who is now at the National Renewable Energy Laboratory; Stefania Gill, John Higgins and Nick Caggiano of Princeton University; and Nicola Pugno from the University of Trento and Queen Mary University of London. Support was provided in part by the Princeton Center for Complex Materials and the US National Science Foundation.

– This press release was originally published on the Princeton University website

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Electric cars continue to ignite in Florida https://imphos.org/electric-cars-continue-to-ignite-in-florida/ Sat, 29 Oct 2022 05:53:00 +0000 https://imphos.org/electric-cars-continue-to-ignite-in-florida/ Hurricane Ian caused billions of damage and upended lives, but few expected it to cause electric vehicles ignite. But that’s exactly what happened. In the days following Hurricane Ian, saltwater flooding in coastal areas caused lithium-ion batteries in electric vehicles to burn out. The Naples fire brigade, for example, had to put out six flames […]]]>

Hurricane Ian caused billions of damage and upended lives, but few expected it to cause electric vehicles ignite.

But that’s exactly what happened.

In the days following Hurricane Ian, saltwater flooding in coastal areas caused lithium-ion batteries in electric vehicles to burn out.

The Naples fire brigade, for example, had to put out six flames in electric vehicles that had been submerged in seawater.

Firefighter spokeswoman Heather Mazurkiewicz said firefighters need “thousands and thousands” of gallons of water to put out electric vehicle fires, far more than a typical gas-powered car fire would require.

Worse still, one of the electric vehicles ignited, destroying two houses.

Related: This solar-powered town in Florida was built to withstand hurricanes. Did it work?

Why electric vehicles burn

Eric Wachsman, director of the Maryland Energy Institute, told CNBC that lithium-ion battery cells have electrodes close together and are filled with a flammable liquid electrolyte.

When battery cells are damaged or defective, “this flammable liquid can go into what’s called a thermal runaway situation, where it begins to boil, causing a fire,” Wachsman said.

For this reason, some companies, such as Tesla and Ford, are turning to lithium iron phosphate (LFP) batteries, which are far less combustible.

But that doesn’t stop cars that already have lithium-ion batteries from catching fire.

Florida takes action

To protect first responders and firefighters, Jack Danielson, executive director of the National Highway Traffic Safety Administration, ordered those “not involved in immediate rescue missions” to identify flooded electric vehicles with lithium batteries. -ion ​​and move them “at least 50 feet”. other structures, vehicles and fuels.

Senator Rick Scott also wrote a letter to US Transportation Secretary Pete Buttigieg, D, calling for action.

“This emerging threat has forced local fire departments to divert resources from hurricane recovery to control and contain these dangerous fires,” Scott wrote. “Alarmingly, even after car fires have been extinguished, they can reignite in an instant.”

There are more than 95,000 electric vehicles registered in Florida, the second highest number in the country.

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Altech Appoints Principal Engineer for Solid-State Battery Plant DFS Study https://imphos.org/altech-appoints-principal-engineer-for-solid-state-battery-plant-dfs-study/ Wed, 26 Oct 2022 21:11:25 +0000 https://imphos.org/altech-appoints-principal-engineer-for-solid-state-battery-plant-dfs-study/ Altech takes another step towards commercialization of its sodium alumina solid state battery technology, following the appointment of a principal engineer for the definitive feasibility study. The German company Leadec Automation & Engineering GmbH will carry out engineering work for the CERENERGY® 100MWh Sodium Alumina 100 megawatt-hour solid-state battery project to be built in Saxony. […]]]>

Altech takes another step towards commercialization of its sodium alumina solid state battery technology, following the appointment of a principal engineer for the definitive feasibility study.

The German company Leadec Automation & Engineering GmbH will carry out engineering work for the CERENERGY® 100MWh Sodium Alumina 100 megawatt-hour solid-state battery project to be built in Saxony.

Leadec, one of the world’s leading specialists in services for plants throughout their life cycle and associated infrastructure, has 60 years of experience in supporting customers in manufacturing industries: from planning, installation and factory automation.

This includes supporting OEMs and suppliers in the area of ​​battery production and e-mobility with coverage across the spectrum, from the production of cells, modules and packs to solutions in the area of ​​recycling and dismantling the batteries.

Team up for more power

Altech Chemicals (ASX: ATC) entered into a joint venture in September 2022 with the world-leading German battery institute Fraunhofer IKTS to commercialize the latter’s CERENERGY® sodium alumina solid-state battery technology.

It will achieve this by building the battery factory on Altech’s land in Schwarze Pumpe, Saxony, with the Altech group owning 75% of the JV company.

Managing Director Iggy Tan said, “We are delighted to appoint Leadec as the Principal Engineer for Altech’s CERENERGY® 100MWh project.”

“Leadec has extensive experience in battery manufacturing and will play a key role in advancing the definitive feasibility study to commercialize CERENERGY® Sodium Alumina solid-state batteries.”

Potential game changer

Fraunhofer IKTS uses solid-state ceramic technology, common table salt, and nickel to make fireproof and explosion-proof batteries with a lifespan of over 15 years, up to twice the life of life of lithium-ion batteries.

These batteries are also capable of operating in extremely cold and desert climates.

Perhaps the most important point in its favor is that the batteries do not require lithium, cobalt, graphite or copper, which eliminates exposure to critical metal prices and supply chain issues.

Energy capacity is comparable to lithium iron phosphate (LFP) batteries, although they require longer charge times which make them more suitable for on-grid storage where very high power over a short period of time (such as vehicles high-power electrical) is not required.

Altech’s proposed plant will produce solid-state sodium alumina batteries, at a production cost about 40% to 50% cheaper than lithium-ion batteries.

Altech Chemicals Interactive Investor Center

Engage directly with Altech by asking questions, watching video summaries and seeing what other shareholders have to say about it, as well as past announcements, on our Investor Hub: Investorhub.altechchemicals.com

This article was developed in conjunction with Altech Chemicals, a Stockhead advertiser at the time of publication.

This article does not constitute advice on financial products. You should consider obtaining independent advice before making any financial decisions.

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Morocco – one of the main producers of fertilizers – could hold the key to the world’s food supply https://imphos.org/morocco-one-of-the-main-producers-of-fertilizers-could-hold-the-key-to-the-worlds-food-supply/ Sun, 23 Oct 2022 23:22:16 +0000 https://imphos.org/morocco-one-of-the-main-producers-of-fertilizers-could-hold-the-key-to-the-worlds-food-supply/ Morocco has a large fertilizer industry with enormous production capacity and international reach. It is one of the top four fertilizer exporters in the world after Russia, China and Canada. October 24, 2022 6 minute read Workers fill sacks of fertilizer in Meknes, northern Morocco. Photo by Fadel Senna/AFP via Getty Images Morocco has a […]]]>

Morocco has a large fertilizer industry with enormous production capacity and international reach. It is one of the top four fertilizer exporters in the world after Russia, China and Canada.


October 24, 2022

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6 minute read

Workers fill sacks of fertilizer in Meknes, northern Morocco.
Photo by Fadel Senna/AFP via Getty Images

Morocco has a large fertilizer industry with enormous production capacity and international reach. It is one of the four first fertilizer exporters after Russia, China and Canada.

Fertilizers tend to fall into three main categories; nitrogen fertilizers, phosphorus fertilizers, potassium fertilizers. In 2020, the fertilizer market size was approximately US$190 billion.

Morocco has a clear advantage in the production of phosphate fertilizers. He owns more 70% of the world’s phosphate rock reserves, from which the phosphorus used in fertilizers comes. And that makes Morocco a guardian of global food supply chains, as all food crops need the element phosphorus to grow. Indeed, the same is true for all plant life. Unlike other limited resources, such as fossil fuels, there is no alternative to phosphorus.

In 2021, the global phosphorus fertilizer market amounted to on 59 billion US dollars. In Morocco, the sector’s 2020 revenues amounted to US$5.94 billion. Office Chérifien des Phosphates, the Moroccan state-owned producer, represented about 20% of the kingdom’s export earnings. It is also the largest employer in the country, providing employment to 21,000 people.

Morocco plans to produce an additional 8.2 million tons of phosphorus fertilizers by 2026. Currently in production is about 12 million tons.

The state corporation recently announcement that it would increase its fertilizer production for the year by 10%. This would put an additional 1.2 million tons on the world market by the end of the year. This will help the markets considerably.

But, as I argue in a new report, Morocco faces new challenges. Its fertilizer production is threatened by increasingly daunting environmental and economic challenges. They include the COVID pandemic and the severe supply chain disruptions that have followed.

The timing of this is crucial.

Russia is currently the first the biggest fertilizer exporter – 15.1% of total fertilizer exported. And fertilizers represent one of the greatest vulnerabilities for Europe and Africa. For example, the EU27 (all 27 member states of the European Union) as a whole depends on Russia to 30% of its fertilizer supply. Russia’s advantageous position is amplified by its status as the world’s second largest producer of natural gas. Gas is a main component of all phosphorus fertilizers as well as nitrogen fertilizers.

For this reason, Russia’s invasion of Ukraine has serious implications for global food security. Both in terms of supply, and also because fertilizers can be used as a weapon or an economic tool.

Morocco could therefore become a central part of the global fertilizer market and a guardian of the global food supply that could offset the attempt to use fertilizers as a weapon.

The trip

Morocco began mining phosphorus in 1921. During the 1980s and 1990s, it began producing its own fertilizer. Chérifien Phosphates Office built the largest fertilizer production center in the world in Jorf Lasfar on the Atlantic coast of Morocco.

Before the outbreak of the Russian-Ukrainian war, the company had more than 350 customers on five continents. About 54% of phosphate fertilizers purchased in Africa come from Morocco. Moroccan fertilizers also represent significant domestic market shares in India (50%), Brazil (40%) and Europe (41%). India and Brazil reached out their hand in Morocco to fill additional supply gaps.

Image taken from OCP’s 2020 sustainability report.

The Moroccan economy has reaped the benefits of transformation into an international fertilizer export giant. And in sub-Saharan Africa in particular, the combination of joint venture partnerships in the local production of fertilizers and direct awareness to farmers has led to a remarkable boost to African agricultural yields.

He also expanded the influence of Morocco’s soft power across the continent. For example, Morocco provides more than 90% of Nigeria’s annual fertilizer demand.

But how Morocco handles the challenges of the industry will affect both its own economic development and the stability of food supplies across the world.

Challenges

Water and energy constraints

Phosphate mining and fertilizer production consume a lot of energy and water. The Moroccan phosphate and fertilizer industry consumes about 7% of its annual energy production and 1% of its water.

But Morocco is one of the countries suffering the most of water scarcity. This is due to a dry climate, high water demand, climate change and contamination and siltation of reservoirs.

Morocco is trying to solve this problem through a National Water Plan 2020-2050. It plans to build new dams and desalination plants and expand irrigation networks, among other measures, to support agriculture and ecosystems. This is estimated cost about 40 billion US dollars.

Natural Gas Costs

Nitrogen is the other basic nutrient that plants need. Diammonium phosphate, the most popular type of phosphorus fertilizer in the world (and which Morocco makes with monoammonium), is made up of 46% phosphorus and 18% nitrogen. Natural gas represents at least 80% the variable cost of nitrogen fertilizers.

This means that the price of natural gas massively affects production costs. But Morocco has few natural gas resources. And natural gas prices have skyrocketed.

How Morocco manages the food-water-energy nexus will affect both its own economic development and the stability of food supplies around the world.

Some answers

The key is to expand its renewable energy sector. Morocco holds considerable solar and wind resources. Fertilizer manufacturing could be powered by renewable energy, and the renewable energy could be used in the fertilizer itself.

In 2020, the state fertilizer company covered 89% its energy needs through cogeneration (production of two or more forms of energy from a single fuel source) and renewable energy sources. Its objective is to cover 100% of its energy needs in the long term.

Renewable energy could also be used in the fertilizer itself. Instead of importing ammonia derived from natural gas, Morocco could produce its own using hydrogen produced from its domestic renewable energy resources.

According to the state corporation, 31% of its water needs are met by “unconventional” water resources, including treated wastewater and desalinated seawater.

Morocco’s growing reliance on desalination plants to meet industrial, agricultural and residential needs will require significant new investment in power generation from renewable energy sources. Desalination plants require 10 times the amount of energy to produce the same volume of water as conventional surface water treatment.

To sustain operations and develop the production of green ammonia, Morocco will need to find a careful balance between its fertilizer exports, its efforts to develop its high value-added agricultural exports and the supply of drinking water to its population.

By using its significant solar energy resources to power the production of green hydrogen and green ammonia, as well as desalination, Morocco could escape the vicious circle of upward spiraling prices in the food-energy-water nexus.

The conversation

Michael TanchumSenior Fellow at the Austrian Institute for European and Security Studies (AIES), non-resident researcher in the Economics and Energy Program at the Middle East Institute (MEI) and Professor, University of Navarre

This article is republished from The conversation under Creative Commons license. Read it original article. The article was published in July 2022.

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VIVOS INC Management report and analysis of the financial situation and operating results. (Form 10-Q) https://imphos.org/vivos-inc-management-report-and-analysis-of-the-financial-situation-and-operating-results-form-10-q/ Wed, 19 Oct 2022 20:04:07 +0000 https://imphos.org/vivos-inc-management-report-and-analysis-of-the-financial-situation-and-operating-results-form-10-q/ Except for statements of historical fact, certain information described in this Form 10-Q report contains "forward-looking statements" that involve substantial risks and uncertainties. You can identify these statements by forward-looking words such as "anticipate," "believe," "could," "estimate," "expect," "intend," "may," "should," "will," "would" or similar words. The statements that contain these or similar words should […]]]>
Except for statements of historical fact, certain information described in this
Form 10-Q report contains "forward-looking statements" that involve substantial
risks and uncertainties. You can identify these statements by forward-looking
words such as "anticipate," "believe," "could," "estimate," "expect," "intend,"
"may," "should," "will," "would" or similar words. The statements that contain
these or similar words should be read carefully because these statements discuss
the Company's future expectations, including its expectations of its future
results of operations or financial position, or state other "forward-looking"
information. Vivos Inc. believes that it is important to communicate its future
expectations to its investors. However, there may be events in the future that
the Company is not able to accurately predict or to control. Further, the
Company urges you to be cautious of the forward-looking statements which are
contained in this Form 10-Q report because they involve risks, uncertainties and
other factors affecting its operations, market growth, service, products and
licenses. The risk factors in the section captioned "Risk Factors" in Item 1A of
the Company's previously filed Form 10-K, as well as other cautionary language
in this Form 10-Q report, describe such risks, uncertainties and events that may
cause the Company's actual results and achievements, whether expressed or
implied, to differ materially from the expectations the Company describes in its
forward-looking statements. The occurrence of any of the events described as
risk factors could have a material adverse effect on the Company's business,
results of operations and financial position.

Vivos Inc. is a radiation oncology medical device company engaged in the
development of its yttrium-90 ("Y-90") based brachytherapy device, RadioGel™,
for the treatment of non-resectable tumors. A prominent team of radiochemists,
scientists and engineers, collaborating with strategic partners, including
national laboratories, universities and private corporations, lead the Company's
development efforts. The Company's overall vision is to globally empower
physicians, medical researchers and patients by providing them with new isotope
technologies that offer safe and effective treatments for cancer.

In 2013 the FDA issued the determination that RadioGel™ is a device for human
therapy for non-resectable cancers in humans. This should result in a faster
path than a drug for final approval.

In January 2018, the Center for Veterinary Medicine Product Classification Group
ruled that RadioGelTM should be classified as a device for animal therapy of
feline sarcomas and canine soft tissue sarcomas. Additionally, after a legal
review, the Company believes that the device classification obtained from the
Food and Drug Administration ("FDA") Center for Veterinary Medicine is not
limited to canine and feline sarcomas, but rather may be extended to a much
broader population of veterinary cancers, including all or most solid tumors in
animals. We expect the result of such classification and label review will be
that no additional regulatory approvals are necessary for the use of IsoPet® for
the treatment of solid tumors in animals. The FDA does not have premarket
authority over devices with a veterinary classification, and the manufacturers
are responsible for assuring that the product is safe, effective, properly
labeled, and otherwise in compliance with all applicable laws and regulations.

Based on the FDA's recommendation, RadioGelTM will be marketed as "IsoPet®" for
use by veterinarians to avoid any confusion between animal and human therapy.
The Company already has trademark protection for the "IsoPet®" name. IsoPet® and
RadioGelTM are used synonymously throughout this document. The only distinction
between IsoPet® and RadioGelTM is the FDA's recommendation that we use "IsoPet®"
for veterinarian usage, and reserve "RadioGelTM" for human therapy. Based on
these developments, the Company has shifted its primary focus to the development
and marketing of Isopet® for animal therapy, through the Company's IsoPet®
Solutions division.

The Company's IsoPet Solutions division was established in May 2016 to focus on
the veterinary oncology market, namely engagement of university veterinarian
hospital to develop the detailed therapy procedures to treat animal tumors and
ultimately use of the technology in private clinics. The Company has worked with
three different university veterinarian hospitals on IsoPet® testing and
therapy. Washington State University treated five cats for feline sarcoma and
served to develop the procedures which are incorporated in our label. They
concluded that the product was safe and effective in killing cancer cells.
Colorado State University demonstrated the CT and PET-CT imaging of IsoPet®. A
contract was signed with University of Missouri to treat canine sarcomas and
equine sarcoids starting in November 2017.

22





The dogs were treated for canine soft tissue sarcoma. Response evaluation
criteria in solid tumors ("RECIST") is a set of published rules that define when
tumors in cancer patients improve (respond), stay the same (stabilize), or
worsen (progress) during treatment. The criteria were published by an
international collaboration including the European Organisation for Research and
Treatment of Cancer ("EORTC"), National Cancer Institute of the United States,
and the National Cancer Institute of Canada Clinical Trials Group.

The testing at the University of Missouri met its objective to demonstrate the
safety of IsoPet®. Using its advanced CT and PET equipment it was able to
demonstrate that the dose calculations were accurate and that the injections
perfused into the cell interstices and did not stay concentrated in a bolus.
This results in a more homogeneous dose distribution. There was insignificant
spread of Y-90 outside the points of injection demonstrating the effectiveness
of the particles and the gel to localize the radiation with no spreading to the
blood or other organs nor to urine or fecal material. This confirms that IsoPet®
is safe for same day therapy.

The effectiveness of IsoPet® for life extension was not the prime objective, but
it resulted in valuable insights. Of the cases one is still cancer-free but the
others eventually recurred since there was not a strong focus on treating the
margins. The University of Missouri has agreed to become a regional center to
administer IsoPet® therapy and will incorporate the improvements suggested by
the testing program.

The Company anticipates that future profits, if any, will be derived from direct
sales of RadioGel™ (under the name IsoPet®) and related services, and from
licensing to private medical and veterinary clinics in the U.S. and
internationally. The Company intends to report the results from the IsoPet®
Solutions division as a separate operating segment in accordance with GAAP.

Commencing in July 2019, the Company recognized its first commercial sale of
IsoPet®. A veterinarian from Alaska brought his cat with a re-occurrent spindle
cell sarcoma tumor on his face. The cat had previously received external beam
therapy, but now the tumor was growing rapidly. He was given a high dose of
400Gy with heavy therapy at the margins. This sale met the revenue recognition
requirements under ASC 606 as the performance obligation was satisfied. The
Company completed sales for an additional four animals that received the IsoPet®
during 2019.

Our plan is to incorporate the data assembled from our work with Isopet® in
animal therapy to support the Company's efforts in the development of our
RadioGel™ device candidate, including obtaining approval from the FDA to market
and sell RadioGel™ as a Class II medical device. RadioGel™ is an injectable
particle-gel for brachytherapy radiation treatment of cancerous tumors in people
and animals. RadioGel™ is comprised of a hydrogel, or a substance that is liquid
at room temperature and then gels when reaching body temperature after injection
into a tumor. In the gel are small, less than two microns, Y-90 phosphate
particles. Once injected, these inert particles are locked in place inside the
tumor by the gel, delivering a very high local radiation dose. The radiation is
beta, consisting of high-speed electrons. These electrons only travel a short
distance so the device can deliver high radiation to the tumor with minimal dose
to the surrounding tissue. Optimally, patients can go home immediately following
treatment without the risk of radiation exposure to family members. Since Y-90
has a half-life of 2.7 days, the radioactivity drops to 5% of its original value
after ten days.

Recently, the Company modified its Indication for Use from skin cancel to
cancerous tissue or solid tumors pathologically associated with locoregional
papillary thyroid carcinoma and recurrent papillary thyroid carcinoma having
discernable tumors associated with metastatic lymph nodes or extranodal disease
in patients who are not surgical candidates or who have declined surgery, or
patients who require post-surgical remnant ablation (for example, after prior
incomplete radioiodine therapy). Papillary thyroid carcinoma belongs to the
general class of head and neck tumors for which tumors are accessible by
intraoperative direct needle injection. The Company's Medical Advisory Board
felt that demonstrating efficacy in clinical trials was much easier with this
new indication.

The Company's lead brachytherapy products, including RadioGel™, incorporate
patented technology developed for Battelle Memorial Institute ("Battelle") at
Pacific Northwest National Laboratory, a leading research institute for
government and commercial customers. Battelle has granted the Company an
exclusive license to patents covering the manufacturing, processing and
applications of RadioGel™ (the "Battelle License"). This exclusive license is to
terminate upon the expiration of the last patent included in this agreement (May
2022). Other intellectual property protection includes proprietary production
processes and trademark protection in 17 countries.

23





Intellectual Property

Our original license with Battelle National Laboratory reaches its end of life. Over the past few years, in anticipation of this, we have expanded our proprietary knowledge and protection of trademarks and patents.


We have expanded our trademark protection from RadioGel to now include IsoPet.
We obtained the International Certificate of Registration for ISOPET, which is
the first step to file in several countries.

The company has received the Patent Cooperation Treaty (“PCT”) international search report for our patent application (no. 1811.191). Seven of our claims were immediately found to have novelty, inventive step and industrial applicability. This gives us the basis to extend patent protection for our proprietary Yttrium-90 phosphate particles used in Isopet® and Radiogel™ for many years.


Our patent team filed our particle patent in more than ten patent offices that
collectively cover 63 countries throughout the world. We filed a
continuation-in-part applications number 1774054 in the USA to expand the claims
on our particle patent. The US Patent office recently gave us the Notice of
Allowance for our patent to produce our yttrium phosphate microparticles, US
Patent Application Serial No: 16-459,466. We also filed an amendment to correct
the wording on our claims at make them consistent with the USE claims. Ref:
4207-0005; European Patent Application NO. 20 834 229.5; VIVOS INC; Our Ref:
FS/53791.

We filed a hydrogel utility patent in the USA and PCT based on the last eighteen
months of development work to optimize our hydrogel component. These include
reducing the polymer production time and increasing the output by a factor of
three. We have also further reduced the level of trace contaminants to be well
below the FDA guidelines.

We are continuously improving our injection system. We completed the development
of a syringe shield and vial holder. We are now testing an advanced cooling
system to hold the vial and syringes. We are also testing commercially available
systems for deep injections, which will be useful in treating lung and
pancreatic caners. We are considering filing a provisional patent on these
injection system developments.

Regional IsoPet Clinics

We currently have four regional therapy clinics:

  ? Vista Veterinary Hospital - Kennewick, WA
  ? University of Missouri - Columbia, MO
  ? Johns Hopkins University - Baltimore, MD
  ? New England Equine Practice - Patterson, NY



Vista Veterinary Hospital ("Vista") was selected as the pilot private clinic to
initiate commercial sales of IsoPet®. It is good management practice to
implement and learn from a pilot program before spreading to regional clinics
across the country. Vista is located in the Tri-Cities Washington area which is
convenient for interactions with key personnel of the Company. The pilot is
being used to

? Refine the Memorandum of Understanding to define all relevant interfaces,

roles and responsibilities between Vista inc. and private clinics, including

pilot responsiveness to document and share key aspects of all therapies with

the company;

? Create and implement proprietary certification training modules;

? Modify the authorization of radioactive material from the production center of IsoTherapeutics,

the Company’s IsoPet® production center, to enable distribution for commercial purposes

apps;

? Work with the pilot program to obtain a license for radioactive materials in a

    NRC agreement state;
  ? Create equipment and supplies list;
  ? Create and post regulatory signage;
  ? Explore different IsoPet® pricing options;
  ? Evaluate different approaches to obtain patients;
  ? Optimize patient scheduling practices to reduce cost to the pet owners;

? Develop communication materials and accountability document for pet owners;

    and
  ? Further refine the therapy techniques for advanced cancers.



24





Vista Veterinary Hospital has done well on two audits by the Washington State
Department of Health. The Company is working closely with the Washington State
Department of Health to refine and improve the radioactive material license. The
Company has added several detailed procedures, which will benefit future
regional clinics. In addition, a second veterinarian has completed all the
preliminary requirements to become certified. All that remains is to demonstrate
proficiency in three therapies.

Tests at universities and at Vista Veterinary Hospital demonstrated that IsoPet® is effective in killing cancerous tissue near injections. It is most effective in early cases before the cancer starts to spread. Advanced-stage cancers are more difficult to treat because the tendrils of the primary cancer site are not well defined and therefore may lead to recurrence.


There has been 97 expressions of interest in IsoPet® therapy from across the
United States, but only about 10% of these were treated and they were very
advanced cases. The reasons are instructive. Most of the cases were for so
advanced that the pet parents found out about IsoPet® on the Internet as a last
hope. Several others were internal cancers that could not be reached, for
example deep in the throat. Several cases were treatable, but the pets weighed
more than 20 pounds and the pet parents were not willing to fly them in the
"Safe Cargo" holds. Those patients would have been treated by regional clinics
once we implement that strategy. Several cases were mast cell cancers. The
Company is confident that those tumors could have been treated, but once killed
they release mast cells in a process called granulation. This could cause a
shock to the animal's system. The Company will focus one of our clinical studies
on the optimum approach for those therapies.

Vista Veterinary Hospital accepted advanced cancer cases and has gained
experience to extend the animal's lives. The first cat was terminally ill and
had previously had external beam, surgery and chemotherapy. The facial tumor was
treated with 400 Gy and the biopsy confirmed that the cancer was killed. In
about seven months the cancer returned in the throat and could not be treated so
the cat had to be put down. Dr. Bauder, the veterinarian pet parent, was still
elated about the life extension and is asking us to use him as a reference. The
other cases were also very advanced with multiple tumors and they recurred since
they had already spread before therapy. One animal, Yukon had a large tumor on
his leg that was recommended for amputation. The tumor size decreased 50% after
the first treatment, but then stopped decreasing. For the first time a second
therapy was administered and the tumor has continued to decrease in size.
Yukon's life was extended for more than a year until she finally succumbed to
metastatic cancer in another location.

Since IsoPet® has shown to be effective in killing cancer at the site of
injection the current focus is in optimizing the techniques to help the pet
resorb the necrotic tissue rapidly. In addition, IsoPet® was used to treat a
mast cell tumor. When these cancers are destroyed, they release their mast cell.
The animal was treated with a steroid to counter this effect and to date is
doing well.

The Company's efforts are now to obtain more early-stage cancer patients. The
biggest obstacle is to convince the veterinarians of the pet parents to agree
with IsoPet® therapy rather than using a more traditional method such as
surgery. This is a slow process due to the conservative nature of the
veterinarian professions. This is the prime motivation to continue with
additional clinical trials and to publish the results.

The Company worked closely with FX Masse to develop nine certification training
modules for use in potential regional clinics. These modules are necessary to
satisfy the radioactive material handling licenses. This approach is very cost
effective.

Johns Hopkins University VCTN, Veterinary Clinical Trials Network, is now an
Isopet® regional clinic. Additionally, Johns Hopkins will also perform new
Isopet® animal studies on various specific cancers. They have the required
radioactive material license and have completed their training certification for
Isopet®. This important relationship will also help meet our objective of
obtaining high quality data on a range of cancers that can be published in
leading journals. These publications are the optimal way to increase awareness
of Isopet® and to gain broader acceptance from the veterinarian/oncology
community.

Our objective is to open several regional clinics by the end of 2022 and to
participate in a minimum of three conferences to spread the word about IsoPet in
the veterinarian community for treating tumors in small animals and horses. We
just created a Marketing Steering Board to provide advice on obtaining new
pet
patients.

25





Regulatory History

Human Therapy

RadioGel™ has a long regulatory history with the Food and Drug Administration
("FDA"). Initially, the Company submitted a presubmission (Q130140) to obtain
FDA feedback about the proposed product. The FDA requested that the Company file
a request for designation with the Office of Combination Products (RFD130051),
which led to the determination that RadioGel™ is a device for human therapy for
non-resectable cancers, which must be reviewed and ultimately regulated by the
Center for Devices and Radiological Health ("CDRH"). The Company then submitted
a 510(k) notice for RadioGel™ (K133368), which was found Not Substantially
Equivalent due to the lack of a suitable predicate, and RadioGel™ was assigned
to the Class III product code NAW (microspheres). Class III products or devices
are generally the highest risk devices and are therefore subject to the highest
level of regulatory review, control and oversight. Class III products or devices
must typically be approved by FDA before they are marketed. Class II devices
represent lower risk products or devices than Class III and require fewer
regulatory controls to provide reasonable assurance of the product's or device's
safety and effectiveness. In contrast, Class I products and devices are deemed
to be lower risk than Class I or II, and are therefore subject to the least
regulatory controls.

A pre-submission meeting (Q140496) was held with the FDA on June 17, 2014,
during which the FDA maintained that RadioGel™ should be considered a Class III
device and therefore subject to pre-market approval. On December 29, 2014, the
Company submitted a de novo petition for RadioGel™ (DEN140043). The de novo
petition was denied by the FDA on June 1, 2015, with the FDA providing numerous
comments and questions. On September 29, 2015, the Company submitted a follow-up
pre-submission informational meeting request with the FDA (Q151569). This
meeting took place on November 9, 2015, at which time the FDA indicated
acceptance of the Company's applied dosimetry methods and clarified the FDA's
outstanding questions regarding RadioGel™. Following the November 2015
pre-submission meeting, the Company prepared a new pre-submission package to
obtain FDA feedback on the proposed testing methods, intended to address the
concerns raised by the FDA staff and to address the suitability of RadioGel™ for
de novo reclassification. This pre-submission package was presented to the FDA
in a meeting on August 29, 2017. During the August 2017 meeting, the FDA
clarified their position on the remaining pre-clinical testing needed for
RadioGel™. Specifically, the FDA addressed proposed dosimetry calculating
techniques, dosimetry distribution between injections, hydrogel viscoelastic
properties, and the details of the Company's proposed animal testing.

The Company believes that its submissions to the FDA to date have addressed all
the FDA staff's feedback over the past four years. Of particular importance, the
Company has provided corresponding supporting data for proposed future testing
of RadioGel™ to address any remaining questions raised by the FDA. We believe,
although no assurances can be given, that the clinical testing modifications
presented to the FDA in August 2017 will result in a de novo reclassification
for RadioGel™ by the FDA. In addition, in previous FDA submittals, the Company
proposed applying RadioGel™ for a very broad range of cancer therapies, referred
to as Indication for Use. The FDA requested that the Company reduce its
Indications for Use. To comply with that request, the Company expanded its
Medical Advisory Board ("MAB") and engaged doctors from respected hospitals who
have evaluated the candidate cancer therapies based on three criteria: (1)
potential for FDA approval and successful therapy? (2) notable advantage over
current therapies? and (3) probability of wide-spread acceptance by the medical
community.

In November 2020 the Company submitted a request for a Breakthrough Device
Designation. Ultimately, this was denied, but the FDA acknowledged, "The FDA
does believe that RadioGel™ meets criterion #2a: Device represents breakthrough
technology. Your device does meet this criterion because it is a novel
application of a brachytherapy device outside of the liver." More importantly
the process resulted in a rapid review of our existing data and approach. It led
to a redirection of our efforts on writing the IDE and saved the Company much
time in the review of that future application.

26





Based on advice from the FDA the Company has scheduled a Pre-Submission meeting
on November 30, 2021 to discuss a draft of an Investigational Device Exemptions
(IDEs) for Early Feasibility Medical Device Clinical Studies, Including Certain
First in Human (FIH) Studies. Using this process results in more rapid feedback
to prepare the final IDE.

The FDA was very supportive and had suggested this Q-Submission path for rapid
turnaround and dialog. The Mayo Clinic physicians did an excellent job
presenting the need for Radiogel™ to treat recurrent thyroid cancer and to
answer a range of questions from the new FDA review team. The FDA provided many
helpful suggestions on a range of subjects from labeling to dosimetry to the
Mayo protocol for clinical testing, and the need for some additional specific
testing. They suggested having another Q-Sub Review and conference call
dedicated to the details of the dosimetry calculations.

In May of 2022 the Company held another Pre-Sub meeting with the FDA. They
concurred with our dosimetry techniques and requested one more animal test to
confirm that the Y-90 stays at the injection site. We will be proposed a Pre-Sub
meeting to discuss this new animal test of VX-2 tumors in rabbits at Johns
Hopkins University. We have a meeting scheduled with the FDA in October to
obtain their feedback on our new animal test plan. In the meantime, the Company
is working to complete all the other required pre-clinical testing, such as
biocompatibility since they are required for the submittal of the IDE.

At the same time, the Company working with the Mayo Clinic principal investigators to improve the clinical trial protocol of their Institutional Review Board.

The MAB selected eighteen applications for RadioGel™, each of which meet the
criteria described above. This large number confirms the wide applicability of
the device and defines the path for future business growth. The Company's
application establishes a single Indication for Use - treatment of cancerous
tissue or solid tumors pathologically associated with locoregional papillary
thyroid carcinoma and recurrent papillary thyroid carcinoma. We anticipate that
this initial application will facilitate each subsequent application for
additional Indications for Use, and the testing for many of the subsequent
applications could be conducted in parallel, depending on available resources.
We are in initial discussions with Mayo Clinic physicians about the potential
for RadioGel to treat lung and pancreatic cancers.

Funding and Strategy


The Company's stock offering under Regulation A+ was qualified by the Securities
and Exchange Commission ("SEC") on June 3, 2020. A second Regulation A+ was
qualified by the SEC on September 15, 2021 to raise capital for 50,000,000
shares at a price of $0.10 for a maximum of $5,000,000. The Company amended this
and was able to raise $1,200,000 in July 2022 at $0.08 per share (15,000,0000
shares) and sold 20,000,000 warrants for $20,000. An amended Regulation A+ was
filed in October 2022 to raise the remaining $3,800,000 of the $5,000,000.

The company’s A+ rule has raised approximately $5,200,000 from the sale of shares and uses the proceeds generated as follows:

For the pet therapy market:

? Fund the effort to communicate the benefits of IsoPet® to the veterinarian

community and pet owners.

? Conduct additional clinical studies to generate more data for the veterinarian

community

? Subsidize certain IsoPet® therapies, if necessary, to ensure that all

applicants are processed.

? Assisting a new regional clinic with its licensing and certification training.




For the human market:

? Improve the pedigree of the quality management system.

? Complete the preclinical tests previously defined and the additional tests on

an animal model closely aligned with our revised indication for use. Report

the results to the FDA at a pre-submission meeting.

? Use feedback from this meeting to write the IDE (Investigational Device

Exemption), which is necessary to initiate clinical trials.




Research and development of the Company's brachytherapy product line has been
funded with proceeds from the sale of equity and debt securities. The Company
may require additional funding of approximately $2 million annually to maintain
current operating activities. Over the next 12 to 24 months, the Company
believes it will cost approximately $9 million to: (1) fund the FDA approval
process to conduct human clinical trials, (2) conduct Phase I, pilot, clinical
trials, (3) activate several regional clinics to administer IsoPet® across the
county, (4) create an independent production center within the current
production site to create a template for future international manufacturing, and
(5) initiate regulatory approval processes outside of the United States. The
proceeds to be raised from the recent qualified Regulation A+ will be used to
continue to fund this development.

27





The continued deployment of the brachytherapy products and a worldwide
regulatory approval effort will require additional resources and personnel. The
principal variables in the timing and amount of spending for the brachytherapy
products in the next 12 to 24 months will be the FDA's classification of the
Company's brachytherapy products as Class II or Class III devices (or otherwise)
and any requirements for additional studies which may possibly include clinical
studies. Thereafter, the principal variables in the amount of the Company's
spending and its financing requirements would be the timing of any approvals and
the nature of the Company's arrangements with third parties for manufacturing,
sales, distribution and licensing of those products and the products' success in
the U.S. and elsewhere. The Company intends to fund its activities through
strategic transactions such as licensing and partnership agreements or from
proceeds to be raised from the recent qualified Regulation A+.

Following receipt of required regulatory approvals and financing, in the U.S.,
the Company intends to outsource material aspects of manufacturing,
distribution, sales and marketing. Outside of the U.S., the Company intends to
pursue licensing arrangements and/or partnerships to facilitate its global
commercialization strategy.

In the longer-term, subject to the Company receiving adequate funding,
regulatory approval for RadioGel™ and other brachytherapy products, and
thereafter being able to successfully commercialize its brachytherapy products,
the Company intends to consider resuming research efforts with respect to other
products and technologies intended to help improve the diagnosis and treatment
of cancer and other illnesses.

Based on the Company's financial history since inception, the Company's
independent registered public accounting firm has expressed substantial doubt as
to the Company's ability to continue as a going concern. The Company has limited
revenue, nominal cash, and has accumulated deficits since inception. If the
Company cannot obtain sufficient additional capital, the Company will be
required to delay the implementation of its business strategy and may not be
able to continue operations.

The Company has been affected by the effects of COVID-19. The registered office of the Company is located at Northeast Washington However, the pet therapy market has focused on the North West sector of United States. The Company is continuing its commercialization in the animal therapy market and is trying to increase exposure to its product and generate revenue accordingly.


As of September 30, 2022, the Company has $1,987,732 cash on hand. There are
currently commitments to vendors for products and services purchased. To
continue the development of the Company's products, the current level of cash
may not be enough to cover the fixed and variable obligations of the Company.

There can be no assurance that the Company will be able to raise additional funds or do so at a favorable price.

Product Features

The company’s RadioGel™ device has the following features:

? Beta particles only travel a short distance so that the device can provide high

radiation to the tumor with minimal dose to nearby normal tissue. In

medical terms Y-90 the beta emitter has a high efficiency rate;

? Benefiting from the short penetration distance, the patient can go home

immediately without fear of exposure to family members, and there is a large

reduction of radiation risk for the doctor. A simple plastic tube around the

a syringe, gloves and safety glasses are sufficient. Other gamma

emitting products require much more protection;

? A half-life of 2.7 days means that only 5% of the radiation remains after ten

days. This is in contrast to the industry standard gamma irradiation product,

which has a half-life of 17 days;



28




? The short half-life also means that any medical waste can be stored for thirty

days and then disposed of as normal hospital waste;

? RadioGel™ can be administered with small diameter needles (27 gauge)

is minimal damage to normal tissue. This is in contrast to the injection

metallic seeds, which do considerable damage; and

? After about 120 days, the gel resorbs through a normal biological cycle, called

Krebs cycle. The only remaining evidence of treatment is phosphate

particles of diameter so small that they require a high resolution microscope

to find them. This contrasts with the permanent presence of metallic germs.

Stages from production to therapy

Device manufacturing


During the next two years, the Company intends to outsource material aspects of
manufacturing and distribution. As future product volume increases, the Company
will reassess its make-buy decision on manufacturing and will analyze the
cost/benefit of a centrally located facility.

Manufacture of the hydrogel


RadioGel™ is manufactured with a proprietary process under ventilated sterile
hood by following strict Good Laboratory Practices ("GLP") procedures. It is
made in large batches that are frozen for up to three months. When the product
is ready to ship, a small quantity of the gel is dissolved in a sterile saline
solution. It is then passed through an ultra-fine filter to ensure sterility.

Production of Yttrium-90 phosphate particles


The Y-90 particles are produced with simple ingredients via a proprietary
process, again following strict GLP procedures. They are then mixed into a
phosphate-buffered saline solution. They can be produced in large batches for
several shipments. The number of particles per shipment is determined by the
dose prescribed by the doctor.

Dispatch


RadioGel™ is shipped in two containers, one with a solution of the gel and the
other with a solution of the particles. Before shipment they are subjected to
sterility testing, again by strict procedures. The vial with the Y-90 is put
through a special radiation calibrator, which measures beta particles. The vials
can be shipped via FedEx or UPS by following the proper protocols.

At the user

The user receives the two vials. The solution containing the RadioGel™ is mixed
with the solution containing the Y-90 particles. This is then shaken to ensure
homogeneity and withdrawn into a syringe. The quantities that are mixed are
calculated from the information on the product label.

The specific injection technique depends on the Indication for Use. For small
tumors, one centimeter in diameter or less, the cancer is treated with a single
injection. For larger tumors, the cancer is treated with a series of small
injections from the same syringe or multiple syringes.

Main markets

The Company currently pursues two synergistic business lines, medical and veterinary, each of which is summarized below.

29





Medical Sector

RadioGel™ is currently fully developed, requiring only FDA approval before
commercialization. The Company has been seeking FDA approval of RadioGel™ for
almost five years. Recent progress has been delayed due to a lack of adequate
funding. The principal issue preventing approval is that the Company attempted
to obtain regulatory approval for a broad range of Indications for Use,
including all non-resectable cancers, without sufficient supporting data.

Building on the FDA's ruling of RadioGel™ as a device, the Company is currently
developing test plans to address issues raised in the Company's prior FDA
submittal regarding RadioGel™. The Company intends to request FDA approval to
submit RadioGel™ for de novo classification, which would reclassify the device
from a Class III device to a Class II device and accelerate the regulatory
approval path.

After analyzing the Company’s data and the last five years of communication from the FDA, the Company has taken the following measures:

1. Under new leadership, the Society implements all past recommendations

from the FDA. The Company intends to restrict the Indications for Use,

provide test plans for FDA review to address all previous FDA responses

questions, and request a pre-submission meeting;

2. Prepare a pre-submission request document and an FDA meeting request to obtain

feedback on the test plans in order to launch the tests, present the

content proposed for the final application and to ask permission to

submit a de novo;

3. Submit an Investigational Device Exemption (“IDE”) for permission to

     conduct human clinical studies; and

  4. File a de novo or Pre-Market Approval application.


The critical path is the testing required – in vitro, animal testing, human clinical studies – all of which are resource dependent.

In previous submittals, the Company proposed applying a very broad range of
cancer therapies, referred to as Indications for Use, to RadioGel™. The FDA has
strongly advised the Company to reduce its Indications for Use. To comply with
that request, the Company has expanded its MAB, consisting of Drs. Barry D.
Pressman (Chairman), Albert DeNittis, and Howard Sandler.

The MAB evaluated the candidate cancer therapies based on three criteria: (i)
the potential for FDA approval and successful therapy; (ii) notable advantages
of RadioGel™ over current therapies; and (iii) the likelihood that RadioGel™ can
be widely accepted by the medical community and profitably commercialized.

The MAB selected eighteen Indications for Use for RadioGel™, each of which meets
the above-mentioned criteria. These eighteen Indications for Use are listed
below. This large number confirms the wide applicability of the device and
defines the path for future growth. The Company intends to apply to the FDA for
a single Indication for Use, followed by subsequent applications for additional
Indications for Use. The initial application should facilitate each subsequent
application, and the testing for many of the subsequent applications could be
conducted in parallel, depending on available resources.

?   Skin cancer                                  ?   Non-dendritic brain
?   Involved lymph nodes                         ?   Pediatric cancers - several types
?   Bladder                                      ?   Rectal
?   Liver                                        ?   Gynecological
?   Localized prostate                           ?   Spinal
?   Pancreas                                     ?   Recurrent esophageal
?   Head and neck (including sino-nasal and      ?   Breast cancer resection cavity
    oropharyngeal)
?   Ocular melanoma                              ?   Anaplastic thyroid



30





Veterinary Sector
There are approximately 150 million pet dogs and cats in the United States.
Nearly one-half of dogs and one-third of cats are diagnosed with cancer at some
point in their lifetime. The Veterinary Oncology & Hematology Center in Norwalk,
Connecticut, reports that cancer is the number one natural cause of death in
older cats and dogs, accounting for nearly 50 percent of pet deaths each year.
The American Veterinary Medical Association reports that half of the dogs ten
years or older will die because of cancer. The National Cancer Institute reports
that about six million dogs are diagnosed with cancer each year, translating to
more than 16,000 a day.

The Company's IsoPet® operating division focuses on the veterinary oncology
market. Dr. Alice Villalobos, a founding member of the Veterinary Cancer Society
and the Chair of our Veterinary Medicine Advisory Board, has been providing
guidance to management regarding this market. The Veterinary Medicine Advisory
Board gives us recommendations regarding the overall strategy for our animal
business sector. Specially, they recommended the university veterinary hospitals
for demonstration therapies, the specific cancers to be treated, and have
provided business contact information to the private clinics.

Development of the product and application techniques and animal testing is
allowed under FDA regulation. Commercial sales of RadioGelTM for animals
requires confirmation by the FDA Center for Veterinary Medicine ("CVM"). In
January 2018, the Center for Veterinary Medicine Product Classification Group,
the entity within the CVM that is responsible for determining the classification
of a product, ruled that RadioGelTM should be classified as a device for animal
therapy of feline sarcomas and canine soft tissue sarcomas.

Additionally, after a legal review, the Company believes that the device
classification obtained from the FDA Center for Veterinary Medicine is not
limited to canine and feline sarcomas, but rather may be extended to a much
broader population of veterinary cancers, including all or most all solid tumors
in animals. We expect the result of such classification and label approval will
be that no additional regulatory approvals are necessary for the use of
RadioGelTM for the treatment of solid tumors in animals. The FDA does not have
premarket authority over devices with a veterinary classification, and the
manufacturers are responsible for assuring that the product is safe, effective,
properly labeled, and otherwise in compliance with all applicable laws and
regulations.

The Company currently intends to utilize university veterinary hospitals for
therapy development, given that veterinary hospitals offer superior and
plentiful veterinarians and students, a large number of animal patients,
radioactive material handling licenses, and are respected by private veterinary
centers and hospitals.

Competitors

The Company is competitive in a market characterized by technological innovation, considerable research efforts and significant competition.


The pharmaceutical and biotechnology industries are intensely competitive and
subject to rapid and significant technological changes. A number of companies
are pursuing the development of pharmaceuticals and products that target the
same diseases and conditions that our products target. We cannot predict with
accuracy the timing or impact of the introduction of potentially competitive
products or their possible effect on our sales. Certain potentially competitive
products to our products may be in various stages of development. Also, there
may be many ongoing studies with currently marketed products and other
developmental products, which may yield new data that could adversely impact the
use of our products in their current and potential future Indications for Use.
The introduction of competitive products could significantly reduce our sales,
which, in turn would adversely impact our financial and operating results.

There are a wide variety of cancer treatments approved and marketed in the U.S.
and globally. General categories of treatment include surgery, chemotherapy,
radiation therapy and immunotherapy. These products have a diverse set of
success rates and side effects. The Company's products, including RadioGel™,
fall into the brachytherapy treatment category. There are a number of
brachytherapy devices currently marketed in the U.S. and globally. The
traditional iodine-125 (I-125) and palladium-103 (Pd-103) technologies for
brachytherapy are well entrenched with powerful market players controlling the
market. The industry-standard I-125-based therapy was developed by Oncura, which
is a unit of General Electric Company. Additionally, C.R. Bard, a major industry
player competes in the I-125 brachytherapy marketplace. These market competitors
are also involved in the distribution of Pd-103 based products. Cs-131
brachytherapy products are sold by IsoRay. Several Y-90 therapies have been FDA
approved including SIR-Spheres by Sirtex, TheraSphere by Biocompatibles UK and
Zevalin by Spectrum Pharmaceuticals.

31





Raw Materials

The Company currently subcontracts the manufacturing of RadioGelTM at
IsoTherapeutics. Prior to 2021, Eckert and Ziegler was the only supplier of Y-90
in the United States, and was the sole supplier of the Y-90 used by
IsoTherapeutics to manufacture the Company's RadioGel™. The Company obtains
supplies, hardware, handling equipment and packaging from several different U.S.
suppliers.

In 2021, used Akina, Inc. as an alternative supplier of its hydrogel polymer component.

Clients


The Company anticipates that potential customers for our potential brachytherapy
products likely would include those institutions and individuals that currently
purchase brachytherapy products or other oncology treatment products.

Government regulations


The Company's present and future intended activities in the development,
manufacturing and sale of cancer therapy products, including RadioGel™, are
subject to extensive laws, regulations, regulatory approvals and guidelines.
Within the United States, the Company's therapeutic radiological devices must
comply with the U.S. Federal Food, Drug and Cosmetic Act, which is enforced by
FDA. The Company is also required to adhere to applicable FDA Quality System
Regulations, also known as the Good Manufacturing Practices, which include
extensive record keeping and periodic inspections of manufacturing facilities.

In the United States, the FDA regulates, among other things, new product
clearances and approvals to establish the safety and efficacy of these products.
We are also subject to other federal and state laws and regulations, including
the Occupational Safety and Health Act and the Environmental Protection Act.

The Federal Food, Drug, and Cosmetic Act and other federal statutes and
regulations govern or influence the research, testing, manufacture, safety,
labeling, storage, record keeping, approval, distribution, use, reporting,
advertising and promotion of such products. Noncompliance with applicable
requirements can result in civil penalties, recall, injunction or seizure of
products, refusal of the government to approve or clear product approval
applications, disqualification from sponsoring or conducting clinical
investigations, preventing us from entering into government supply contracts,
withdrawal of previously approved applications, and criminal prosecution.

In the United States, medical devices are classified into three different
categories over which the FDA applies increasing levels of regulation: Class I,
Class II, and Class III. Most Class I devices are exempt from premarket
notification 510(k); most Class II devices require premarket notification
510(k); and most Class III devices require premarket approval. RadioGel™ is
currently classified as a Class III device.

Approval of new Class III medical devices is a lengthy procedure and can take a
number of years and require the expenditure of significant resources. There is a
shorter FDA review and clearance process for Class II medical devices, the
premarket notification or 510(k) process, whereby a company can market certain
Class II medical devices that can be shown to be substantially equivalent to
other legally marketed devices.

The Company intends to apply for a de novo with an anticipated expenditure of
$10.0 million over the next four years. This expenditure estimate includes
anticipated costs associated with in vitro and in vivo pre-clinical testing, our
application for an Investigational Device Exemption, Phase I and Phase II
clinical trials and our application for a de novo.

32




As a registered medical device manufacturer with the FDA, we are subject to
inspection to ensure compliance with FDA's current Good Manufacturing Practices,
or cGMP. These regulations require that we and any of our contract manufacturers
design, manufacture and service products, and maintain documents in a prescribed
manner with respect to manufacturing, testing, distribution, storage, design
control, and service activities. Modifications or enhancements that could
significantly affect the safety or effectiveness of a device or that constitute
a major change to the intended use of the device require a new 510(k) premarket
notification for any significant product modification.

The Medical Device Reporting regulation requires that we provide information to
the FDA on deaths or serious injuries alleged to be associated with the use of
our devices, as well as product malfunctions that are likely to cause or
contribute to death or serious injury if the malfunction were to recur. Labeling
and promotional activities are regulated by the FDA and, in some circumstances,
by the Federal Trade Commission.

As a medical device manufacturer, we are also subject to laws and regulations
administered by governmental entities at the federal, state and local levels.
For example, our facility is licensed as a medical device manufacturing facility
in the State of Washington and is subject to periodic state regulatory
inspections. Our customers are also subject to a wide variety of laws and
regulations that could affect the nature and scope of their relationships with
us.

In the United States, as a manufacturer of medical devices and devices utilizing
radioactive byproduct material, we are subject to extensive regulation by not
only federal governmental authorities, such as the FDA and FAA, but also by
state and local governmental authorities, such as the Washington State
Department of Health, to ensure such devices are safe and effective. In
Washington State, the Department of Health, by agreement with the federal
Nuclear Regulatory Commission ("NRC"), regulates the possession, use, and
disposal of radioactive byproduct material as well as the manufacture of
radioactive sealed sources to ensure compliance with state and federal laws and
regulations. RadioGel™ constitutes both medical devices and radioactive sealed
sources and are subject to these regulations.

Moreover, our use, management, and disposal of certain radioactive substances
and wastes are subject to regulation by several federal and state agencies
depending on the nature of the substance or waste material. We believe that we
are in compliance with all federal and state regulations for this purpose.

Environmental regulations


Our business does not require us to comply with any extraordinary environmental
regulations. Our RadioGel™ product is manufactured in an independently owned and
operated facility. Any environmental effects or contamination event that could
result would be from the shipping company during shipment and misuse by the
treatment facility upon arrival.

Human capital

From September 30, 2022, the Company had a full-time staff. The Company uses several independent contractors to assist in its operations. The Company has not concluded a collective agreement with any of its employees and considers that its relations with its personnel are good.

Operating results

Comparison of the nine months ended September 30, 2022 and 2021

The following table sets forth information from our income statements for the nine months ended September 30, 2022 and 2021:

                                  Nine Months Ended        Nine Months Ended
                                  September 30, 2022       September 30, 2021
Revenues                         $             30,000     $             14,887
Cost of goods sold                            (18,053 )                 (6,000 )
Gross profit                                   11,947                    8,887
Operating expenses                         (1,824,043 )             (2,292,245 )
Operating loss                             (1,812,096 )             (2,283,358 )
Non-operating income (expense)                 47,588                  (66,178 )
Net loss                         $         (1,764,508 )   $         (2,349,536 )



33




Revenue and Cost of Goods Sold


Revenue was $30,000 and $14,887 for the nine months ended September 30, 2022 and
2021, respectively. All revenue recognized in the nine months ended September
30, 2022 and 2021 relate to consulting income with respect to the IsoPet®
therapies.

Management does not anticipate that the Company will generate sufficient revenue
to sustain operations until such time as the Company secures multiple
revenue-generating arrangements with respect to RadioGel™ and/or any of our
other brachytherapy technologies.

Functionnary costs

Operating expenses for the nine months ended September 30, 2022 and 2021, respectively consist of the following elements:


                                                         Nine months ended  

End of nine months

                                                         September 30, 2022       September 30, 2021
Professional fees, including stock-based compensation   $          1,191,807     $          1,786,028
Payroll expenses                                                     208,818                  202,428
Research and development                                             312,066                  221,154
General and administrative expenses                                  111,352                   82,635
Total operating expenses                                $          

$1,824,043 2,292,245




Operating expenses for the nine months ended September 30, 2022 and 2021 was
$1,824,043 and $2,292,245, respectively. The decrease in operating expenses from
2021 to 2022 can be attributed to the decrease in professional fees ($1,786,028
for the nine months ended September 30, 2021 versus $1,191,807 for the nine
months ended September 30, 2022) related to the vesting of the RSUs in 2022
versus 2021; the increase in general and administrative expense ($82,635 for the
nine months ended September 30, 2021 versus $111,352 for the nine months ended
September 30, 2022); the increase in research and development ($221,154 for the
nine months ended September 30, 2021 versus $312,066 for the nine months ended
September 30, 2022) as the Company ramped up the development of their products
to include studies that are required to continue to have their products accepted
by the FDA, and an increase in payroll expenses ($202,428 for the nine months
ended September 30, 2021 versus $208,818 for the nine months ended September 30,
2022) related to the CEOs employment contract.

Non-operating income (expenses)

Non-operating income (expenses) for the nine months ended September 30, 2022 and 2021 includes the following:

                                  Nine months ended        Nine months ended
                                  September 30, 2022      September 30, 2021
Interest expense                 $                  -     $           (19,628 )
Forgiveness of debt                            47,588                 129,745
Loss on debt extinguishment                         -                (176,295
Non-operating income (expense)   $             47,588     $           (66,178 )



34




Non-operating income (expense) for the nine months ended September 30, 2022
varied from the nine months ended September 30, 2021 primarily due to a decrease
in interest expense from $19,628 for the nine months ended September 30, 2021 to
$0 for the nine months ended September 30, 2022 as a result of conversions and
repayments of notes payable. In addition, the Company converted a note in
January 2021 which resulted in a loss on conversion and recognized a gain on
forgiveness of debt on old payables as they satisfied agreements with vendors to
pay a portion of the payable with the remaining amount forgiven in both 2021 and
2022.

Net Loss

Our net loss for the nine months ended September 30, 2022 and 2021 was
$(1,764,508) and $(2,349,536)respectively.

Comparison of the three months ended September 30, 2022 and 2021

The following table presents information from our income statements for the three months ended September 30, 2022 and 2021:

                                 Three Months Ended      Three Months Ended
                                 September 30, 2022      September 30, 2021
Revenues                         $             6,500     $            14,887
Cost of goods sold                           (13,035 )                (6,000 )
Gross profit                                  (6,535 )                 8,887
Operating expenses                          (270,530 )              (203,470 )
Operating loss                              (277,065 )              (194,583 )
Non-operating income (expense)                     -                  (6,577 )
Net loss                         $          (277,065 )   $          (201,160 )



35




Revenue and Cost of Goods Sold


Revenue was $6,500 and $14,887 for the three months ended September 30, 2022 and
2021, respectively. All revenue recognized in the three months ended September
30, 2022 and 2021 relate to consulting income with respect to the
IsoPet®therapies.

Management does not anticipate that the Company will generate sufficient revenue
to sustain operations until such time as the Company secures multiple
revenue-generating arrangements with respect to RadioGel™ and/or any of our
other brachytherapy technologies.

Functionnary costs

Operating expenses for the three months ended September 30, 2022 and 2021, respectively consist of the following elements:


                                                         Three months ended 

Three months completed

                                                         September 30, 2022       September 30, 2021
Professional fees, including stock-based compensation   $             93,300     $             55,583
Payroll expenses                                                      68,163                   64,925
Research and development                                              70,765                   60,831
General and administrative expenses                                   38,302                   22,131
Total operating expenses                                $            270,530     $            203,470



Operating expenses for the three months ended September 30, 2022 and 2021 was
$270,530 and $203,470, respectively. The increase in operating expenses from
2021 to 2022 can be attributed to the increase in professional fees ($55,583 for
the three months ended September 30, 2021 versus $93,300 for the three months
ended September 30, 2022) related to the vesting of the RSUs in 2022 versus 2021
and amending the Regulation A+; the increase in general and administrati0ve
expense ($22,131 for the three months ended September 30, 2021 versus $38,302
for the three months ended September 30, 2022); the increase in research and
development ($60,831 for the three months ended September 30, 2021 versus
$70,765 for the three months ended September 30, 2022) as the Company ramped up
the development of their products to include studies that are required to
continue to have their products accepted by the FDA, and an increase in payroll
expenses ($64,925 for the three months ended September 30, 2021 versus $68,163
for the three months ended September 30, 2022) related to the CEOs employment
contract and bonus in 2021.

Non-operating income (expenses)

Non-operating income (expenses) for the three months ended September 30, 2022 and 2021 includes the following:

                                  Three months ended       Three months ended
                                  September 30, 2022       September 30, 2021
Interest expense                 $                  -     $             (6,577 )
Forgiveness of debt                                 -                        -
Non-operating income (expense)   $                  -     $             (6,577 )



36





Non-operating income (expense) for the three months ended September 30, 2022
varied from the three months ended September 30, 2021 primarily due to a
decrease in interest expense from $6,577 for the three months ended September
30, 2021 to $0 for the three months ended September 30, 2022 as a result of
conversions and repayments of notes payable. In addition, the Company recognized
a gain on forgiveness of debt on old payables as they satisfied agreements with
vendors to pay a portion of the payable with the remaining amount forgiven
in
2022.

Net Loss

Our net loss for the three months ended September 30, 2022 and 2021 was
($277,065) and ($201,160)respectively.

Cash and capital resources


At September 30, 2022, the Company had working capital of $1,885,197, as
compared to working capital of $1,467,383 at December 31, 2021. During the nine
months ended September 30, 2022 and 2021, the Company experienced negative cash
flow from operations of $838,391 and $728,351 and realized $1,220,000 and
$1,811,238 of cash flows from financing activities. As of September 30, 2022,
the Company did not have any commitments for capital expenditures.

Cash used in operating activities increased from $728,351 for the nine months
ended September 30, 2021 to $838,391 for the nine months ended September 30,
2022. Cash used in operating activities was primarily a result of the Company's
non-cash items, such as loss from operations, stock based compensation, loss
conversion of debt as well as forgiveness of debt as well as the changes in
prepaid expenses and accounts payable. Cash provided from financing activities
decreased from $1,811,238 for the nine months ended September 30, 2021 to
$1,220,000 for the nine months ended September 30, 2022. The decrease in cash
provided from financing activities was primarily a result of increase in
proceeds from the Regulation A+ where the Company raised $1,811,238 from common
stock and warrant issuances in 2021 versus, $1,220,000 in 2022.

The Company has generated material operating losses since inception. The Company
had a net loss of $1,764,508 for the nine months ended September 30, 2022, and a
net loss of $2,349,536 for the nine months ended September 30, 2021. The Company
expects to continue to experience net operating losses for the foreseeable
future. Historically, the Company has relied upon investor funds to maintain its
operations and develop the Company's business. The Company anticipates raising
additional capital within the next twelve months for working capital as well as
business expansion, although the Company can provide no assurance that
additional capital will be available on terms acceptable to the Company, if at
all. If the Company is unable to obtain additional financing to meet its working
capital requirements, it may have to curtail its business or cease all
operations.

In July 2022, the Company raised $1,220,000 through the sale of common stock and
warrants through the Regulation A+, and in October 2022 amended the Regulation
A+ in an attempt to raise the additional $3,800,000.

The Company requires funding of at least $5 million per year to maintain current
operating activities. Over the next 24 months, the Company believes it will cost
approximately $9 million to fund: (1) fund the FDA approval process to conduct
human clinical trials, (2) conduct Phase I, pilot, clinical trials, (3) activate
several regional clinics to administer IsoPet® across the county, (4) create an
independent production center within the current production site to create a
template for future international manufacturing, and (5) initiate regulatory
approval processes outside of the United States.

The principal variables in the timing and amount of spending for the
brachytherapy products in the next 12 to 24 months will be the FDA's
classification of the Company's brachytherapy products as Class II or Class III
devices (or otherwise) and any requirements for additional studies, which may
possibly include clinical studies. Thereafter, the principal variables in the
amount of the Company's spending and its financing requirements would be the
timing of any approvals and the nature of the Company's arrangements with third
parties for manufacturing, sales, distribution and licensing of those products
and the products' success in the U.S. and elsewhere. The Company intends to fund
its activities through strategic transactions such as licensing and partnership
agreements or additional capital raises.

Although the Company is seeking to raise additional capital and has engaged in
numerous discussions with investment bankers and investors, to date, the Company
has not received firm commitments for the required funding. Based upon its
discussions, the Company anticipates that if the Company is able to obtain the
funding required to retire outstanding debt, pay past due payables and maintain
its current operating activities, that the terms associated with such funding
will result in material dilution to existing shareholders.

Recent geopolitical events, including the inherent instability and volatility in
global capital markets, as well as the lack of liquidity in the capital markets,
could impact the Company's ability to obtain financing and its ability to
execute its business plan.

37




Accounting policies and estimates


The preparation of financial statements and related disclosures in conformity
with accounting principles generally accepted in the United States of America
requires management to make estimates and assumptions that affect the amounts
reported in the unaudited condensed financial statements and accompanying notes.
Management bases its estimates on historical experience and on various other
assumptions that are believed to be reasonable under the circumstances. Actual
results could differ from these estimates under different assumptions or
conditions. During the period ended September 30, 2022, we believe there have
been no significant changes to the items disclosed as significant accounting
policies in management's notes to the financial statements in our annual report
on Form 10-K for the year ended December 31, 2021, filed on March 7, 2022.

Off-balance sheet arrangements


The Company does not have any off-balance sheet arrangements that are reasonably
likely to have a current or future effect on the Company's financial condition,
revenues, results of operations, liquidity or capital expenditures.

© Edgar Online, source Previews

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How advanced optical tweezers revolutionized cell manipulation https://imphos.org/how-advanced-optical-tweezers-revolutionized-cell-manipulation/ Thu, 13 Oct 2022 18:30:19 +0000 https://imphos.org/how-advanced-optical-tweezers-revolutionized-cell-manipulation/ Optical tweezers (OT), also known as optical traps, are highly focused laser beams that can be used to trap and manipulate microscopic objects with non-contact force. Employed in a wide range of nano- and micro-scale operations, OTs have become particularly useful in the manipulation of biological objects, including human cells. A new journal published in […]]]>

Optical tweezers (OT), also known as optical traps, are highly focused laser beams that can be used to trap and manipulate microscopic objects with non-contact force. Employed in a wide range of nano- and micro-scale operations, OTs have become particularly useful in the manipulation of biological objects, including human cells.

A new journal published in EPJ More conveys the latest achievements in OT over the past decades. The review is authored by researchers from the College of Information Science and Engineering, Northeastern University, Shenyang, China?—?Sheng Hu, Jun-yan Ye, Yong Zhao, and Cheng-Liang Zhu?.

“It is well known that the cell is the basic unit of human life. If we could understand the mutation, proliferation and necrosis of cells, diseases inside the human body would be discovered and solved at the cell level,” Hu says. “Thus, optical tweezers can be seen as a pioneer used to confine these molecules so that more precise bio-measurement can capture changes in a cell, including proteins, mitochondria, and DNA.”

The authors begin by explaining the origins of OT dating back to the work of James Clerk Maxwell and the fact that light, despite its lack of mass, can possess momentum. Thus, the momentum of light could create a mechanical effect in matter. This concept will later be developed in the idea that small particles could be suspended by optical devices.

The authors point out that the advent of laser instruments – coherent light with both high intensity and good monochromatic characteristics – led to the optical manipulation of such microparticles, with the stable trapping of microparticles achieved in 1986.

OTs have now reached the stage where they can be used to trap, sort, transport and enrich various biological particles. For more complicated and delicate tasks, simple optical beams are now enhanced by devices such as acousto-optic modulators and electric vibrating mirrors.

The researchers add that OTs can now be used to accompany a new microscopy setup called the “human bright eye” to manifest the microstructure composed of micro/nano-particles. This means that OTs can act like a “thin human finger” gently holding these particles while this fake human eye probes them.

The team details the advantages OTs offer over similar techniques, such as atomic force microscopes (AFM), magnetic tweezers (MT), and acoustic tweezers (AT). These benefits include finer force intensity, their non-invasive nature, and the fact that they are made up of multiple optical components.

This means that optical manipulation and OTs have specifically found uses in fields as diverse as biology, pharmacology and clinical research fields by capturing nano and microparticles from molecules to cells.

“Given the potential ‘real-world’ applications of OT, there is still a long way to go,” Hu concluded. “For example, the problem of radiation exposure of cells or proteins needs to be improved. Moreover, achieving stability of optical patterns to submicron-scale particles is still difficult, reflecting complicated optical tuning. Although it can lead to confusion and sometimes even frustration, the intriguing biological presentations motivate us to facilitate the progression of the technique.

– This press release was originally published on the Springer website

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How to clean your chimney? https://imphos.org/how-to-clean-your-chimney/ Tue, 11 Oct 2022 19:03:04 +0000 https://imphos.org/how-to-clean-your-chimney/ Nothing beats a warm, roaring fire on a cold winter night. However, if you don’t maintain a clean hearth, soot, ash, and other particles can begin to enter your living spaces. The Chimney Safety Institute of America advises having a certified chimney sweep from any top notch house cleaning service such as Household Muffetta to […]]]>

Nothing beats a warm, roaring fire on a cold winter night. However, if you don’t maintain a clean hearth, soot, ash, and other particles can begin to enter your living spaces. The Chimney Safety Institute of America advises having a certified chimney sweep from any top notch house cleaning service such as Household Muffetta to assess and clean your fireplace once a year, but you should also clean it regularly yourself.

Any fireplace should be cleaned frequently and seasonally to stay attractive and safe. This tutorial will teach you more about cleaning a chimney and the proper cleaning products required for this essential element. Housekeeping task.

Everything you might need to clean your home

  • Drop cloths 8×11 (2)
  • basket of firewood
  • chimney shovel
  • portable broom and dustpan set
  • retail vacuum
  • retail vacuum bag
  • newspaper
  • spray container
  • clear vinegar
  • the water
  • outdoor and indoor gloves
  • nylon cleaning brush
  • mixing bowl
  • cornstarch
  • measuring spoons
  • fiber based fabric

How to Clean a Gas Fireplace

While a wood fireplace produces smoke and ashes, a gas fireplace provides heat. It heats a space faster and more efficiently than a gas heater. A gas fireplace, however, can get dirty over time. Due to the manufacturing chemicals used to create natural gas products, burning gas can cause a fireplace’s glass door to turn white or foggy. Here is a basic procedure for cleaning a gas fireplace:

  • Disconnect the gas valve.
  • Before cleaning, allow the burners to cool completely.
  • Using a vacuum cleaner, clean the area around the fireplace and/or one of its vents.
  • Open the fireplace door(s).
  • Dust ceramic gas logs and any decorative fireplace grate with a dry brush or towel.
  • Glass cleaner and paper towels are used to clean glass doors. Instead, consider using a specialized fireplace glass cleaner if there is a white coating.
  • Use dish soap and water to thoroughly clean andirons and tools. If necessary, follow up with a metal polish.

Here’s an extra tip: In a gas fireplace with faulty logs or vents, soot can build up. Make sure your gas fireplace is in good working order by contacting a plumber from a high-end housekeeping service.

How to Deep Clean a Chimney

Over time, soot, dander, dust and dirt can build up. When you light your gas fireplace, musty odors may begin to appear. Keep reading to learn how to clean a gas fireplace that hasn’t been cleaned recently or hasn’t been used much.

The first step is to disconnect the gas valve. Be sure before cleaning to allow the burners to cool completely to avoid heat injury. Before removing any pieces from your fireplace, take a picture of them. When reassembling the items, refer to the picture. Next, carefully remove the ceramic logs and lay them on a drop cloth or old towel. Keep in mind that ceramic gas logs should be dusted with a dry brush or towel.

All stones should be removed and placed in a container. Swish the stones while adding more cleaning solution to the container. Clean the stones, then lay them out to dry naturally on an old cloth. Before vacuuming, put the glass wool in a storage container if your home has one.

Dust and debris should be completely removed from around and under the gas grille and unit using a hand vacuum, shop vac, or vacuum hose. Seek help from a House cleaning professional could be helpful. You can also do it yourself. If you have a flue, don’t forget to vacuum it. Clean the floor and walls of your fireplace of all dirt and grime. Stiff bristle brushes soaked in cleaning solution are essential for scrubbing. Start from top to bottom. If necessary, perform this step several times. Prevent your gas appliance and grill from getting too wet.

After that, with a clean cloth, wipe the floor and walls of your fireplace. Using a cloth lightly dampened with the cleaning solution, wipe down the gas grid and the appliance. Allow the floor and walls of your fireplace to dry. Restock the fireplace with your logs, stones, andirons, glass wool and other accessories. Use glass cleaner and paper towels to clean any glass doors you have.

Tips for cleaning an electric fireplace

Electric fireplaces are cleaner than gas or wood fireplaces since they heat the air with a heater. However, they require cleaning, just like any other aspect of the house. To learn how to use a wall-mounted electric fireplace, consult the manufacturer’s instructions. Learn how to clean an electric fireplace using the methods below.

Now we know that an essential step is to turn off the device. Open or remove the glass doors.

With a clean cloth, dust your hearth, andirons, logs and stones. To make your metal andirons even shinier, use metal polish. Use a handheld vacuum or hose attachment to clean the vents.

The inside and outside of the walls of your fireplace should be cleaned with a feather duster or a clean, damp cloth. The glass doors of your fireplace need to be cleaned. Use a clean cloth or paper towels with standard window cleaning. Any top notch house cleaning service will do the work for you.

How to clean an old-fashioned wood-burning fireplace

Traditional fireplaces are common, especially in older homes. A traditional crackling and roaring fire is produced using wood. Ash, soot and creosote build up with continued use. A metal grate is the only thing in a fireplace that burns. It will feature a damper, although it may or may not have glass doors or a built-in screen.

Here’s how to clean a wood-burning fireplace.

  • Turn off all fire. A chimney shovel can be used to spread the embers. With ashes or a little baking soda, cover the embers. Give it a day.
  • Create a deep cleaning agent. In a large bucket, combine dish soap, 1/4 cup heavy-duty cleaner, and 1 gallon of warm water.
  • To get rid of burnt wood, use a shovel and your hands.
  • Take out the hearth grate and the andirons. Put as much of the ashes and other debris back into the fireplace as you can.
  • Use a broom and dustpan to sweep up the ashes. To completely remove residue, use a vacuum hose, shop vacuum, or handheld vacuum.
  • Use a stiff bristle brush and cleaning solution to scrub the inside of the fireplace. Start from top to bottom.
  • Using a pumice stone dipped in dish soap, wash the bricks around a fireplace. Try a trisodium phosphate cleaner for particularly hard-to-remove soot stains.
  • Use glass cleaner and paper towels to clean any glass doors you have. Or see how to use wood ash to clean the fireplace glass.
  • Hot water is first applied to a paper towel, then to ashes. Clean the glass by rubbing it. Use a paper towel to pat dry after rinsing.
  • Give the floor and walls of your fireplace enough time to dry completely.
  • Use dish soap and water to wash irons and equipment. If necessary, follow up with a metal polish.

Additional tips

Find a licensed chimney sweep who has passed a standards and codes test and knows proper construction methods when arranging for a chimney cleaning and inspection. In the event of an accident, he should also have insurance and workers’ compensation.

Creosote, a tar-like result of burning wood, should be cleaned from the chimney when it is 1/8 inch or thicker on the chimney walls, according to the Chimney Safety Institute. Schedule cleaning at the end of the season because the humidity combined with the creosote can cause strong aromas and the acids contained in the creosote can damage the mortar of the fireplace.

The floor will be covered with a drop cloth during professional cleaning, a vacuum system will be connected and a variety of equipment and brushes will be available. A firm brush is used to clean the damper rim and the inside walls of the chimney while the vacuum is running.

The chimney sweep should check your chimney during the same appointment to make sure there are no major cracks, no missing or loose bricks or mortar, the damper is installed and working properly, the chimney cap is in good condition and that the chimney is structurally sound.

Endnotes

It is simple to learn how to clean a chimney. You can clean your electric or wood-burning fireplace in an afternoon with a few simple tools. Always begin by draping a drop cloth or tarp over the area where you will be working. Furniture and rugs should be moved. A trash can or bucket should be nearby. When using strong cleaners, it is extremely important to wear cleaning gloves, eye protection and a face shield. Make sure these steps will make your cleaning process easier. There is always the possibility of enjoying a top notch housekeeping and house cleaning service.

Image source: https://unsplash.com/s/photos/chimney

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Game over? Nick Lane wants another round https://imphos.org/game-over-nick-lane-wants-another-round/ Fri, 07 Oct 2022 23:02:35 +0000 https://imphos.org/game-over-nick-lane-wants-another-round/ Image: A scene from “Molecular Machines – ATP Synthase: The Power Plant of the Cell”, via Discovery Institute. The score is 36-0, but Darwin’s team is not ready to take it. Lehigh University biochemist Michael Behe, writing for World Magazine (see our coverage here), described how he attended a conference of scientists to hear Nobel […]]]>

Image: A scene from “Molecular Machines – ATP Synthase: The Power Plant of the Cell”, via Discovery Institute.

The score is 36-0, but Darwin’s team is not ready to take it. Lehigh University biochemist Michael Behe, writing for World Magazine (see our coverage here), described how he attended a conference of scientists to hear Nobel Prize winner John E. Walker, the world’s expert on ATP synthase, explain how it might have evolved. For design advocates, this rotary motor is a model of smart design. Walker, who shared a Nobel Prize for elucidating the rotary mechanism of the engine, spent all of his time describing the intricacies of this molecular machine and never offered an evolutionary explanation until the Q&A session. Then he was asked directly how an insane process could produce such stunning work. Walker stumbled, offering only a shred of speculation that he must have arisen “Slowly, through some sort of intermediary or other.” It was then that Behe, out of earshot, whispered two simple words, “Game over.”

Game over. The losing team heads for the showers with their heads down. Team Darwin’s MVP had just been retired in the bottom of the ninth. Calling the game in such an obvious wipeout would have been redundant. The crowd comes out of the stands. Suddenly, eight players are running on the field! “Wait! Wait!” they are crying. “Let’s have a batting time!”

The rescue team, led by Nick Lane of University College London, waves a paper above their heads. It’s just off the press PLOS Biology, titled “A Prebiotic Basis for ATP as a Universal Energy Currency”. Lane shouts, We have the middleman! It’s ACP! One of the referees looks at the paper for a minute. Will it be worth calling teams back to the field for another round?

A plausible scenario?

The gist of the hypothesis is that acetyl phosphate (AcP), a simple molecule with the formula C2H5O5P, can phosphorylate ADP to ATP in water, if the ferric ion (Fe3+) is present. The team believe their lab work offers a plausible scenario for the formation of prebiotic ATP without the need for ATP synthase.

ATP is universally conserved as the primary energy currency in cells, driving metabolism through phosphorylation and condensation reactions. Such deep preservation suggests that ATP appeared at an early stage of biochemical evolution. Still the synthesis of purines requires 6 phosphorylation steps linked to the hydrolysis of ATP.This autocatalytic requirement for ATP to synthesize ATP implies the need for a prebiotic ATP equivalentwhich could lead protometabolism before purine synthesis. Why this early phosphorylating agent was replaced, and specifically by ATP rather than other nucleoside triphosphates, remains a mystery. Here we show that the deep conservation of ATP might reflect its prebiotic chemistry in relationship with another universally conserved intermediate, acetyl phosphate (AcP), which bridges thioester and phosphate metabolism by linking acetyl CoA to phosphorylation at the substrate of ADP. We confirm the previous results showing that AcP can phosphorylate ADP to ATP in nearly 20% yield in water in the presence of Fe3+ions. We then show that Fe3+ and AcP are surprisingly favored. [Emphasis added.]

It looks impressive. Can this work?

The team informs the referee of the surprising additional advantages of their intermediary. Visions of the Miller spark apparatus come to mind:

Surprisinglyour results show that maximum ATP synthesis occurred at high water activity and low ion concentrations, indicating that prebiotic ATP synthesis would be more feasible in freshwater systems.Likewise, ferrous iron can be oxidized to ferric iron by photochemical reactions or oxidants such as NO derived from volcanic emissions, meteorite impacts or lightning strikes, which also refers to terrestrial geothermal systems as a plausible environment for aqueous ATP synthesis.

questions and answers

What about hydrothermal vents?, asks the referee. Aren’t they the preferred places for prebiotic environments? “[O]Our results do not exclude submarine hydrothermal systems as potential environments for this chemistry,” they rejoice. But that could not happen today, they explain, because “high concentrations of Mg2+ (50 mM) and Ca2+ (10 mM) prevented ATP synthesis, implying that this chemistry would not be favored in modern oceans. The referee, frowning a little, senses a special pleading unfolding.

Other referees approach to see what it is. After listening, they start asking questions.

Have you tried this in a natural setting? No, we purchased chemicals from Fischer and Sigma-Aldrich and then mixed them in our lab under controlled conditions. (See Materials and Methods section.)

How did you go about linking the ingredients? We used store-bought catalysts and mixed them with store-bought nucleotides and phosphorylating agents. Then we shook them and heated them.

Why do you think this represents a plausible prebiotic environment? “AcP is unique among a panel of relevant phosphorylating agents in that it can phosphorylate ADP to ATP, in water, in the presence of Fe3+. AcP is readily formed by prebiotic chemistry and remains central to prokaryotic metabolism, making it the most plausible precursor to ATP as a biochemical phosphorylator.

Are you likely to find sufficient concentrations of AcP and ferric ions in natural water conditions for this to occur on early Earth? Uh, we haven’t tested that.

Wait a second; adenosine is a nucleoside base that includes ribose. How did it form in water? It’s a problem, we agree.

Have you tested chirality? Uh no.

Did you find a plausible container to hold the ATP? That wasn’t part of our investigation, no.

OK, so you get ATP under special conditions. ATP has a half-life of less than 5 minutes in water. Do you expect it to hang around long enough to be useful in a protocell? We haven’t thought about it in this article, no.

The ATP is obviously not alive. What would happen next? Presumably some primitive metabolic process could use it to produce energy.

Like what? “Recent experimental work shows that the core of autotrophic metabolism can occur spontaneously in the absence of genes and enzymes. This includes non-enzymatic equivalents of the acetyl-CoA pathway and parts of the reverse Krebs cycle, glycolysis and pentose phosphate pathway, gluconeogenesis, and amino acid biosynthesis. Recent work demonstrates that some nucleobases can also be formed following universally conserved biosynthetic pathways, using transition metal ions as catalysts. The idea that ATP might have arisen as a product of protometabolism from H2 and CO2 is therefore not unreasonable…”.

What exactly is “protometabolism”? Does it have meaning outside of a living context? (Silent gazes.)

Who decides what is reasonable? I suppose so.

The article states that “the biological synthesis of purines specifically involves 6 phosphorylation steps that are catalyzed by ATP in modern cells”. Adenine is a purine. How do you overcome the chicken and egg problem of needing ATP to make ATP?“If ATP did indeed form in a monomer via biomimetic protometabolism, then an earlier ATP equivalent must have driven the phosphorylation steps in purine synthesis.”

Can you describe a plausible earlier ATP equivalent? In fact, “a major question for prebiotic chemistry is how an energy money power might work” if not ATP.

And how did the ATP come to replace him, whoever he is? “Why this early phosphorylating agent was replaced, and specifically by ATP rather than other nucleoside triphosphates, remains a mystery.”

So how did your simple ATP generation process get replaced by ATP synthase? Well, it is well known that “ATP synthase fuels an imbalance in the ratio of ADP to ATP that is 10 orders of magnitude above the balance in the cytosol of modern cells. The drivers molecules such as ATP synthase use ratchet-like mechanical mechanisms to convert environmental redox imbalances into a highly skewed ratio of ADP to ATP, but we cannot say how this happened.

But how could a simple prebiotic system composed mostly of monomers sustain an imbalance in the ATP to ADP ratio that fuels labor? Well, “One possibility is that dynamic environments can maintain critical imbalances over short distances such as protocellular membranes.”

Didn’t you just assume the existence of a protocell with a membrane? Where did they come from? Listen, we’re not trying to paint a complete picture of the origin of life. We are simply trying to explain why ATP is the universal energy currency for life as it exists today, and how it came to emerge.

Emerged…by chance, you mean? Isn’t that circular reasoning? How? What other possibility is there?

There is intelligence, the only cause ever observed capable of assembling complex parts into a functional whole. Sorry; we thought it was a science baseball field.

He is. So what is your explanation of functional information in the simplest life? Your newspaper admits that “ATP links energy metabolism to genetic information. What is the source of this genetic information? Uh, some kind of middleman or whatever.

The referees gather and shout “GAME OVER!”

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