August 1, 2017
Youngsters leave a football field in 2015 after playing at halftime at a game between the Buffalo Bills and the Carolina Panthers. AP Photo/Bill Wippert Russell M. Bauer, University of Florida and Michael S. Jaffee, University of Florida For many, American football is a beautiful game that is simple to enjoy but complex to master. Choreographed with a mixture of artistry and brutality, it features the occasional “big hit” or bone-jarring tackle, forcing a fumble and turning the tide of the game. But with this part of football comes justified concern about the long-term health effects of engaging in this type of activity over time, concerns that abound in practically every high-impact contact sport. It is possible that effects of continued involvement may accumulate quietly in the background until they show themselves, later in life. A recent study appeared to give a “big hit” to the game of football itself, with findings that nearly all the brains of 111 deceased NFL players studied showed signs of chronic traumatic encephalopathy, or CTE. At the University of Florida, our interdisciplinary team has studied brain injuries in athletes, military veterans and civilians for many years. Regarding sports concussion, there are many gaps in our knowledge and many associated issues to consider as we develop ways to keep our athletes, both young and old, safe. The concussion ‘explosion’ Concussions result from mechanical impact to the brain that produces transient changes in awareness or consciousness and a range of other symptoms. A 2016 study reported that between 1.1 million and 1.9 million concussions occur each year in children. Although diagnosed concussions have been the primary focus, they are not the only, or maybe even the main, problem. There is also rising concern about subconcussive impacts, repetitive blows that may not be severe enough to cause clinical symptoms. There may be hundreds of subconcussive impacts per player, per year. In response to widespread concern, organized sports organizations from Pop Warner to the NCAA to professional levels have developed and implemented concussion management protocols to help in the identification and management of concussions. Yet the massive attention given to concussion management and prevention has produced a level of public pseudo-awareness about CTE that currently outstrips what is scientifically known about the disorder. Missing links and gaps in knowledge Several scientific studies have linked repetitive brain trauma to CTE. CTE is a “tauopathy” in which the normally occurring protein tau becomes misfolded and accumulates at the depths of the folds (sulci) of the brain, in regions that may also be susceptible to mechanical forces during head impacts. The abnormal accumulation of the tau protein gives rise to a cascade of brain pathology that leads to cognitive impairment, neuropsychiatric problems (depression, anxiety, aggression, reduced impulse control), functional decline and, eventually, death. Researchers are trying to find the best helmet to prevent concussions, just as doctors are studying the best way to treat them. Steve Cukrov/Shutterstock.com The study published July 25 that showed CTE in 110 of 111 deceased, former NFL players reflected a startling 99 percent prevalence rate. The results were reported by news outlets across the world, leading many people to think that CTE is an all but inevitable outcome of playing football or other sports. But is it? And most importantly for parents, coaches and fans, what is the actual risk to my kids, my players and my team? The answers to these questions are not yet known, though the risk to the individual player is very likely to be considerably less than would be suggested by available research findings. Two important facts should be considered. First, studies of CTE have all been conducted on small samples of brains delivered to CTE research centers by families of former players who have had concern about post-retirement cognitive, psychiatric or behavioral problems and symptoms. The likelihood of finding brain pathology in these brains of symptomatic players is high, but these results cannot be generalized to all former football players, many of whom are living healthy lives in retirement. Second, no study has evaluated even a single living player to determine whether he or she exhibits the cognitive, psychiatric or behavioral signs of CTE and then followed that person to autopsy to verify that CTE-associated pathology actually exists in their brains. So, we do not know the actual prevalence of CTE in the general population of players, though it is assuredly much lower than those quoted by studies of symptomatic players. Why do some get CTE and others do not? We also don’t know much about who develops CTE and who doesn’t. There are over 10,000 living NFL retirees, yet the entire science of CTE is based on samples of less than a few hundred former NFL players and a handful of athletes from other sports. This means that some of those exposed to the risk of repetitive head impacts develop CTE, but most do not. There are several factors that may contribute to the development of brain dysfunction and disease, including: medical or genetic risk factors medical and psychiatric problems such as depression, anxiety, sleep disorders and abuse of prescription medications or other drugs and substances reduced educational attainment or literacy, or socioeconomic deprivation In addition, some athletes have poor adjustments to retirement, leading to psycho-social and psychiatric maladjustment, marital or financial difficulties, substance abuse and other behavioral problems. Repetitive head impacts may heighten risk of CTE, but other factors are undoubtedly involved in determining whether risk becomes reality. Reducing risk of CTE will involve targeting and treating these other factors as well. What parents, coaches and athletes need to know We need to take seriously the possible health consequences of prolonged exposure to repetitive head impacts and concussions. That said, parental decisions to remove children from contact sports should be weighed against the many proven positive aspects of participation in team sports. Decisions should not be based on inflated risk assessment. Several studies have shown that recreational or scholastic athletic participation in youth conveys no significant added risk to brain health later in life. Still, the developing brain may be more susceptible to injury and may take longer to recover. Knowledge of the individual player and his or her response to injury should guide parents, coaches and athletes in decision-making. Some youth are more injury-prone than others, and some have other conditions (e.g., ADHD, learning disability) that may affect how they react to head impact. When all factors are considered, the strongest predictor of recovery is the severity of initial symptoms. All states now have legislation requiring public schools to have a concussion program in place. Parents should ask their school or athletic organization what their policies are regarding concussion management. While helmet manufacturers are developing helmets that might provide greater protection, there is not enough evidence to recommend one over another. We do know, however, that appropriate fitting of helmets and protective gear is necessary to get the full protective benefit. Some measures to reduce possible exposure and risk have been implemented. The Dartmouth University football program has significantly reduced contact practices for its football team. Other Ivy League teams and organizations have followed suit. The NCAA has recently recommended the elimination of two-a-day practices and restricted the number of contact practices allowed in football. Physicians and athletic trainers at the University of Florida are using data from helmet sensors originally designed to help detect concussions to inform coaching staff on which specific practice drills and pad configurations may incur higher risk so that such drills can be adjusted. Ongoing research for this important issue is focused on developing techniques for accurate diagnosis while an individual is alive and understanding the exact pathophysiology that might inform future disease-modifying treatment, in addition to our current treatments aimed at reduction of symptoms. For those athletes who choose to continue the sports they love, we hope for continued innovations and policies that make their participation as safe as possible. Russell M. Bauer, Professor, Clinical & Health Psychology and Neurology, University of Florida and Michael S. Jaffee, Vice chair, Department of Neurology, University of Florida This article was originally published on The Conversation. Read the original article.
July 31, 2017
Growing up in rural Cameroon, Africa, Calistus Ngonghala watched helplessly as malaria and HIV-stricken neighbors traveled on foot for hours or days to reach clinics with antibiotics and antiretrovirals. Others made the journey by piling six to eight into compact cars designed for four. These haunting memories fuel the mathematician's ambitions. In a field known for working equations, Ngonghala puts equations to work for the world's sick and poor. The University of Florida assistant professor of mathematical biology uses math to understand the complex biological and socio-economic processes that characterize vicious cycles of poverty and disease in developing countries, and make predictions and policy recommendations for ending the cycles. Ngonghala argues that math should work to solve real world problems, and that governments can utilize mathematical models to help the world’s most impoverished people climb out of poverty traps. “Mathematics is not just the equations done in elementary and high schools around the world,” Ngonghala said. “There’s this idea that math is just solving equations and it’s not all that useful in everyday life. Actually, math is a special language, a fundamental tool, for critical thinking in almost every walk of life. My ambition is to put equations into practical use. And I’m trying to do it in a way that relates directly to me, to my home country, and to the problems I experienced growing up.” As a visiting professor in the masters of public health program at the French School of Public Health in Paris, a postdoctoral associate at the National Institute for Mathematical and Biological Synthesis, a research fellow at Harvard Medical School, and now an assistant professor in UF’s mathematics department and an affiliate of UF’s Emerging Pathogens Institute, for years, Ngonghala has developed models to investigate the connections between poverty and disease in the world's most impoverished places. In Cameroon, Ngonghala noticed a cycle of poverty, disease and pests, which kept his friends and family members from reaching their fullest potential. When people were too sick to work, they became too poor to afford health care. If they were too poor to afford health care, they certainly were not able to afford pest control to rid their homes of insects like malaria-carrying mosquitoes. “If you’re poor, you’re more likely to get sick. And if you’re poor, you’re more likely to stay sick longer,” Ngonghala said. “As you can imagine, that’s lost income if the sick person is the breadwinner of the family.” Of course, things are only made worse when local clinics cannot adequately treat common diseases, are understaffed, and when people have to walk long distances to reach a doctor. “Infectious disease is just one of the drivers of poverty. There are other things, too, like loss of renewable resources, population growth, land use changes, agricultural pests, and the list goes on,” Ngonghala said, pointing out that people in extremely poor parts of the world rely mostly on their immediate surrounding for subsistence. “So I’m developing mathematical models that explain reinforcing feedbacks between poverty and these drivers, and using the models to inform policy on ways to disintegrate such feedbacks.” He recently led a team of scientists that developed a combination of economic, ecological and epidemiological models used to understand how relationships between biological and economic systems can lead to poverty traps. The team’s findings appear this month in Nature Ecology and Evolution. For the study, Ngonghala used economic and disease data from 83 countries, ranging from the poorest to the wealthiest nations. His team looked at factors like annual income, disease and death rates, and financial losses resulting from disease. They found high rates of disease and instances of unaffordable, or unavailable, health care were significantly higher in extremely poor countries. Ngonghala’s models show what he calls “two different worlds.” In the first world, poor people live in a place with low rate of disease among people, crops and animals, and are often able to escape poverty with economic aid. But in the second world, places like Madagascar, where the average income is less than $2 a day and disease is widespread, poverty traps are common and the poor are unable to dig themselves out. In these cases, the numbers are against the poor and sick. Ngonghala’s team found that unsustained economic aid and health care might not be enough for the poor to permanently break free of these poverty traps. But Ngonghala’s models show that there’s a way to turn these numbers around. His analysis found that with sustained efforts to address the root causes of severe poverty, poverty traps can dissolve. His models also show that affordable, robust health care is a key determinant of sustainable economic growth for the poor. Ngonghala created the models with an end result in mind of influencing policy in the developing world. He hopes the models will eventually encourage developing countries to adopt similar action as Rwanda did in 2015, when the Sub-Saharan country achieved all of its Millennium Development Goals, a series of international development goals. Rwanda did this through universal health coverage with social insurance systems and providing broad access to health care for the poor. Since then, economic growth in Rwanda has been among the highest in Africa. Ngonghala’s models still need to be tested using more detailed data from surveys done on the ground in developing countries. So, he is partnering with Pivot, a nonprofit that provides health care in Madagascar, to collect data, test the models and validate their efficiency. Once data is collected and the models validated, Ngonghala will be able to make predictions and recommendations, which governments and nonprofits can use to combat poverty traps. “The problems in Madagascar are in many ways like the problems in Cameroon and other developing countries,” Ngonghala said. “When we finish testing in Madagascar, then from there we’ll go to other of the most impoverished countries and continue implementing the models.” By the end of his career, Ngonghala hopes to have contributed substantially to ending poverty and disease in some of the most impoverished areas of the world — including at home, in Cameroon. “There were just so many times when it could’ve been different,” Ngonghala said, recalling the past. “And it all goes back to poverty and disease.”
July 28, 2017
A newly discovered imaging biomarker could be used to track changes in the brain associated with the progression of Parkinson’s disease, findings that represent a significant advancement that could aid in development of new drugs to slow progression of the neurodegenerative disease. The team of University of Florida neuroscientists who made the discovery has validated the finding in data collected as part of an international multicenter study published in the current issue of the journal Brain. The study shows that on diffusion MRI scans there is an increase over one year in “free-water,” or fluid unconstrained by brain tissue, in a part of the brain called the substantia nigra in a large cohort of more than 100 newly diagnosed, unmedicated Parkinson’s disease patients. This change is not seen in people without Parkinson’s. Additionally, in a subgroup of Parkinson’s disease patients who have been followed for up to four years across Europe and North America, analysis of the diffusion MRI data revealed that free-water in the posterior substantia nigra continued to increase. Use of this noninvasive biomarker tool could lead to new ways of testing treatment of the progressively debilitating movement disorder, said senior author Dr. David Vaillancourt, a professor of applied physiology and kinesiology in UF’s College of Health and Human Performance and a member of the Evelyn F. and William L. McKnight Brain Institute of the University of Florida. “This could change the way studies are conducted for disease-modifying trials in Parkinson’s disease,” Vaillancourt said. Until now, Parkinson’s disease has generally been diagnosed based on a patient’s symptoms. “It’s been 200 years since the behavioral symptoms of Parkinson’s disease have been described, and we still use symptoms in testing therapies,” he said. “This is not the way it occurs in cancer; it’s not the way it occurs in heart disease or multiple sclerosis. But symptoms are still the hallmark of what’s used in Parkinson’s disease because there are few options out there.” Now, this could change. Two years ago, Vaillancourt’s team published findings based on a type of MRI technique known as diffusion MRI that revealed changes in free-water in the posterior substantia nigra that are specific to Parkinson’s patients. Now, the team’s new study validates findings in data collected across 10 sites, from the Michael J. Fox Foundation for Parkinson’s Progression Marker Initiative database. “To evaluate and validate an imaging marker, it is important to confirm results across data collection sites, and the Michael J. Fox Foundation database provides a unique opportunity to do that,” said lead author Roxana G. Burciu, Ph.D., a research assistant professor. The database provides a collection of clinical, imaging and biological data available for researchers to use in order to advance knowledge on Parkinson’s disease. A key finding of the new study is that results were consistent across sites. Another important finding is that the one- and two-year increase in free-water in the posterior substantia nigra predicts long-term progression of disease symptoms. “We found that the increase in the free-water measurement in the substantia nigra goes up every year and keeps going up over four years,” Vaillancourt said. 'This means if you want to start designing studies to slow the progression of Parkinson’s disease, testing a drug on that measurement in the substantia nigra might be a good way to go. If the measurement in the substantia nigra is increasing year after year after year, and if you can stop that from occurring, you’re likely to slow or possibly stop the progression of the disease,” he said. “This has never been shown before,” Vaillancourt added. The study also found that the increase in the free-water measurement over one year’s time predicted a patient’s four-year clinical change in motor function. “It suggests if you were able to control that measurement with medication as early as possible, then you could control long-term clinical progression,” Vaillancourt said. “This finding is a potential game changer as it could shift the way Parkinson’s disease clinical trials are designed and conducted,” said Dr. Michael S. Okun, a professor and chair of neurology at the University of Florida and medical director for the Parkinson’s Foundation. “Free-water is a validated measurement that will likely decrease the number of patients required to demonstrate the slowing of clinical progression.” The study, titled “Progression Marker of Parkinson’s Disease: A 4-Year Multi-Site Imaging Study,” was funded by the National Institutes of Health and the National Institute of Neurological Disorders and Stroke.
July 26, 2017
Sen. John McCain (R-Ariz.) returned to the Capitol July 25 to cast what was a tie-breaking vote to proceed to debate a bill to repeal Obamacare. AP Photo/Andrew Harnik Duane Mitchell, University of Florida As a naval aviator, John McCain was shot down during the Vietnam War and spent five and a half years as a prisoner of war. He received inadequate medical care for injuries that nearly killed him, enduring years of unimaginable deprivation and torture. He persevered with a remarkable resilience and fighting attitude that made him an American hero and helped him grow into the role of public servant and, as a United States senator, a leader on a national stage. Now, McCain faces another remorseless enemy that will again test him in body and spirit – glioblastoma, a malignant brain cancer that kills about 13,000 Americans each year. As the co-director of the Preston A. Wells Jr. Center for Brain Tumor Therapy at the University of Florida, I engage continually with patients and their families in the battle against glioblastoma. And I know firsthand how patients can often be swept into despair by the devastating diagnosis. The news of McCain’s condition – and his return to Washington July 25 to participate in the health care vote – provides an opportunity to remind the public about important and potentially game-changing research into therapies with the promise of greatly extending survivability for those with glioblastoma. Some of these therapies are in clinical trials and offer the ultimate hope of someday turning a cancer perceived as a quick killer into a curable disease. Stats are one thing, but people are another One thing often misunderstood by the public when talking about cancer in general is survivability. Projections for how long a person might be expected to survive are just that – projections. Each person is different, and each person’s cancer is different. In the case of glioblastoma, survivability is 15 to 18 months, with standard treatments such as surgery, chemotherapy, radiation and, recently, alternating electric field therapy. These very short survival times cast an understandable pall over talk of the disease. We also know, however, that some patients with the cancer, with even just standard treatments, have lived very long – even decades after their diagnosis. Granted, those numbers are a small subset of patients. But we do measure two- to three-year survival rates, and now from some promising clinical trials, five- and 10-year survival rates. Glioblastomas typically arise from genetic changes to cells inside the brain. There is no behavior that contributes to their random appearance, and there are no clear risk factors. And, there is no definitively curative therapy for glioblastoma. It is a relentlessly aggressive tumor. What makes these cancer cells so challenging is the fact that they migrate in the brain, very far from the origin of the tumor. Though surgeons can remove a large percentage of the tumor cells, unfortunately, islands of invasive cells remain. They often move into other areas of the brain that we cannot eradicate with surgery. Radiation and chemotherapy can slow the growth of invasive brain tumor cells, but limitations on the intensity of these treatments that can be tolerated within the brain and the existence of resistant tumor cells hinder the overall effectiveness. Enlisting the immune system While patients with glioblastoma, like all patients with cancer, often feel as if they have been betrayed by their own bodies, it is one of the most remarkable aspects of every person’s physical makeup that provides perhaps the greatest promise in fighting the disease: the immune system. Using the immune system to fight cancer is not a new concept. The idea that the immune system could be goaded into potentially recognizing cancers and lead to their rejection was advanced more than a century ago. But the science and our understanding of the immune system and human genomics required time to catch up to our ambitions. Immunotherapy, combined with an ever-increasing understanding of genomics, leaves us on a cusp of a revolution in cancer treatment. A pipette and test tubes in a lab such as those used to research immunotherapy. CI Photos/Shutterstock.com In genomics, we seek to understand how genes are altered in cancer. We can profile a patient’s tumor and understand the landscape of alterations that are present in those cancer cells. That has allowed us in some cases to predict how those tumors are likely to behave. It also allows us in some cases to select therapies that may be more effective in targeting those cancers. We can also identify specific proteins produced by these tumor cells and essentially program immune cells to home in on them and kill the cancer. This leads to a personalized treatment approach where you direct a patient’s immune system against a cancer, boosting or enhancing a patient’s immune response against specific alterations found in their tumor. At the University of Florida, one of the immunotherapy approaches we are advancing is called adoptive T cell therapy. In this work, we generate large numbers of “killer T cells” designed to recognize a patient’s specific tumor and transfer those T cells back to the patient with the hope that these activated cells can seek out and destroy remaining tumor cells. We have active clinical trials exploring this approach in patients with aggressive brain tumors. Additionally, we are exploring new ways to take advantage of drugs called immune checkpoint inhibitors, which elevate the activation state of the immune system of a patient so that it can more effectively combat cancer. We currently do not have any immunotherapies that are approved by the Food and Drug Administration for the treatment of brain cancer, although a number are being investigated in clinical trials at UF and other leading medical centers. One of the things we know about our immune system is that it is essentially designed to handle almost an infinite number of unknown external threats. It’s a remarkable system that, once harnessed, might be the most effective tool in battling brain cancers. A matter of heart But perhaps one of the most critical tools fighting glioblastoma is the one that is in McCain’s own heart. It is the will to fight and engage an enemy. It is the resilient spirit to battle against great odds. We all have experienced in the field of clinical research or clinical care those patients whose outlook and approach to tackling their disease seems to lead to better outcomes. We don’t necessarily have a quantitative assessment of how these factors impact the duration and quality of life in patients battling cancer, but we seem to agree that they matter. With glioblastoma, we can’t ignore what the data and the numbers tell us about its aggressiveness. But I think bringing to bear all your personal resources, spiritual and emotional support and the obstinate will to fight can lead to better outcomes. And nobody doubts John McCain’s deep reservoir of resilience. Duane Mitchell, Professor of Neurosurgery, University of Florida This article was originally published on The Conversation. Read the original article.
July 25, 2017
The ADA helped make college possible for disabled students like freshman Christopher Rhoades. AP Photo/Chris O'Meara Jean Crockett, University of Florida In July 1990, President George H. W. Bush signed the Americans with Disabilities Act (ADA) into law in an action that “gave voice to the nation’s highest ideals.” As we celebrate 27 years of ADA, we can see the significance of this law. It has challenged discrimination and helped remove many barriers so that roughly 56.7 million Americans with disabilities can lead independent lives. But it’s important to note that the promise of ADA cannot be fulfilled unless those without disabilities act on its “clear, strong, consistent and enforceable standards.” I’ve certainly observed this to be the case on college campuses. In my work as a special educator, I have observed how students, faculty and administrators are helping to fulfill this promise by sponsoring inclusive organizations, teaching to specific learning needs and making campus policies more equitable. President H. W. Bush signed the Americans with Disabilities Act on the White House South Lawn on July 26, 1990. AP Photo/Barry Thumma A proclamation of emancipation The ADA was introduced to ensure that people with disabilities get equal opportunities to fully participate in all aspects of community life, to live independently and to achieve economic self-sufficiency. The ADA builds on 20 years of disability-specific legislation to eliminate the historic and pervasive isolation and segregation of Americans with disabilities. Before that, they were viewed as objects of pity, unable to work, go to school or live on their own. The ADA altered this view by making buildings, transportation and services adapt so that people with disabilities could participate. Former Senator Tom Harkin, the chief sponsor of the ADA in Congress, referred to the law as the “20th century emancipation proclamation for people with disabilities.” As President of the United States from 1933-1945, FDR often hid his disability in order to avoid the associated stigma. D. B. King, CC BY In 2008, new amendments to the ADA broadened the definition of a disability, extending protections to individuals with substantial limitations in a variety of major life activities – including reading, concentrating and working. The amendments also extended protections to those using a variety of supports such as cochlear implants, hearing aids and prosthetics. What has changed on campus About 11 percent of undergraduates in the U.S. have documented disabilities, including dyslexia, Attention Deficit/Hyperactivity Disorder (ADD/ADHD), sensory and mobility issues, mental illness, and health impairments. Full-time enrollment of disabled students grew by 45 percent between 2000 and 2010. Part-time enrollment grew by 26 percent. There are also about 250,000 higher education faculty members who have disabilities. I see the impact of the ADA every day on our campus: students and faculty using wheelchairs, accessible e-readers for those with low vision, sign language interpreters and other technologies that allow people to learn and to work. As an instructor, I get help from the campus disability resource center to make sure I provide reasonable instructional accommodations in my classes (such as repeating or clarifying directions or providing a note-taker) to students who need them. Today’s undergraduates grew up in a post-ADA world where people with disabilities are expected to be included in – not segregated from – campus life. Many attended elementary and secondary schools alongside students with disabilities. College leaders use principles of universal design to prevent discrimination against students and employees. Universal design makes things accessible and desirable to as many people as possible. (For example, curb-cuts in the sidewalk were made for wheelchair users, but are used by everyone.) Universal design informs architects planning out dormitories, classrooms and labs. It also impacts the design of curriculum materials and teaching methods, which can encourage students to participate and respond to instruction in a variety of ways. Programs in disability education and disability studies can promote campus awareness about the experiences of people with disabilities. Many universities offer courses that can help reduce the stigma still associated with disabilities. On my campus at the University of Florida, students from different fields, including business, design, engineering, nursing, education, pre-law and medicine, enroll in the Disabilities in Society minor so they’ll be prepared to interact successfully with future coworkers, customers and neighbors with disabilities. The way forward Despite 27 years of advocacy, equity and inclusion are still out of reach for many Americans with disabilities. More needs to be done to fulfill the promise of the law. The disturbing fact is that students with disabilities tend to leave school after two years and graduate at half the rate of their classmates. They’re also employed at half the rate of workers their own age who do not have disabilities. In short, the ADA is not just about people with disabilities; it’s about society at large. Ensuring equity, access and inclusion is a shared responsibility. This is an updated version of an article originally published on July 26, 2015. Jean Crockett, Professor of Special Education, University of Florida This article was originally published on The Conversation. Read the original article.
WEEKLY NEWS: July 27, 2017