The Millennium Cohort Study, the US Department of Defense's largest and longest running study, was conceived in 1999 to investigate the effects of military service on service member health and ...well-being by prospectively following active duty, Reserve, and National Guard personnel from all branches during and following military service. In commemoration of the Study's 20th anniversary, this paper provides a summary of its methods, key findings, and future directions.
Recruitment and enrollment of the first 5 panels occurred between 2001 and 2021. After completing a baseline survey, participants are requested to complete follow-up surveys every 3–5 years.
Study research projects are categorized into 3 core portfolio areas (psychological health, physical health, and health-related behaviors) and several cross-cutting areas and have culminated in more than 120 publications to date. For example, some key Study findings include that specific military service-related factors (e.g., experiencing combat, serving in certain occupational subgroups) were associated with adverse health-related outcomes and that unhealthy behaviors and mental health issues may increase following the transition from military service to veteran status.
The Study will continue to foster stakeholder relationships such that research findings inform and guide policy initiatives and health promotion efforts.
BackgroundResearch on predictors of adverse birth outcomes has focused on maternal characteristics. Much less is known about the role of paternal factors. Paternal education is an important ...socioeconomic marker that may predict birth outcomes over and above maternal socioeconomic indicators.MethodsUsing data from the 2006 Canadian Birth-Census Cohort, we estimated the associations between paternal education and preterm birth, small-for-gestational-age (SGA) birth, stillbirth and infant mortality in Canada, controlling for maternal characteristics. Binomial regression was used to estimate risk ratios and risk differences for adverse birth outcomes associated with paternal education, after controlling for maternal education, age, marital status, parity, ethnicity and nativity.ResultsA total of 131 285 singleton births were included in the present study. Comparing the lowest to the highest paternal education category, adjusted risk ratios (95% CIs) were 1.22 (1.10 to 1.35) for preterm birth, 1.13 (1.03 to 1.23) for SGA birth, 1.92 (1.28 to 2.86) for stillbirth and 1.67 (1.01 to 2.75) for infant mortality. Consistent patterns of associations were observed for absolute risk differences.ConclusionsOur study suggests that low paternal education increases the risk of adverse birth outcomes, and especially of fetal and infant mortality, independently from maternal characteristics.
This study examined the influence of a strength and power program on tackling ability in rugby league players. Twenty-four semiprofessional rugby league players (mean ± SD age, 23.4 ± 3.1 years) ...underwent tests of upper-body strength (3 repetition maximum RM bench press), lower-body strength (3RM squat), upper-body power (plyometric push-up), and lower-body power (countermovement jump CMJ). Muscular strength relative to body mass was also calculated. Tackling ability of the players was assessed using video analysis of a standardized one-on-one tackling drill. The players then underwent 8 weeks of strength and power training as part of their preseason training before being retested. Training resulted in significant (p ≤ 0.01) improvements in absolute and relative measures of squat, bench press, CMJ peak power, and plyometric push-up peak power. The strongest correlates of change in tackling ability were changes in 3RM squat (r = 0.60; p < 0.01) and squat relative to body mass (r = 0.54; p < 0.01). The players with the greatest improvements in 3RM squat and squat relative to body mass (i.e., responders) had significantly greater improvements in tackling ability than nonresponding players (p = 0.04; effect size ES ≥ 0.85). A small, nonsignificant difference (p = 0.20; ES = 0.56) in tackling ability was found between responders and nonresponders for lower-body power. The findings of this study demonstrate that the enhancement of lower-body muscular strength, and to a lesser extent muscular power, contribute to improvements in tackling ability in semiprofessional rugby league players.
The electrical response of pancreatic beta-cells to step increases in glucose concentration is biphasic, consisting of a prolonged depolarization with action potentials (Phase 1) followed by membrane ...potential oscillations known as bursts. We have proposed that the Phase 1 response results from the combined depolarizing influences of potassium channel closure and an inward, nonselective cation current (ICRAN) that activates as intracellular calcium stores empty during exposure to basal glucose (Bertram et al., 1995). The stores refill during Phase 1, deactivating ICRAN and allowing steady-state bursting to commence. We support this hypothesis with additional simulations and experimental results indicating that Phase 1 duration is sensitive to the filling state of intracellular calcium stores. First, the duration of the Phase 1 transient increases with duration of prior exposure to basal (2.8 mM) glucose, reflecting the increased time required to fill calcium stores that have been emptying for longer periods. Second, Phase 1 duration is reduced when islets are exposed to elevated K+ to refill calcium stores in the presence of basal glucose. Third, when extracellular calcium is removed during the basal glucose exposure to reduce calcium influx into the stores, Phase 1 duration increases. Finally, no Phase 1 is observed following hyperpolarization of the beta-cell membrane with diazoxide in the continued presence of 11 mm glucose, a condition in which intracellular calcium stores remain full. Application of carbachol to empty calcium stores during basal glucose exposure did not increase Phase 1 duration as the model predicts. Despite this discrepancy, the good agreement between most of the experimental results and the model predictions provides evidence that a calcium release-activated current mediates the Phase 1 electrical response of the pancreatic beta-cell.
Analysis of urine samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS) has previously revealed high rates of non-adherence to antihypertensive medication. It is unclear whether ...these rates represent those in the general population. This study aimed to investigate whether it is feasible to collect urine samples in a primary care setting and analyse them using LC-MS/MS to detect non-adherence to antihypertensive medication. This study used a prospective, observational cohort design. Consecutive patients were recruited opportunistically from five general practices in UK primary care. They were aged ≥65 years with hypertension and had at least one antihypertensive prescription. Participants were asked to provide a urine sample for analysis of medication adherence. Samples were sent to a laboratory via post and analysed using LC-MS/MS. Predictors of adherence to medication were explored with multivariable logistic regression. Of 349 consecutive patients approached for the study, 214 (61.3%) gave informed consent and 191 (54.7%) provided a valid urine sample for analysis. Participants were aged 76.2 ± 6.6 years and taking a median of 2 antihypertensive medications (IQR 1-3). A total of 27/191 participants (14.2%) reported not taking all of their medications on the day of urine sample collection. However, LC-MS/MS analysis of samples revealed only 4/27 (9/191 in total; 4.7%) were non-adherent to some of their medications. Patients prescribed more antihypertensive medications were less likely to be adherent (OR 0.24, 95%CI 0.09-0.65). Biochemical testing for antihypertensive medication adherence is feasible in routine primary care, although non-adherence to medication is generally low, and therefore widespread testing is not indicated.
The lung naturally resists
(
) in healthy individuals, but multiple conditions can disrupt this resistance, leading to lethal invasive infections. Core processes of natural resistance and its ...breakdown are undefined. We investigated three distinct conditions predisposing to lethal aspergillosis-severe SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, influenza A viral pneumonia, and systemic corticosteroid use-in human patients and murine models. We found a conserved and essential coupling of innate B1a lymphocytes,
-binding natural immunoglobulin G antibodies, and lung neutrophils. Failure of this axis concealed
from neutrophils, allowing rapid fungal invasion and disease. Reconstituting the axis with immunoglobulin therapy reestablished resistance, thus representing a realistic pathway to repurpose currently available therapies. Together, we report a vital host resistance pathway that is responsible for protecting against life-threatening aspergillosis in the context of distinct susceptibilities.
Atomic-Scale Visualization of Inertial Dynamics Lindenberg, A. M; Larsson, J; Sokolowski-Tinten, K ...
Science (American Association for the Advancement of Science),
04/2005, Letnik:
308, Številka:
5720
Journal Article
Recenzirano
Odprti dostop
The motion of atoms on interatomic potential energy surfaces is fundamental to the dynamics of liquids and solids. An accelerator-based source of femtosecond x-ray pulses allowed us to follow ...directly atomic displacements on an optically modified energy landscape, leading eventually to the transition from crystalline solid to disordered liquid. We show that, to first order in time, the dynamics are inertial, and we place constraints on the shape and curvature of the transition-state potential energy surface. Our measurements point toward analogies between this nonequilibrium phase transition and the short-time dynamics intrinsic to equilibrium liquids.
Regulation of intestinal T-cell responses is crucial for immune homeostasis and prevention of inflammatory bowel disease (IBD). A vital cytokine in regulating intestinal T cells is transforming ...growth factor-β (TGFβ), which is secreted by cells as a latent complex that requires activation to function. However, how TGFβ activation is regulated in the human intestine, and how such pathways are altered in IBD is completely unknown. Here we show that a key activator of TGFβ, integrin αvβ8, is highly expressed on human intestinal dendritic cells (DCs), specifically on the CD1c
but not the CD141
intestinal DC subset. Expression was significantly upregulated on intestinal DC from IBD patients, indicating that inflammatory signals may upregulate expression of this key TGFβ-activating molecule. Indeed, we found that the Toll-like receptor 4 ligand lipopolysaccharide upregulates integrin αvβ8 expression and TGFβ activation by human DC. We also show that DC expression of integrin αvβ8 enhanced induction of FOXP3 in CD4
T cells, suggesting functional importance of integrin αvβ8 expression by human DC. These results show that microbial signals enhance the TGFβ-activating ability of human DC via regulation of integrin αvβ8 expression, and that intestinal inflammation may drive this pathway in patients with IBD.
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