Innovative wood use can enable carbon-beneficial forest management in California.

Responsible stewardship of temperate forests can address key challenges posed by climate change through sequestering carbon, producing low-carbon products, and mitigating climate risks. Forest thinning and fuel reduction can mitigate climate-related risks like catastrophic wildfire. These treatments are often cost prohibitive, though, in part because of low demand for low-value wood "residues." Where treatment occurs, this low-value wood is often burned or left to decay, releasing carbon. In this study, we demonstrate that innovative use of low-value wood, with improved potential revenues and carbon benefits, can support economical, carbon-beneficial forest management outcomes in California. With increased demand for wood residues, forest health-oriented thinning could produce up to 7.3 million (M) oven-dry tonnes of forest residues per year, an eightfold increase over current levels. Increased management and wood use could yield net climate benefits between 6.4 and 16.9 million tonnes of carbon dioxide equivalent (M tCO2e) per year when considering impacts from management, wildfire, carbon storage in products, and displacement of fossil carbon-intensive alternatives over a 40-y period. We find that products with durable carbon storage confer the greatest benefits, as well as products that reduce emissions in hard-to-decarbonize sectors like industrial heat. Concurrently, treatment could reduce wildfire hazard on 4.9 M ha (12.1 M ac), a quarter of which could experience stand-replacing effects without treatment. Our results suggest that innovative wood use can support widespread fire hazard mitigation and reduce net CO2 emissions in California.

The neuropathology of intimate partner violence.

Lifelong brain health consequences of traumatic brain injury (TBI) include the risk of neurodegenerative disease. Up to one-third of women experience intimate partner violence (IPV) in their lifetime, often with TBI, yet remarkably little is known about the range of autopsy neuropathologies encountered in IPV. We report a prospectively accrued case series from a single institution, the New York City Office of Chief Medical Examiner, evaluated in partnership with the Brain Injury Research Center of Mount Sinai, using a multimodal protocol comprising clinical history review, ex vivo imaging in a small subset, and comprehensive neuropathological assessment by established consensus protocols. Fourteen brains were obtained over 2 years from women with documented IPV (aged 3rd-8th decade; median, 4th) and complex histories including prior TBI in 6, nonfatal strangulation in 4, cerebrovascular, neurological, and/or psychiatric conditions in 13, and epilepsy in 7. At autopsy, all had TBI stigmata (old and/or recent). In addition, white matter regions vulnerable to diffuse axonal injury showed perivascular and parenchymal iron deposition and microgliosis in some subjects. Six cases had evidence of cerebrovascular disease (lacunes and/or chronic infarcts). Regarding neurodegenerative disease pathologies, Alzheimer disease neuropathologic change was present in a single case (8th decade), with no chronic traumatic encephalopathy neuropathologic change (CTE-NC) identified in any. Findings from this initial series then prompted similar exploration in an expanded case series of 70 archival IPV cases (aged 2nd-9th decade; median, 4th) accrued from multiple international institutions. In this secondary case series, we again found evidence of vascular and white matter pathologies. However, only limited neurodegenerative proteinopathies were encountered in the oldest subjects, none meeting consensus criteria for CTE-NC. These observations from this descriptive exploratory study reinforce a need to consider broad co-morbid and neuropathological substrates contributing to brain health outcomes in the context of IPV, some of which may be potentially modifiable.

Financial, Social, and Health Impacts from the COVID-19 Pandemic: Findings from the Healthy Chicago Survey.

BACKGROUND: This study examines self-reported impacts of the COVID-19 pandemic among Chicago residents and disparities of these impacts across demographic characteristics. Six logistic regression models were developed to identify demographic and socioeconomic factors associated with each COVID-19 impact. METHOD: The study used de-identified and weighted data from the 2020 Healthy Chicago Survey (HCS). HCS is an annual survey using an address-based random sampling method administered by the Chicago Department of Public Health (CDPH) across the city of Chicago on adults aged 18 or older living between July 17 and November 11, 2020, and received 4517 responses. RESULTS: Chicago residents with lower socioeconomic status had a higher likelihood of food and housing insecurity. Non-Hispanic (NH) Black residents were more likely to report being unable to obtain food (OR: 2.996; 95% CI: 2.268-2.324); being unable to pay for rent, mortgage, or bills (OR: 2.352; 95% CI: 2.325-2.380); and grief from a loss of someone to COVID-19 (OR: 2.037; 95% CI: 2.013-2.061) compared to NH White residents. NH White residents were more likely than other racial/ethnic groups to report loss of social connections, worsened mental health, and canceling or postponing medical care. CONCLUSIONS: The analysis showed higher odds of social contact loss and worsened mental health from COVID-19 in NH White and higher education populations. By implementing strategies to address specific challenges faced by different racial groups, Chicago may effectively mitigate pandemic's adverse effects. These strategies can promote a more inclusive approach to distributing COVID investments for programs and policies.

Roles for Wildlife in the Development of Place Meanings Ascribed to a Protected Area.

Wildlife play prominent roles in popular images of America's outdoor landscapes, yet our understanding of their contribution to place meanings is not fully developed. Although environmental management agencies have a long history of stewarding wildlife for hunting and fishing, they have been less inclined to prioritize non-consumptive uses such as the contribution of wildlife to sense of place. Given that agencies are increasingly challenged to implement policies that align with citizen priorities, connecting wildlife to sense of place could lead to more effective decisions. Our research explored the plurality of connections that residents made with wildlife in multiple protected areas across the USA region of Interior Alaska. Residents of nine communities were engaged over a five-year period, followed by a thematic analysis of interview data, which resulted in the identification of seven place meaning themes. These themes reflected qualities of the local environment that were appreciated by residents, including: 1) desirable travel destination, 2) distinct sense of community, 3) landscape of subsistence and tradition, 4) landscape of wildlife habitat, 5) natural resources in need of harvesting, 6) rural Alaskan lifestyle, and 7) wildland areas tied to recreation. Native wildlife species-from traditionally charismatic species like moose (Alces alces) to less iconic species such as snowshoe hare (Lepus americanus) - were discussed in the context of all seven place meaning themes. Wildlife provided a basis for study participants to interpret landscapes and ascribe meanings to places, thus supporting our argument that shared influences of wildlife and place meanings should be prioritized in environmental planning and management.

Revisiting the Wald Test in Small Case-Control Studies With a Skewed Covariate.

The Wald test is routinely used in case-control studies to test for association between a covariate and disease. However, when the evidence for association is high, the Wald test tends to inflate small P values as a result of the Hauck-Donner effect (HDE). Here, we investigate the HDE in the context of genetic burden, both with and without additional covariates. First, we examine the burden-based P values in the absence of association using whole-exome sequence data from 1000 Genomes Project reference samples (n = 54) and selected preterm infants with neonatal complications (n = 74). Our careful analysis of the burden-based P values shows that the HDE is present and that the cause of the HDE in this setting is likely a natural extension of the well-known cause of the HDE in 2 × 2 contingency tables. Second, in a reanalysis of real data, we find that the permutation test provides increased power over the Wald, Firth, and likelihood ratio tests, which agrees with our intuition since the permutation test is valid for any sample size and since it does not suffer from the HDE. Therefore, we propose a powerful and computationally efficient permutation-based approach for the analysis and reanalysis of small case-control association studies.

Neurodegenerative Disease Mortality among Former Professional Soccer Players.

BACKGROUND: Neurodegenerative disorders have been reported in elite athletes who participated in contact sports. The incidence of neurodegenerative disease among former professional soccer players has not been well characterized. METHODS: We conducted a retrospective cohort study to compare mortality from neurodegenerative disease among 7676 former professional soccer players (identified from databases of Scottish players) with that among 23,028 controls from the general population who were matched to the players on the basis of sex, age, and degree of social deprivation. Causes of death were determined from death certificates. Data on medications dispensed for the treatment of dementia in the two cohorts were also compared. Prescription information was obtained from the national Prescribing Information System. RESULTS: Over a median of 18 years, 1180 former soccer players (15.4%) and 3807 controls (16.5%) died. All-cause mortality was lower among former players than among controls up to the age of 70 years and was higher thereafter. Mortality from ischemic heart disease was lower among former players than among controls (hazard ratio, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P = 0.02), as was mortality from lung cancer (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.001). Mortality with neurodegenerative disease listed as the primary cause was 1.7% among former soccer players and 0.5% among controls (subhazard ratio [the hazard ratio adjusted for competing risks of death from ischemic heart disease and death from any cancer], 3.45; 95% CI, 2.11 to 5.62; P<0.001). Among former players, mortality with neurodegenerative disease listed as the primary or a contributory cause on the death certificate varied according to disease subtype and was highest among those with Alzheimer's disease (hazard ratio [former players vs. controls], 5.07; 95% CI, 2.92 to 8.82; P<0.001) and lowest among those with Parkinson's disease (hazard ratio, 2.15; 95% CI, 1.17 to 3.96; P = 0.01). Dementia-related medications were prescribed more frequently to former players than to controls (odds ratio, 4.90; 95% CI, 3.81 to 6.31; P<0.001). Mortality with neurodegenerative disease listed as the primary or a contributory cause did not differ significantly between goalkeepers and outfield players (hazard ratio, 0.73; 95% CI, 0.43 to 1.24; P = 0.24), but dementia-related medications were prescribed less frequently to goalkeepers (odds ratio, 0.41; 95% CI, 0.19 to 0.89; P = 0.02). CONCLUSIONS: In this retrospective epidemiologic analysis, mortality from neurodegenerative disease was higher and mortality from other common diseases lower among former Scottish professional soccer players than among matched controls. Dementia-related medications were prescribed more frequently to former players than to controls. These observations need to be confirmed in prospective matched-cohort studies. (Funded by the Football Association and Professional Footballers' Association.).

Concussion leads to widespread axonal sodium channel loss and disruption of the node of Ranvier.

Despite being a major health concern, little is known about the pathophysiological changes that underly concussion. Nonetheless, emerging evidence suggests that selective damage to white matter axons, or diffuse axonal injury (DAI), disrupts brain network connectivity and function. While voltage-gated sodium channels (NaChs) and their anchoring proteins at the nodes of Ranvier (NOR) on axons are key elements of the brain's network signaling machinery, changes in their integrity have not been studied in context with DAI. Here, we utilized a clinically relevant swine model of concussion that induces evolving axonal pathology, demonstrated by accumulation of amyloid precursor protein (APP) across the white matter. Over a two-week follow-up post-concussion with this model, we found widespread loss of NaCh isoform 1.6 (Nav1.6), progressive increases in NOR length, the appearance of void and heminodes and loss of ßIV-spectrin, ankyrin G, and neurofascin 186 or their collective diffusion into the paranode. Notably, these changes were in close proximity, yet distinct from APP-immunoreactive swollen axonal profiles, potentially representing a unique, newfound phenotype of axonal pathology in DAI. Since concussion in humans is non-fatal, the clinical relevance of these findings was determined through examination of post-mortem brain tissue from humans with higher levels of acute traumatic brain injury. Here, a similar loss of Nav1.6 and changes in NOR structures in brain white matter were observed as found in the swine model of concussion. Collectively, this widespread and progressive disruption of NaChs and NOR appears to be a form of sodium channelopathy, which may represent an important substrate underlying brain network dysfunction after concussion.

Neurodegenerative disease risk among former international rugby union players.

BACKGROUND: Autopsy studies of former contact sports athletes, including soccer and rugby players, frequently report chronic traumatic encephalopathy, a neurodegenerative pathology associated with traumatic brain injury. Nevertheless, little is known about the risk of neurodegenerative disease in these populations. We hypothesised that neurodegenerative disease risk would be higher among former elite rugby union players than the general population. METHODS: We conducted a retrospective cohort study accessing national electronic records on death certification, hospital admissions and dispensed prescriptions for a cohort of 412 male Scottish former international rugby union players and 1236 members of the general population, matched to former players by age, sex and area socioeconomic status. Mortality and incident neurodegenerative disease diagnoses among former rugby players were then compared with the matched comparison group. RESULTS: Over a median 32 years follow-up from study entry at age 30 years, 121 (29.4%) former rugby players and 381 (30.8%) of the matched comparison group died. All-cause mortality was lower among former rugby players until 70 years of age with no difference thereafter. During follow-up, 47 (11.4%) former rugby players and 67 (5.4%) of the comparison group were diagnosed with incident neurodegenerative disease (HR 2.67, 95% CI 1.67 to 4.27, p<0.001). CONCLUSIONS: This study adds to our understanding of the association between contact sports participation and the risk of neurodegenerative disease. While further research exploring this interaction is required, in the meantime strategies to reduce exposure to head impacts and head injuries in sport should be promoted.

Telephone triage of young adults with chest pain: population analysis of NHS24 calls in Scottish unscheduled care.

BACKGROUND: Telephone triage is increasingly used to manage unscheduled care demand. Younger adults are frequent users, and commonly call with chest pain. We compared pathways of care in younger adults calling with chest pain, and associations of patient characteristics and telephone triage recommendation with hospital admission. METHODS: A retrospective study of all triage calls with chest pain to NHS24 advice line by people aged 15-34 years between 1 January 2015 and 31 December 2017 where chest pain was recorded as the call reason. Recommended outcome and subsequent use of services were determined using the continuous urgent care pathways (CUPs) database which records single episodes of care spanning multiple services. We determined the number of services involved, the proportion of patients with inpatient admission, those with an admission for an 'acute-and-serious' diagnosis, and the association between the triage call recommendation and these outcomes. RESULTS: There were 102 822 CUPs identified, with 1251 different combinations of services. The most common pathway was an NHS24 call then attendance at a primary care out-of-hours (PCOOH) centre, accounting for 38 643 (37.6%) CUPs. 9060 (8.8%) CUPs ended with hospital admission, 3030 (3.0%) the result of an 'acute-and-serious' diagnosis. 8453 (8.2%) were given 'self-care' advice and not referred further, while 46.9% ended at PCOOH and 15.2% at ED. 'Asthma, unspecified' was the most frequent 'acute-and-serious' diagnosis. Compared with people given self-care advice, referral to other services had increased odds of inpatient admission (adjusted OR (aOR) for ambulance called 28.7, 95% CI 22.6 to 36.3; for 1-hour in-home general practitioner (GP) visit arranged aOR 36.8, 95% CI 23.2 to 58.5) and for admission with an 'acute-and-serious' diagnosis (aOR ambulance called 23.9, 95% CI 16.2 to 35.4; aOR 1-hour GP visit 48.3, 95% CI 25.5 to 91.6). CONCLUSION: Chest pain triage by NHS24 appears safe, but care pathways can involve multiple service contacts. While acuity assigned to the call is strongly related to the odds of hospital admission and odds of an 'acute-and-serious' diagnosis, 'overtriage' means few patients are directed to self-care advice.

Learning pathways for engagement: Understanding drivers of pro-environmental behavior in the context of protected area management.

The participation of local communities in management decisions is critically important to the long-term salience and therefore, success, of protected areas. Engaging community members in meaningful ways requires knowledge of their behavior and its antecedents, particularly values. Understanding how learning influences cooperation in conservation initiatives is also fundamentally important for supporting decisions being made about public lands. However, there is little empirical evidence of how learning from different information sources works in conjunction with values that shape behavior. Using data from a household survey of residents living in the Denali region of Interior Alaska, U.S, we estimated a two-step structural equation model to understand the psychological reasons why stakeholders made decisions to collectively benefit the environment. Results showed that more diverse pathways by which learning occurred were instrumental in explaining why residents performed pro-environmental behaviors over the past year. Additionally, values that reflected the goals of eudaimonia influenced the transfer and negotiation of knowledge exchange among stakeholders as a correlate of behavior. Environmental concern and personal norms were positively associated with reported behaviors operationalized as social environmentalism and living in an environmentally conscientious manner, whereas environmental concern and willingness to pay for protected area management positively influenced civic engagement. We argue that broadening the range of learning spaces and considering a more diverse array of values in communities surrounding protected areas will encourage daily lifestyle changes, social interactions to support environmentalism, and more robust, pluralistic forms of public engagement in natural resource management.

A decision-making framework for evaluating environmental tradeoffs in enhancing ecosystem services across complex agricultural landscapes.

Decision-making processes to ensure sustainability of complex agro-ecosystems must simultaneously accommodate production goals, environmental soundness, and social relevancy. This means that besides environmental indicators and human activities, stakeholders' perceptions need to be considered in the decision-making process to enable the adoption of mitigation practices. Thus, the decision-making process equates to a multi-criteria and multi-objective problem, requiring additional tools and methods to analyze the possible tradeoffs among decision alternatives based on social acceptability. This study was aimed at establishing a decision support system that integrates hydro-ecologic models and socio-cultural perspectives to identify and assess feasible land management alternatives that can enhance the Kaskaskia River Watershed (KRW) ecosystem services in Illinois (USA). The Soil and Water Assessment Tool (SWAT) was used to simulate the spatio-temporal response of nine environmental predictors to four major management alternatives (crop rotation, cover cropping, reduced tillage, modified fertilizer application) based on stakeholder acceptability and environmental soundness, under 32 distinct climate projections. The stochastic multicriteria acceptability analysis (SMAA) was then applied to classify the management alternatives from the least to the most efficient based on three preference schemes: no preference, expert stakeholders' preference, and non-expert stakeholders' preference. Results showed that preference information on watershed ecosystem services is crucial to guide the decision-making process when a broad spectrum of criteria is considered to assess the management alternatives' systemic response. The disparity between expert and non-expert stakeholders' preferences showed different rankings of alternatives across several subcatchments, where the two-year corn one-year soybean rotation scheme was expected to offer the best management alternative to ensure a sustainable agro-production system in the highly cultivated subcatchments of the KRW. In contrast, non-conventional tillage practices were expected to contravene agricultural production, and therefore should be discarded unless combined with complementary measures. This study will enable stakeholders to identify the most suitable management practices to adapt to natural and anthropogenic changes and encourage engagement between government institutions and local communities (multi-stakeholder consensus) to provide a better platform for decision-making.

Dose-response association between device-measured physical activity and incident dementia: a prospective study from UK Biobank.

BACKGROUND: Previous cohort studies have investigated the relationship between self-reported physical activity (PA) and dementia. Evidence from objective device-measured PA data is lacking. This study aimed to explore the association of device-measured PA with the risk of dementia incidence and common subtypes (Alzheimer's disease [AD] and vascular dementia) using the UK Biobank study. METHODS: 84,854 participants (55.8% women), invited to participate in the device-measured PA between 2013 and 2015, were included in this prospective cohort study. Wrist accelerometers were used to measure light, moderate, vigorous, moderate-to-vigorous PA (MVPA) and total PA intensity and duration (MET/min/week). Incident dementia (fatal and non-fatal) was extracted from hospital episodes records for incidence and death register for mortality. Incidence follow-up was carried out until the end of March 2021in England and Scotland and the end of March 2018 in Wales. Mortality data were available until February 2021. Nonlinear associations were first investigated using penalised cubic splines fitted in the Cox proportional hazard models. In addition, using MVPA, five categories were created. Associations of these categories with the outcomes were investigated using Cox proportional hazard models. Analyses were adjusted for sociodemographic, lifestyle and health-related factors. RESULTS: After a median follow-up of 6.3 years, 678 individuals were diagnosed with dementia. Evidence of nonlinearity was observed for all PA modes and all-cause dementia. For categories of MVPA, there was a significant trend towards a low risk of overall dementia when higher levels of MVPA were achieved (HRtrend 0.66 [95% CI 0.62 to 0.70]. The lowest risk was identified in individuals who performed more than 1200 MET/min/week, those who had 84% (95% CI 0.12 to 0.21) lower risk of incident dementia compared to those who performed < 300 MET/min/week. CONCLUSIONS: Participants with higher PA levels had a lower risk of incident dementia than those less active, independently of sociodemographic, lifestyle factors and comorbidity. Considering that the majority of previous studies have reported this association using self-reported data, our findings highlight the strong inverse association between PA objectively measured and incident dementia.

Tau immunophenotypes in chronic traumatic encephalopathy recapitulate those of ageing and Alzheimer's disease.

Traumatic brain injury (TBI) is a risk factor for neurodegenerative disease, including chronic traumatic encephalopathy (CTE). Preliminary consensus criteria define the pathognomonic lesion of CTE as patchy tau pathology within neurons and astrocytes at the depths of cortical sulci. However, the specific tau isoform composition and post-translational modifications in CTE remain largely unexplored. Using immunohistochemistry, we performed tau phenotyping of CTE neuropathologies and compared this to a range of tau pathologies, including Alzheimer's disease, primary age-related tauopathy, ageing-related tau astrogliopathy and multiple subtypes of frontotemporal lobar degeneration with tau inclusions. Cases satisfying preliminary consensus diagnostic criteria for CTE neuropathological change (CTE-NC) were identified (athletes, n = 10; long-term survivors of moderate or severe TBI, n = 4) from the Glasgow TBI Archive and Penn Neurodegenerative Disease Brain Bank. In addition, material from a range of autopsy-proven ageing-associated and primary tauopathies in which there was no known history of exposure to TBI was selected as non-injured controls (n = 32). Each case was then stained with a panel of tau antibodies specific for phospho-epitopes (PHF1, CP13, AT100, pS262), microtubule-binding repeat domains (3R, 4R), truncation (Tau-C3) or conformation (GT-7, GT-38) and the extent and distribution of staining assessed. Cell types were confirmed with double immunofluorescent labelling. Results demonstrate that astroglial tau pathology in CTE is composed of 4R-immunoreactive thorn-shaped astrocytes, echoing the morphology and immunophenotype of astrocytes encountered in ageing-related tau astrogliopathy. In contrast, neurofibrillary tangles of CTE contain both 3R and 4R tau, with post-translational modifications and conformations consistent with Alzheimer's disease and primary age-related tauopathy. Our observations establish that the astroglial and neurofibrillary tau pathologies of CTE are phenotypically distinct from each other and recapitulate the tau immunophenotypes encountered in ageing and Alzheimer's disease. As such, the immunohistochemical distinction of CTE neuropathology from other mixed 3R/4R tauopathies of Alzheimer's disease and ageing may rest solely on the pattern and distribution of pathology.

FREQMAX provides an alternative approach for determining high-resolution allele frequency thresholds in carrier screening.

As whole-genome data become available for increasing numbers of individuals across diverse populations, the list of genomic variants of unknown significance (VOUS) continues to grow. One powerful tool in VOUS interpretation is determining whether an allele is too common to be considered pathogenic. As genetic and epidemiological parameters vary across disease models, so too does the pathogenic allele frequency threshold for each disease gene. One threshold-setting approach is the maximum credible allele frequency (MCAF) method. However, estimating some of the input values MCAF requires, especially those involving heterogeneity, can present nontrivial statistical challenges. Here, we introduce FREQMAX, our alternative approach for determining allele frequency thresholds in carrier screening. FREQMAX makes efficient use of the data available for well-studied traits and exhibits flexibility for traits where information may be less complete. For cystic fibrosis, more alleles are excluded as benign by FREQMAX than by MCAF. For less-comprehensively characterized traits like ciliary dyskinesia and Smith-Lemli-Opitz syndrome, FREQMAX is able to set the allele frequency threshold without requiring a priori estimates of maximum genetic and allelic contributions. Furthermore, though we describe FREQMAX in the context of carrier screening, its classical population genetics framework also provides context for adaptation to other trait models.

Mental health and suicide in former professional soccer players.

INTRODUCTION: There is growing recognition of an association between contact sports participation and increased risk of neurodegenerative disease, including Alzheimer's disease and chronic traumatic encephalopathy. In addition to cognitive impairment, a range of mental health disorders and suicidality are proposed as diagnostic features of traumatic encephalopathy syndrome, the putative clinical syndrome associated with chronic traumatic encephalopathy. However, to date, epidemiological data on contact sport participation and mental health outcomes are limited. METHODS: For a cohort of former professional soccer players (n=7676) with known high neurodegenerative mortality and their matched general population controls (n=23 028), data on mental health outcomes were obtained by individual-level record linkage to national electronic records of hospital admissions and death certification. RESULTS: Compared with matched population controls, former professional soccer players showed lower risk of hospital admission for anxiety and stress related disorders, depression, drug use disorders, alcohol use disorders and bipolar and affective mood disorders. Among soccer players, there was no significant difference in risk of hospitalisation for mental health disorders between outfield players and goalkeepers. There was no significant difference in rate of death by suicide between soccer players and controls. CONCLUSIONS: Among a population of former professional soccer players with known high neurodegenerative disease mortality, hospital admissions for common mental health disorders were lower than population controls, with no difference in suicide. Our data provide support for the reappraisal of currently proposed diagnostic clinical criteria for traumatic encephalopathy syndrome, in particular the inclusion of mental health outcomes.

Prediction of short-term neonatal complications in preterm infants using exome-wide genetic variation and gestational age: a pilot study.

BACKGROUND: Preterm birth is the leading cause of mortality and morbidity in young children, with over a million deaths per year worldwide arising from neonatal complications (NCs). NCs are moderately heritable although the genetic causes are largely unknown. Therefore, we investigated the impact of accumulated genetic variation (burden) on NCs in non-Hispanic White (NHW) and non-Hispanic Black (NHB) preterm infants. METHODS: We sequenced 182 exomes from infants with gestational ages from 26 to 31 weeks. These infants were cared for in the same time period and hospital environment. Eighty-one preterm infants did not develop NCs, whereas 101 developed at least one severe complication. We measured the effect of burden at the single-gene and exome-wide levels and derived a polygenic risk score (PRS) from the top 10 genes to predict NCs. RESULTS: Burden across the exome was associated with NCs in NHW (p = 0.05) preterm infants suggesting that multiple genes influence susceptibility. In a post hoc analysis, we find that PRS alone predicts NCs (AUC = 0.67) and that PRS is uncorrelated with GA ([Formula: see text] = 0.05; p = 0.53). When PRS and GA at birth are combined, the AUC is 0.87. CONCLUSIONS: Our results support the hypothesis that genetic burden influences NCs in NHW preterm infants.

Accelerating fishes increase propulsive efficiency by modulating vortex ring geometry.

Swimming animals need to generate propulsive force to overcome drag, regardless of whether they swim steadily or accelerate forward. While locomotion strategies for steady swimming are well characterized, far less is known about acceleration. Animals exhibit many different ways to swim steadily, but we show here that this behavioral diversity collapses into a single swimming pattern during acceleration regardless of the body size, morphology, and ecology of the animal. We draw on the fields of biomechanics, fluid dynamics, and robotics to demonstrate that there is a fundamental difference between steady swimming and forward acceleration. We provide empirical evidence that the tail of accelerating fishes can increase propulsive efficiency by enhancing thrust through the alteration of vortex ring geometry. Our study provides insight into how propulsion can be altered without increasing vortex ring size and represents a fundamental departure from our current understanding of the hydrodynamic mechanisms of acceleration. Our findings reveal a unifying hydrodynamic principle that is likely conserved in all aquatic, undulatory vertebrates.

Chronic traumatic encephalopathy is a common co-morbidity, but less frequent primary dementia in former soccer and rugby players.

Chronic traumatic encephalopathy (CTE) is reported at high prevalence in selected autopsy case series of former contact sports athletes. Nevertheless, the contribution of CTE pathology to clinical presentation and its interaction with co-morbid neurodegenerative pathologies remain unclear. To address these issues, we performed comprehensive neuropathology assessments on the brains of former athletes with dementia and considered these findings together with detailed clinical histories to derive an integrated clinicopathological diagnosis for each case. Consecutive, autopsy-acquired brains from former soccer and rugby players with dementia were assessed for neurodegenerative pathologies using established and preliminary consensus protocols. Thereafter, next of kin interviews were conducted to obtain detailed accounts of the patient's clinical presentation and course of disease to inform a final, integrated clinicopathological diagnosis. Neuropathologic change consistent with CTE (CTE-NC) was confirmed in five of seven former soccer and three of four former rugby players' brains, invariably in combination with mixed, often multiple neurodegenerative pathologies. However, in just three cases was the integrated dementia diagnosis consistent with CTE, the remainder having alternate diagnoses, with the most frequent integrated diagnosis Alzheimer's disease (AD) (four cases; one as mixed AD and vascular dementia). This consecutive autopsy series identifies neuropathologic change consistent with preliminary diagnostic criteria for CTE (CTE-NC) in a high proportion of former soccer and rugby players dying with dementia. However, in the majority, CTE-NC appears as a co-morbidity rather than the primary, dementia causing pathology. As such, we suggest that while CTE-NC might be common in former athletes with dementia, in many cases its clinical significance remains uncertain.

Replication, reanalysis, and gene expression: ME2 and genetic generalized epilepsy.

OBJECTIVE: Genetic generalized epilepsy (GGE) consists of epileptic syndromes with overlapping symptoms and is considered to be largely genetic. Previous cosegregation and association studies have pointed to malic enzyme 2 (ME2) as a candidate susceptibility gene for adolescent-onset GGE. In this article, we present new evidence supporting ME2's involvement in GGE. METHODS: To definitively test ME2's influence on GGE, we used 3 different approaches. First, we compared a newly recruited GGE cohort with an ethnically matched reference sample from 1000 Genomes Project, using an efficient test of association (POPFAM+). Second, we used POPFAM+ to reanalyze a previously collected data set, wherein the original controls were replaced with ethnically matched reference samples to minimize the confounding effect of population stratification. Third, in a post hoc analysis of expression data from healthy human prefrontal cortex, we identified single nucleotide polymorphisms (SNPs) influencing ME2 messenger RNA (mRNA) expression; and then we tested those same SNPs for association with GGE in a large case-control cohort. RESULTS: First, in the analysis of our newly recruited GGE Cohort, we found a strong association between an ME2 SNP and GGE (P = 0.0006 at rs608781). Second, in the reanalysis of previously collected data, we confirmed the Greenberg et al (2005) finding of a GGE-associated ME2 risk haplotype. Third, in the post hoc ME2 expression analysis, we found evidence for a possible link between GGE and ME2 gene expression in human brain. SIGNIFICANCE: Overall, our research, and the research of others, provides compelling evidence that ME2 influences susceptibility to adolescent-onset GGE.

Induction of a transmissible tau pathology by traumatic brain injury.

Traumatic brain injury is a risk factor for subsequent neurodegenerative disease, including chronic traumatic encephalopathy, a tauopathy mostly associated with repetitive concussion and blast, but not well recognized as a consequence of severe traumatic brain injury. Here we show that a single severe brain trauma is associated with the emergence of widespread hyperphosphorylated tau pathology in a proportion of humans surviving late after injury. In parallel experimental studies, in a model of severe traumatic brain injury in wild-type mice, we found progressive and widespread tau pathology, replicating the findings in humans. Brain homogenates from these mice, when inoculated into the hippocampus and overlying cerebral cortex of naïve mice, induced widespread tau pathology, synaptic loss, and persistent memory deficits. These data provide evidence that experimental brain trauma induces a self-propagating tau pathology, which can be transmitted between mice, and call for future studies aimed at investigating the potential transmissibility of trauma associated tau pathology in humans.