An individual's chronotype reflects how the circadian system embeds itself into the 24-h day with rhythms in physiology, cognition and behavior occurring accordingly earlier or later. In view of an ...increasing number of people working at unusual times and linked health and safety risks, the wide range in human chronotypes may provide opportunities to allow people to work (and sleep) at times that are in synch with their circadian physiology. We aimed at estimating the distribution of chronotypes in the US population by age and sex. Twelve years (2003-2014) of pooled diary data from the American Time Use Survey were used to calculate chronotype based on mid-point of sleep on weekends (MSFWe, n = 53,689). We observed a near-normal distribution overall and within each age group. The distribution's mean value is systematically different with age, shifting later during adolescence, showing a peak in 'lateness' at ~19 years, and shifting earlier thereafter. Men are typically later chronotypes than women before 40, but earlier types after 40. The greatest differences are observed between 15 and 25 for both sexes, equaling more than 50% of the total chronotype difference across all age groups. The variability in chronotype decreases with age, but is generally higher in males than females. This is the first study to estimate the distribution and prevalence of individual chronotypes in the US population based on a large-scale, nationally representative sample. Our finding that adolescents are on average the latest chronotypes supports delaying school start times to benefit their sleep and circadian alignment. The generally wide range in chronotypes may provide opportunities for tailored work schedules by matching external and internal time, potentially decreasing long- and short-term health and safety risks.
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SUMMARY
The Gutenberg–Richter b-value is thought to be a proxy of stress conditions in the crust and therefore able to locate asperities as zones of stress concentration responsible for the ...nucleation of strong events. The scientific literature contains a broad range of case studies showing precursory drops of b, just before the occurrence of strong events, and subsequent rises, during the early part of aftershocks sequences. Translating these results into hazard assessment, the b-value has assumed the status of a candidate precursor to the occurrence of an imminent large event. This issue is analysed here for three major seismic sequences that occurred recently in Italy. In comparison to previous studies, this investigation indicates that the variability of b may not be a reliable indicator of stress or a significant precursor in these examples, and instead may be assigned to a combination of chance, inhomogeneities in the data and inefficiencies in estimation methodologies. Consequently, extreme caution is required when we interpret b-values both as a proxy of physical processes involved in a seismic sequence and as a precursor to the occurrence of imminent strong events.
Falls are the leading cause of unintentional injuries in the U.S.; however, national estimates for all community-dwelling adults are lacking. This study estimated the national incidence of falls and ...fall-related injuries among community-dwelling U.S. adults by age and gender and the trends in fall-related injuries across the adult life span.
Nationally representative data from the National Health Interview Survey (NHIS) 2008 Balance and Dizziness supplement was used to develop national estimates of falls, and pooled data from the NHIS was used to calculate estimates of fall-related injuries in the U.S. and related trends from 2004-2013. Costs of unintentional fall-related injuries were extracted from the CDC's Web-based Injury Statistics Query and Reporting System.
Twelve percent of community-dwelling U.S. adults reported falling in the previous year for a total estimate of 80 million falls at a rate of 37.2 falls per 100 person-years. On average, 9.9 million fall-related injuries occurred each year with a rate of 4.38 fall-related injuries per 100 person-years. In the previous three months, 2.0% of older adults (65+), 1.1% of middle-aged adults (45-64) and 0.7% of young adults (18-44) reported a fall-related injury. Of all fall-related injuries among community-dwelling adults, 32.3% occurred among older adults, 35.3% among middle-aged adults and 32.3% among younger adults. The age-adjusted rate of fall-related injuries increased 4% per year among older women (95% CI 1%-7%) from 2004 to 2013. Among U.S. adults, the total lifetime cost of annual unintentional fall-related injuries that resulted in a fatality, hospitalization or treatment in an emergency department was 111 billion U.S. dollars in 2010.
Falls and fall-related injuries represent a significant health and safety problem for adults of all ages. The findings suggest that adult fall prevention efforts should consider the entire adult lifespan to ensure a greater public health benefit.
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Previous studies of failure mechanisms leading to revision total knee replacement (TKR) performed between 1986 and 2000 determined that many failed early, with a disproportionate amount accounted for ...by infection and implant-associated factors including wear, loosening and instability. Since then, efforts have been made to improve implant performance and instruct surgeons in best practice. Recently our centre participated in a multi-centre evaluation of 844 revision TKRs from 2010 to 2011. The purpose was to report a detailed analysis of failure mechanisms over time and to see if failure modes have changed over the past 10 to 15 years. Aseptic loosening was the predominant mechanism of failure (31.2%), followed by instability (18.7%), infection (16.2%), polyethylene wear (10.0%), arthrofibrosis (6.9%) and malalignment (6.6%). The mean time to failure was 5.9 years (ten days to 31 years), 35.3% of all revisions occurred at less than two years, and 60.2% in the first five years. With improvements in implant and polyethylene manufacture, polyethylene wear is no longer a leading cause of failure. Early mechanisms of failure are primarily technical errors. In addition to improving implant longevity, industry and surgeons must work together to decrease these technical errors. All reports on failure of TKR contain patients with unexplained pain who not infrequently have unmet expectations. Surgeons must work to achieve realistic patient expectations pre-operatively, and therefore, improve patient satisfaction post-operatively.
Abstract
MicroRNAs (miRs) are small non-coding RNA molecules, which are involved in the development of various malignancies, including prostate cancer (PCa). miR-17-5p is considered the most ...prominent member of the miR-17-92 cluster, with an essential regulatory function of fundamental cellular processes. In many malignancies, up-regulation of miR-17-5p is associated with worse outcome. In PCa, miR-17-5p has been reported to increase cell proliferation and the risk of metastasis. In this study, prostatectomy specimens from 535 patients were collected. Tissue microarrays were constructed and in situ hybridization was performed, followed by scoring of miR-17-5p expression on different tumor compartments. High expression of miR-17-5p in tumor epithelium was associated with biochemical failure (BF,
p
< 0.001) and clinical failure (CF,
p
= 0.019). In multivariate analyses, high miR-17-5p expression in tumor epithelial cells was an independent negative prognostic factor for BF (HR 1.87, 95% CI 1.32–2.67,
p
< 0.001). In vitro analyses confirmed association between overexpression of miR-17-5p and proliferation, migration and invasion in prostate cancer cell lines (PC3 and DU145). In conclusion, our study suggests that a high cancer cell expression of miR-17-5p was an independent negative prognostic factor in PCa.
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Impairments in neuronal intracellular calcium (
Ca
) handling may contribute to Alzheimer's disease (AD) development. Metabolic dysfunction and progressive neuronal loss are associated with AD ...progression, and mitochondrial calcium (
Ca
) signaling is a key regulator of both of these processes. Here, we report remodeling of the
Ca
exchange machinery in the prefrontal cortex of individuals with AD. In the 3xTg-AD mouse model impaired
Ca
efflux capacity precedes neuropathology. Neuronal deletion of the mitochondrial Na
/Ca
exchanger (NCLX, Slc8b1 gene) accelerated memory decline and increased amyloidosis and tau pathology. Further, genetic rescue of neuronal NCLX in 3xTg-AD mice is sufficient to impede AD-associated pathology and memory loss. We show that
Ca
overload contributes to AD progression by promoting superoxide generation, metabolic dysfunction and neuronal cell death. These results provide a link between the calcium dysregulation and metabolic dysfunction hypotheses of AD and suggest
Ca
exchange as potential therapeutic target in AD.
Falls are the leading cause of injury in almost all age-strata in the U.S. However, fall-related injuries (FI) and their circumstances are under-studied at the population level, particularly among ...young and middle-aged adults. This study examined the circumstances of FI among community-dwelling U.S. adults, by age and gender.
Narrative texts of FI from the National Health Interview Survey (1997-2010) were coded using a customized taxonomy to assess place, activity, initiating event, hazards, contributing factors, fall height, and work-relatedness of FI. Weighted proportions and incidence rates of FI were calculated across six age-gender groups (18-44, 45-64, 65+ years; women, men).
The proportion of FI occurring indoors increased with age in both genders (22%, 30%, and 48% among men, and 40%, 49% and 62% among women for 18-44, 45-64, 65+ age-groups, respectively). In each age group the proportion of indoor FI was higher among women as compared to men. Among women, using the stairs was the second leading activity (after walking) at the time of FI (19%, 14% and 10% for women in 18-44, 45-64, 65+ age groups, respectively). FI associated with tripping increased with age among both genders, and women were more likely to trip than men in every age group. Of all age-gender groups, the rate of FI while using ladders was the highest among middle-aged men (3.3 per 1000 person-year, 95% CI 2.0, 4.5). Large objects, stairs and steps, and surface contamination were the three most common hazards noted for 15%, 14% and 13% of fall-related injuries, respectively.
The rate and the circumstances of FI differ by age and gender. Understanding these differences and obtaining information about circumstances could be vital for developing effective interventions to prevent falls and FI.
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SUMMARY
The operational earthquake forecasting (OEF) is a procedure aimed at informing communities on how seismic hazard changes with time. This can help them live with seismicity and mitigate risk ...of destructive earthquakes. A successful short-term prediction scheme is not yet produced, but the search for it should not be abandoned. This requires more research on seismogenetic processes and, specifically, inclusion of any information about earthquakes in models, to improve forecast of future events, at any spatio-temporal-magnitude scale.
The short- and long-term forecast perspectives of earthquake occurrence followed, up to now, separate paths, involving different data and peculiar models. But actually they are not so different and have common features, being parts of the same physical process. Research on earthquake predictability can help to search for a common path in different forecast perspectives.
This study aims to improve the modelling of long-term features of seismicity inside the epidemic type aftershock sequence (ETAS) model, largely used for short-term forecast and OEF procedures. Specifically, a more comprehensive estimation of background seismicity rate inside the ETAS model is attempted, by merging different types of data (seismological instrumental, historical, geological), such that information on faults and on long-term seismicity integrates instrumental data, on which the ETAS models are generally set up. The main finding is that long-term historical seismicity and geological fault data improve the pseudo-prospective forecasts of independent seismicity.
The study is divided in three parts. The first consists in models formulation and parameter estimation on recent seismicity of Italy. Specifically, two versions of ETAS model are compared: a ‘standard’, previously published, formulation, only based on instrumental seismicity, and a new version, integrating different types of data for background seismicity estimation. Secondly, a pseudo-prospective test is performed on independent seismicity, both to test the reliability of formulated models and to compare them, in order to identify the best version. Finally, a prospective forecast is made, to point out differences and similarities in predicting future seismicity between two models.
This study must be considered in the context of its limitations; anyway, it proves, beyond argument, the usefulness of a more sophisticated estimation of background rate, inside short-term modelling of earthquakes.
Stochastic models provide quantitative evaluations about the occurrence of earthquakes. A basic component of this type of models are the uncertainties in defining main features of an intrinsically ...random process. Even if, at a very basic level, any attempting to distinguish between types of uncertainty is questionable, an usual way to deal with this topic is to separate epistemic uncertainty, due to lack of knowledge, from aleatory variability, due to randomness. In the present study this problem is addressed in the narrow context of short-term modeling of earthquakes and, specifically, of ETAS modeling. By mean of an application of a specific version of the ETAS model to seismicity of Central Italy, recently struck by a sequence with a main event of Mw6.5, the aleatory and epistemic (parametric) uncertainty are separated and quantified. The main result of the paper is that the parametric uncertainty of the ETAS-type model, adopted here, is much lower than the aleatory variability in the process. This result points out two main aspects: an analyst has good chances to set the ETAS-type models, but he may retrospectively describe and forecast the earthquake occurrences with still limited precision and accuracy.
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Mitochondrial calcium (sub.mCasup.2+) has a central role in both metabolic regulation and cell death signalling, however its role in homeostatic function and disease is controversial. Slc8b1 encodes ...the mitochondrial Nasup.+/Casup.2+ exchanger (NCLX), which is proposed to be the primary mechanism for sub.mCasup.2+ extrusion in excitable cells. Here we show that tamoxifen-induced deletion of Slc8b1 in adult mouse hearts causes sudden death, with less than 13% of affected mice surviving after 14 days. Lethality correlated with severe myocardial dysfunction and fulminant heart failure. Mechanistically, cardiac pathology was attributed to sub.mCasup.2+ overload driving increased generation of superoxide and necrotic cell death, which was rescued by genetic inhibition of mitochondrial permeability transition pore activation. Corroborating these findings, overexpression of NCLX in the mouse heart by conditional transgenesis had the beneficial effect of augmenting sub.mCasup.2+ clearance, preventing permeability transition and protecting against ischaemia-induced cardiomyocyte necrosis and heart failure. These results demonstrate the essential nature of sub.mCasup.2+ efflux in cellular function and suggest that augmenting sub.mCasup.2+ efflux may be a viable therapeutic strategy in disease.
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