Objective
To examine the effect of age of first exposure to tackle football on chronic traumatic encephalopathy (CTE) pathological severity and age of neurobehavioral symptom onset in tackle football ...players with neuropathologically confirmed CTE.
Methods
The sample included 246 tackle football players who donated their brains for neuropathological examination. Two hundred eleven were diagnosed with CTE (126 of 211 were without comorbid neurodegenerative diseases), and 35 were without CTE. Informant interviews ascertained age of first exposure and age of cognitive and behavioral/mood symptom onset.
Results
Analyses accounted for decade and duration of play. Age of exposure was not associated with CTE pathological severity, or Alzheimer's disease or Lewy body pathology. In the 211 participants with CTE, every 1 year younger participants began to play tackle football predicted earlier reported cognitive symptom onset by 2.44 years (p < 0.0001) and behavioral/mood symptoms by 2.50 years (p < 0.0001). Age of exposure before 12 predicted earlier cognitive (p < 0.0001) and behavioral/mood (p < 0.0001) symptom onset by 13.39 and 13.28 years, respectively. In participants with dementia, younger age of exposure corresponded to earlier functional impairment onset. Similar effects were observed in the 126 CTE‐only participants. Effect sizes were comparable in participants without CTE.
Interpretation
In this sample of deceased tackle football players, younger age of exposure to tackle football was not associated with CTE pathological severity, but predicted earlier neurobehavioral symptom onset. Youth exposure to tackle football may reduce resiliency to late‐life neuropathology. These findings may not generalize to the broader tackle football population, and informant‐report may have affected the accuracy of the estimated effects. Ann Neurol 2018;83:886–901
This book states that we live our lives through our emotions, and that it is our emotions which give our lives meaning. What interests or fascinates us, who we love, what angers us, what moves us, ...what bores us; all of this defines us, gives us character, constitutes who we are. This book illuminates the rich life of the emotions: why we don't really understand them, what they really are, and how they make us human and give meaning to life. The book provides a guide to cutting-edge scientific research, as well as to what philosophers and psychologists have said on the subject, but it also emphasizes the personal and ethical character of our emotions. The book shows that emotions are not something that happen to us, nor are they irrational in the literal sense; rather, they are judgments we make about the world, and they are strategies for living in it. Fear, anger, love, guilt, jealousy, compassion—they are all essential to our values, to living happily, healthily, and well.
Beneficial associations between plants and microbes play an important role in both natural and agricultural ecosystems. For example, associations between fungi of the genus Epichloë, and cool‐season ...grasses are known for their ability to increase resistance to insect pests, fungal pathogens and drought. However, little is known about the molecular changes induced by endophyte infection. To study the impact of endophyte infection, we compared the expression profiles, based on RNA sequencing, of perennial ryegrass infected with Epichloë festucae with noninfected plants. We show that infection causes dramatic changes in the expression of over one third of host genes. This is in stark contrast to mycorrhizal associations, where substantially fewer changes in host gene expression are observed, and is more similar to pathogenic interactions. We reveal that endophyte infection triggers reprogramming of host metabolism, favouring secondary metabolism at a cost to primary metabolism. Infection also induces changes in host development, particularly trichome formation and cell wall biogenesis. Importantly, this work sheds light on the mechanisms underlying enhanced resistance to drought and super‐infection by fungal pathogens provided by fungal endophyte infection. Finally, our study reveals that not all beneficial plant–microbe associations behave the same in terms of their effects on the host.
Summary Background ALK gene rearrangement defines a new molecular subtype of non-small-cell lung cancer (NSCLC). In a recent phase 1 clinical trial, the ALK tyrosine-kinase inhibitor (TKI) crizotinib ...showed marked antitumour activity in patients with advanced, ALK-positive NSCLC. To assess whether crizotinib affects overall survival in these patients, we did a retrospective study comparing survival outcomes in crizotinib-treated patients in the trial and crizotinib-naive controls screened during the same time period. Methods We examined overall survival in patients with advanced, ALK-positive NSCLC who enrolled in the phase 1 clinical trial of crizotinib, focusing on the cohort of 82 patients who had enrolled through Feb 10, 2010. For comparators, we identified 36 ALK-positive patients from trial sites who were not given crizotinib (ALK-positive controls), 67 patients without ALK rearrangement but positive for EGFR mutation, and 253 wild-type patients lacking either ALK rearrangement or EGFR mutation. To assess differences in overall survival, we assessed subsets of clinically comparable ALK-positive and ALK-negative patients. Findings Among 82 ALK-positive patients who were given crizotinib, median overall survival from initiation of crizotinib has not been reached (95% CI 17 months to not reached); 1-year overall survival was 74% (95% CI 63–82), and 2-year overall survival was 54% (40–66). Overall survival did not differ based on age, sex, smoking history, or ethnic origin. Survival in 30 ALK-positive patients who were given crizotinib in the second-line or third-line setting was significantly longer than in 23 ALK-positive controls given any second-line therapy (median overall survival not reached 95% CI 14 months to not reached vs 6 months 4–17, 1-year overall survival 70% 95% CI 50–83 vs 44% 23–64, and 2-year overall survival 55% 33–72 vs 12% 2–30; hazard ratio 0·36, 95% CI 0·17–0·75; p=0·004). Survival in 56 crizotinib-treated, ALK-positive patients was similar to that in 63 ALK-negative, EGFR-positive patients given EGFR TKI therapy (median overall survival not reached 95% CI 17 months to not reached vs 24 months 15–34, 1-year overall survival 71% 95% CI 58–81 vs 74% 61–83, and 2-year overall survival 57% 40–71 vs 52% 38–65; p=0·786), whereas survival in 36 crizotinib-naive, ALK-positive controls was similar to that in 253 wild-type controls (median overall survival 20 months 95% CI 13–26 vs 15 months 13–17; p=0·244). Interpretation In patients with advanced, ALK-positive NSCLC, crizotinib therapy is associated with improved survival compared with that of crizotinib-naive controls. ALK rearrangement is not a favourable prognostic factor in advanced NSCLC. Funding Pfizer Inc, V Foundation for Cancer Research.
New Findings
What is the topic of this review?
This review discusses the evidence of the benefits of exercise training for β‐cell health through improvements in function, proliferation and survival ...which may have implications in the treatment of diabetes.
What advances does it highlight?
This review highlights how exercise may modulate β‐cell health in the context of diabetes and highlights the need for further exploration of whether β‐cell preserving effects of exercise translates to T1D.
Physical exercise is a core therapy for type 1 and type 2 diabetes. Whilst the benefits of exercise for different physiological systems are recognised, the effect of exercise specifically on the pancreatic β‐cell is not well described. Here we review the effects of physical exercise on β‐cell health. We show that exercise improves β‐cell mass and function. The improved function manifests primarily through the increased insulin content of the β‐cell and its increased ability to secrete insulin in response to a glucose stimulus. We review the evidence relating to glucose sensing, insulin signalling, β‐cell proliferation and β‐cell apoptosis in humans and animal models with acute exercise and following exercise training programmes. Some of the mechanisms through which these benefits manifest are discussed.
The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 provides an up-to-date analysis of the burden of diarrhoea in 195 countries. This study assesses cases, deaths, and ...aetiologies in 1990–2016 and assesses how the burden of diarrhoea has changed in people of all ages.
We modelled diarrhoea mortality with a Bayesian hierarchical modelling platform that evaluates a wide range of covariates and model types on the basis of vital registration and verbal autopsy data. We modelled diarrhoea incidence with a compartmental meta-regression tool that enforces an association between incidence and prevalence, and relies on scientific literature, population representative surveys, and health-care data. Diarrhoea deaths and episodes were attributed to 13 pathogens by use of a counterfactual population attributable fraction approach. Diarrhoea risk factors are also based on counterfactual estimates of risk exposure and the association between the risk and diarrhoea. Each modelled estimate accounted for uncertainty.
In 2016, diarrhoea was the eighth leading cause of death among all ages (1 655 944 deaths, 95% uncertainty interval UI 1 244 073–2 366 552) and the fifth leading cause of death among children younger than 5 years (446 000 deaths, 390 894–504 613). Rotavirus was the leading aetiology for diarrhoea mortality among children younger than 5 years (128 515 deaths, 105 138–155 133) and among all ages (228 047 deaths, 183 526–292 737). Childhood wasting (low weight-for-height score), unsafe water, and unsafe sanitation were the leading risk factors for diarrhoea, responsible for 80·4% (95% UI 68·2–85·0), 72·1% (34·0–91·4), and 56·4% (49·3–62·7) of diarrhoea deaths in children younger than 5 years, respectively. Prevention of wasting in 1762 children (95% UI 1521–2170) could avert one death from diarrhoea.
Substantial progress has been made globally in reducing the burden of diarrhoeal diseases, driven by decreases in several primary risk factors. However, this reduction has not been equal across locations, and burden among adults older than 70 years requires attention.
Bill & Melinda Gates Foundation.
Restoration of coronary blood flow after a heart attack can cause reperfusion injury potentially leading to impaired cardiac function, adverse tissue remodeling and heart failure. Iron is an ...essential biometal that may have a pathologic role in this process. There is a clinical need for a precise noninvasive method to detect iron for risk stratification of patients and therapy evaluation. Here, we report that magnetic susceptibility imaging in a large animal model shows an infarct paramagnetic shift associated with duration of coronary artery occlusion and the presence of iron. Iron validation techniques used include histology, immunohistochemistry, spectrometry and spectroscopy. Further mRNA analysis shows upregulation of ferritin and heme oxygenase. While conventional imaging corroborates the findings of iron deposition, magnetic susceptibility imaging has improved sensitivity to iron and mitigates confounding factors such as edema and fibrosis. Myocardial infarction patients receiving reperfusion therapy show magnetic susceptibility changes associated with hypokinetic myocardial wall motion and microvascular obstruction, demonstrating potential for clinical translation.
I have developed a theoretical framework which I call ‘an Aristotelian approach to business’ to talk about corporations and organizations in general. Although Aristotle is famous largely as an enemy ...of business, he was the first economist and he might well be called the first business ethicist as well. We can no longer accept the amoral idea that ‘business is business’ (not really a tautology but an excuse for being socially irresponsible and personally insensitive). According to Aristotle, one has to think of oneself as a member of the larger community—the Polis for him, the corporation, the neighborhood, the city or the country (and the world) for us—and strive to excel, to bring out what is best in ourselves and our shared enterprise. What is best in us—our virtues—are in turn defined by that larger community, and there is therefore no ultimate split or antagonism between individual self-interest and the greater public good. The Aristotelian approach to business ethics, rather, begins with the two-pronged idea that it is individual virtue and integrity that count, and that good corporate and social policy encourage and nourish individual virtue and integrity.
Building Trust Solomon, Robert C; Flores, Fernando
04/2003
eBook
Everyone agrees that trust is essential for decent human relationships, but our understanding of trust too often collapses in platitudes and falsehoods. It is typically treated as some sort of ...inarticulate bond between people, a social “glue” or interpersonal lubricant. In what Francis Fukuyama has famously called “high trust” societies, it functions as a kind of cultural “atmosphere” or “climate.” In personal relationships, we usually confuse trust with an unthinking, taken‐for‐granted attitude of unquestioning acceptance, or what we call “simple trust,” like the trust of a child for its parents. In business, we too readily conflate trust with contractual agreements and the enforcement that goes along with them. What we argue in this book is that trust is first of all a matter of decision, commitment, and action, whether in an intimate relationship like a marriage or in the businesslike atmosphere of a corporation. We introduce the notion of authentic trust, trust that is neither naïve nor “blind” but trust with its eyes wide open. It is a risky and uncertain world, but trust is what allows us to navigate it successfully, together. Our aim is not only to understand trust but also to give the reader the tools to build and maintain trust in personal and business relationships and to restore trust even when it has been lost or betrayed. Building Trust has grown out of many decades of experience, consulting with both corporations and couples.
Introduction
Validity of the 2014 traumatic encephalopathy syndrome (TES) criteria, proposed to diagnose chronic traumatic encephalopathy (CTE) in life, has not been assessed.
Methods
A total of 336 ...consecutive brain donors exposed to repetitive head impacts from contact sports, military service, and/or physical violence were included. Blinded to clinical information, neuropathologists applied National Institute on Neurological Disorders and Stroke/National Institute of Biomedical Imaging and Bioengineering CTE criteria. Blinded to neuropathological information, clinicians interviewed informants and reviewed medical records. An expert panel adjudicated TES diagnoses.
Results
A total of 309 donors were diagnosed with TES; 244 donors had CTE pathology. TES criteria demonstrated sensitivity and specificity of 0.97 and 0.21, respectively. Cognitive (odds ratio OR = 3.6; 95% confidence interval CI: 1.2–5.1), but not mood/behavior or motor symptoms, were significantly associated with CTE pathology. Having Alzheimer's disease (AD) pathology was significantly associated with reduced TES accuracy (OR = 0.27; 95% CI: 0.12–0.59).
Discussion
TES criteria provided good evidence to rule out, but limited evidence to rule in, CTE pathology. Requiring cognitive symptoms in revised criteria and using AD biomarkers may improve CTE pathology prediction.
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