Background: Variation in platelet reactivity contributes to disorders of hemostasis and thrombosis, but the molecular mechanisms are not well understood. Objectives: To discover associations between ...interindividual platelet variability and the responsible platelet genes, and to begin to define the molecular mechanisms altering platelet gene expression. Subjects/methods: Two hundred and eighty‐eight healthy subjects were phenotyped for platelet responsiveness. Platelet RNA from subjects demonstrating hyperreactivity (n = 18) and hyporeactivity (n = 11) was used to screen the human transcriptome. Results: Distinctly different mRNA profiles were observed between subjects with differing platelet reactivity. Increased levels of mRNA for VAMP8/endobrevin, a critical v‐SNARE involved in platelet granule secretion, were associated with platelet hyperreactivity (Q = 0.0275). Validation studies of microarray results showed 4.8‐fold higher mean VAMP8 mRNA levels in hyperreactive than hyporeactive platelets (P = 0.0023). VAMP8 protein levels varied 13‐fold among platelets from these normal subjects, and were 2.5‐fold higher in hyperreactive platelets (P = 0.05). Among our cohort of 288 subjects, a VAMP8 single‐nucleotide polymorphism (rs1010) was associated with platelet reactivity in an age‐dependent manner (P < 0.003). MicroRNA‐96 was predicted to bind to the 3′‐untranslated regionof VAMP8 mRNA and was detected in platelets. Overexpression of microRNA‐96 in VAMP8‐expressing cell lines caused a dose‐dependent decrease in VAMP8 protein and mRNA, suggesting a role in VAMP8 mRNA degradation. Conclusions: These findings support a role for VAMP8/endobrevin in the heterogeneity of platelet reactivity, and suggest a role for microRNA‐96 in the regulation of VAMP8 expression.
The CHIME Pulsar Project: System Overview Amiri, M.; Bandura, K. M.; Boyle, P. J. ...
The Astrophysical journal. Supplement series,
07/2021, Volume:
255, Issue:
1
Journal Article
Peer reviewed
Open access
Abstract
We present the design, implementation, and performance of the digital pulsar observing system constructed for the Canadian Hydrogen Intensity Mapping Experiment (CHIME). Using accelerated ...computing, this system processes independent, digitally steered beams formed by the CHIME correlator to simultaneously observe up to 10 radio pulsars and transient sources. Each of these independent streams is processed by the CHIME/Pulsar back-end system, which can coherently dedisperse, in real time, up to dispersion measure values of 2500 pc cm
−3
. The tracking beams and real-time analysis system are autonomously controlled by a priority-based algorithm that schedules both known sources and positions of interest for observation with observing cadences as rapid as 1 day. Given the distribution of known pulsars and radio-transient sources and the dynamic scheduling, the CHIME/Pulsar system can monitor 400–500 positions once per sidereal day and observe most sources with declinations greater than −20° once every ∼4 weeks. We also discuss the extensive science program enabled through the current modes of data acquisition for CHIME/Pulsar that centers on timing and searching experiments.
Objectives The aim of this study was to describe differences in treatment and in-hospital mortality of early, late, and very late stent thrombosis (ST). Background Early, late, and very late ST may ...differ in clinical presentation, management, and in-hospital outcomes. Methods We analyzed definite (angiographically documented) ST cases identified from February 2009 to June 2010 in the CathPCI Registry. We stratified events by timing of presentation: early (≤1 month), late (1 to 12 months), or very late (≥12 months) following stent implantation. Multivariable logistic regression modeling was performed to compare in-hospital mortality for each type of ST after adjusting for baseline comorbidities. Results During the study period, 7,315 ST events were identified in 7,079 of 401,662 patients (1.8%) presenting with acute coronary syndromes. This ST cohort consisted of 1,391 patients with early ST (19.6%), 1,370 with late ST (19.4%), and 4,318 with very late ST (61.0%). Subjects with early ST had a higher prevalence of black race and diabetes, whereas subjects with very late ST had a higher prevalence of white race and a lower prevalence of prior myocardial infarction or diabetes. In-hospital mortality was significantly higher in early ST (7.9%) compared with late (3.8%) and very late ST (3.6%, p < 0.001). This lower mortality for late and very late ST persisted after multivariable adjustment (odds ratio: 0.53 95% confidence interval (CI): 0.36 to 0.79 and 0.58 95% CI: 0.43 to 0.79, respectively). Conclusions Significant differences exist in the presentation and outcomes of early, late, and very late ST. Among patients with acute coronary syndromes who are undergoing percutaneous coronary intervention for angiographically documented ST, early ST is associated with the highest in-hospital mortality.
Globally, collapse of ecosystems—potentially irreversible change to ecosystem structure, composition and function—imperils biodiversity, human health and well‐being. We examine the current state and ...recent trajectories of 19 ecosystems, spanning 58° of latitude across 7.7 M km2, from Australia's coral reefs to terrestrial Antarctica. Pressures from global climate change and regional human impacts, occurring as chronic ‘presses’ and/or acute ‘pulses’, drive ecosystem collapse. Ecosystem responses to 5–17 pressures were categorised as four collapse profiles—abrupt, smooth, stepped and fluctuating. The manifestation of widespread ecosystem collapse is a stark warning of the necessity to take action. We present a three‐step assessment and management framework (3As Pathway Awareness, Anticipation and Action) to aid strategic and effective mitigation to alleviate further degradation to help secure our future.
Global climate pressures and regional human impacts are causing increasing collapse of ecosystems across Australia and reaching to Antarctica. Ecosystems are experiencing multiple pressures simultaneously, either chronically (e.g. increasing air temperatures) and/or as extreme, short events (e.g. storms, fires), with their deterioration exhibiting a range of patterns. Knowing these patterns can alert conservation managers to impending collapse. We provide a new framework (the 3As) to use in conservation that focuses on preventing collapse (Awareness of ecosystem values; Anticipation of the range of pressure; Action to stop pressures), as well as guidance as to the types of conservation options available.
Summary
Lumbar epidural is the gold standard for labour analgesia. Low concentrations of local anaesthetic are recommended. This network meta‐analysis investigated whether further reducing the ...concentration of local anaesthetic can improve maternal and neonatal outcomes without compromising analgesia. We conducted a systematic search of relevant databases for randomised controlled trials comparing high (>0.1%), low (>0.08% to ≤0.1%) or ultra‐low (≤0.08%) concentration local anaesthetic (bupivacaine or equivalent) for labour epidural. Outcomes included mode of delivery, duration of labour and maternal/neonatal outcomes. Bayesian network meta‐analysis with random‐effects modelling was used to calculate odds ratios or weighted mean differences and 95% credible intervals. A total of 32 studies met inclusion criteria (3665 women). The total dose of local anaesthetic received increased as the concentration increased; ultra‐low compared with low (weighted mean difference −14.96 mg, 95% credible interval −28.38 to −1.00) and low compared with high groups (weighted mean difference −14.99 −28.79 to −2.04), though there was no difference in the number of rescue top‐ups administered between the groups. Compared with high concentration, ultra‐low concentration local anaesthetic was associated with increased likelihood of spontaneous vaginal delivery (OR 1.46 1.18 to 1.86), reduced motor block (Bromage score >0; OR 0.32 0.18 to 0.54) and reduced duration of second stage of labour (weighted mean difference −13.02 min −21.54 to −4.77). Compared with low, ultra‐low concentration local anaesthetic had similar estimates for duration of second stage of labour (weighted mean difference −1.92 min −14.35 to 10.20); spontaneous vaginal delivery (OR 1.07 0.75 to 1.56; assisted vaginal delivery (OR 1.35 0.75 to 2.26); caesarean section (OR 0.76 0.49 to 1.22); pain (scale 1–100, weighted mean difference −5.44 −16.75 to 5.93); and maternal satisfaction. Although a lower risk of an Apgar score < 7 at 1 min (OR 0.43 0.15 to 0.79) was reported for ultra‐low compared with low concentration, this was not sustained at 5 min (OR 0.12 0.00 to 2.10). Ultra‐low concentration local anaesthetic for labour epidural achieves similar or better maternal and neonatal outcomes as low and high concentration, but with reduced local anaesthetic consumption.
We assessed the effect of surgical resection of colorectal cancer (CRC) on perioperative plasma vitamin D (25OHD) and C-reactive protein (CRP) level. We investigated the relationship between ...circulating vitamin D level and CRC survival.
We sequentially sampled 92 patients undergoing CRC resection, and measured plasma 25OHD and CRP. For survival analyses, we assayed 25OHD and CRP in two temporally distinct CRC patient cohorts (n=2006, n=2100) and investigated the association between survival outcome, circulating vitamin D and systemic inflammatory response.
Serial sampling revealed a postoperative fall (mean 17.3 nmol/L; p=3.6e-9) in plasma 25OHD (nadir days 1-2). CRP peaked 3-5 days postoperatively (143.1 mg/L; p=1.4e-12), yet the postoperative fall in 25OHD was independent of CRP. In cohort analyses, 25OHD was lower in the 12 months following operation (mean=48.8 nmol/L) than preoperatively (54.8 nmol/L; p=1.2e-5) recovering after 24 months (52.2 nmol/L; p=0.002). Survival analysis in American Joint Committee on Cancer stages I-III demonstrated associations between 25OHD tertile and CRC mortality (HR=0.69; 95% CI 0.46 to 0.91) and all-cause mortality (HR=0.68; 95% CI 0.50 to 0.85), and was independent of CRP. We observed interaction effects between plasma 25OHD and rs11568820 genotype (functional
polymorphism) with a strong protective effect of higher 25OHD only in patients with GG genotype (HR=0.51; 95% CI 0.21 to 0.81). We developed an online tool for predicted survival (https://apps.igmm.ed.ac.uk/mortalityCalculator/) that incorporates 25OHD with clinically useful predictive performance (area under the curve 0.77).
CRC surgery induces a fall in circulating 25OHD. Plasma 25OHD level is a prognostic biomarker with low 25OHD associated with poorer survival, particularly in those with rs11568820 GG genotype. A randomised trial of vitamin D supplementation after CRC surgery has compelling rationale.
There has been limited empirical study allowing athletes to voice their opinions on transgender participation in elite sport. This study surveyed 175 national, elite and world class athletes eligible ...to compete in the female category regarding transgender inclusion and eligibility. The study compared current Olympic versus current Olympic Recognised sports, elite versus world class, and current versus retired Olympic sport athletes. Most athletes favoured biological sex categorisation (58%) and considered it unfair for trans women to compete in the female category, except for precision sports. This view was held most strongly by world class athletes regarding their own sport (77% unfair, 15% fair). For trans men inclusion in the male category, most athletes considered it fair, except for Olympic sport athletes regarding contact sports (49% unfair, 27% fair) and sports heavily reliant on physical capacity (53% unfair, 29% fair). Notwithstanding those views, athletes (81%) believed sporting bodies should improve inclusivity for transgender athletes. Opinion varied somewhat according to career stage, competitive level and sport type. Nevertheless, athletes in the present study favoured categorisation by biological sex and did not support trans women eligibility for the female category in sports reliant on performance-related biological factors that differ between sexes.
Socio-economic deprivation is associated with adverse maternal and childhood outcomes. Epidural analgesia, the gold standard for labour analgesia, may improve maternal well-being. We assessed the ...association of socio-economic status with utilisation of epidural analgesia and whether this differed when epidural analgesia was advisable for maternal safety. This was a population-based study of NHS data for all women in labour in Scotland between 1 January 2007 and 23 October 2020, excluding elective caesarean sections. Socio-economic status deciles were defined using the Scottish Index of Multiple Deprivation. Medical conditions for which epidural analgesia is advisable for maternal safety (medical indications) and contraindications were defined according to national guidelines. Of 593,230 patients in labour, 131,521 (22.2%) received epidural analgesia. Those from the most deprived areas were 16% less likely to receive epidural analgesia than the most affluent (relative risk 0.84 95%CI 0.82-0.85), with the inter-decile mean change in receiving epidural analgesia estimated at -2% (95%CI -2.2% to -1.7%). Among the 21,219 deliveries with a documented medical indication for epidural analgesia, the socio-economic gradient persisted (relative risk 0.79 95%CI 0.75-0.84, inter-decile mean change in receiving epidural analgesia -2.5% 95%CI -3.1% to -2.0%). Women in the most deprived areas with a medical indication for epidural analgesia were still less likely (absolute risk 0.23 95%CI 0.22-0.24) to receive epidural analgesia than women from the most advantaged decile without a medical indication (absolute risk 0.25 95%CI 0.24-0.25). Socio-economic deprivation is associated with lower utilisation of epidural analgesia, even when epidural analgesia is advisable for maternal safety. Ensuring equitable access to an intervention that alleviates pain and potentially reduces adverse outcomes is crucial.
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