659 research outputs found

    Earthquake Source Spectra And Attenuation In Southeastern Canada

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    Definition of the spectrum of ground motion as a function of earthquake magnitude and distance is a crucial component of seismic hazard evaluations of engineered structures. This study uses an empirical approach to investigate the Fourier spectra of earthquake ground motions in southeastern Canada. The primary dataset is comprised of 1500 digital seismograms, from 100 earthquakes of magnitude 3.0 to 6.5 recorded on 30 stations of the Eastern Canada Telemetered Network (ECTN). The distance range of the observations is 10 to 1700 km; focal depths are from 5 to 30 km.;Regression analyses of the ECTN data are used to determine the source spectrum for each event and describe its attenuation with distance. Simulations demonstrate that observed ground motions can be accurately modeled using the regression results, in conjunction with a simple stochastic model.;The attenuation curve has three distance sections. At distances (R) less than 70 km, corresponding to attenuation of direct S-waves, Fourier spectral amplitudes decay as R{dollar}\sp{lcub}-1.1{rcub}{dollar}. Between 70 and 130 km, where the direct-wave is joined by S{dollar}\sb{lcub}\rm m{rcub}{dollar}S, spectral amplitudes are approximately constant. Beyond 130 km, corresponding to the Lg-phase, amplitudes decay at a rate that is consistent with R{dollar}\sp{lcub}-0.5{rcub}{dollar} and Q = 670 f{dollar}\sp{lcub}0.33{rcub}{dollar}. The findings indicate that postcritical reflections from the Moho discontinuity play a significant role in determining the shape of the attenuation curve. However the influence of S{dollar}\sb{lcub}\rm m{rcub}{dollar}S is subtle, allowing the shape to be approximated by simple functional forms. There is little evidence for any dependence of attenuation on focal depth or tectonic province.;A database for source spectral amplitude in eastern North America (ENA) is compiled for earthquakes of 3 {dollar}{dollar} 4. The proposed source model has significant implications for ENA ground motion relations and seismic hazard assessment

    Rho GTPase CDC42 regulates directionality and random movement via distinct MAPK pathways in neutrophils

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    Neutrophil transmigration into tissue is a multiple-step process that results from a coordinated rearrangement of the cytoskeleton and adhesion complexes. Assembly and disassembly of actin and adhesion structures dictate motility behavior, while polarity and gradient sensing provide directionality to the cell movement. Here, using mice deficient in the CDC42 regulator CDC42 GTPase-activating protein (CDC42GAP), we demonstrate that CDC42 activity separately regulates neutrophil motility and directionality. CDC42GAP–/– neutrophils showed increased motility, while directed migration was defective. Podosome-like structures present at the leading edge in wild-type neutrophils were significantly reduced in CDC42GAP–/– cells. CDC42GAP–/– neutrophils also showed increased lateral and tail filopodia-like formation, and excess membrane protrusions. We further suggest that CDC42GAP-mediated extracellular signal–regulated kinase (ERK) activity regulates motility associated with podosome-like structures at the cell leading edge, while CDC42GAP-induced p38MAPK phosphorylation regulates directed migration by antagonizing filopodia assembly. Overall, this study reveals that CDC42 activity regulates both motility and directionality in neutrophils, but via distinct mitogen-activated protein kinase (MAPK) pathways

    A state of delirium: deciphering the effect of inflammation on tau pathology in Alzheimer's disease

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    Alzheimer's disease (AD), the predominant form of dementia, is highly correlated with the abnormal hyperphosphorylation and aggregation of tau. Immune responses are key drivers of AD and how they contribute to tau pathology in human disease remains largely unknown. This review summarises current knowledge on the association between inflammatory processes and tau pathology. While, preclinical evidence suggests that inflammation can indeed induce tau hyperphosphorylation at both pre- and post-tangles epitopes, a better understanding of whether this develops into advanced pathological features such as neurofibrillary tangles is needed. Microglial cells, the immune phagocytes in the central nervous system, appear to play a key role in regulating tau pathology, but the underlying mechanisms are not fully understood. Their activation can be detrimental via the secretion of pro-inflammatory mediators, particularly interleukin-1β, but also potentially beneficial through phagocytosis of extracellular toxic tau oligomers. Nevertheless, anti-inflammatory treatments in animal models were found protective, but whether or not they affect microglial phagocytosis of tau species is unknown. However, one major challenge to our understanding of the role of inflammation in the progression of tau pathology is the preclinical models used to address this question. They mostly rely on the use of septic doses of lipopolysaccharide that do not reflect the inflammatory conditions experienced AD patients, questioning whether the impact of inflammation on tau pathology in these models is dose-dependent and relevant to the human disease. The use of more translational models of inflammation corroborated with verification in clinical investigations are necessary to progress our understanding of the interplay between inflammation and tau pathology

    ‘Sustaining masculinity’:a scoping review of anabolic androgenic steroid use by older males

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    In the past, research, policy and media have reported the use of anabolic androgenic steroids (AAS) primarily among younger males. However, recent studies have indicated the presence of an older cohort of men who use AAS in comparison to previous years. We carried out a scoping review of the extant literature to map and describe what is known about the use of AAS by older men (>40 years). A systematic search collected and analysed empirical research and grey literature relevant to the research question. Following application of inclusion and exclusion criteria, 44 studies were included which were subsequently charted and thematically analysed. The records included originated from the UK, USA, Canada, Australia, Slovenia, Norway, Spain, Turkey, Switzerland, Japan, and five global studies and were published between 1996 and 2021. Age ranged overall from 14 to 78 years old, however our review only discussed findings pertaining to those older than 40. Three main themes with subthemes were generated as follows: 1) Characteristics of AAS Use; Self-reported Adverse Effects from AAS Use; and Harms Diagnosed by Medical Professional. The review highlights the significant risks to hypothalamic-pituitary testicular function, cardiovascular health, and other organ systems as a result of the ageing man who is motivated to sustain masculine characteristics such as muscularity, youthfulness, sexual function, and perceived desirability and attractiveness. Future research is required to further understand the motivations of older men who use AAS. Furthermore, there is a need for age-specific research and recommendations to inform future policy and practice pertaining so that age-appropriate healthcare and policy decisions can be made in the future

    Increasing Tau 4R Tau Levels Exacerbates Hippocampal Tau Hyperphosphorylation in the hTau Model of Tauopathy but Also Tau Dephosphorylation Following Acute Systemic Inflammation

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    Copyright © 2020 Barron, Gartlon, Dawson, Atkinson and Pardon. Inflammation is considered a mechanistic driver of Alzheimer's disease, thought to increase tau phosphorylation, the first step to the formation of neurofibrillary tangles (NFTs). To further understand how inflammation impacts the development of tau pathology, we used (hTau) mice, which express all six, non-mutated, human tau isoforms, but with an altered ratio of tau isoforms favoring 3R tau due to the concomitant loss of murine tau (mTau) that is predominantly 4R. Such an imbalance pattern has been related to susceptibility to NFTs formation, but whether or not this also affects susceptibility to systemic inflammation and related changes in tau phosphorylation is not known. To reduce the predominance of 3R tau by increasing 4R tau availability, we bred hTau mice on a heterozygous mTau background and compared the impact of systemic inflammation induced by lipopolysaccharide (LPS) in hTau mice hetero- or homozygous mTau knockout. Three-month-old male wild-type (Wt), mTau+/-, mTau-/-, hTau/mTau+/-, and hTau/mTau-/- mice were administered 100, 250, or 330 μg/kg of LPS or its vehicle phosphate buffer saline (PBS) [intravenously (i.v.), n = 8-9/group]. Sickness behavior, reflected by behavioral suppression in the spontaneous alternation task, hippocampal tau phosphorylation, measured by western immunoblotting, and circulating cytokine levels were quantified 4 h after LPS administration. The persistence of the LPS effects (250 μg/kg) on these measures, and food burrowing behavior, was assessed at 24 h post-inoculation in Wt, mTau+/-, and hTau/mTau+/- mice (n = 9-10/group). In the absence of immune stimulation, increasing 4R tau levels in hTau/mTau+/- exacerbated pS202 and pS396/404 tau phosphorylation, without altering total tau levels or worsening early behavioral perturbations characteristic of hTau/mTau-/- mice. We also show for the first time that modulating 4R tau levels in hTau mice affects the response to systemic inflammation. Behavior was suppressed in all genotypes 4 h following LPS administration, but hTau/mTau+/- exhibited more severe sickness behavior at the 100 μg/kg dose and a milder behavioral and cytokine response than hTau/mTau-/- mice at the 330 μg/kg dose. All LPS doses decreased tau phosphorylation at both epitopes in hTau/mTau+/- mice, but pS202 levels were selectively reduced at the 100 μg/kg dose in hTau/mTau-/- mice. Behavioral suppression and decreased tau phosphorylation persisted at 24 h following LPS administration in hTau/mTau+/- mice

    Validation of an abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) among patients on antihypertensive medications

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    <p>Abstract</p> <p>Background</p> <p>The 14-item Treatment Satisfaction Questionnaire for Medication (TSQM) Version 1.4 is a reliable and valid instrument to assess patients' satisfaction with medication, providing scores on four scales – side effects, effectiveness, convenience and global satisfaction. In naturalistic studies, administering the TSQM with the side effects domain could provoke the physician to assess the presence or absence of adverse events in a way that is clinically atypical, carrying the potential to interfere with routine medical care. As a result, an abbreviated 9-item TSQM (TSQM-9), derived from the TSQM Version 1.4 but without the five items of the side effects domain was created. In this study, an interactive voice response system (IVRS)-administered TSQM-9 was psychometrically evaluated among patients taking antihypertensive medication.</p> <p>Methods</p> <p>A total of 3,387 subjects were invited to participate in the study from an online panel who self-reported taking a prescribed antihypertensive medication. The subjects were asked to complete the IVRS-administered TSQM-9 at the start of the study, along with the modified Morisky scale, and again within 7 to 14 days. Standard psychometric analyses were conducted; including Cronbach's alpha, intraclass correlation coefficients, structural equation modeling, Spearman correlation coefficients and analysis of covariance (ANCOVA).</p> <p>Results</p> <p>A total of 396 subjects completed all the study procedures. Approximately 50% subjects were male with a good racial/ethnic mix: 58.3% white, 18.9% black, 17.7% Hispanic and 5.1% either Asian or other. There was evidence of construct validity of the TSQM-9 based on the structural equation modeling findings of the observed data fitting the Decisional Balance Model of Treatment Satisfaction even without the side effects domain. TSQM-9 domains had high internal consistency as evident from Cronbach's alpha values of 0.84 and greater. TSQM-9 domains also demonstrated good test-retest reliability with high intraclass correlation coefficients exceeding 0.70. As expected, the TSQM-9 domains were able to differentiate between individuals who were low, medium and high compliers of medication, with moderate to high effect sizes. There was evidence of convergent validity with significant correlations with the medication adherence scale.</p> <p>Conclusion</p> <p>The IVRS-administered TSQM-9 was found to be a reliable and valid measure to assess treatment satisfaction in naturalistic study designs, in which there is potential that the administration of the side effects domain of the TSQM would interfere with routine clinical care.</p

    Surveillance quality correlates with surgical site infection rates in knee and hip arthroplasty and colorectal surgeries: A call to action to adjust reporting of SSI rates.

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    OBJECTIVE The incidence of surgical site infections may be underreported if the data are not routinely validated for accuracy. Our goal was to investigate the communicated SSI rate from a large network of Swiss hospitals compared with the results from on-site surveillance quality audits. DESIGN Retrospective cohort study. PATIENTS In total, 81,957 knee and hip prosthetic arthroplasties from 125 hospitals and 33,315 colorectal surgeries from 110 hospitals were included in the study. METHODS Hospitals had at least 2 external audits to assess the surveillance quality. The 50-point standardized score per audit summarizes quantitative and qualitative information from both structured interviews and a random selection of patient records. We calculated the mean National Healthcare Safety Network (NHSN) risk index adjusted infection rates in both surgery groups. RESULTS The median NHSN adjusted infection rate per hospital was 1.0% (interquartile range [IQR], 0.6%-1.5%) with median audit score of 37 (IQR, 33-42) for knee and hip arthroplasty, and 12.7% (IQR, 9.0%-16.6%), with median audit score 38 (IQR, 35-42) for colorectal surgeries. We observed a wide range of SSI rates and surveillance quality, with discernible clustering for public and private hospitals, and both lower infection rates and audit scores for private hospitals. Infection rates increased with audit scores for knee and hip arthroplasty (P value for the slope = .002), and this was also the case for planned (P = .002), and unplanned (P = .02) colorectal surgeries. CONCLUSIONS Surveillance systems without routine evaluation of validity may underestimate the true incidence of SSIs. Audit quality should be taken into account when interpreting SSI rates, perhaps by adjusting infection rates for those hospitals with lower audit scores
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