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Despite being underreported, American football boasts the highest incidence of concussion among all team sports, likely due to exposure to head impacts that vary in number and magnitude over the season. This study compared a biological marker of head trauma in American football athletes with non-contact sport athletes and examined changes over the course of a season. Baseline serum neurofilament light polypeptide (NFL) was measured after 9 weeks of no contact and compared with a non-contact sport. Serum NFL was then measured over the course of the entire season at eight time-points coincident with expected changes in likelihood of increased head impacts. Data were compared between starters (n = 11) and non-starters (n = 9). Compared with non-starters (mean ± standard deviation) (7.30 ± 3.57 pg•mL−1) and controls (6.75 ± 1.68 pg•mL−1), serum NFL in starters (8.45 ± 5.90 pg•mL−1) was higher at baseline (mean difference; ±90% confidence interval) (1.69;  ± 1.96 pg•mL−1 and 1.15;  ± 1.4 pg•mL−1, respectively). Over the course of the season, an increase (effect size [ES] = 1.8; p < 0.001) was observed post-camp relative to baseline (1.52 ± 1.18 pg•mL−1), which remained elevated until conference play, when a second increase was observed (ES = 2.6; p = 0.008) over baseline (4.82 ± 2.64 pg•mL−1). A lack of change in non-starters resulted in substantial differences between starters and non-starters over the course of the season. These data suggest that a season of collegiate American football is associated with elevations in serum NFL, which is indicative of axonal injury, as a result of head impacts.

Early-onset type 2 diabetes (defined as type 2 diabetes diagnosed in people aged <40 years) is an increasingly prevalent condition with a more aggressive disease trajectory than late-onset type 2 diabetes. It is associated with accelerated microvascular and macrovascular complications, reduced life expectancy, and adverse pregnancy outcomes. Despite its rising incidence, global management strategies have mostly been extrapolated from studies in older adults with limited evidence specific to younger populations. In this Series paper, we aim to highlight the unique challenges in the management of early-onset type 2 diabetes and why current models of care are inadequate. We emphasise that early-onset type 2 diabetes necessitates proactive and combination treatment strategies to address weight, faster β-cell decline, worse insulin resistance, and rapidly progressing hyperglycaemia compared with late-onset type 2 diabetes. However, there is minimal evidence on how best to address these factors and clinical inertia risks contributing to glycaemic burden. Cardiovascular risk assessment tools underestimate long-term risk, contributing to low use of statin and antihypertensive therapy. Reproductive health remains a key concern, yet preconception and pregnancy care are inadequate, with low adherence to recommended interventions. Health-care systems are not optimised to address the distinct needs of young adults, and gaps in transitional care (from paediatric to adult services) contribute to disengagement and adverse outcomes. Addressing these challenges requires tailored management strategies that consider the unique metabolic and psychosocial factors in this population. In this Series paper, we summarise the evidence base for the management of early-onset type 2 diabetes, key evidence gaps, and discuss the multisectoral and transdisciplinary elements needed to achieve population-level prevention to reverse these concerning trends.

The essential omega-3 fatty acids (ω-3 FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exhibit vital biological roles and are critical for cardiovascular and neurologic health. Compared with the general population, football athletes may be at an increased risk of cardiovascular disease. Further, those same athletes are also exposed to repetitive head impacts, which may lead to long-term neurologic deficits. Both diets high in ω-3 FAs and supplementation with ω-3 FAs have been reported to reduce the risk of cardiovascular disease, and early evidence suggests a potential neuroprotective effect of supplementation. To determine the (1) erythrocyte content of DHA and EPA, as measured by the Omega-3 Index, expressed as a percentage of total fatty acids, in National Collegiate Athletic Association Division I football athletes and (2) distribution across the Omega-3 Index risk zones established for cardiovascular disease: high risk, <4%; intermediate risk, 4% to 8%; and low risk, >8%. Cross-sectional descriptive study. Multicenter trial. Deidentified data including complete erythrocyte fatty acid profile from the 2017-2018 season, age at time of testing, height, weight, and ethnicity were collected from 404 athletes. Omega-3 Index. About 34% of athletes (n = 138) had an Omega-3 Index considered high risk (<4%), and 66% (n = 266) had a risk considered intermediate (4%-8%). None had a low-risk Omega-3 Index. The Omega-3 Index is a simple, minimally invasive test of ω-3 FA status. Our data indicate that football athletes may be deficient in the ω-3 FAs DHA and EPA. The fact that no athlete had an Omega-3 Index associated with low risk suggests football athletes may be at increased risk for cardiovascular disease in later life.

American football athletes are routinely exposed to sub-concussive impacts over the course of the season. This study sought to examine the effect of a season of American football on plasma tau, a potential marker of axonal damage. Nineteen National Collegiate Athletic Association (NCAA) football athletes underwent serial blood sampling over the course of the 2014–2015 season at those times in which the number and magnitude of head impacts likely changed. Non-contact sport controls (NCAA men's swim athletes; n = 19) provided a single plasma sample for comparison. No significant differences were observed between control swim athletes and football athletes following a period of non-contact (p = 0.569) or a period of contact (p = 0.076). Football athletes categorized as starters (n = 11) had higher tau concentrations than non-starters (n = 8) following a period of non-contact (p = 0.039) and contact (p = 0.036), but not higher than swimmers (p = 1.000 and p = 1.000, respectively). No difference was noted over the course of the season in football athletes, irrespective of starter status. Despite routine head impacts common to the sport of American football, no changes were observed over the course of the season in football athletes, irrespective of starter status. Further, no difference was observed between football athletes and non-contact control swim athletes following a period of non-contact or contact. These data suggest that plasma tau is not sensitive enough to detect damage associated with repetitive sub-concussive impacts sustained by collegiate–level football athletes.

Variation in the UCP2-UCP3 Gene Cluster Predicts the Development of Type 2 Diabetes in Healthy Middle-Aged Men David R. Gable 1 , Jefferey W. Stephens 2 , Jackie A. Cooper 1 , George J. Miller 3 and Steve E. Humphries 1 1 Centre For Cardiovascular Genetics, Royal Free and University College London (UCL) Medical School, Rayne Institute, London, U.K 2 Medical School, University of Wales Swansea, Singleton Park, Swansea, U.K 3 Medical Research Council Cardiovascular Group, Centre for Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, Charterhouse Square, London, U.K Address correspondence and reprint requests to David Gable, Centre For Cardiovascular Genetics, Royal Free and UCL Medical School, The Rayne Institute, 5 University St., London, WC1E 6JJ, U.K. E-mail: d.gable{at}ucl.ac.uk Abstract The impact of the UCP2 −866G>A and UCP3 −55C>T variants on prospective risk of type 2 diabetes was examined over 15 years in 2,936 healthy middle-aged men (mean age 56 years). Conversion to diabetes ( n = 169) was associated with higher BMI, blood pressure, cholesterol, triglycerides and C-reactive protein. The hazard ratio (HR) for diabetes of a BMI >30 kg/m 2 was 3.96 (95% CI 2.87–5.47). Homozygosity for the UCP2 A or UCP3 T alleles accelerated the onset of diabetes, with significant differences in risk of diabetes at 10 years (HR [95% CI] UCP2 AA vs. GA+GG 1.94 [1.18–3.19], P = 0.009; UCP3 TT vs. CC+ CT 2.06 [1.06–3.99], P = 0.03) but less so at 15 years ( UCP2 AA 1.42 [0.92–2.19], P = 0.1; UCP3TT 1.57 [0.87–2.04], P = 0.13). Men who were homozygous for both UCP2 AA and UCP3 TT (1.5% of men) had a risk for diabetes at 10 years of 4.20 (1.70–10.37), P = 0.002. These genotype effects were additive with obesity, and men with a BMI >30 kg/m 2 and this genotype combination had a 10-year risk of diabetes of 19.23 [5.63–63.69], P < 0.0001. Functional promoter variants UCP2 and UCP3 increase the prospective risk of diabetes. Although the mechanism of the UCP2 effect is likely to be caused by increased expression in the pancreas and subsequent reduced insulin secretion, the mechanism of the UCP3 effect is currently unknown. Both effects are exacerbated by obesity. CRP, C-reactive protein NPHSII, Second Northwick Park Heart Study ROS, reactive oxygen species UCP, uncoupling protein Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted January 30, 2006. Received December 20, 2005. DIABETES

Background: Increased oxidative stress is associated with coronary heart disease (CHD). We examined the association between plasma markers of oxidative stress and CHD in a cross-sectional sample of patients with diabetes and prospective CHD risk in a sample of men predominantly without diabetes. Methods: Plasma total antioxidant status (TAOS) and the ratio of oxidized LDL (Ox-LDL) to LDL-cholesterol (LDL-C) were determined in a cross-section of 761 Caucasian individuals with diabetes (UDACS study). Plasma TAOS was also determined in 310 baseline samples from a 10-year prospective cohort of 3012 healthy males (NPHSII). Results: Within UDACS, males with CHD had lower mean (SD) plasma TAOS [no CHD, 43.4 (13.2)%; CHD, 40.3 (13.8)%; P = 0.04]. The prevalence of CHD was higher in the lowest compared with the upper quartiles (32.7% vs 19.7%; P = 0.004). We observed a significant association between plasma Ox-LDL:LDL-C and CHD status [no CHD vs CHD, 16.9 (3.1) vs 19.3 (5.0) units/mmol; P = 0.04], with the prevalence of CHD being higher among men in the upper compared with lower quartiles (18.4% vs 35.1%; P = 0.003). No association was observed in females. In NPHSII, TAOS was lower in those who developed CHD [35.1 (8.0)% vs 37.1 (7.9)%; P = 0.04]. The odds ratio for CHD in the lowest compared with the upper quartile was 1.91 (95% confidence interval, 0.99–3.70; P = 0.04). This remained unchanged after adjustment for classic risk factors. Conclusions: A cross-sectional and prospective association exists between baseline plasma measures of oxidative stress and CHD risk. The association with prospective CHD risk remained after adjustment for “traditional” risk factors, implying an independent role for oxidative stress in CHD risk.

Pierre Boulez (1925-2016) had many careers--as a conductor, an arts administrator, a founder of institutions, a critic, and a composer--but the need to express himself by writing music was the engine driving all of the other careers, each aimed at creating a more hospitable environment for the art he loved. Gable provides a retrospective of the composer's career.

Young adults (18-39 years) with type 2 diabetes have an increased loss of life expectancy and a greater risk of complications such as retinopathy, sexual health problems and foot disease than people diagnosed with type 2 diabetes later in life. Globally, there are increasing numbers of young adults with type 2 diabetes. Evidence describes both care (for example, prescribing) and improvement practices (for example, case management) that improve outcomes for people with type 2 diabetes. The National Diabetes Audit (NDA) provides feedback describing variation in both care and outcomes in young adults. Feedback facilitation can increase the effectiveness of audit feedback. Working collaboratively between researchers, audit providers, patients, clinicians and policy-makers, we have developed two feedback facilitation interventions deliverable at scale across England. We will evaluate whether theory-informed virtual educational materials with email support (low-intensity intervention) and / or virtual workshops (medium-intensity intervention) improve outcomes for young adults with type 2 diabetes. An efficient, pragmatic cluster randomised controlled trial using routine data with a theory-informed process and economic evaluation. The interventions will be delivered alongside the NDA to primary care networks (small groups of general practices) across England. Our primary outcome will be HbA1c level at 16-months post-randomisation in young adults with type 2 diabetes and baseline HbA1c ≥ 58 mmol/mol. Secondary outcomes assess the proportion with an HbA1c below recommended thresholds, prescription consistent with recommendations and delivery of recommended care processes. We will investigate impacts on equity. We will explore implementation, engagement and fidelity through interviews, observations, documentary analysis and surveys. An economic evaluation will estimate cost-effectiveness and budget impact. Our study embeds a further evaluation within the NDA, strengthening its role as a national diabetes learning health system. Our findings will have implications for intervention providers and funders seeking improvement in care and outcomes, and for our understanding of large-scale implementation strategies. ISRCTN 52205353 Registered 12 March 2025. https://www.isrctn.com/ISRCTN52205353.

Masterful essays honoring the great pianist and critic Charles Rosen, on masterpieces from Bach and Beethoven to Chopin, Verdi, and Stockhausen.Charles Rosen, the pianist and man of letters, is perhaps the single most influential writer on music of the past half-century. While Rosen's vast range as a writer and performer is encyclopedic, it has focused particularly on theliving \"canonical\" repertory extending from Bach to Boulez. Inspired in its liveliness and variety of critical approaches by Charles Rosen's challenging work, Variations on the Canon offers original essays by some of the world's most eminent musical scholars. Contributors address such issues as style and compositional technique, genre, influence and modeling, and reception history; develop insights afforded by close examination of compositional sketches; and consider what language and metaphors might most meaningfully convey insights into music. However diverse the modes of inquiry, each essay sheds new light on the works of those composers posterity has deemed central to the modern Western musical tradition. Contributors: Pierre Boulez, Scott Burnham, Elliott Carter, Robert Curry, Walter Frisch, David Gable, Philip Gossett, Jeffrey Kallberg, Joseph Kerman, Richard Kramer, William Kinderman, Lewis Lockwood, Sir Charles Mackerras, Robert L. Marshall, Robert P. Morgan, Charles Rosen, Julian Rushton, David Schulenberg, László Somfai, Leo Treitler, James Webster, and Robert Winter. Robert Curry is principalof the Conservatorium High School and honorary senior lecturer in the Centre for Medieval Studies, University of Sydney; David Gable is Assistant Professor of Music at Clark-Atlanta University; Robert L. Marshall is Louis, Frances, and Jeffrey Sachar Professor Emeritus of Music at Brandeis University.

Charles Rosen, the pianist and man of letters, is perhaps the single most influential writer on music of the past half-century. While Rosen's vast range as a writer and performer is encyclopedic, it has focused particularly on the living \"canonical\" repertory extending from Bach to Boulez. Inspired in its liveliness and variety of critical approaches by Charles Rosen's challenging work, Variations on the Canon offers original essays by some of the world's most eminent musical scholars. Contributors address such issues as style and compositional technique, genre, influence and modeling, and reception history; develop insights afforded by close examination of compositional sketches; and consider what language and metaphors might most meaningfully convey insights into music. However diverse the modes of inquiry, each essay sheds new light on the works of those composers posterity has deemed central to the modern Western musical tradition. Contributors: Pierre Boulez, Scott Burnham, Elliott Carter, Robert Curry, Walter Frisch, David Gable, Philip Gossett, Jeffrey Kallberg, Joseph Kerman, Richard Kramer, William Kinderman, Lewis Lockwood, Sir Charles Mackerras, Robert L. Marshall, Robert P. Morgan, Charles Rosen, Julian Rushton, David Schulenberg, László Somfai, Leo Treitler, James Webster, and Robert Winter. Robert Curry is principal of the Conservatorium High School and honorary senior lecturer in the Centre for Medieval Studies, University of Sydney; David Gable is Assistant Professor of Music at Clark-Atlanta University; Robert L. Marshall is Louis, Frances, and Jeffrey Sachar Professor Emeritus of Music at Brandeis University.