Explore the vast range of titles available.

Introduction In Aotearoa New Zealand, human papillomavirus (HPV) self-testing was introduced simultaneously with HPV primary screening in September 2023 to improve access and reduce inequities for priority populations, including Indigenous Māori, Pacific and under-screened people. To contribute policy-relevant information, we implemented non-standard engagement and screening strategies, including text message invitation, mailed test kits, at-home self-testing, telehealth support and follow-up by a central nurse-led co-ordination team. Methods We partnered with an Auckland primary health organisation (PHO) with high enrolment of priority populations. We invited people eligible for cervical screening aged 30—69 years by text message to receive mailed test kits (April–October 2023); people who did not respond were re-invited (October–November 2023). Offering a financial incentive to return a sample (intervention group) was compared with no offer (control group) in a sub-group of eligible Māori and Pacific who received a repeat mailed test kit in a nested randomised controlled trial (April–May 2024). Self-tested participants were invited by text message to an online survey. Results We invited 25,315 people and 24.0% opted in. Lower initial consent rates were increased after additional re-invitation reminders for Māori (20.0% to 30.4%) and Pacific (13.7% to 24.9%), with the final consent rate in Māori equal to European/Other (29.2%; p  = 0.284). Almost half (48.2%) of consenting participants returned a sample, giving a self-test uptake of 11.6% ( n  = 2,925). Uptake was significantly lower (all p  < 0.001) for Māori (12.7%) and Pacific (8.4%) vs. European/Other (19.0%), and for those under-screened (10.5%) vs. those overdue by < 6 months (19.4%). In the RCT, sample return rate did not differ significantly ( p  = 0.704) between the intervention (7.9%) and control (8.5%) groups. HPV was detected in 7.7% of 3,018 valid results. Follow-up test rates were high (96.8% for cytology, 90.5% for colposcopy). Almost all survey respondents preferred a mailed at-home self-test for their next screen (91.9%; n  = 193 of 210). Discussion Invitation by text message to mailed at-home HPV self-testing engaged priority populations in cervical screening. Central co-ordination support achieved high rates of sample return and follow-up testing where required. A mailed at-home testing option, strongly preferred by survey respondents, warrants consideration in a broader programme to improve access to cervical screening, with additional targeted strategies to improve sample return rates for priority populations. Clinical trial registration While the overall study did not reach the ICJME or WHO criteria for clinical trial registration, the nested RCT was retrospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12625000798460) and World Health Organization (WHO UTN U1111—1324—8454).

Understanding the complex network that regulates transcription elongation requires the quantitative analysis of RNA polymerase II (Pol II) activity in a wide variety of regulatory environments. We performed native elongating transcript sequencing (NET-seq) in 41 strains of Saccharomyces cerevisiae lacking known elongation regulators, including RNA processing factors, transcription elongation factors, chromatin modifiers, and remodelers. We found that the opposing effects of these factors balance transcription elongation and antisense transcription. Different sets of factors tightly regulate Pol II progression across gene bodies so that Pol II density peaks at key points of RNA processing. These regulators control where Pol II pauses with each obscuring large numbers of potential pause sites that are primarily determined by DNA sequence and shape. Antisense transcription varies highly across the regulatory landscapes analyzed, but antisense transcription in itself does not affect sense transcription at the same locus. Our findings collectively show that a diverse array of factors regulate transcription elongation by precisely balancing Pol II activity.

AbstractObjectiveTo estimate effects of a policy introducing universal, no-cost public coverage for prescription contraception on use in British Columbia, Canada.DesignPopulation based, controlled, interrupted time series analysis.Setting10 Canadian provinces.ParticipantsPrescription medications dispensed to reproductive aged (15-49 years) female residents of British Columbia, Canada, compared with a synthetic control derived from the nine other Canadian provinces and a population based cohort of 859 845 female individuals in British Columbia (age 15-49 years) between 1 April 2021 and 30 June 2024.InterventionIntroduction of a universal contraception coverage policy in April 2023, where the public insurer pays 100% of prescription costs.Outcome measuresNumber of monthly dispensations for long-acting reversible contraception (LARC) and number of monthly dispensations for all forms of prescription contraception (including LARC), percentage of reproductive aged female residents using LARC and using all forms of prescription contraception, and the proportion of people using prescription contraception who use LARC (LARC market share). Segmented regression models were used to estimate policy effects by comparing the expected outcome values after 15 months of the policy (ie, the counterfactual, derived from trends before the policy and changes in the control) with the observed values, with 95% confidence intervals (CIs) estimated using bootstrapping.ResultsIn April 2021, 3249 (95% CI 3066 to 3391) LARC prescriptions were dispensed in British Columbia, with a declining slope trend of −17 (−30 to −7) fewer dispensed per month before the policy. Monthly LARC dispensations increased by 1050 (942 to 1487) immediately after British Columbia’s policy change and saw a steady increasing trend after the policy introduction. An additional 1273 (963 to 1698) monthly LARC prescriptions were dispensed 15 months after policy implementation compared with the expected volume, representing an estimated 1.49-fold (1.34 to 1.77) increase. Dispensations for all prescription contraception (including LARC) increased by 1981 (356 to 3324) per month, representing a 1.04-fold (1.01 to 1.07) increase. Among the 859 845 female residents aged 15-49 years in the population, 9.1% were using LARC in April 2021. 15 months after the policy, 11 375 (10 273 to 13 013) more individuals were using LARC than expected without the policy, representing an additional 1.3% (1.2% to 1.5%) of the population. The policy led to an additional 1.7% (1.5% to 2.3%) of the population using any prescription contraception. 15 months after the policy, the LARC market share was 1.9% (1.2% to 2.3%) higher than expected.ConclusionsUniversal, no-cost public coverage in British Columbia increased prescription contraception use overall, driven by increased LARC use. As such, cost seems to be an important contributor to contraception use and method selection at the population level.

A growing community is constructing a next-generation file format (NGFF) for bioimaging to overcome problems of scalability and heterogeneity. Organized by the Open Microscopy Environment (OME), individuals and institutes across diverse modalities facing these problems have designed a format specification process (OME-NGFF) to address these needs. This paper brings together a wide range of those community members to describe the cloud-optimized format itself—OME-Zarr—along with tools and data resources available today to increase FAIR access and remove barriers in the scientific process. The current momentum offers an opportunity to unify a key component of the bioimaging domain—the file format that underlies so many personal, institutional, and global data management and analysis tasks.

Background Preterm birth (PTB) is a complex disorder associated with significant neonatal mortality and morbidity and long-term adverse health consequences. Multiple lines of evidence suggest that genetic factors play an important role in its etiology. This study was designed to identify genetic variation associated with PTB in oxytocin pathway genes whose role in parturition is well known. Methods To identify common genetic variants predisposing to PTB, we genotyped 16 single nucleotide polymorphisms (SNPs) in the oxytocin ( OXT ), oxytocin receptor ( OXTR ), and leucyl/cystinyl aminopeptidase ( LNPEP ) genes in 651 case infants from the U.S. and one or both of their parents. In addition, we examined the role of rare genetic variation in susceptibility to PTB by conducting direct sequence analysis of OXTR in 1394 cases and 1112 controls from the U.S., Argentina, Denmark, and Finland. This study was further extended to maternal triads (maternal grandparents-mother of a case infant, N =309). We also performed in vitro analysis of selected rare OXTR missense variants to evaluate their functional importance. Results Maternal genetic effect analysis of the SNP genotype data revealed four SNPs in LNPEP that show significant association with prematurity. In our case–control sequence analysis, we detected fourteen coding variants in exon 3 of OXTR , all but four of which were found in cases only. Of the fourteen variants, three were previously unreported novel rare variants. When the sequence data from the maternal triads were analyzed using the transmission disequilibrium test, two common missense SNPs (rs4686302 and rs237902) in OXTR showed suggestive association for three gestational age subgroups. In vitro functional assays showed a significant difference in ligand binding between wild-type and two mutant receptors. Conclusions Our study suggests an association between maternal common polymorphisms in LNPEP and susceptibility to PTB. Maternal OXTR missense SNPs rs4686302 and rs237902 may have gestational age-dependent effects on prematurity. Most of the OXTR rare variants identified do not appear to significantly contribute to the risk of PTB, but those shown to affect receptor function in our in vitro study warrant further investigation. Future studies with larger sample sizes are needed to confirm the findings of this study.

This article describes major topics discussed from the ‘Economics of Physical Inactivity Consensus Workshop’ (EPIC), held in Vancouver, Canada, in April 2011. Specifically, we (1) detail existing evidence on effective physical inactivity prevention strategies; (2) introduce economic evaluation and its role in health policy decisions; (3) discuss key challenges in establishing and building health economic evaluation evidence (including accurate and reliable costs and clinical outcome measurement) and (4) provide insight into interpretation of economic evaluations in this critically important field. We found that most methodological challenges are related to (1) accurately and objectively valuing outcomes; (2) determining meaningful clinically important differences in objective measures of physical inactivity; (3) estimating investment and disinvestment costs and (4) addressing barriers to implementation. We propose that guidelines specific for economic evaluations of physical inactivity intervention studies are developed to ensure that related costs and effects are robustly, consistently and accurately measured. This will also facilitate comparisons among future economic evidence.

Background Fall-related hip fractures result in significant personal and societal consequences; importantly, up to half of older adults with hip fracture never regain their previous level of mobility. Strategies of follow-up care for older adults after fracture have improved investigation for osteoporosis; but managing bone health alone is not enough. Prevention of fractures requires management of both bone health and falls risk factors (including the contributing role of cognition, balance and continence) to improve outcomes. Methods/Design This is a parallel group, pragmatic randomized controlled trial to test the effectiveness of a post-fracture clinic compared with usual care on mobility for older adults following their hospitalization for hip fracture. Participants randomized to the intervention will attend a fracture follow-up clinic where a geriatrician and physiotherapist will assess and manage their mobility and other health issues. Depending on needs identified at the clinical assessment, participants may receive individualized and group-based outpatient physiotherapy, and a home exercise program. Our primary objective is to assess the effectiveness of a novel post-discharge fracture management strategy on the mobility of older adults after hip fracture. We will enrol 130 older adults (65 years+) who have sustained a hip fracture in the previous three months, and were admitted to hospital from home and are expected to be discharged home. We will exclude older adults who prior to the fracture were: unable to walk 10 meters; diagnosed with dementia and/or significant comorbidities that would preclude their participation in the clinical service. Eligible participants will be randomly assigned to the Intervention or Usual Care groups by remote allocation. Treatment allocation will be concealed; investigators, measurement team and primary data analysts will be blinded to group allocation. Our primary outcome is mobility, operationalized as the Short Physical Performance Battery at 12 months. Secondary outcomes include frailty, rehospitalizations, falls risk factors, quality of life, as well as physical activity and sedentary behaviour. We will conduct an economic evaluation to determine health related costs in the first year, and a process evaluation to ascertain the acceptance of the program by older adults, as well as clinicians and staff within the clinic. Trial registration number ClinicalTrials.gov: NCT01254942

Neuronal activity shapes brain development and refines synaptic connectivity in part through dynamic changes in gene expression. While activity-regulated transcriptional programs have been extensively characterized, the holistic effects of neuronal activity on the full RNA life cycle remain relatively unexplored. Here, we show that neuronal activity influences multiple stages of RNA metabolism and . Among these, RNA stability emerges as a previously underappreciated regulator of gene expression, exerting a stronger influence than transcription on total RNA levels for ∼15% of activity-dependent genes. We go on to profile 3'UTR mRNA motifs that are sufficient to modulate activity-dependent mRNA stability and employ machine learning to identify the neuronal-specific RNA-binding protein HuD as a key regulator of activity-dependent mRNA stabilization. We demonstrate that HuD shapes activity-dependent mRNA abundance of hundreds of transcripts in both soma and distal neuronal processes and that neuronal activity drives the reorganization of HuD-interacting proteins, thereby stabilizing HuD-bound mRNAs and directing them into translationally active granules. Finally, we find that many variants associated with autism spectrum disorder (ASD) and other neurodevelopmental disorders disrupt or promote aberrant activity-dependent changes in mRNA stability. These findings reveal mRNA stability as a widespread mechanism of stimulus-responsive gene regulation in neurons with direct implications for the understanding of neurodevelopmental disorders.