925 research outputs found
COVID-19 model-based practice changes in managing a large prostate cancer practice: following the trends during a month-long ordeal
Coronavirus (COVID-19) has been a life-changing experience for both individuals and institutions. We describe changes in our practice based on real-time assessment of various national and international trends of COVID-19 and its effectiveness in the management of our resources. Initial risk assessment and peak resource requirement using the COVID-19 Hospital Impact Model for Epidemics (CHIME) and McKinsey models. Strengths, weaknesses, opportunities, and threats (SWOT) analysis of our practice\u2019s approach during the pandemic. Based on CHIME the community followed 60% social distancing, the number of expected new patients hospitalized at maximum surge would be 401, with 100 patients requiring ventilator support. In contrast, when the community followed 15% social distancing, the maximum surge of hospitalized new patients would be 1823 and 455 patients would require a ventilator. on April 15, the expected May requirement of ICU beds at peak would be 68, with 61 patients needing ventilators. The estimated surge numbers improved throughout April, and on April 22 the expected ICU bed peak in May would be 11.7, and those requiring ventilator would be 10.5. Simultaneously, within a month, our surgical waitlist grew from 585 to over 723 patients. Our SWOT analysis revealed our internal strengths and inherent weakness, relevant to the pandemic. A graded and a guarded response to this type of situation is crucial in managing patients in a large practice
Does Birth Weight Influence Physical Activity in Youth? A Combined Analysis of Four Studies Using Objectively Measured Physical Activity
Animal models suggest growth restriction in utero leads to lower levels of motor activity. Furthermore, individuals with very low birth weight report lower levels of physical activity as adults. The aim of this study was to examine whether birth weight acts as a biological determinant of physical activity and sedentary time. This study uses combined analysis of three European cohorts and one from South America (nâ=â4,170). Birth weight was measured or parentally reported. Height and weight were measured and used to calculate Body Mass Index (BMI). PA was objectively measured using accelerometry for â„3 days, â„10 hours day. Data was standardized to allow comparisons between different monitors. Total physical activity was assessed as counts per minute (cpm), with time spent above moderate activity (MVPA) >2,000 counts and time spent sedentary (<100 counts). There was no evidence for an association between birth weight and total physical activity (pâ=â0.9) or MVPA (pâ=â0.7). Overall there was no evidence for an association between birth weight and sedentary time (pâ=â0.8). However in the Pelotas study we did find an association between higher birth weight (kg) and lower overall physical activity (cpm) (ÎČâ=ââ31, 95%CI: â58, â46, pâ=â0.03) and higher birth weight and greater sedentary time (mins/day) (ÎČâ=â16.4, 95%CI: 5.3, 27.5, pâ=â0.004), although this was attenuated and no longer significant with further adjustment for gestational age. Overall this combined analysis suggests that birth weight may not be an important biological determinant of habitual physical activity or sedentary behaviour in children and adolescents
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Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series
The largest kindred with inherited prion disease P102L, historically Gerstmann-StrÀussler-Scheinker syndrome, originates from central England, with émigrés now resident in various parts of the English-speaking world. We have collected data from 84 patients in the large UK kindred and numerous small unrelated pedigrees to investigate phenotypic heterogeneity and modifying factors. This collection represents by far the largest series of P102L patients so far reported. Microsatellite and genealogical analyses of eight separate European kindreds support multiple distinct mutational events at a cytosine-phosphate diester-guanidine dinucleotide mutation hot spot. All of the smaller P102L kindreds were linked to polymorphic human prion protein gene codon 129M and were not connected by genealogy or microsatellite haplotype background to the large kindred or each other. While many present with classical Gerstmann-StrÀussler-Scheinker syndrome, a slowly progressive cerebellar ataxia with later onset cognitive impairment, there is remarkable heterogeneity. A subset of patients present with prominent cognitive and psychiatric features and some have met diagnostic criteria for sporadic Creutzfeldt-Jakob disease. We show that polymorphic human prion protein gene codon 129 modifies age at onset: the earliest eight clinical onsets were all MM homozygotes and overall age at onset was 7 years earlier for MM compared with MV heterozygotes (P = 0.02). Unexpectedly, apolipoprotein E4 carriers have a delayed age of onset by 10 years (P = 0.02). We found a preponderance of female patients compared with males (54 females versus 30 males, P = 0.01), which probably relates to ascertainment bias. However, these modifiers had no impact on a semi-quantitative pathological phenotype in 10 autopsied patients. These data allow an appreciation of the range of clinical phenotype, modern imaging and molecular investigation and should inform genetic counselling of at-risk individuals, with the identification of two genetic modifiers
Cardiorespiratory fitness is associated with hard and light intensity physical activity but not time spent sedentary in 10â14 year old schoolchildren: the HAPPY study
Sedentary behaviour is a major risk factor for developing chronic diseases and is associated with low cardiorespiratory fitness in adults. It remains unclear how sedentary behaviour and different physical activity subcomponents are related to cardiorespiratory fitness in children. The purpose of this study was to assess how sedentary behaviour and different physical activity subcomponents are associated with 10â14 year-old schoolchildren's cardiorespiratory fitness
First Results from High Angular Resolution ALMA Observations Toward the HL Tau Region
We present Atacama Large Millimeter/submillimeter Array (ALMA) observations
from the 2014 Long Baseline Campaign in dust continuum and spectral line
emission from the HL Tau region. The continuum images at wavelengths of 2.9,
1.3, and 0.87 mm have unprecedented angular resolutions of 0.075 arcseconds (10
AU) to 0.025 arcseconds (3.5 AU), revealing an astonishing level of detail in
the circumstellar disk surrounding the young solar analogue HL Tau, with a
pattern of bright and dark rings observed at all wavelengths. By fitting
ellipses to the most distinct rings, we measure precise values for the disk
inclination (46.72pm0.05 degrees) and position angle (+138.02pm0.07 degrees).
We obtain a high-fidelity image of the 1.0 mm spectral index (), which
ranges from in the optically-thick central peak and two
brightest rings, increasing to 2.3-3.0 in the dark rings. The dark rings are
not devoid of emission, we estimate a grain emissivity index of 0.8 for the
innermost dark ring and lower for subsequent dark rings, consistent with some
degree of grain growth and evolution. Additional clues that the rings arise
from planet formation include an increase in their central offsets with radius
and the presence of numerous orbital resonances. At a resolution of 35 AU, we
resolve the molecular component of the disk in HCO+ (1-0) which exhibits a
pattern over LSR velocities from 2-12 km/s consistent with Keplerian motion
around a ~1.3 solar mass star, although complicated by absorption at low
blue-shifted velocities. We also serendipitously detect and resolve the nearby
protostars XZ Tau (A/B) and LkHa358 at 2.9 mm.Comment: 11 pages, 5 figures, 2 tables, accepted for publication in the
Astrophysical Journal Letter
Structure-based discovery of opioid analgesics with reduced side effects
Morphine is an alkaloid from the opium poppy used to treat pain. The potentially lethal side effects of morphine and related opioidsâwhich include fatal respiratory depressionâare thought to be mediated by ÎŒ-opioid-receptor (ÎŒOR) signalling through the ÎČ-arrestin pathway or by actions at other receptors. Conversely, G-protein ÎŒOR signalling is thought to confer analgesia. Here we computationally dock over 3 million molecules against the ÎŒOR structure and identify new scaffolds unrelated to known opioids. Structure-based optimization yields PZM21âa potent Gi activator with exceptional selectivity for ÎŒOR and minimal ÎČ-arrestin-2 recruitment. Unlike morphine, PZM21 is more efficacious for the affective component of analgesia versus the reflexive component and is devoid of both respiratory depression and morphine-like reinforcing activity in mice at equi-analgesic doses. PZM21 thus serves as both a probe to disentangle ÎŒOR signalling and a therapeutic lead that is devoid of many of the side effects of current opioids
Effectiveness and cost-effectiveness of the GoActive intervention to increase physical activity among UK adolescents: A cluster randomised controlled trial
Background: Less than 20% of adolescents globally meet recommended levels of physical activity, and not meeting these recommended levels is associated with social disadvantage and rising disease risk. The determinants of physical activity in adolescents are multilevel and poorly understood, but the schoolâs social environment likely plays an important role. We conducted a cluster randomised controlled trial to assess the effectiveness of a school-based programme (GoActive) to increase moderate-to-vigorous physical activity (MVPA) among adolescents. Methods and findings: Non-fee-paying, co-educational schools including Year 9 students in the UK counties of Cambridgeshire and Essex were eligible for inclusion. Within participating schools (n = 16), all Year 9 students were eligible and invited to participate. Participants were 2,862 13- to 14-year-olds (84% of eligible students). After baseline assessment, schools were computer-randomised, stratified by school-level pupil premium funding (below/above county-specific median) and county (control: 8 schools, 1,319 participants, mean [SD] participants per school n = 165 [62]; intervention: 8 schools, 1,543 participants, n = 193 [43]). Measurement staff were blinded to allocation. The iteratively developed, feasibility-tested 12-week intervention, aligned with self-determination theory, trained older adolescent mentors and in-class peer-leaders to encourage classes to conduct 2 new weekly activities. Students and classes gained points and rewards for engaging in any activity in or out of school. The primary outcome was average daily minutes of accelerometer-assessed MVPA at 10-month follow-up; a mixed-methods process evaluation evaluated implementation. Of 2,862 recruited participants (52.1% male), 2,167 (76%) attended 10-month follow-up measurements; we analysed the primary outcome for 1,874 participants (65.5%). At 10 months, there was a mean (SD) decrease in MVPA of 8.3 (19.3) minutes in the control group and 10.4 (22.7) minutes in the intervention group (baseline-adjusted difference [95% confidence interval] â1.91 minutes [â5.53 to 1.70], p = 0.316). The programme cost ÂŁ13 per student compared with control; it was not cost-effective. Overall, 62.9% of students and 87.3% of mentors reported that GoActive was fun. Teachers and mentors commented that their roles in programme delivery were unclear. Implementation fidelity was low. The main methodological limitation of this study was the relatively affluent and ethnically homogeneous sample. Conclusions: In this study, we observed that a rigorously developed school-based intervention was no more effective than standard school practice at preventing declines in adolescent physical activity. Interdisciplinary research is required to understand educational-setting-specific implementation challenges. School leaders and authorities should be realistic about expectations of the effect of school-based physical activity promotion strategies implemented at scale. Trial registration: ISRCTN Registry ISRCTN31583496
Establishing temperate crustose early Holocene coralline algae as archives for palaeoenvironmental reconstructions of the shallow water habitats of the Mediterranean Sea
Over the past decades, coralline algae have increasingly been used as archives of palaeoclimate information due to their seasonal growth bands and their vast distribution from high latitudes to the tropics. Traditionally, these reconstructions have been performed mainly on high latitude species, limiting the geographical area of their potential use. Here we assess the use of temperate crustose fossil coralline algae from shallow water habitats for palaeoenvironmental reconstruction to generate records of past climate change. We determine the potential of three different species of coralline algae, Lithothamnion minervae, Lithophyllum stictaeforme and Mesophyllum philippii, with different growth patterns, as archives for pH (ÎŽ11B) and temperature (Mg/Ca) reconstruction in the Mediterranean Sea. Mg concentration is driven by temperature but modulated by growth rate, which is controlled by speciesâspecific and intraspecific growth patterns. L. minervae is a good temperature recorder, showing a moderate warming trend in specimens from 11.37 cal ka BP (from 14.2 ± 0.4°C to 14.9 ± 0.15°C) to today. In contrast to Mg, all genera showed consistent values of boron isotopes (ÎŽ11B) suggesting a common control on boron incorporation. The recorded ÎŽ11B in modern and fossil coralline specimens is in agreement with literature data about early Holocene pH, opening new perspectives of corallineâbased, highâresolution pH reconstructions in deep time
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