Sarcopenia is defined as an age associated decline in skeletal muscle mass. The pathophysiology of sarcopenia is multifactorial, with decreased caloric intake, muscle fiber denervation, intracellular ...oxidative stress, hormonal decline, and enhanced myostatin signaling all thought to contribute. Prevalence rates are as high as 29% and 33% in elderly community dwelling and long-term care populations, respectively, with advanced age, low body mass index, and low physical activity as significant risk factors. Sarcopenia shares many characteristics with other disease states typically associated with risk of fall and fracture, including osteoporosis, frailty, and obesity. There is no current universally accepted definition of sarcopenia. Diagnosing sarcopenia with contemporary operational definitions requires assessments of muscle mass, muscle strength, and physical performance. Screening is recommended for both elderly patients and those with conditions that noticeably reduce physical function. Sarcopenia is highly prevalent in orthopedic patient populations and correlates with higher hospital costs and rates of falling, fracture, and mortality. As no muscle building agents are currently approved in the United States, resistance training and nutritional supplementation are the primary methods for treating sarcopenia. Trials with various agents, including selective androgen receptor modulators and myostatin inhibitors, show promise as future treatment options. Increased awareness of sarcopenia is of great importance to begin reaching consensus on diagnosis and to contribute to finding a cure for this condition.
•Sarcopenia is defined as an age associated decline in muscle mass•Current definitions of sarcopenia involve assessments of muscle mass, muscle strength, and physical performance•Sarcopenia shares similarities with other diseases associated with fall and fracture, including frailty and osteoporosis•No approved muscle building agents are currently available in the United States, with clinical trials ongoing•Primary treatment options at this time include resistance training and nutritional supplementation
Natural disasters interact to affect the resilience and prosperity of communities and disproportionately affect low income families and communities of colour. However, due to lack of a common ...theoretical framework, these are rarely quantified. Observing severe weather events (e.g. hurricanes and tornadoes) and epidemics (e.g. COVID‐19) unfolding in southeastern US communities led us to conjecture that interactions among catastrophic disturbances might be much more considerable than previously recognized. For instance, hurricane evacuations increase human aggregation, a factor that affects the transmission of acute infections like SARS‐CoV‐2. Similarly, weather damage to health infrastructure can reduce a community's ability to provide services to people who are ill. As globalization and human population and movement continue to increase and weather events are becoming more intense, such complex interactions are expected to magnify and significantly impact environmental and human health.
Social vulnerability, hurricanes, and COVID‐19 outcomes intersect in the Southeastern United States.
Mitochondrial respiratory chain (RC) disease therapies directed at intra-mitochondrial pathology are largely ineffective. Recognizing that RC dysfunction invokes pronounced extra-mitochondrial ...transcriptional adaptations, particularly involving dysregulated translation, we hypothesized that translational dysregulation is itself contributing to the pathophysiology of RC disease. Here, we investigated the activities, and effects from direct inhibition, of a central translational regulator (mTORC1) and its downstream biological processes in diverse genetic and pharmacological models of RC disease. Our data identify novel mechanisms underlying the cellular pathogenesis of RC dysfunction, including the combined induction of proteotoxic stress, the ER stress response and autophagy. mTORC1 inhibition with rapamycin partially ameliorated renal disease in B6.Pdss2(kd/kd) mice with complexes I-III/II-III deficiencies, improved viability and mitochondrial physiology in gas-1(fc21) nematodes with complex I deficiency, and rescued viability across a variety of RC-inhibited human cells. Even more effective was probucol, a PPAR-activating anti-lipid drug that we show also inhibits mTORC1. However, directly inhibiting mTORC1-regulated downstream activities yielded the most pronounced and sustained benefit. Partial inhibition of translation by cycloheximide, or of autophagy by lithium chloride, rescued viability, preserved cellular respiratory capacity and induced mitochondrial translation and biogenesis. Cycloheximide also ameliorated proteotoxic stress via a uniquely selective reduction of cytosolic protein translation. RNAseq-based transcriptome profiling of treatment effects in gas-1(fc21) mutants provide further evidence that these therapies effectively restored altered translation and autophagy pathways toward that of wild-type animals. Overall, partially inhibiting cytosolic translation and autophagy offer novel treatment strategies to improve health across the diverse array of human diseases whose pathogenesis involves RC dysfunction.
For English-speaking readers, this book serves as an introduction to an important French intellectual whose work, especially on the issues of antisemitism and anti-Zionism, runs counter to the ...hostility shown toward Jews by some representatives of contemporary critical theory. It presents for the first time in English five essays by Éric Marty, previously published in France, with a new preface by the author addressed to his American readers. The focus of these essays is the debate in France and elsewhere in Europe concerning the "Jew." The first essay on Jean Genet, one of postwar France's most important literary figures, investigates the nature of Genet's virulent antisemitism and hatred of Israel and its significance for an understanding of contemporary phenomena. The curious reappearance of St. Paul in theological and political discourse is discussed in another essay, which describes and analyses the interest that secular writers of the far left have shown in Paul's "universalism" placed over and against Jewish or Israeli particularism. The remaining essays are more polemical in nature and confront the anti-Israeli attacks by Alain Badiou and Gilles Deleuze.
The statistics of epidemic transitions Drake, John M; Brett, Tobias S; Chen, Shiyang ...
PLOS computational biology/PLoS computational biology,
05/2019, Letnik:
15, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Emerging and re-emerging pathogens exhibit very complex dynamics, are hard to model and difficult to predict. Their dynamics might appear intractable. However, new statistical approaches-rooted in ...dynamical systems and the theory of stochastic processes-have yielded insight into the dynamics of emerging and re-emerging pathogens. We argue that these approaches may lead to new methods for predicting epidemics. This perspective views pathogen emergence and re-emergence as a "critical transition," and uses the concept of noisy dynamic bifurcation to understand the relationship between the system observables and the distance to this transition. Because the system dynamics exhibit characteristic fluctuations in response to perturbations for a system in the vicinity of a critical point, we propose this information may be harnessed to develop early warning signals. Specifically, the motion of perturbations slows as the system approaches the transition.
To support decision-making and policy for managing epidemics of emerging pathogens, we present a model for inference and scenario analysis of SARS-CoV-2 transmission in the USA. The stochastic ...SEIR-type model includes compartments for latent, asymptomatic, detected and undetected symptomatic individuals, and hospitalized cases, and features realistic interval distributions for presymptomatic and symptomatic periods, time varying rates of case detection, diagnosis, and mortality. The model accounts for the effects on transmission of human mobility using anonymized mobility data collected from cellular devices, and of difficult to quantify environmental and behavioral factors using a latent process. The baseline transmission rate is the product of a human mobility metric obtained from data and this fitted latent process. We fit the model to incident case and death reports for each state in the USA and Washington D.C., using likelihood Maximization by Iterated particle Filtering (MIF). Observations (daily case and death reports) are modeled as arising from a negative binomial reporting process. We estimate time-varying transmission rate, parameters of a sigmoidal time-varying fraction of hospitalized cases that result in death, extra-demographic process noise, two dispersion parameters of the observation process, and the initial sizes of the latent, asymptomatic, and symptomatic classes. In a retrospective analysis covering March–December 2020, we show how mobility and transmission strength became decoupled across two distinct phases of the pandemic. The decoupling demonstrates the need for flexible, semi-parametric approaches for modeling infectious disease dynamics in real-time.
Epidemic transitions are an important feature of infectious disease systems. As the transmissibility of a pathogen increases, the dynamics of disease spread shifts from limited stuttering chains of ...transmission to potentially large scale outbreaks. One proposed method to anticipate this transition are early-warning signals (EWS), summary statistics which undergo characteristic changes as the transition is approached. Although theoretically predicted, their mathematical basis does not take into account the nature of epidemiological data, which are typically aggregated into periodic case reports and subject to reporting error. The viability of EWS for epidemic transitions therefore remains uncertain. Here we demonstrate that most EWS can predict emergence even when calculated from imperfect data. We quantify performance using the area under the curve (AUC) statistic, a measure of how well an EWS distinguishes between numerical simulations of an emerging disease and one which is stationary. Values of the AUC statistic are compared across a range of different reporting scenarios. We find that different EWS respond to imperfect data differently. The mean, variance and first differenced variance all perform well unless reporting error is highly overdispersed. The autocorrelation, autocovariance and decay time perform well provided that the aggregation period of the data is larger than the serial interval and reporting error is not highly overdispersed. The coefficient of variation, skewness and kurtosis are found to be unreliable indicators of emergence. Overall, we find that seven of ten EWS considered perform well for most realistic reporting scenarios. We conclude that imperfect epidemiological data is not a barrier to using EWS for many potentially emerging diseases.
Albumprovides an unparalleled look into Roland Barthes's life of letters. It presents a selection of correspondence, from his adolescence in the 1930s through the height of his career and up to the ...last years of his life, covering such topics as friendships, intellectual adventures, politics, and aesthetics. It offers an intimate look at Barthes's thought processes and the everyday reflection behind the composition of his works, as well as a rich archive of epistolary friendships, spanning half a century, among the leading intellectuals of the day.Barthes was one of the great observers of language and culture, andAlbumshows him in his element, immersed in heady French intellectual culture and the daily struggles to maintain a writing life. Barthes's correspondents include Maurice Blanchot, Michel Butor, Jacques Derrida, Michel Foucault, Julia Kristeva, Claude Lévi-Strauss, Georges Perec, Raymond Queneau, Alain Robbe-Grillet, Marthe Robert, and Jean Starobinski, among others. The book also features documents, letters, and postcards reproduced in facsimile; unpublished material; and notes and transcripts from his seminars. The first English-language publication of Barthes's letters,Albumis a comprehensive testimony to one of the most influential critics and philosophers of the twentieth century and the world of letters in which he lived and breathed.
Despite great promises of cellulose nanofibers for water treatment, current technologies have lacked the exclusive use of cellulose nanofibers (CNF) in high-flux filters having an affinity for a ...desired contaminant. To tackle this, we prepared porous and functionalized filters via solvent exchange, supercritical drying, and freeze-drying of cationic CNF and compared them to conventional CNF filters obtained by the paper-making process. Porosity and pore size were evaluated in the dry state qualitatively and quantitatively via scanning electron microscopy and mercury intrusion porosimetry, respectively. The permeance of water and a solution containing a negatively charged model molecule (humic acid) through these filters was measured at various pressures and correlated to the filters’ structure. As compared to the CNF filters made via paper-making, the porosity, pore size, and permeance were increased after processing via solvent exchange, supercritical drying, and freeze-drying routes. Those filters which were prepared via freeze-drying displayed the highest permeance reported so far for CNF filters, which is about an order of magnitude higher than the permeance of CNF filters made via paper-making and having the same grammage. While the permeability was clearly affected by the processing technique, the functional filters showed a comparable adsorption capacity for humic acid. The filtration of a humic acid solution provided an initial removal of nearly 100% without noticeable reduction in flow. Considering the diluted concentration of HA in natural waters, we expect that large volumes of HA solution could be treated with the present CNF filters, with the possibility to regenerate these filters for multiple utilizations. The present concept of utilizing functional cellulose nanofibers in highly permeable filters working on the adsorption principle may be extended to encompass removal of other water contaminants for a better supply of clean water.
Interbody devices in anterior lumbar interbody fusion (ALIF) are currently a focus of innovation due to their potential to improve clinical outcomes. The purpose of the present study was to analyze ...complications and changes in spinopelvic parameters after ALIF with the novel Medacta MectaLIF interbody fusion device.BACKGROUNDInterbody devices in anterior lumbar interbody fusion (ALIF) are currently a focus of innovation due to their potential to improve clinical outcomes. The purpose of the present study was to analyze complications and changes in spinopelvic parameters after ALIF with the novel Medacta MectaLIF interbody fusion device.Patients aged 18 to 80 years who underwent multilevel ALIF using this novel implant were identified. Demographic and surgical data were collected. Patients were divided into short- and long-fusion cohorts. A comparison of outcomes between the short- and long-fusion groups was performed using the Student t test for continuous variables and Fisher's exact test and the χ2 test for categorical variables. Analysis of the pre- vs postoperative radiographic data for the entire cohort was performed using the 2-tailed Student t test.METHODSPatients aged 18 to 80 years who underwent multilevel ALIF using this novel implant were identified. Demographic and surgical data were collected. Patients were divided into short- and long-fusion cohorts. A comparison of outcomes between the short- and long-fusion groups was performed using the Student t test for continuous variables and Fisher's exact test and the χ2 test for categorical variables. Analysis of the pre- vs postoperative radiographic data for the entire cohort was performed using the 2-tailed Student t test.One hundred and eight patients met the inclusion criteria. No significant postoperative change was observed in L1-4 lumbar lordosis (LL). L1-S1 LL increased to a mean of 55.1 ± 12.8 (a mean change of 10.7 ± 14.5), and L4-S1 LL increased to a mean of 38.4 ± 8.7 (a mean increase of 7.5 ± 8.2), with pelvic incidence LL mismatch changing from 8.9 ± 15.1 to 1.1 ± 13.5 (n = 102). Related changes in sacral slope and pelvic tilt were also observed (33.0 ± 11.0 to 37.6 ± 10.9 and 19.6 ± 9.5 to 18.2 ± 9.1 n = 103, respectively). Five patients (4.6%) experienced implant subsidence, 1 (0.9%) had implant migration, and 6 (5.6%) experienced a nonunion. There was no difference in the rates of complications associated with the novel implant in the short- and long-fusion cohorts.RESULTSOne hundred and eight patients met the inclusion criteria. No significant postoperative change was observed in L1-4 lumbar lordosis (LL). L1-S1 LL increased to a mean of 55.1 ± 12.8 (a mean change of 10.7 ± 14.5), and L4-S1 LL increased to a mean of 38.4 ± 8.7 (a mean increase of 7.5 ± 8.2), with pelvic incidence LL mismatch changing from 8.9 ± 15.1 to 1.1 ± 13.5 (n = 102). Related changes in sacral slope and pelvic tilt were also observed (33.0 ± 11.0 to 37.6 ± 10.9 and 19.6 ± 9.5 to 18.2 ± 9.1 n = 103, respectively). Five patients (4.6%) experienced implant subsidence, 1 (0.9%) had implant migration, and 6 (5.6%) experienced a nonunion. There was no difference in the rates of complications associated with the novel implant in the short- and long-fusion cohorts.This novel implant achieves correction of spinopelvic parameters with minimal complications. The ability to modify the implant intraoperatively based on the patient's anatomy can help achieve maximal contact area and therefore help reduce the risk of subsidence.CONCLUSIONThis novel implant achieves correction of spinopelvic parameters with minimal complications. The ability to modify the implant intraoperatively based on the patient's anatomy can help achieve maximal contact area and therefore help reduce the risk of subsidence.This modular implant can achieve correction of spinopelvic parameters with minimal medical and surgical complications.CLINICAL RELEVANCEThis modular implant can achieve correction of spinopelvic parameters with minimal medical and surgical complications.
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