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Background Centralising specialist cancer surgical services is an example of major system change. High-volume centres are recommended to improve specialist cancer surgery care and outcomes. Objective Our aim was to use a mixed-methods approach to evaluate the centralisation of specialist surgery for prostate, bladder, renal and oesophago-gastric cancers in two areas of England [i.e. London Cancer (London, UK), which covers north-central London, north-east London and west Essex, and Greater Manchester Cancer (Manchester, UK), which covers Greater Manchester]. Design Stakeholder preferences for centralising specialist cancer surgery were analysed using a discrete choice experiment, surveying cancer patients (n = 206), health-care professionals (n = 111) and the general public (n = 127). Quantitative analysis of impact on care, outcomes and cost-effectiveness used a controlled before-and-after design. Qualitative analysis of implementation and outcomes of change used a multisite case study design, analysing documents (n = 873), interviews (n = 212) and non-participant observations (n = 182). To understand how lessons apply in other contexts, we conducted an online workshop with stakeholders from a range of settings. A theory-based framework was used to synthesise these approaches. Results Stakeholder preferences – patients, health-care professionals and the public had similar preferences, prioritising reduced risk of complications and death, and better access to specialist teams. Travel time was considered least important. Quantitative analysis (impact of change) – only London Cancer’s centralisations happened soon enough for analysis. These changes were associated with fewer surgeons doing more operations and reduced length of stay [prostate –0.44 (95% confidence interval –0.55 to –0.34) days; bladder –0.563 (95% confidence interval –4.30 to –0.83) days; renal –1.20 (95% confidence interval –1.57 to –0.82) days]. The centralisation meant that renal patients had an increased probability of receiving non-invasive surgery (0.05, 95% confidence interval 0.02 to 0.08). We found no evidence of impact on mortality or re-admissions, possibly because risk was already low pre-centralisation. London Cancer’s prostate, oesophago-gastric and bladder centralisations had medium probabilities (79%, 62% and 49%, respectively) of being cost-effective, and centralising renal services was not cost-effective (12% probability), at the £30,000/quality-adjusted life-year threshold. Qualitative analysis, implementation and outcomes – London Cancer’s provider-led network overcame local resistance by distributing leadership throughout the system. Important facilitators included consistent clinical leadership and transparent governance processes. Greater Manchester Cancer’s change leaders learned from history to deliver the oesophago-gastric centralisation. Greater Manchester Cancer’s urology centralisations were not implemented because of local concerns about the service model and local clinician disengagement. London Cancer’s network continued to develop post implementation. Consistent clinical leadership helped to build shared priorities and collaboration. Information technology difficulties had implications for interorganisational communication and how reliably data follow the patient. London Cancer’s bidding processes and hierarchical service model meant that staff reported feelings of loss and a perceived ‘us and them’ culture. Workshop – our findings resonated with workshop attendees, highlighting issues about change leadership, stakeholder collaboration and implications for future change and evaluation. Limitations The discrete choice experiment used a convenience sample, limiting generalisability. Greater Manchester Cancer implementation delays meant that we could study the impact of only London Cancer changes. We could not analyse patient experience, quality of life or functional outcomes that were important to patients (e.g. continence). Future research Future research may focus on impact of change on care options offered, patient experience, functional outcomes and long-term sustainability. Studying other approaches to achieving high-volume services would be valuable. Study registration National Institute for Health and Care Research (NIHR) Clinical Research Network Portfolio reference 19761. Funding This project was funded by the NIHR Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 11, No. 2. See the NIHR Journals Library website for further project information.

To provide a description of primary idiopathic immune-mediated polyarthritis, including long-term outcome and relapse rates, for dogs starting treatment with corticosteroids alone or corticosteroids with a second immunosuppressant.Medical records were reviewed between January 2012 and December 2017 to identify dogs diagnosed with primary immune-mediated polyarthritis. Data including signalment, clinicopathological findings, type and duration of treatment, relapse and outcome were recorded.Seventy-three dogs were included. Fifty-four dogs were started on corticosteroid monotherapy (an additional immunosuppressant was introduced later in 27/54 dogs) and 19 dogs were treated with multi-modal immunosuppression from the outset. Ninety-five percent (69/73) of dogs responded favourably to therapy although death was attributed to immune-mediated polyarthritis in 19% (14/73) of dogs. Relapse of clinical signs was reported in 53% (39/73) dogs (31/39 while on treatment), with multiple relapses observed in 17 dogs. Complete cure (permanent withdrawal of immunosuppressive medication) was achieved in 46 dogs (63%). Overall, 81% of dogs had a well-managed disease for an extended timeframe (≥1131 days). Fourteen of 19 (74%) dogs that started treatment with multi-modal immunosuppression and 32 of 54 (59%) started on corticosteroids alone achieved a complete cure.This study provides extended follow-up information for a large cohort of dogs with primary immune-mediated polyarthritis. Immunosuppressive therapy was discontinued in the majority of dogs but disease-associated mortality remains high.

Background Few studies have focused on the immune response to more recent influenza vaccine formulations such as cell-cultured inactivated influenza vaccine (ccIIV4) or live attenuated influenza vaccine (LAIV4) in older children and young adults, or differences in immunoglobulin response using newer antibody landscape technology. Methods Participants ages 4-21 were randomized to receive ccIIV4 (n =112) or LAIV4 (n=118). A novel high-throughput multiplex influenza antibody detection assay (MIADA) was used to provide detailed IgG, IgA, and IgM antibody isotypes, along with hemagglutination inhibition levels (HAI), measured pre- and 28 days post vaccination. Results The HAI and immunoglobulin isotype response to ccIIV4 was greater than LAIV4, with significant increases in IgG but not IgA or IgM. The youngest participants had the highest LAIV4 response. Prior LAIV4 vaccination was associated with a higher response to current season ccIIV4. Cross-reactive A/Delaware/55/2019(H1N1)pdm09 antibodies were present pre-vaccination and increased in response to ccIIV4, but not LAIV4. Immunoglobulin assays strongly correlated with and confirmed the findings of HAI titers to measure immune response. Conclusions Age and prior season vaccination may play a role in the immune response in children and young adults to ccIIV4 and LAIV4. While immunoglobulin isotypes provide high level antigen-specific information, HAI titers alone can provide a meaningful representation of day 28 post vaccination response.

Contains fulltext : 291600.pdf (Publisher’s version ) (Open Access) BACKGROUND: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. OBJECTIVE: To present consensus voting results for select questions from APCCC 2022. DESIGN, SETTING, AND PARTICIPANTS: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members ("panellists") who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1-3. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. RESULTS AND LIMITATIONS: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. CONCLUSIONS: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials. PATIENT SUMMARY: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions.

As the older Indigenous population in the United States expands, there is a growing demand for programs to address age-related needs. Although Title VI of the OAA provides culturally responsive strategies to support elders through home- and community-based nutrition services, these programs have not been the subject of a national evaluation; our study is the first.We conducted a mixed-methods study to assess the impact of the Title VI programs on elders. We used quantitative data from a national survey of Indigenous elders (n = 1175) and qualitative data collected through interviews (n = 36) and focus groups (18, n = 161) with a subgroup of elders receiving services. We compared outcomes for social and cultural connectedness and physical and mental well-being for different subgroups within our sample of elders based on elders' use of Title VI services and the level of services provided to these elders. Results were adjusted for community characteristics.Elders receiving Title VI services had significantly fewer hospitalizations and falls per year (hospitalizations: 0.9 vs. 1.2, p 0.05; falls: 1.0 versus 1.1, p 0.05) and significantly more social and cultural engagements per month (social engagements: 92.6% vs. 75.6%, p 0.05; cultural practices: 78.8% vs. 64.8%, p 0.05) compared with elders who did not participate in Title VI services. These findings were confirmed by our qualitative data.Our findings highlight the vital role that the Title VI program plays in promoting elders' overall health and well-being through decreased hospitalizations and falls and increased connectedness.

Introduction Sexuality-based stigma is prevalent in the USA and is, in part, based on religious and gender norms. In the South—compared to other regions—religiosity is more salient, gender norms are more conservative, and sexual and reproductive health (SRH) inequities are more prevalent. Methods Guided by a stakeholder Advisory Committee, the researchers conducted 20 in-depth interviews with Protestant religious leaders in Georgia from 2018 to 2019 to explore how faith leaders describe sexuality-based stigma, including toward abortion and sexual and gender minorities. Interviews were transcribed and thematically analyzed using team-based, iterative coding. Results Religious leaders held a wide range of abortion and sexuality attitudes and norms. Some described traditional judgment around the “sins” of abortion, “homosexuality,” and/or “transgender people” based on Scripture and constructs of the cisgender binary and sexual purity. But the researchers noted tension between that judgment and Christian ideologies of “love” and “all people [being] welcomed…[no] matter who you are.” Several participants provided counter-examples for building supportive and empathic abortion and sexuality norms—including LGBTQ inclusivity—through de-stigmatizing testimony and personal relationships. Conclusions There are linkages between abortion stigma and stigma against sexual/gender minorities among Southern religious leaders. However, there is also support for abortion and LGBTQ inclusivity. We assert that assets-based engagement of religious leaders is critical for building effective, inclusive faith-based SRH programming. Policy Implications These findings demonstrate the need for national, state, and local policies that protect comprehensive sex education, abortion access, and LGBTQ people.

Hypertension, which can be brought on by excess sodium intake, affects nearly one half of U.S. adults and is a major risk factor for heart disease, the leading cause of death in the United States (1). In 2019, the National Academies of Sciences, Engineering, and Medicine (NASEM) established the Chronic Disease Risk Reduction (CDRR) intake, a chronic-disease-specific recommendation for dietary sodium of 2,300 mg/day. Reducing daily sodium to CDRR intake is expected to reduce chronic disease risk among healthy persons, primarily by lowering blood pressure (2). Although the 2019 sodium CDRR intake is equivalent in number to the 2005 Tolerable Upper Limit (UL) released by NASEM (then known as the Institute of Medicine), the UL was intended to provide guidance on safe intake levels, not to serve as an intake goal (2). To describe excess sodium intake in the context of the CDRR intake goal, this report analyzed National Health and Nutrition Examination Survey (NHANES) data from 2003 to 2016 to yield temporal trends in usual sodium intake >2,300 mg/day and in mean sodium intake, unadjusted and adjusted for total energy intake, among U.S. adults aged ≥19 years. The percentage of U.S. adults with sodium intake above CDRR intake was 87.0% during 2003-2004 and 86.7% during 2015-2016. Among U.S. adults overall, no significant linear trend was noted from 2003 to 2016 in unadjusted or energy intake-adjusted mean sodium intake. Small, significant declines were observed in mean usual sodium intake among some groups (adults aged 19-50 years, non-Hispanic White adults, adults experiencing obesity, and adults without hypertension). However, after energy adjustment, only adults aged ≥71 years and Mexican American adults demonstrated significant change in usual sodium intake. Many U.S. adults might be at risk for chronic disease associated with sodium intake above CDRR intake, and efforts to lower sodium intake could improve population cardiovascular health. The results of this report support enhanced efforts to reduce population sodium intake and cardiovascular disease risk, including the Food and Drug Administration's (FDA's) recently released guidance for the reduction of sodium in the commercially processed, packaged, and prepared food supply.

This article evaluates the introduction of an online assessment protocol to student officers on a Police Constable Degree Apprenticeship (PCDA) programme in the aftermath of the implementation of the COVID-19 global pandemic lockdown. This evaluation comes from conducting two cycles of action research to examine and improve the provision of an online multiple choice/short question exam which came about as a result of the lockdown, and the necessary withdrawal of university staff from face-to-face contact. The study shows that the introduction of the online exam was successful and contributed to a positive student experience, while providing vital feedback to the programme team to make continual improvements and can be progressed after lockdown and into the ‘new normal’.

Background #KindnessbyPost (KbP) is a “national kindness exchange”. Participants send and receive a card by post to different, unknown people containing messages of good will. Previous evidence suggests participation in KbP may improve loneliness and wellbeing. We evaluated the outcomes and associated costs of KbP and explored the feasibility of collecting health economic measures for future research. Methods We used a pre-post, observational study design. Participants in two KbP exchanges in 2021 were invited to complete an online questionnaire. It included self-reported measures of psychological wellbeing and loneliness, capability, and healthcare service use. Data were collected at three time-points: exchange start (baseline), exchange-end (2 weeks), and 3-months post-exchange. Additional cost data were obtained from the KbP programme organisers. Results Across exchanges, baseline data were obtained for 1,285 participants (from 1,142 individuals). In total, 623 (48%) of participants were followed up at exchange-end, and 414 (32%) at 3-months. 70% of participants were aged between 31 and 60 (n = 789). 94% of participants were female (1,075) and 95% of white ethnicity (1,078). Compared to baseline, loneliness and wellbeing improved at exchange end (‑0.21, 95% CI: -0.29 to -0.12; 0.68, 0.47 to 0.88 respectively) and at 3 months follow up (-0.40, -0.50 to -0.30; 1.01, 0.77 to 1.25 respectively). We observed no difference from baseline in capability at both follow up points (mean (SD) at baseline: 0.52(0.22); exchange-end: 0.53(0.22); 3-months: 0.53(0.22)). The average cost of delivering the intervention was £0.67–0.87 per participant. Conclusions We observed a small, sustained improvement to people’s wellbeing and loneliness following participation in a KbP exchange. Given the study design, causal attribution to KbP is uncertain. However, our results are consistent with previous evaluations and offer preliminary evidence that KbP may be an effective mental wellbeing intervention. Given its cheap cost (estimated at £0.67-£0.87 per participant) and highly scalable design, KbP could be an effective and cost-effective intervention for improving public mental health, which warrants definitive evaluation of effectiveness and cost-effectiveness in future. Our study also demonstrates the feasibility of collecting the wellbeing and health economic outcome measures needed for this research.

This article describes our experience of conducting a 5-year, culturally responsive evaluation of a federal program with Indigenous communities. It describes how we adapted tenets from “participatory evaluation models” to ensure cultural relevance and empowerment. We provide recommendations for evaluators engaged in similar efforts. The evaluation included stakeholder engagement through a Steering Committee and an Evaluation Working Group in designing and implementing the evaluation. That engagement facilitated attention to Indigenous cultural values in developing a program logic model and medicine wheel and in gathering local perspectives through storytelling to facilitate understanding of community traditions. Our ongoing assessment of program grantees’ needs shaped our approach to evaluation capacity building and development of a diverse array of experiential learning opportunities and user-friendly tools and resources. We present practical strategies from lessons learned during the evaluation design and implementation phases of our project that might be useful for other evaluators.

Humankind has lived with the danger of endemic, epidemic and pandemic disease for thousands of years. The effects of these outbreaks have often devastated human populations. Sixteen pandemic events causing an estimated 147 million deaths have occurred since the eighth century, The Black Death and the influenza pandemic of 1918-1920 probably having the greatest impact. Animal populations, both wild and domestic, have similarly suffered devastating outbreaks of disease which, on occasions, have translated into serious effects on human health. The deliberate or accidental introduction of animals into virgin areas has given rise to unforeseen disease events occasionally leading to extinction. Similarly, human intent or negligence and the vagaries of nature itself has resulted in ill health and loss of life. This paper describes the history of pandemics, epidemics and disasters, and the attempts to bring them under control.

Spin qubits in quantum dots define an attractive platform for quantum information because of their compatibility with semiconductor manufacturing, their long coherence times, and the ability to operate above one Kelvin. However, despite demonstrations of SWAP oscillations, the integration of this two-qubit gate together with single-qubit control to create a universal gate set as originally proposed for single spins in quantum dots has remained elusive. Here, we show that we can overcome these limitations and execute a multitude of native two-qubit gates, together with single-qubit control, in a single device, reducing the operation overhead to perform quantum algorithms. We demonstrate single-qubit rotations, together with the two-qubit gates CROT, CPHASE, and SWAP, on a silicon double quantum dot. Furthermore, we introduce adiabatic and diabatic composite sequences that allow the execution of CPHASE and SWAP gates on the same device, despite the finite Zeeman energy difference. Both two-qubit gates can be executed in less than 100 ns and, by theoretically analyzing the experimental noise sources, we predict control fidelities exceeding 99%, even for operation above one Kelvin.

IntroductionCrohn’s disease (CD) is characterised by discontinuous, relapsing enteric inflammation. Instituting advanced therapies at an early stage to suppress inflammation aims to prevent future complications such as stricturing or penetrating disease, and subsequent surgical resection. Therapeutics are effective but associated with certain side-effects and relatively expensive. There is therefore an urgent need for robust methods to predict which newly diagnosed patients will develop disabling disease, to identify patients who are most likely to benefit from early, advanced therapies. We aim to determine if magnetic resonance enterography (MRE) features at diagnosis improve prediction of disabling CD within 5 years of diagnosis.Methods and analysisWe describe the protocol for a multicentre, non-randomised, single-arm, prospective study of adult patients with newly diagnosed CD. We will use patients already recruited to the METRIC study and extend their clinical follow-up, as well as a separate group of newly diagnosed patients who were not part of the METRIC trial (MRE within 3 months of diagnosis), to ensure an adequate sample size. Follow-up will extend for at least 4 years. The primary outcome is to evaluate the comparative predictive ability of prognostic models incorporating MRE severity scores (Magnetic resonance Enterography Global Score (MEGS), simplified MAgnetic Resonance Index of Activity (sMaRIA) and Lémann Index) versus models using standard characteristics alone to predict disabling CD (modified Beaugerie definition) within 5 years of new diagnosis.Ethics and disseminationThis study protocol achieved National Health Service Research Ethics Committee (NHS REC), London—Hampstead Research Ethics Committee approval (IRAS 217422). Our findings will be disseminated via conference presentations and peer-reviewed publications.Trial registration numberISRCTN76899103.

Background The COVID-19 pandemic had a significant impact on the quality of healthcare provision across all specialities and disciplines. However, there are limited data on the scale of its disruption to cardiac procedure activity from a national perspective and whether procedural outcomes different before and during the COVID-19 pandemic. Methods Major cardiac procedures (n=374,899) performed between 1st January and 31st May for the years 2018, 2019 and 2020 were analysed, stratified by procedure type and time-period (pre-COVID: January-May 2018 and 2019 and January-February 2020 and COVID: March-May 2020). Multivariable logistic regression modelling was undertaken to examine the odds ratio (OR) of 30-day mortality for procedures performed in the COVID period (vs. pre-COVID). Results There was a deficit of 45,501 procedures during the COVID period compared to the monthly averages (March-May) in 2018–2019. Cardiac catheterisation and cardiac electronic device implantations were the most affected in terms of numbers (n=19,637 and n=10,453) while surgical procedures including mitral valve replacement, other valve replacement/repair, atrial and ventricular septal defect repair, and CABG were the most affected as a relative percentage difference (D) to previous years' averages. TAVR was the least affected (D-10.6%). No difference in 30-day mortality was observed between pre-COVID and COVID time-periods for all cardiac procedures except cardiac catheterisation (OR 1.25 95% confidence interval (CI) 1.07–1.47, p=0.006) and cardiac device implantation (OR 1.35 95% CI 1.15–1.58, p Conclusion There was a significant decline in national cardiac procedural activity in England during the COVID-19 pandemic, with a deficit in excess of 45000 procedures over the study period. However, there was no increase in risk of mortality for most cardiac procedures performed during the pandemic. While health service pressures are gradually easing given the increased roll out of vaccination and decline in infection rates, there is a need for major restructuring of cardiac services deal with this significant backlog of procedures, which would inevitably impact longer-term morbidity and mortality. Funding Acknowledgement Type of funding sources: None.

Genetically encoded biosensors can be used to track signaling events in living cells by measuring changes in fluorescence emitted by one or more fluorescent proteins. Here, we describe the use of genetically encoded biosensors based on Forster resonance energy transfer (FRET), combined with high-content microscopy, to image dynamic signaling events simultaneously in thousands of neurons in response to drug treatments. We first applied this approach to examine intercellular variation in signaling responses among cultured striatal neurons stimulated with multiple drugs. Using high-content FRET imaging and immunofluorescence, we identified neuronal subpopulations with unique responses to pharmacological manipulation and used nuclear morphology to identify medium spiny neurons within these heterogeneous striatal cultures. Focusing on protein kinase A (PKA) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in the cytoplasm and nucleus, we noted pronounced intercellular differences among putative medium spiny neurons, in both the magnitude and kinetics of signaling responses to drug application. Importantly, a conventional “bulk” analysis that pooled all cells in culture yielded a different rank order of drug potency than that revealed by single-cell analysis. Using a single-cell analytical approach, we dissected the relative contributions of PKA and ERK1/2 signaling in striatal neurons and unexpectedly identified a novel role for ERK1/2 in promoting nuclear activation of PKA in striatal neurons. This finding adds a new dimension of signaling crosstalk between PKA and ERK1/2 with relevance to dopamine D1 receptor signaling in striatal neurons. In conclusion, high-content single-cell imaging can complement and extend traditional population-level analyses and provides a novel vantage point from which to study cellular signaling. SIGNIFICANCE STATEMENT High-content imaging revealed substantial intercellular variation in the magnitude and pattern of intracellular signaling events driven by receptor stimulation. Since individual neurons within the same population can respond differently to a given agonist, interpreting measures of intracellular signaling derived from the averaged response of entire neuronal populations may not always reflect what happened at the single-cell level. This study uses this approach to identify a new form of cross-talk between PKA and ERK1/2 signaling in the nucleus of striatal neurons.

IntroductionHypoaccommodation is common in children born prematurely and those with hypoxic ischaemic encephalopathy (HIE), with the potential to affect wider learning. These children are also at risk of longer-term cerebral visual impairment. It is also well recognised that early intervention for childhood visual pathology is essential, because neuroplasticity progressively diminishes during early life. This study aims to establish the feasibility and acceptability of conducting a randomised controlled trial to test the effectiveness of early near vision correction with spectacles in infancy, for babies, at risk of visual dysfunction.Methods and analysisThis is a parallel group, open-label, randomised controlled (feasibility) study to assess visual outcomes in children with perinatal brain injury when prescribed near vision spectacles compared with the current standard care—waiting until a problem is detected. The study hypothesis is that accommodation, and possibly other aspects of vision, may be improved by intervening earlier with near vision glasses. Eligible infants (n=75, with either HIE or Ethics and disseminationThe South-Central Oxford C Research Ethics Committee has approved the study. Members of the PPI committee will give advice on dissemination of results through peer-reviewed publications, conferences and societies.Trial registration numberISRCTN14646770, NCT05048550, NIHR ref: PB-PG-0418-20006.

Introduction: Hypertension is a leading risk factor for cardiovascular disease in the US. Approximately one in ten to one in six women of reproductive age (WRA; aged 18-44 years) have hypertension. Control of hypertension through lifestyle behaviors and anti-hypertensive medication can prevent complications across the life course. Characterizing the current use of anti-hypertensive medication among WRA by urban/rural status offers opportunities to inform public health action. Methods: Data from 59,407 WRA responding to the 2019 Behavioral Risk Factor Surveillance System was used to determine hypertension prevalence from 49 states (New Jersey did not meet data collection standards), District of Columbia, Guam, and Puerto Rico. Among the subset of 6,855 who self-reported hypertension, estimates of current anti-hypertensive medication use were calculated. Prevalence ratios were used to estimate the association between urban/rural status and self-reported use of anti-hypertensive medications, adjusting for age, race/ethnicity, education, and insurance status. Results: The estimated hypertension prevalence among WRA was 10.7% (95%CI:10.3%-11.1%) with 14.0% (95%CI:12.7%-15.5%) in rural and 10.4% (95%CI:10.0%-10.9%) in urban counties. An estimated 45.1% (95%CI:43.1%-47.2%) of WRA with hypertension reported currently using anti-hypertensive medication with estimates of 57.1% (95%CI:51.9%-62.1%) in rural and 44.0% (95%CI:41.9%-46.2%) in urban counties. WRA with hypertension living in rural counties were 1.29 times (95%CI:1.17-1.41) more likely to report currently using anti-hypertensive medication compared to those living in urban counties. Conclusion: Less than half of WRA with hypertension were currently using anti-hypertensive medication. Living in rural counties was associated with a higher frequency of use of anti-hypertensive medication. Ensuring appropriate blood pressure control through engagement in healthy lifestyle behaviors and appropriate use of medication when needed in WRA can improve cardiovascular health and reduce disparities.

Introduction: Pregnant Black women are at disproportionate risk for adverse birth outcomes, in part associated with higher prevalence of stress. Stress increases risk of depression, a known risk factor for preterm birth. In addition, multiple dimensions of stress, including perceived stress and stressful life events, are associated with adverse birth outcomes, independent of their association with prenatal depression. We use an intersectional and contextualized measure of gendered racial stress to assess whether gendered racial stress constitutes an additional dimension to prenatal depression, independent of stressful life events and perceived stress. Methods: In this cross-sectional study of 428 Black women, we assessed gendered racial stress (using the 39-item Jackson Hogue Phillips Reduced Common Contextualized Stress Measure), perceived stress (using the Perceived Stress Scale), and stressful life events (using a Stressful Life Event Index) as psychosocial predictors of depressive symptoms (measured by the Edinburgh Depression Scale). We used bivariate analyses and multivariable regression to assess the association between the measures of stress and prenatal depression. Results: Results revealed significant bivariate associations between participant scores on the full Jackson Hogue Phillips Reduced Common Contextualized Stress Measure and its 5 subscales, and the Edinburgh Depression Scale. In multivariable models that included participant Perceived Stress Scale and/or Stressful Life Event Index scores, the Jackson Hogue Phillips Reduced Common Contextualized Stress Measure contributed uniquely and significantly to Edinburgh Depression Scale score, with the burden subscale being the strongest contributor among all variables. No sociodemographic characteristics were found to be significant in multivariable models. Conclusion: For Black women in early pregnancy, gendered racial stress is a distinct dimension of stress associated with increased depressive symptoms. Intersectional stress measures may best uncover nuances within Black women’s complex social environment.

One of the main bottlenecks in the pursuit of a large-scale--chip-based quantum computer is the large number of control signals needed to operate qubit systems. As system sizes scale up, the number of terminals required to connect to off-chip control electronics quickly becomes unmanageable. Here, we discuss a quantum-dot spin-qubit architecture that integrates on-chip control electronics, allowing for a significant reduction in the number of signal connections at the chip boundary. By arranging the qubits in a two-dimensional (2D) array with $\sim$12 $\mu$m pitch, we create space to implement locally integrated sample-and-hold circuits. This allows to offset the inhomogeneities in the potential landscape across the array and to globally share the majority of the control signals for qubit operations. We make use of advanced circuit modeling software to go beyond conceptual drawings of the component layout, to assess the feasibility of the scheme through a concrete floor plan, including estimates of footprints for quantum and classical electronics, as well as routing of signal lines across the chip using different interconnect layers. We make use of local demultiplexing circuits to achieve an efficient signal-connection scaling leading to a Rent's exponent as low as $p = 0.43$. Furthermore, we use available data from state-of-the-art spin qubit and microelectronics technology development, as well as circuit models and simulations, to estimate the operation frequencies and power consumption of a million-qubit processor. This work presents a novel and complementary approach to previously proposed architectures, focusing on a feasible scheme to integrating quantum and classical hardware, and significantly closing the gap towards a fully CMOS-compatible quantum computer implementation., Comment: 19 pages, 16 figures