Industrial-Age Doubling of Snow Accumulation in the Alaska Range Linked to Tropical Ocean Warming

Future precipitation changes in a warming climate depend regionally upon the response of natural climate modes to anthropogenic forcing. North Pacific hydroclimate is dominated by the Aleutian Low, a semi-permanent wintertime feature characterized by frequent low-pressure conditions that is influenced by tropical Pacific Ocean temperatures through the Pacific-North American (PNA) teleconnection pattern. Instrumental records show a recent increase in coastal Alaskan precipitation and Aleutian Low intensification, but are of insufficient length to accurately assess low frequency trends and forcing mechanisms. Here we present a 1200-year seasonally- to annually-resolved ice core record of snow accumulation from Mt. Hunter in the Alaska Range developed using annual layer counting and four ice-flow thinning models. Under a wide range of glacier flow conditions and layer counting uncertainty, our record shows a doubling of precipitation since ~1840 CE, with recent values exceeding the variability observed over the past millennium. The precipitation increase is nearly synchronous with the warming of western tropical Pacific and Indian Ocean sea surface temperatures. While regional 20th Century warming may account for a portion of the observed precipitation increase on Mt. Hunter, the magnitude and seasonality of the precipitation change indicate a long-term strengthening of the Aleutian Low

Sample size and power considerations for ordinary least squares interrupted time series analysis: a simulation study.

Interrupted time series (ITS) analysis is being increasingly used in epidemiology. Despite its growing popularity, there is a scarcity of guidance on power and sample size considerations within the ITS framework. Our aim of this study was to assess the statistical power to detect an intervention effect under various real-life ITS scenarios. ITS datasets were created using Monte Carlo simulations to generate cumulative incidence (outcome) values over time. We generated 1,000 datasets per scenario, varying the number of time points, average sample size per time point, average relative reduction post intervention, location of intervention in the time series, and reduction mediated via a 1) slope change and 2) step change. Performance measures included power and percentage bias. We found that sample size per time point had a large impact on power. Even in scenarios with 12 pre-intervention and 12 post-intervention time points with moderate intervention effect sizes, most analyses were underpowered if the sample size per time point was low. We conclude that various factors need to be collectively considered to ensure adequate power for an ITS study. We demonstrate a means of providing insight into underlying sample size requirements in ordinary least squares (OLS) ITS analysis of cumulative incidence measures, based on prespecified parameters and have developed Stata code to estimate this

Menopausal symptoms by HIV status and association with health-related quality of life among women in Zimbabwe: a cross-sectional study.

BACKGROUND: The scale-up of antiretroviral therapy programmes has resulted in increased life expectancy of people with HIV in Africa. Little is known of the menopausal experiences of African women, including those living with HIV. We aimed to determine the prevalence and severity of self-reported menopause symptoms in women at different stages of menopause transition, by HIV status, and evaluate how symptoms are related to health-related quality of life (HRQoL). We further sought to understand factors associated with menopause symptoms. METHODS: A cross-sectional study recruited women resident in Harare, Zimbabwe, sampled by age group (40-44/45-49/50-54/55-60 years) and HIV status. Women recruited from public-sector HIV clinics identified two similarly aged female friends (irrespective of HIV status) with phone access. Socio-demographic and medical details were recorded and women staged as pre-, peri- or post-menopause. The Menopausal Rating Scale II (MRS), which classified symptom severity, was compared between those with and without HIV. Linear and logistic regression determined factors associated with menopause symptoms, and associations between symptoms and HRQoL. RESULTS: The 378 women recruited (193[51.1%] with HIV), had a mean (SD) age of 49.3 (5.7) years; 173 (45.8%), 51 (13.5%) and 154 (40.7%) were pre-, peri and post-menopausal respectively. Women with HIV reported more moderate (24.9% vs. 18.1%) and severe (9.7% vs. 2.6%) menopause symptoms than women without HIV. Peri-menopausal women with HIV reported higher MRS scores than those pre- and post-menopausal, whereas in HIV negative women menopausal stage was not associated with MRS score (interaction p-value = 0.014). With increasing severity of menopause symptoms, lower mean HRQoL scores were observed. HIV (OR 2.02[95% CI 1.28, 3.21]), mood disorders (8.80[2.77, 28.0]), ≥ 2 falls/year (4.29[1.18, 15.6]), early menarche (2.33[1.22, 4.48]), alcohol consumption (2.16[1.01, 4.62]), food insecurity (1.93[1.14, 3.26]) and unemployment (1.56[0.99, 2.46]), were all associated with moderate/severe menopause symptoms. No woman reported use of menopausal hormone therapy. CONCLUSIONS: Menopausal symptoms are common and negatively impact HRQoL. HIV infection is associated with more severe menopause symptoms, as are several modifiable factors, including unemployment, alcohol consumption, and food insecurity. Findings highlight an unmet health need in ageing women in Zimbabwean, especially among those living with HIV

The influence of mode of anaesthesia on perioperative outcomes in people with hip fracture: a prospective cohort study from the National Hip Fracture Database for England, Wales and Northern Ireland

Background: Delirium is common after hip fracture surgery, affecting up to 50% of patients. The incidence of delirium may be influenced by mode and conduct of anaesthesia. We examined the effect of spinal anaesthesia (with and without sedation) compared with general anaesthesia on early outcomes following hip fracture surgery, including delirium. Methods: We used prospective data on 107,028 patients (2018 to 2019) from the National Hip Fracture Database, which records all hip fractures in patients aged 60 years and over in England, Wales and Northern Ireland. Patients were grouped by anaesthesia: general (58,727; 55%), spinal without sedation (31,484; 29%), and spinal with sedation (16,817; 16%). Outcomes (4AT score on post-operative delirium screening; mobilisation day one post-operatively; length of hospital stay; discharge destination; 30-day mortality) were compared between anaesthetic groups using multivariable logistic and linear regression models. Results: Compared with general anaesthesia, spinal anaesthesia without sedation (but not spinal with sedation) was associated with a significantly reduced risk of delirium (odds ratio (OR)=0.95, 95% confidence interval (CI)=0.92–0.98), increased likelihood of day one mobilisation (OR=1.06, CI=1.02–1.10) and return to original residence (OR=1.04, CI=1.00–1.07). Spinal without sedation (p<0.001) and spinal with sedation (p=0.001) were both associated with shorter hospital stays compared with general anaesthesia. No differences in mortality were observed between anaesthetic groups. Conclusions: Spinal and general anaesthesia achieve similar outcomes for patients with hip fracture. However, this equivalence appears to reflect improved perioperative outcomes (including a reduced risk of delirium, increased likelihood of mobilisation day one post-operatively, shorter length of hospital stay and improved likelihood of returning to previous residence on discharge) among the sub-set of patients who received spinal anaesthesia without sedation. The role and effect of sedation should be studied in future trials of hip fracture patients undergoing spinal anaesthesia

NEID Reveals that The Young Warm Neptune TOI-2076 b Has a Low Obliquity

TOI-2076 b is a sub-Neptune-sized planet ($R=2.39 \pm 0.10 \mathrm{R_\oplus}$) that transits a young ($204 \pm 50 \mathrm{MYr}$) bright ($V = 9.2$) K-dwarf hosting a system of three transiting planets. Using spectroscopic observations with the NEID spectrograph on the WIYN 3.5 m Telescope, we model the Rossiter-McLaughlin effect of TOI-2076 b, and derive a sky-projected obliquity of $\lambda=-3_{-15}^{+16\:\circ}$. Using the size of the star ($R=0.775 \pm0.015 \mathrm{R_\odot}$), and the stellar rotation period ($P_{\mathrm{rot}}=7.27\pm0.23$ days), we estimate a true obliquity of $\psi=18_{-9}^{+10\:\circ}$ ($\psi < 34^\circ$ at 95% confidence), demonstrating that TOI-2076 b is on a well-aligned orbit. Simultaneous diffuser-assisted photometry from the 3.5 m Telescope at Apache Point Observatory rules out flares during the transit. TOI-2076 b joins a small but growing sample of young planets in compact multi-planet systems with well-aligned orbits, and is the fourth planet with an age $\lesssim 300$ Myr in a multi-transiting system with an obliquity measurement. The low obliquity of TOI-2076 b and the presence of transit timing variations in the system suggest the TOI-2076 system likely formed via convergent disk migration in an initially well-aligned disk.Comment: Submitted to ApJL, 13 pages, 4 figures, 3 table

Impact of TNF inhibitor therapy on joint replacement rates in rheumatoid arthritis: a matched cohort analysis of BSRBR-RA UK registry data.

OBJECTIVES: Previous ecological data suggest a decline in the need for joint replacements in RA patients following the introduction of TNF inhibitor (TNFi) therapy, although patient-level data are lacking. Our primary aim was to estimate the association between TNFi use and subsequent incidence of total hip replacement (THR) and total knee replacement. METHODS: A propensity score matched cohort was analysed using the British Society for Rheumatology Biologics Registry (2001-2016) for RA data. Propensity score estimates were used to match TNFi users to similar conventional synthetic DMARD users (with replacement) using a 1:1 ratio. Weighted multivariable Cox regression was used to estimate the impact of TNFi on study outcomes. Effect modification by baseline age and disease severity were investigated. Joint replacement at other sites was also analysed. An instrumental variable sensitivity analysis was also performed. RESULTS: The matched analysis contained a total of 19 116 patient records. Overall, there was no significant association between TNFi use vs conventional synthetic DMARD on rates of THR (hazard ratios = 0.86 [95% CI: 0.60, 1.22]) although there was significant effect modification by age (P 60 years old (hazard ratio = 0.60 [CI: 0.41, 0.87]) but not in younger patients. No significant associations were found for total knee replacement or other joint replacement. CONCLUSION: Overall, no association was found between the use of TNFi and subsequent incidence of joint replacement. However, TNFi was associated with a 40% relative reduction in THR rates among older patients

Comparative anti-fracture effectiveness of different oral anti-osteoporosis therapies based on "real-world" data: a meta-analysis of propensity-matched cohort findings from the UK Clinical Practice Research Database and the Catalan SIDIAP Database.

PURPOSE: This paper aims to compare the clinical effectiveness of oral anti-osteoporosis drugs based on the observed risk of fracture while on treatment in primary care actual practice. MATERIALS AND METHODS: We investigated two primary care records databases covering UK National Health Service (Clinical Practice Research Datalink, CPRD) and Catalan healthcare (Information System for Research in Primary Care, SIDIAP) patients during 1995-2014 and 2006-2014, respectivey. Treatment-naive incident users of anti-osteoporosis drugs were included and followed until treatment cessation, switching, death, transfer out, or study completion. We considered hip fracture while on treatment as main outcome and major osteoporotic fractures (hip, clinical spine, wrist, and proximal humerus) as secondary outcome. Users of alendronate (reference group) were compared to those of (1) OBP, (2) strontium ranelate (SR), and (3) selective estrogen receptor modulators (SERMs), after matching on baseline characteristics using propensity scores. Multiple imputation was used to handle missing data on confounders and competing risk modelling for the calculation of relative risk according to therapy. Country-specific data were analyzed separately and meta-analyzed. RESULTS: A total of 163,950 UK and 145,236 Catalan patients were identified. Hip (sub-hazard ratio [SHR] [95% CI] 1.04 [0.77-1.40]) and major osteoporotic (SHR [95% CI] 1 [0.78-1.27]) fracture risks were similar among OBP compared to alendronate users. Both hip (SHR [95% CI] 1.26 [1.14-1.39]) and major osteoporotic (SHR [95% CI] 1.06 [1.02-1.12]) fracture risk were higher in SR compared to alendronate users. SERM users had a reduced hip (SHR [95% CI] 0.75 [0.60-0.94]) and major osteoporotic (SHR [95% CI] 0.77 [0.72-0.83]) fracture risk compared to alendronate users. CONCLUSION: We found a 26% excess hip fracture risk among SR compared to matched alendronate users, in line with placebo-controlled RCT findings. Conversely, in a lower risk population, SERM users had a 25% reduced hip fracture risk compared to alendronate users. Head-to-head RCTs are needed to confirm these findings