Back in January, ultrarunning star Jim Walmsley eked out a qualifier for next Februarys Olympic Marathon Trials at the Houston half marathon, hitting the 1:04:00 entry standard right on the nose. The tantalizing prospect of mountain man Walmsley challenging for an Olympic berth on the roads stirred up yet another round of the long-running marathoner vs. ultramarathoner debate.

Of course, such comparisons depend on the details of the challenge. Even a truly world-class road specialist with a marathon best of 2:05, Walmsley told the Citius podcast, wouldnt be able to keep up with him on the long, mountainous trails he specializes in: The way I attack the downhills... I will break your quads and you wont be able to jog the flats anymore, he said. Find your 2:05 guy, give me a couple hours in the canyon, Ill be the first one out.

Bold words. But does he have a point? Marathons are generally thought to be a reasonably straightforward test of physiology: VO2max (how quickly you deliver oxygen for your muscles to use), running economy (how efficiently they use it), and lactate threshold (a proxy for how long you can sustain a hard effort). Ultramarathons, according to conventional wisdom, are different. Durability is more important than efficiency, which is why ultrarunners wear heavier shoes and take shorter strides. An iron stomach, to handle lots of eating and running, is more useful than a heart of steel. And the mind is the most important factor of all.

Few studies have actually tested these claims, though, and theres a countervailing school of thought that if a few second-tier Kenyan and Ethiopian marathoners dove into the trail ultra scene, theyd immediately mop up the competition. One of the most hilarious passages in Adharanand Finns recent book The Rise of the Ultra Runners follows his efforts to crowdfund Kenyan and Ethiopian runners to big ultra races in Britain and the United States. A series of mishaps, ranging from a sore toe to the raging wildfires that canceled the North Face 50-mile race in California last year, scuppers every attempt, so the question remains unanswered.

But with the growth of ultrarunning, researchers are becoming increasingly interested in the topic. At a recent conference on sport innovation, University of Guelph researcher and former elite triathlete Alexandra Coates presented some preliminary data from a study of runners at the Sulphur Springs Trail Race, an event in Ontario that includes 50K, 80K, and 160K distances around a course with 20K loops that gain and lose 620 meters each time. Coates and her colleagues put 42 runners (25 men, 17 women) through a series of baseline tests, including the usual physiology tests in the lab, and also assessed their training history and monitored their hydration status during the race. Then they asked a simple question: which variables best predict race performance?

When all the racers were grouped together, performance (quantified by percent of winning time) was best predicted by the highest speed the subjects reached in their treadmill VO2max test. By looking at the speed during the treadmill test, rather than just VO2max itself, you get a measure that reflects both your VO2max and your running economy. In other words, as Coates put it during her talk, those with the best running fitness notched the highest finishesnot a huge surprise, and the same thing youd expect to see in a regular road marathon.

The second-best predictor is perhaps a little more surprising: those who lost the most weight during the race tended to finish faster. Thats also consistent with previous findings from road marathons and other endurance races. What this means is up for debate. One possibility is that drinking too much slows you downby making you heavier, compared to simply drinking when youre thirsty and allowing yourself to get a bit dehydrated. Alternately, the causal arrow may be the other way around: faster and more experienced runners may be better at judging how much (or how little) fluid they need, while slower newbies tend to be overly cautious and drink more. Thats a debate for another time, but its interesting that this pattern once again shows up even in longer races.

Notably missing from the picture is anything related to training history. How much the subjects reported running each week, or over the past year, how much strength training they did, how many years theyd been running, how many previous marathons or ultramarathons theyd completednone of this had any significant impact on finishing performance. Now, dont misread this to imply that training doesnt matter for ultrarunning! But in this particular cohort of recreational runners training, on average, about eight hours per week, the differences between those doing a little more and those doing a little less werent what determined finishing place.

Another interesting detail is what happens when you break down the results by finishing distance. There were 21 runners in the 50K, 13 in the 80K, and just 8 in the 160K, so you have to take the sub-analyses with a big grain of salt. But for what its worth, heres what you find.

The 50K looks a lot like the marathon, with plenty of straightforward physiological predictors. Speed at VO2max is the best one for both men and women; when you combine the genders, percent change in body mass is the best. Other basic health measures like body massindex, age, resting heart rate, and blood pressure also have some predictive power.

But as you go to longer distances, the picture changes. At 80K, the only significant predictor is speed at VO2max. And at 160K, none of the variables measured had any relationship with the eventual performance of the runners. In a sense, this corroborates what ultrarunners like Jim Walmsley have been saying for years: the traits that make you a great marathoner wont necessarily make you a great ultramarathoner, and the differences get wider and wider as the distance gets longer.

I asked Coates what sorts of additional measurements she would add to her study if she were doing it again and wanted to get a better prediction of ultra success. She mentioned strength testing and neuromuscular fatigue resistance, to get a sense of how well your leg muscles can stand up to the prolonged pounding. In-race nutrition strategies is another big one, though its tricky to study in the field: some of the subjects were hallucinating from fatigue by the time they got to her research tent, which makes it hard to get reliable information on what they had eaten. And psychological characteristics are undoubtedly important: how well do you handle adversity and pain?

Of course, all of those ultra-specific traits are important to varying degrees even in shorter road races. Theyre not two different sports, just two ends of a spectrum. And thats what makes Walmsleys upcoming appearance at the Olympic Marathon Trials so much fun to contemplate. Even in the marathon, the standard physiological prediction equations dont always capture everything that matters.

My book, Endure: Mind, Body, and the Curiously Elastic Limits of Human Performance, with a foreword by Malcolm Gladwell, is now available. For more, join me on Twitter and Facebook, and sign up for the Sweat Science email newsletter.

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Why Ultrarunning Success Is Hard to Predict - Outside

DEERFIELD, Ill., Nov. 17, 2019 /PRNewswire/ -- Mezzion Pharma Co. Ltd. (140410: KOSDAQ) today announces the presentation of data from its pivotal clinical trial for its new orphan drug for the treatment of adolescents with single ventricle heart disease.

Dr. David Goldberg, Pediatric Cardiologist, Children's Hospital of Philadelphia presented the top line results from the FUEL (Fontan Udenafil Exercise Longitudinal Trial) at the Annual Scientific Session of the American Heart Association (AHA) and in a Mezzion Sponsored scientific symposium titled "Fontan Physiology and Results of the FUEL Trial". The primary aim of the FUEL trial was to improve the exercise capacity in adolescents with congenital single ventricle heart disease who have undergone a series of surgeries to palliate the effect of a missing ventricle in their heart. The results of the 400 subject, double-blind, placebo-controlled study showed that the primary aim of improving exercise capacity in adolescents with congenital single ventricle heart disease (SVHD) was achieved.

The top line data from the FUEL trial, which was designed to evaluate the safety and efficacy of udenafil for the treatment of SVHD adolescents, showed that subjects taking udenafil over a 6-month period had a significant improvement in exercise capacity as measured by oxygen consumption at the ventilatory anerobic threshold (VO2 at VAT). Work rate at VAT and ventilatory equivalents of carbon dioxide at the VAT (VE/VCO2) were likewise improved. While peak VO2 also improved, the data did not reach statistical significance. VO2 at VAT measures the level of oxygen consumption at which one changes from aerobic to anaerobic activity, a clinically relevant level of exertion that is typical of what is encountered in routine exercise activity. Work rate measures the power (watts) generated at the VAT while VE/VCO2 is an index comparing the volume of CO2 with the total respiratory volume. All of these measures demonstrated statistically significant improvement in the udenafil treated group compared to the placebo treated group, as described later in this Press Release.

The FUEL trial was conducted in partnership with the Pediatric Heart Network (PHN) at a total of 30 Pediatric Heart Network [http://www.pediatricheartnetwork.org] and auxiliary sites throughout the U.S., Canada, and Korea. The PHN is funded by the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.

The Fontan Surgery

The Fontan operation is a palliative procedure for children born with functional single ventricle congenital heart disease. Following the Fontan operation there is no ventricular pump to propel blood into the pulmonary arteries. Instead the blood returns to the lungs via passive flow from the systemic veins. This results in a circulation characterized by elevated central venous pressure and a chronically low cardiac output. Over time, these inherent characteristics of Fontan physiology result in a predictable, persistent deterioration of cardiovascular efficiency, as marked by a progressive decline in exercise performance, a decline that accelerates after puberty. This decline in cardiovascular efficiency is associated with the development of substantial morbidities and a significantly shortened life expectancy.

The Fontan Physiology and Exercise Capacity: VO2at VAT is the appropriate measure in Fontan subjects

Exercise capacity of study participants was measured in an exercise lab using a special stationary exercise bicycle that is programmed to increase resistance so that their maximum effort can be assessed. The subject peddles the bicycle while wearing a special mask that allows for the measurement of oxygen consumption. The bicycle automatically increases in resistance requiring the subjects to increase their effort and consume increasingly more oxygen up to their maximum effort.

In the symposium, Dr. Stephen Paridon, Pediatric Cardiologist and Exercise Physiologist, Children's Hospital of Philadelphia explained that exercise capacity can be measured by evaluating the maximal oxygen consumption at the subject's maximal effort (peak VO2) or by measuring the oxygen consumption at the ventilatory anerobic threshold (VO2 at VAT). Peak VO2 is the classical measurement of oxygen capacity in those with two functional ventricles, and therefore was used as the primary outcome measurement in the FUEL trial. Dr. Paridon explained that the new finding from the FUEL trial and other relatively recent research suggest that peak VO2 is not the most appropriate measurement to assess exercise capacity due the unique physiology resulting from the Fontan palliation. Fontan subjects do not have a ventricle to pump the venous blood to the lung. Blood flow to the lung depends solely on the central venous pressure in the body. The central venous pressure in those who have undergone the Fontan operation is elevated at baseline, and typically rises to the degree needed to meet metabolic demands at high levels of exertion, thereby creating a limit to the amount of exercise that can be achieved. While peak VO2 demonstrated improvement of about 3.2% in the udenafil treated group vs 0% in the placebo group, statistical significance (p value=0.07) was not achieved.

Dr. Paridon further explained that VO2 at VAT, may be a more relevant measure of exercise capacity in the Fontan physiology because it occurs at a lower central venous pressure and appears to be less limited by this unique physiology. VO2 at VAT improved by 2.9% in the udenafil group versus a 1.0 % decline in the placebo group and was statistically significant (p value=0.009). Significant improvement also was achieved in two other key parameters which independently demonstrate the Fontan subjects' improved exercise capacity at the ventilatory anerobic threshold: work rate at VAT and ventilatory efficiency (VE/VCO2) at VAT. Dr. Paridon explained that any improvement in VO2 at VAT is clinically relevant to the SVHD patient population.

Regulatory Status

A meeting with the Cardiovascular and Renal Division (DCaRP) of the US FDA was held on October, 8, 2019 for the purpose of presenting the topline data from the FUEL trial and to reach a concurrence with the FDA on the path forward toward submitting a new drug application (NDA) for the approval of udenafil for improving the exercise capacity in subjects with SVHD.

The FDA provided very helpful and constructive guidance. Based on its initial review of the top line data from the FUEL trial, the FDA confirmed that Mezzion can proceed with the submission of the NDA for udenafil for improving the exercise capacity of SVHD subjects and that the submission would be "fileable" provided that the submission contained all of the required information.

Accordingly, in view of the positive results from the FUEL Trial and the safety data collected about udenafil, and in view of the constructive guidance by the FDA, Mezzion intends to expeditiously submit a New Drug Application to the FDA to seek approval for the use of udenafil to treat patients with SVHD who have undergone Fontan palliation.

Mezzion's Clinical Program

In addition to the pivotal FUEL trial, Mezzion continues forward in its clinical program in partnership with the PHN with a long-term study to evaluate the safety of udenafil (FUEL-OLE Study) ClinicalTrials.gov Identifier: NCT03013751) and a study to evaluate the effect of treatment on Fontan-associated Liver Disease (FALD study). Because of the elevated central venous pressure, liver fibrosis, which can lead to liver cirrhosis, is prevalent in almost all Fontan subjects starting at a very early age. (ClinicalTrials.gov Identifier: NCT03430583).

Orphan Drug and Rare Pediatric Disease Status

On 31 August 2015, The Office of Orphan Products Development (OOPD) granted orphan drug status for udenafil in the treatment of single ventricle congenital heart disease with Fontan physiology [FDA Letter, OOPD, Designation Request #14-4497]. On 20 April 2017, OOPD designated udenafil for treatment of single ventricle congenital heart disease as a drug for "rare pediatric disease".

New Patents

Mezzion has submitted patent filings based on the new findings from the FUEL trial. The new patents, if the claims are allowed, should further strengthen the patent position for Mezzion in the United States and elsewhere. Mezzion is not only protected by different patent families, but its exclusivity is further enhanced by other forms of protection such as regulatory and proprietary know-how. We believe that this matrix of intellectual property provides Mezzion with a unique position to provide a much-needed new pharmacotherapy to Fontan patients.

Udenafil

Udenafil is a unique phosphodiesterase (PDE)-5 inhibitor being developed in the United States (US) to improve and maintain exercise capacity in adolescents with Fontan physiology. PDE5 inhibitors are a class of medications that have demonstrated utility in reducing pulmonary vascular resistance and improving ventricular performance in patients with pulmonary hypertension (Galie et al 2005; Humpl et al 2005; Behling et al 2008; Nagayama et al 2009; Guazzi et al 2011). Udenafil is a unique PDE5 inhibitor that that has undergone Phase III testing in adolescents with Fontan physiology and has demonstrated excellent safety and tolerability in this population, in which cardiac output and exercise are limited by the absence of a sub-pulmonary ventricle.

Mezzion Pharma Co. Ltd.

Mezzion Pharma is headquartered in South Korea. Mezzion Pharma and its wholly owned subsidiary, Mezzion Pharmaceuticals, Inc., have administrative offices in Deerfield, Illinois and Boca Raton, Florida. Mezzion Pharma is an innovation-driven pharmaceutical company that is focused on discovering, developing, and commercializing novel therapeutics in the field of rare pediatric diseases. Mezzion Pharma is a publicly-listed pharmaceutical company in Korea on the Korean stock exchange under (140410:KOSDAQ).

Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding: Mezzion Pharma's expectations regarding the potential benefits of udenafil; Mezzion Pharma's expectations regarding the anticipated timing of any future clinical trials; Mezzion Pharma's expectations on regulatory submissions for marketing approval of udenafil for the treatment of Fontan patients to improve exercise capacity in the United States, including the timing of these submissions; and Mezzion Pharma's expectations regarding the potential commercial launch of udenafil, including the timing of a potential approval of udenafil. Risks and uncertainties that contribute to the uncertain nature of the forward-looking statements include: the expectation that Mezzion Pharma will need additional funds to finance its operations; Mezzion Pharma's or any of its collaborative partners' ability to initiate and/or complete clinical trials; the unpredictability of the regulatory process; the possibility that Mezzion Pharma's or any of its clinical trials will not be successful; Mezzion Pharma's dependence on the success of udenafil; Mezzion Pharma's reliance on third parties for the manufacture of Mezzion Pharma's udenafil and udenafil tablets; possible regulatory developments in the United States and foreign countries; and Mezzion Pharma's ability to attract and retain senior management personnel.

These and other risks and uncertainties are described more fully in Mezzion Pharma's most recent filings with the Statements under the Private Securities Litigation Reform Act: with the exception of the historical information contained in this release, the matters described herein contain forward-looking statements that involve risk and uncertainties that may individually or mutually impact the matters herein described, including but not limited to FDA review and approval, product development and acceptance, manufacturing, competition, and/or other factors, which are outside the control of Mezzion Pharma. All forward-looking statements contained in this press release speak only as of the date on which they were made. Mezzion undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

Contact:

Dr. James YeagerTel: +1-847-2122679Email: james.yeager@mezzion.comDeerfield, Illinois, USA

Mr. YT SongTel: +82 2 560 8011Email:ytsong@mezzion.co.krSeoul, Korea

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Mezzion Pharma announces the presentation of the FUEL Trial data at the American Heart Association Meeting in Philadelphia - The Courier-Express

From left are Southeast students Kevin Yaeger, Logan Page and Kory Kasper.

Three Southeast Missouri State University students in the Department of Kinesiology, Nutrition and Recreation captured first place for the second consecutive year in the Student Quiz Bowl at the Central States Chapter of the American College of Sports Medicine (ACSM) Conference Oct. 24-25 in Tulsa, Oklahoma.

The annual Student Quiz Bowl is a jeopardy-style competition amongst undergraduates from universities and colleges from Kansas, Arkansas, Oklahoma and Missouri. Each team of three students is given a question from science-based categories and has 15 seconds to determine an answer, said Dr. Jason Wagganer, professor and interim chair of the Department of Kinesiology, Nutrition and Recreation at Southeast.

The Southeast team was comprised of Logan Page, a senior general health sciences major from Malden, Missouri; Kory Kasper, a senior athletic training major from Springfield, Illinois; and Kevin Yaeger, a senior health sciences major, pre-physical therapy/occupation therapy option, from St. Louis, Missouri. The students were invited to compete based on their academic success in the core curriculum of the health sciences and health management programs.

Kasper plans to become a licensed athletic trainer, and Page aspires to become a perfusionist. Both were members of last years winning team. Yaeger, who plans to pursue a doctorate in physical therapy and work in an outpatient clinic, was a first-year member of the team.

The quiz bowl was the greatest part of the whole conference, said Yaeger. Just before the final question, I was very nervous. I did not want to blow our first place lead on the last question. However, when we found out the topic was anatomy, all nervousness went away. My team and I were calm and ready to take on the question.

In addition to questions on anatomy, students were asked questions about exercise physiology, kinesiology, exercise prescription, ergogenic aids, resistance training, cardiovascular physiology and pathophysiology.

The team now advances to the National ACSM Student Quiz Bowl competition in San Francisco, California, next May. They will represent the Central States region as they compete against teams from the other 11 regions in the ACSM organization.

Wagganer said, Beating larger institutions at the regional Student Quiz Bowl competition is a true testament to the academic program and quality of faculty within the Department of Kinesiology, Nutrition and Recreation, Wagganer said

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Southeast Health Sciences, Athletic Training Students Repeat as Winners of Regional ACSM Quiz Bowl - Southeast Missouri State University News

Our emphasis on boutique funding programs, rather than open discovery science, hampers our prospects.

For the 96th successive year, no Canadian-based discovery was deemed worthy of recognition for a Nobel Prize in physiology or medicine when this years winners were announced on October 7. Fully expecting this outcome, the organizers of a conference in Montreal on October 3 debated why Canada remains unsuccessful.

The conference, Beyond The Nobel Prize: Performing Scientific Excellence in Canada, began with a presentation from Urban Ahlin, the Swedish ambassador to Canada. Then, Nils Hansson from the University of Dusseldorf and Thomas Schlich from McGill University invited Gairdner Foundation president and scientific director Janet Rossant, Canadian Medical Hall of Fame laureate Jacalyn Duffin from Queens University, and the Lancet executive editor Jocalyn Clark from London, as the morning speakers. Although recognizing the noble aspects of awards, the data were clear with respect to the shockingly low level of nominations and awards for Canadians, and for women globally. The speakers acknowledged a lack of transparency, including with the nomination process itself, with the Gairdners being totally open and the Nobel Prizes restricted.

The afternoon session featured examples of specific nominees for the Nobel, with the conference organizers Drs. Hansson and Schlich documenting the highly exclusive networks that have evolved for Nobel nominations and the history of how this has happened. A consensus from the conference was that such awards were of value to science and any effort to improve on Canadas record was to be welcomed, as would an effort to increase radically gender equity for awards.

Today, Nobel Prizes in medicine or physiology are given to scientists who themselves have defined the problem to be solved, how to do it, and then went ahead to put in the hard work to solve the problem with experiments whose outcomes and importance have stood the test of time.

In the life sciences, rewarding scientific excellence in Canada has taken a different route. Boutique funding programs that largely exclude open science are preferred. The Canada First Excellence Research Fund goes to individual universities through the president or principal of that university, who have themselves selected a priority area to support. The Canada Excellence Research Chairs and Canada 150 Research Chairs, also funded by Canadian taxpayers, go to discoveries made outside of Canada, with the investigators who made these discoveries recruited to Canada through this funding mechanism.

By contrast, funding open science by Canadas own investigators has not been seen as a priority. For the life and health sciences, our national funding agency, the Canadian Institutes of Health Research, is now reduced to supporting poorly funded project grants that have a 15 percent success rate and are male dominated. Multiple reports have been written and hand-wringing has ensued in the scientific community, but the priorities of our political decision-makers are elsewhere. The prospects for a future Nobel in physiology or medicine is therefore highly unlikely since discoveries come from open science and rarely from managed, unaccountable top-down decision-makers.

Canada is seen as important to the international network of award recognition for discoveries through the Gairdner Foundation. Ninety-two Gairdner award winners have gone on to win Nobel Prizes, including all three of this years wnners, who were recognized by the Gairdner Foundation in 2010. As the leading predictor of eventual Nobel Prizes in medicine, there is a clamour internationally for Gairdner recognition.

Gender equity is a priority for the Gairdner Foundation. However, the number of nominations and awards for women remains at less than 10 percent. The number of Canadians winning Gairdner International Awards has declined precipitously, regardless of gender, coincident with the lack of priority for funding open discovery research in Canada.

Scientists, especially in Canada, are generally not distracted by the glamour of award recognition. Go into any discovery lab in the life sciences in Canada; they are populated by a majority of women who are largely motivated by the satisfaction of having made discoveries that they themselves know benefit the foundation of knowledge and will impact our health and well-being. The science agenda, meanwhile, was absent from the recent Canadian federal election.

Perhaps as the 100th anniversary approaches to celebrate our one and only Nobel Prize in medicine (Frederick Banting in 1923), we will use that occasion to start a meaningful conversation about the importance of open discovery research in the life sciences.

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Beyond the Nobel Prize in medicine the Canada conundrum - University Affairs