Risk Factors for Boating Incidents in Inuvik, Northwest Territories, Canada

Injury prevention programs that focus on boating and water safety in the Northwest Territories (NWT) have existed for decades; however, rates of boating incidents are much higher in the NWT than southern Canada. To better understand this health disparity, we engaged in community-based participatory research informed by postcolonial feminist theory to examine Aboriginal men’s understandings of the risk factors that contribute to boating incidents in Inuvik, NWT. Participants identified four main risk factors for boating incidents in Inuvik: 1) Gender, 2) age, 3) place, and 4) lack of boating safety education. As a result of these findings and the ways in which they are strongly related to culture, we argue that local community-based approaches should be employed to design and implement boating safety strategies in communities in the NWT

Early changes in pro-inflammatory cytokine levels in neonates with encephalopathy are associated with remote epilepsy.

BackgroundNeonatal seizures are associated with adverse neurologic sequelae including epilepsy in childhood. Here we aim to determine whether levels of cytokines in neonates with brain injury are associated with acute symptomatic seizures or remote epilepsy.MethodsThis is a cohort study of term newborns with encephalopathy at UCSF between 10/1993 and 1/2000 who had dried blood spots. Maternal, perinatal/postnatal, neuroimaging, and epilepsy variables were abstracted by chart review. Logistic regression was used to compare levels of cytokines with acute seizures and the development of epilepsy.ResultsIn a cohort of 26 newborns with neonatal encephalopathy at risk for hypoxic ischemic encephalopathy with blood spots for analysis, diffuse alterations in both pro- and anti-inflammatory cytokine levels were observed between those with (11/28, 39%) and without acute symptomatic seizures. Seventeen of the 26 (63%) patients had >2 years of follow-up and 4/17 (24%) developed epilepsy. Higher levels of pro-inflammatory cytokines IL-6 and TNF-α within the IL-1β pathway were significantly associated with epilepsy.ConclusionsElevations in pro-inflammatory cytokines in the IL-1β pathway were associated with later onset of epilepsy. Larger cohort studies are needed to confirm the predictive value of these circulating biomarkers

Terrain Features and Architecture of Wolverine (Gulo gulo) Resting Burrows and Reproductive Dens on Arctic Tundra

Burrowing species rely on subterranean and subnivean sites to fulfill important life-history and behavioral processes, including predator avoidance, thermoregulation, resting, and reproduction. For these species, burrow architecture can affect the quality and success of such processes, since characteristics like tunnel width and chamber depth influence access by predators, thermal insulation, and energy spent digging. Wolverines (Gulo gulo) living in Arctic tundra environments dig burrows in snow during winter for resting sites and reproductive dens, but there are few published descriptions of such burrows. We visited 114 resting burrows and describe associated architectural characteristics and non-snow structure. Additionally, we describe characteristics of 15 reproductive den sites that we visited during winter and summer. Although many resting burrows were solely excavated in snow, most incorporated terrain structures including cliffs, talus, river shelf ice, thermokarst caves, and stream cutbanks. Burrows typically consisted of a single tunnel leading to a single chamber, though some burrows had multiple entrances, branching tunnels, or both. Tunnels in resting burrows were shorter than those in reproductive dens, and resting chambers were typically located at the deepest part of the burrow. Reproductive dens were associated with snowdrift-forming terrain features such as streambeds, cutbanks on lake edges, thermokarst caves, and boulders. Understanding such characteristics of Arctic wolverine resting and reproductive structures is critical for assessing anthropogenic impacts as snowpack undergoes climate-driven shifts.Les espèces fouisseuses dépendent de lieux enfouis sous la terre et sous la neige pour satisfaire leurs importants processus de vie et de comportement, y compris l’évitement des prédateurs, la thermorégulation, le repos et la reproduction. Pour ces espèces, l’architecture des terriers peut avoir des effets sur la qualité et la réussite des processus, car des caractéristiques comme la largeur des tunnels et la profondeur des chambres influencent l’accès aux terriers par les prédateurs, l’isolation thermique et l’énergie dépensée pour creuser. L’hiver, les carcajous (Gulo gulo) qui vivent dans les environnements de la toundra de l’Arctique creusent des terriers dans la neige afin de s’en servir comme aires de repos et comme tanières de reproduction. Cependant, peu de descriptions de tels terriers ont été publiées. Nous avons visité 114 terriers de repos, puis nous avons décrit leurs caractéristiques architecturales et les structures connexes n’étant pas recouvertes de neige. Par ailleurs, nous décrivons les caractéristiques de 15 tanières de reproduction que nous avons visitées en hiver et en été. Même si de nombreux terriers de repos ont été uniquement creusés dans la neige, la plupart des terriers incorporaient des structures topographiques, dont des falaises, des talus, de la glace de banquise, des grottes thermokarstiques et des hautes berges de cours d’eau. En général, les terriers étaient composés d’un seul tunnel menant à une seule chambre, bien que certains avaient plusieurs entrées, des galeries, ou les deux. Les tunnels des aires de repos étaient moins longs que ceux des tanières de reproduction, et les chambres de repos étaient généralement situées dans la partie la plus profonde des terriers. Les tanières de reproduction étaient installées dans des caractéristiques topographiques où s’amoncelle la neige, comme les lits de cours d’eau, les hautes berges de lacs, les grottes thermokarstiques et les rochers. Il est essentiel de comprendre les caractéristiques des structures de repos et de reproduction des carcajous de l’Arctique afin d’être en mesure d’évaluer les incidences anthropiques au moment où le manteau neigeux subit des changements liés au climat

Genetic and neuronal regulation of sleep by neuropeptide VF

Sleep is an essential and phylogenetically conserved behavioral state, but it remains unclear to what extent genes identified in invertebrates also regulate vertebrate sleep. RFamide-related neuropeptides have been shown to promote invertebrate sleep, and here we report that the vertebrate hypothalamic RFamide neuropeptide VF (NPVF) regulates sleep in the zebrafish, a diurnal vertebrate. We found that NPVF signaling and npvf-expressing neurons are both necessary and sufficient to promote sleep, that mature peptides derived from the NPVF preproprotein promote sleep in a synergistic manner, and that stimulation of npvf-expressing neurons induces neuronal activity levels consistent with normal sleep. These results identify NPVF signaling and npvf-expressing neurons as a novel vertebrate sleep-promoting system and suggest that RFamide neuropeptides participate in an ancient and central aspect of sleep control

A systematic review of the cost-effectiveness of interventions to increase cervical cancer screening among underserved women in Europe.

BACKGROUND: This study aimed to conduct a systematic review of the cost-effectiveness studies of interventions to increase cervical cancer screening uptake rates in underserved women in Europe. METHODS: A search of Embase, Medline, Global Health, PsychINFO, and NHS Economic Evaluation Database was conducted for studies published between January 2000 and September 2022. Studies were eligible if they analysed the cost-effectiveness of any interventions to improve participation in cervical cancer screening among underserved women of any age eligible to participate in cervical cancer screening in European countries, in any language. Study characteristics and cost-effectiveness results were summarised. Study quality was assessed using the Drummond Checklist, and methodological choices were further compared. RESULTS: The searches yielded 962 unique studies, with 17 of these (from twelve European countries) meeting the eligibility criteria for data extraction. All studies focused on underscreened women as an overarching group, with no identified studies focusing on specific subgroups of underserved women. Generally, self-HPV testing and reminder interventions were shown to be cost-effective to increase the uptake rates. There was also research showing that addressing access issues and adopting different screening modalities could be economically attractive in some settings, but the current evidence is insufficient due to the limited number of studies. CONCLUSION: This systematic review has revealed a gap in the literature on the cost-effectiveness of interventions to improve uptake rates of cervical cancer screening through tailored provision for specific groups of underserved women

Genetic and neuronal regulation of sleep by neuropeptide VF

Sleep is an essential and phylogenetically conserved behavioral state, but it remains unclear to what extent genes identified in invertebrates also regulate vertebrate sleep. RFamide-related neuropeptides have been shown to promote invertebrate sleep, and here we report that the vertebrate hypothalamic RFamide neuropeptide VF (NPVF) regulates sleep in the zebrafish, a diurnal vertebrate. We found that NPVF signaling and npvf-expressing neurons are both necessary and sufficient to promote sleep, that mature peptides derived from the NPVF preproprotein promote sleep in a synergistic manner, and that stimulation of npvf-expressing neurons induces neuronal activity levels consistent with normal sleep. These results identify NPVF signaling and npvf-expressing neurons as a novel vertebrate sleep-promoting system and suggest that RFamide neuropeptides participate in an ancient and central aspect of sleep control

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention