Short-term impacts of Universal Basic Income on population mental health inequalities in the UK: A microsimulation modelling study.

BACKGROUND: Population mental health in the United Kingdom (UK) has deteriorated, alongside worsening socioeconomic conditions, over the last decade. Policies such as Universal Basic Income (UBI) have been suggested as an alternative economic approach to improve population mental health and reduce health inequalities. UBI may improve mental health (MH), but to our knowledge, no studies have trialled or modelled UBI in whole populations. We aimed to estimate the short-term effects of introducing UBI on mental health in the UK working-age population. METHODS AND FINDINGS: Adults aged 25 to 64 years were simulated across a 4-year period from 2022 to 2026 with the SimPaths microsimulation model, which models the effects of UK tax/benefit policies on mental health via income, poverty, and employment transitions. Data from the nationally representative UK Household Longitudinal Study were used to generate the simulated population (n = 25,000) and causal effect estimates. Three counterfactual UBI scenarios were modelled from 2023: "Partial" (value equivalent to existing benefits), "Full" (equivalent to the UK Minimum Income Standard), and "Full+" (retaining means-tested benefits for disability, housing, and childcare). Likely common mental disorder (CMD) was measured using the General Health Questionnaire (GHQ-12, score ≥4). Relative and slope indices of inequality were calculated, and outcomes stratified by gender, age, education, and household structure. Simulations were run 1,000 times to generate 95% uncertainty intervals (UIs). Sensitivity analyses relaxed SimPaths assumptions about reduced employment resulting from Full/Full+ UBI. Partial UBI had little impact on poverty, employment, or mental health. Full UBI scenarios practically eradicated poverty but decreased employment (for Full+ from 78.9% [95% UI 77.9, 79.9] to 74.1% [95% UI 72.6, 75.4]). Full+ UBI increased absolute CMD prevalence by 0.38% (percentage points; 95% UI 0.13, 0.69) in 2023, equivalent to 157,951 additional CMD cases (95% UI 54,036, 286,805); effects were largest for men (0.63% [95% UI 0.31, 1.01]) and those with children (0.64% [95% UI 0.18, 1.14]). In our sensitivity analysis assuming minimal UBI-related employment impacts, CMD prevalence instead fell by 0.27% (95% UI -0.49, -0.05), a reduction of 112,228 cases (95% UI 20,783, 203,673); effects were largest for women (-0.32% [95% UI -0.65, 0.00]), those without children (-0.40% [95% UI -0.68, -0.15]), and those with least education (-0.42% [95% UI -0.97, 0.15]). There was no effect on educational mental health inequalities in any scenario, and effects waned by 2026. The main limitations of our methods are the model's short time horizon and focus on pathways from UBI to mental health solely via income, poverty, and employment, as well as the inability to integrate macroeconomic consequences of UBI; future iterations of the model will address these limitations. CONCLUSIONS: UBI has potential to improve short-term population mental health by reducing poverty, particularly for women, but impacts are highly dependent on whether individuals choose to remain in employment following its introduction. Future research modelling additional causal pathways between UBI and mental health would be beneficial.

The Relationship Between Time Spent on Social Media and Adolescent Cigarette, E-cigarette, and Dual Use: A Longitudinal Analysis of the UK Millennium Cohort Study.

INTRODUCTION: To estimate the effect of social media use in 14 year olds on risk of and inequalities in cigarette, e-cigarette, and dual use at 17 years, using the UK-representative Millennium Cohort Study (born 2000-2002). AIMS AND METHODS: The relationship of time spent on social media (using questionnaires [n = 8987] and time-use-diaries [n = 2520]) with cigarette, e-cigarette, and dual use was estimated using adjusted odds ratios (AORs) or relative risk ratios (ARRRs). Effect modification was examined (using parental education as an indicator for socioeconomic circumstances) by comparing adjusted risk differences within low and high-parental education groups. Analyses accounted for prespecified confounders (identified via directed acyclic graphs), baseline outcome measures (to address reverse causality), sample design, attrition, and item-missingness (through multiple imputation). RESULTS: Time spent on social media was associated with increased risk of cigarette, e-cigarette, and dual use in a dose-response manner. Social media use for ≥2 hours/day (vs. 1-<30 minutes) was associated with increased cigarette (AOR 2.76 [95% confidence interval 2.19 to 3.48]), e-cigarette (3.24 [2.59 to 4.05]), and dual use (ARRR 4.11 [2.77 to 6.08]). The risk of cigarette use among 30 minutes-<1 hour/day users (vs. non-users) were smaller in those with high versus low parental education (ARDs 1.4% vs. 12.4%). Similar findings were observed across the higher time categories. Analyses using time-use-diaries, in complete case samples, and with additional adjustment for baseline outcome measures generally revealed similar findings. CONCLUSIONS: After accounting for observed confounders and potential reverse causality, findings suggest social media use increases the risk of cigarette, e-cigarette, and dual use in a dose-response manner. Guidance addressing adolescent online safety should be prioritized. IMPLICATIONS: This study's identification of a dose-response relationship and differential effects across socioeconomic groups, could assist in the development of guidance on time spent on social media. The adverse effects of social media use on adolescent cigarette, e-cigarette, and dual use supports legislation aimed at promoting adolescent online safety. Study findings strengthen calls to prohibit social media marketing of nicotine-related products and importantly highlight the need to increase awareness and understanding of the underlying algorithms which drive adolescent exposure to nicotine-related content on social media to ensure they are functioning in a way that best serves the adolescent population.

Sexual and reproductive health in Britain during the first year of the COVID-19 pandemic: cross-sectional population survey (Natsal-COVID-Wave 2) and national surveillance data.

OBJECTIVES: To assess sexual behaviour, and sexual and reproductive health (SRH) outcomes, after 1 year of the COVID-19 pandemic in Britain. METHODS: 6658 participants aged 18-59 and resident in Britain completed a cross-sectional web-panel survey (Natsal-COVID-Wave 2, March-April 2021), 1 year after the first lockdown. Natsal-COVID-2 follows the Natsal-COVID-Wave 1 survey (July-August 2020) which captured impacts in the initial months. Quota-based sampling and weighting resulted in a quasi-representative population sample. Data were contextualised with reference to the most recent probability sample population data (Natsal-3; collected 2010-12; 15 162 participants aged 16-74) and national surveillance data on recorded sexually transmitted infection (STI) testing, conceptions, and abortions in England/Wales (2010-2020). The main outcomes were: sexual behaviour; SRH service use; pregnancy, abortion and fertility management; sexual dissatisfaction, distress and difficulties. RESULTS: In the year from the first lockdown, over two-thirds of participants reported one or more sexual partners (women 71.8%; men 69.9%), while fewer than 20.0% reported a new partner (women 10.4%; men 16.8%). Median occasions of sex per month was two. Compared with 2010-12 (Natsal-3), we found less sexual risk behaviour (lower reporting of multiple partners, new partners, and new condomless partners), including among younger participants and those reporting same-sex behaviour. One in 10 women reported a pregnancy; pregnancies were fewer than in 2010-12 and less likely to be scored as unplanned. 19.3% of women and 22.8% of men were distressed or worried about their sex life, significantly more than in 2010-12. Compared with surveillance trends from 2010 to 2019, we found lower than expected use of STI-related services and HIV testing, lower levels of chlamydia testing, and fewer conceptions and abortions. CONCLUSIONS: Our findings are consistent with significant changes in sexual behaviour, SRH, and service uptake in the year following the first lockdown in Britain. These data are foundational to SRH recovery and policy planning.

Blinded Predictions and Post Hoc Analysis of the Second Solubility Challenge Data: Exploring Training Data and Feature Set Selection for Machine and Deep Learning Models.

Accurate methods to predict solubility from molecular structure are highly sought after in the chemical sciences. To assess the state of the art, the American Chemical Society organized a "Second Solubility Challenge" in 2019, in which competitors were invited to submit blinded predictions of the solubilities of 132 drug-like molecules. In the first part of this article, we describe the development of two models that were submitted to the Blind Challenge in 2019 but which have not previously been reported. These models were based on computationally inexpensive molecular descriptors and traditional machine learning algorithms and were trained on a relatively small data set of 300 molecules. In the second part of the article, to test the hypothesis that predictions would improve with more advanced algorithms and higher volumes of training data, we compare these original predictions with those made after the deadline using deep learning models trained on larger solubility data sets consisting of 2999 and 5697 molecules. The results show that there are several algorithms that are able to obtain near state-of-the-art performance on the solubility challenge data sets, with the best model, a graph convolutional neural network, resulting in an RMSE of 0.86 log units. Critical analysis of the models reveals systematic differences between the performance of models using certain feature sets and training data sets. The results suggest that careful selection of high quality training data from relevant regions of chemical space is critical for prediction accuracy but that other methodological issues remain problematic for machine learning solubility models, such as the difficulty in modeling complex chemical spaces from sparse training data sets.

Exploring the health and sociodemographic characteristics of people seeking advice with claiming universal credit: a cross-sectional analysis of UK citizens advice data, 2017-2021.

BACKGROUND: The UK Department for Work and Pensions (DWP) administers Universal Credit (UC) - the main UK benefit for people in- and out-of-work. UC is being rolled out nationally from 2013 to 2024. Citizens Advice (CA) is an independent charity that provides advice and support to people making a claim for UC. The aim of this study is to understand who is seeking advice from CA when making a UC claim and how the types of people seeking advice are changing as the rollout of UC continues. METHODS: Co-developed with Citizens Advice Newcastle and Citizens Advice Northumberland we performed longitudinal analysis of national data from Citizens Advice for England and Wales on the health (mental health and limiting long term conditions) and socio-demographic of 1,003,411 observations for people seeking advice with claiming UC over four financial years (2017/18 to 2020/21). We summarised population characteristics and estimated the differences between the four financial years using population-weighted t-tests. Findings were discussed with three people with lived experience of seeking advice to claim UC to help frame our interpretation and policy recommendations. RESULTS: When comparing 2017/18 to 2018/19, there was a significantly higher proportion of people with limiting long term conditions seeking advice with claiming UC than those without (+ 2.40%, 95%CI: 1.31-3.50%). However, as the rollout continued between 2018/29 and 2019/20 (-6.75%, 95%CI: -9.62%--3.88%) and between 2019/20 and 2020/21 (-2.09%, 95%CI: -2.54%--1.64%), there were significantly higher proportions of those without a limiting long term condition seeking advice than with. When comparing 2018/19 to 2019/20 and 2019/20 to 2020/21, there was a significant increase in the proportion of self-employed compared to unemployed people seeking advice with claiming UC (5.64%, 95%CI: 3.79-7.49%) and (2.26%, 95%CI: 1.29-3.23%) respectively. CONCLUSION: As the rollout for UC continues, it is important to understand how changes in eligibility for UC may impact on those who need help with applying for UC. Ensuring that the advice process and application process is responsive to a range of people with different needs can help to reduce the likelihood that the process of claiming UC will exacerbate health inequalities.

The relationship between time spent on social media and adolescent alcohol use: a longitudinal analysis of the UK Millennium Cohort Study.

BACKGROUND: To estimate the effect of social media use in 14 year olds on risk of and inequalities in alcohol use and binge drinking at 17 years. METHODS: Using the UK-representative Millennium Cohort Study, the relationship between time spent on social media (assessed using questionnaires [n = 8987] and time-use-diaries [n = 2520]) with frequency of alcohol use in the past month and binge drinking was estimated using adjusted odds ratios (AORs) or adjusted relative risk ratios (ARRRs). Associations within low and high parental education groups were compared to examine effect modification. Analyses accounted for pre-specified confounders, baseline outcome measures (to address reverse causality), sample design, attrition and item-missingness (through multiple imputation). RESULTS: Questionnaire-reported time spent on social media was associated with increased risk of alcohol use and binge drinking in a dose-response manner. Compared to 1-< 30 min/day social media users, 30 min-<1 h/day users were more likely to report alcohol use ≥6 times/month (ARRR 1.62 [95% confidence interval 1.20 to 2.20]) and binge drinking (AOR 1.51 [1.22 to 1.87]), as were 1-<2 h/day users (ARRR 2.61 [1.90 to 3.58]; AOR 2.06 [1.69 to 2.52]) and ≥2 h/day users (ARRR 4.80 [3.65 to 6.32]; AOR 3.07 [2.54 to 3.70]). Social media measured by time-use-diary was associated with higher risks, although not always demonstrating a dose-response relationship. The effect of social media use (vs no-use) on binge drinking was larger in the higher (vs lower) parental education groups. Analyses repeated in complete case samples, and with adjustment for baseline outcome measures revealed consistent findings. CONCLUSIONS: Findings suggest social media use may increase risk of alcohol use and binge drinking. Regulatory action protecting adolescents from harmful alcohol-related social media content is necessary.

The Impact of Transitions, a Mental Health Literacy Intervention With Embedded Life Skills for Postsecondary Students: Preliminary Findings From a Naturalistic Cohort Study.

OBJECTIVE: Mental illness is a common medical condition to onset during adolescence. Young people who leave for postsecondary life are at an especially challenging period of lifetime when many will leave home and familiar environments for prolonged periods of time. These new circumstances may put young people at risk of developing mental health problems or disorders or exacerbate existing mental disorders. Alternatively, some young people may misinterpret the normal negative emotional states occurring as a result of these new challenges as a mental disorder requiring professional intervention. We conducted a quasiexperimental cohort study to investigate the effectiveness of a mental health literacy intervention Transitions with blended life skills to address these challenges for first-year postsecondary students. METHODS: Students (n = 2,397) from five Canadian postsecondary institutions were assigned to the intervention or the control group and were administered a survey at baseline, postintervention, and at 2-month follow-up (September 2017 to February 2018). We applied generalized linear mixed effects (PROC Mixed procedure) to test the between-group difference in the post-pre/follow-up-pre and to determine the predicted least-square mean values. RESULTS: The findings showed that students who were exposed to the Transitions intervention significantly improved their mental health knowledge, decreased stigma against mental illness, improved help-seeking attitudes and behaviours, and decreased perceived stress when compared to students who had not been exposed to the intervention. However, we did not identify significant changes in general health. This may be due to the relatively short follow-up time (2 months) to determine participants' general health status. CONCLUSIONS: Transitions delivered to first-year postsecondary students may be a beneficial intervention to help young people adjust to their new postsecondary life and improve their mental health.

The Drum Must Beat On: COVID-19 and the U.S. Military's Virtual Health Response in Europe.

In response to COVID-19 international restriction of movement laws, the closure of health care facilities, and an ongoing need to support a medically ready force, the U.S. Department of Defense's Virtual Health Europe (VHE) program spearheaded a campaign for synchronous video virtual health (VH) across 42 specialties. Overcoming the challenges of a VH platform designed for nonclinical video teleconferencing, VHE augmented an existing pool of >300 VH-trained providers with an additional 276 providers who collectively performed >4,000 synchronous VH visits between 71 countries from April 2020 through May 2020. Providers proved eager to utilize VH to bring health care to the point of need, however, new challenges emerged highlighted by unreliable and poor connectivity, military-specific network security challenges, and an unfamiliarity with VH etiquette by patients. Addressing the hypothesized third wave of health care demand due to COVID-19 through VH is critical not only for ongoing military readiness requirements, but holds lessons both good and bad for civilian health care delivery as well.

Increased Prevalence of Moderate and Severe Peripheral Arterial Disease in the American Indian (AI)/Alaskan Native (AN) Population; a Study of 96,000 AI/AN.

BACKGROUND: Peripheral arterial disease (PAD) disproportionally affects racial groups in the United States. Few studies have analyzed the rates of PAD in the American Indian (AI)/Alaskan Native (AN) population. In this article, we compare the prevalence of PAD in the AI/AN as compared with white and nonwhite Americans. METHODS: The study data were provided by Life Line Screening (Independence, OH). The cohort consists of self-referred individuals who paid for vascular screening tests. Mild-to-moderate and severe PAD were defined as having an ankle-brachial index (ABI) in at least one extremity of < 0.9 and < 0.5, respectively. Univariate and multivariate analyses were performed to compare the rates of PAD between AI/AN, Caucasians, and nonwhites. RESULTS: The original sample for which this study was obtained included 3,444,272 people. Of this group there was a predominance of females 64.5% (2,221,555) compared with 35.5% (1,222,716) males. The Native American/AN population was 2.8% of the sample (96,440). In our univariate analysis AI/AN had the highest rates of mild-moderate and severe PAD when compared with whites (odds ratio [OR] 1.78 and 2.14, respectively) and nonwhites (OR 1.52 and 1.82, respectively). We then controlled for atherosclerotic risk factors in our multivariate analysis, and the AI/NA cohort had persistently higher rates of both moderate and severe PAD compared with whites (OR 1.32 and 1.40) but not compared with nonwhites (OR 0.95 and 0.92). CONCLUSIONS: Here we present the largest epidemiology study of PAD in AI/AN to date. AI/NA people have disproportionately high rates of both mild to-moderate and severe PAD when compared with whites and nonwhite Americans. After controlling for atherosclerotic risk factors the rates of PAD remain high for AI/NA when compared with whites but not when compared with nonwhites. While it is possible that a combination of diet and lifestyle choices are responsible for the high rates of PAD in this population, genetic factors may be involved as well, and deserve further investigation. Optimal medical management may help to prevent the complications of PAD in this patient population.

Gender Differences in Aortic Neck Morphology in Patients with Abdominal Aortic Aneurysms Undergoing Elective Endovascular Aneurysm Repair.

BACKGROUND: Previous studies have demonstrated that women tend to have adverse aortic neck morphology leading to exclusion of some women from undergoing endovascular aneurysm repair (EVAR). The objective of this study is to investigate differences in aortic neck morphology in men versus women, changes in the neck morphology and sac behavior after EVAR, and investigate how these features may influence outcomes. METHODS: We conducted a retrospective review of elective EVARs (2004-2013). We excluded patients who underwent elective EVAR with no postoperative imaging available and those patients with fenestrated repairs. Using TeraRecon and volumetric analysis, several features were investigated. These included percent thrombus, shape, length, angulation of the neck, and changes in neck and abdominal aortic aneurysm diameter. RESULTS: A total of 146 patients were found to meet inclusion criteria (115 men and 31 women) with similar baseline characteristics. Neck angulation was greater in women (23.9° vs. 13.5°; P < 0.028). The percent thrombus in women was higher than men (35.4% vs. 31%; P < 0.02). Abdominal aneurysm's were smaller in women at 1 year (4.2 cm vs. 5.1 cm; P < 0.002), and secondary interventions were higher in men (11.3% vs. 0%; P < 0.05). Other features such as neck shape, changes in neck diameter, neck length, and percent oversizing of graft where not statistically different between genders. CONCLUSIONS: Gender differences in neck characteristics and changes in neck morphology do not appear to adversely affect EVAR outcomes. Longer follow-up is necessary to further assess whether these findings are clinically durable.

Sustained weight loss after gastric banding revision for pouch-related problems.

OBJECTIVE: To assess the impact of revisional surgery after laparoscopic adjustable gastric banding (LAGB) on weight loss at 12 and 24 months. BACKGROUND: There is no uniform consensus as to the optimal procedure for patients requiring revision after LAGB. Few studies address the issue of weight loss after band salvage procedures, despite this being a critical factor in deciding which reoperative procedure to choose. METHODS: A retrospective analysis was conducted of adult patients who underwent LAGB from January 1, 2001 to June 30, 2009 at a single institution. Patients who required revision for pouch-related problems including band slippage, pouch dilation, and hiatal hernia were studied. Demographic data, body mass index (BMI), percentage excess weight loss (% EWL), and operative details were recorded. Weights were recorded at 12 and 24 months after revision. These were compared with initial weight, weight before revision, and weight in patients who did not have a reoperation. RESULTS: Of 3876 patients, 390 patients were included in analysis of weight outcomes after revision. The procedure-related mortality was 0%. Early (30-day) complications occurred in 0.5%, late complications (erosion) in 0.5%, and 29 patients (7.4%) required a second revision. For patients undergoing revision, the initial weight was 124.06 ± 21.28 kg and BMI was 44.80 ± 6.12 kg/m. At reoperation, weight was 89.18 ± 20.51 kg, BMI was 32.25 ± 6.50 kg/m and, %EWL was 54.13 ± 21.80%. Twelve months postrevision, weight was 92.24 ± 20.22 kg, BMI was 33.32 ± 6.41 kg/m, and %EWL was 48.81 ± 22.71%. Weight was 92.42 ± 19.91 kg, BMI was 33.53 ± 6.25 kg/m, and %EWL was 47.50 ± 22.91% twenty-four months postrevision. CONCLUSIONS: Reoperation for pouch-related problems after LAGB is safe and effective. Weight loss is maintained after reoperation.

Evaluating the effectiveness of a school-based mental health literacy intervention from a comprehensive demographic and social-cognitive perspective.

Childhood and adolescence are a critical period for the onset of mental and neurodevelopmental disorders and a time when many can be first identified. Research demonstrates that mental health literacy applied in school settings may be an effective approach to address these challenges. In contrast to many existing studies conducted in multicultural and multilingual settings that treated subjects' language as a demographic feature, the present study recognizes English proficiency as a social-cognitive factor and views the school-based mental health literacy (MHL) intervention as a learning process. The present study aimed to assess the effectiveness of school-based mental health literacy intervention and explore how ethnicity and English proficiency as a social-cognitive factor, as a modified, rather than a fixed variable, impacted the intervention outcomes. Grade 9 students (n = 240) from schools in West Canada with diverse social/cultural background received the intervention in the classroom delivered by trained teachers and completed the pre-test and post-test over a 6-month period. The intervention was effective in improving knowledge and help-seeking attitudes among all students. Non-Chinese and native English-speaking students performed the best on all outcomes. Gender demonstrated an association with changes in stigma, stress and wellbeing. English proficiency was linked to knowledge acquisition, while ethnicity was connected to changes of attitude-related outcomes. These findings deepened our understanding of how demographic and social-cognitive factors underlie changes in mental health literacy outcomes, which will facilitate the development of mental health literacy interventions for diverse student populations.

Can an educational video improve the adequacy of bowel preparation for patients undergoing their first colonoscopy? Results of the EBOPS RCT.

Background and study aims The aim of this study was to assess the effect of an educational video on the quality of bowel preparation of patients from a UK population attending for their first colonoscopy. Patients and methods A prospective, endoscopist-blinded trial with 1:1 allocation was performed. Patients referred for their first colonoscopy were recruited between February 2019 and December 2019. All participants were prescribed Moviprep and received the trial site's standard written bowel preparation instructions, with the intervention group also receiving a bespoke educational video. Adequacy of bowel preparation (defined as a Boston Bowel Preparation Scale of ≥2 in each segment of the bowel) and polyp detection rates (PDRs) were compared. Fisher's chi squared test was utilized with P <0.05 as the threshold for significance. Results A total of 509 participants completed the trial from six centers; 251 were randomized to the intervention group. The mean age was 57 years and 52.3% were female. The primary endpoint was met with an adequacy rate of 216 of 251 (86.1%) in the intervention group, compared with 205 of 259 (79.1%) in the control group ( P <0.05, odds ratio [OR] 1.626, 95% CI 1.017-2.614). The PDR was significantly higher in the intervention group (39% vs 30%, OR 1.51, 95% CI 1.04-2.19, P <0.05). Conclusions An educational video leads to improved bowel preparation for patients attending for their first colonoscopy, and is also associated with greater detection of polyps. Widespread adoption of an educational video incurs minimal investment, but would reduce the number of inadequate procedures, missed pathology, and the cost that both these incur.

Structure- and Property-Based Optimization of Efficient Pan-Bromodomain and Extra Terminal Inhibitors to Identify Oral and Intravenous Candidate I-BET787.

The bromodomain and extra terminal (BET) family of bromodomain-containing proteins are important epigenetic regulators that elicit their effect through binding histone tail N-acetyl lysine (KAc) post-translational modifications. Recognition of such markers has been implicated in a range of oncology and immune diseases and, as such, small-molecule inhibition of the BET family bromodomain-KAc protein-protein interaction has received significant interest as a therapeutic strategy, with several potential medicines under clinical evaluation. This work describes the structure- and property-based optimization of a ligand and lipophilic efficient pan-BET bromodomain inhibitor series to deliver candidate I-BET787 (70) that demonstrates efficacy in a mouse model of inflammation and suitable properties for both oral and intravenous (IV) administration. This focused two-phase explore-exploit medicinal chemistry effort delivered the candidate molecule in 3 months with less than 100 final compounds synthesized.

A convergent stereocontrolled synthesis of [3-(14) C]solanesol.

In this communication, we report the synthesis of ~5 mCi of [3-(14) C]solanesol (1) prepared from ethyl [3-(14) C]acetoacetate and (all-E)-octaprenyl bromide (2) in four steps, with a specific radioactivity of 19.83 mCi/mmol and with a chemical/stereochemical and radiochemical purity of ≥ 95%. (Figure ). Position 3 of the chain was selected for (14) C labelling because of the metabolic stability of this position. Unlabelled (all-E)-octaprenyl (18) (Scheme ) necessary for this work was prepared via a convergent iterative 'allyl-allyl' coupling approach of precursors easily derived from readily available inexpensive starting materials.(1)

Child and youth mental health and wellbeing before and after returning to in-person learning in secondary schools in the context of COVID-19.

Background: As children reintegrate with in-person classroom learning after COVID-19, health and education institutions should remain mindful of students' mental health. There is a paucity of data on changes in students' mental health before, during and after their return to in-person classroom learning. Methods: We collected and analyzed data on self-reported wellbeing, general mental health, perceived stress, and help-seeking attitudes from grade 7-12 students in a Catholic school division in Canada (n = 258 at baseline; n = 132 at follow-up). Outcomes were compared according to demographic differences such as gender, grade level, experience accessing mental health services, and presence of support staff between baseline and follow-up. Effects of time points and each demographic variable on each outcome and on the prediction of students' mental health were also analyzed. Results: No significant differences were apparent for outcomes between baseline and follow-up. However, specific subgroups: junior high students, male students, students who had not accessed mental health services, and students who had access to support-staff had better outcomes than their counterparts. From baseline to follow-up, male students reported mental health decline [Mean = 11.79, SD = 6.14; Mean = 16.29, SD = 7.47, F(1, 333) = 8.36, p < 0.01]; students who had not accessed mental health services demonstrated greater stress [Mean = 20.89, SD = 4.09; Mean = 22.28, SD = 2.24, F(1, 352) = 6.20, p < 0.05]; students who did not specify a binary gender reported improved general mental health [Mean = 19.87, SD = 5.89; Mean = 13.00, SD = 7.40, F(1, 333) = 8.70, p < 0.01], and students who did not have access to support-staff improved help-seeking attitudes [Mean = 22.32, SD = 4.62; Mean = 24.76, SD = 4.81; F(1, 346) = 5.80, p < 0.05]. At each time point, students indicated parents, guardians, and close friends as their most-preferred help-seeking sources. High stress predicted lower wellbeing at baseline, but higher wellbeing at follow-up. Conclusion: Students presented stable mental health. Subgroups with decreased mental health may benefit from extra mental health support through building capacity among teachers and health care professionals to support students following public health emergencies.

Contraceptive use and pregnancy planning in Britain during the first year of the COVID-19 pandemic: findings from a large, quasi-representative survey (Natsal-COVID).

BACKGROUND: Contraceptive services were significantly disrupted during the COVID-19 pandemic in Britain. We investigated contraception-related health inequalities in the first year of the pandemic. METHODS: Natsal-COVID Wave 2 surveyed 6658 adults aged 18-59 years between March and April 2021, using quotas and weighting to achieve quasi-representativeness. Our analysis included sexually active participants aged 18-44 years, described as female at birth. We analysed contraception use, contraceptive switching due to the pandemic, contraceptive service access, and pregnancy plannedness. RESULTS: Of 1488 participants, 1619 were at risk of unplanned pregnancy, of whom 54.1% (51.0%-57.1%) reported routinely using effective contraception in the past year. Among all participants, 14.3% (12.5%-16.3%) reported switching or stopping contraception due to the pandemic. 3.2% (2.0%-5.1%) of those using effective methods pre-pandemic switched to less effective methods, while 3.8% (2.5%-5.9%) stopped. 29.3% (26.9%-31.8%) of at-risk participants reported seeking contraceptive services, of whom 16.4% (13.0%-20.4%) reported difficulty accessing services. Clinic closures and cancelled appointments were commonly reported pandemic-related reasons for difficulty accessing services. This unmet need was associated with younger age, diverse sexual identities and anxiety symptoms. Of 199 pregnancies, 6.6% (3.9%-11.1%) scored as 'unplanned'; less planning was associated with younger age, lower social grade and unemployment. CONCLUSIONS: Just under a third of participants sought contraceptive services during the pandemic and most were successful, indicating resilience and adaptability of service delivery. However, one in six reported an unmet need due to the pandemic. COVID-induced inequalities in service access potentially exacerbated existing reproductive health inequalities. These should be addressed in the post-pandemic period and beyond.

School-based mental health literacy training shifts the quantity and quality of referrals to tertiary child and adolescent mental health services: A Western Canada regional study.

BACKGROUND: We aimed to improve mental health referral quality of young people by helping educators build capacity for early identification of youth at risk of mental illness and facilitate referrals between the education and health systems. METHODS: We applied the Go-To Educator mental health literacy training for early identification, triage and support in 208 schools in Calgary, Alberta between 2013 and 2016. Students presenting to mental health services during this time were compared on a number of clinical, system, and demographic variables, based on the training status of the school (untrained schools; before and after training schools), using retrospective cohort design. Based on clinical and system data, bivariate and multivariable logistic regression analysis were employed to compare the three school status domains. RESULTS: After training, referrals differed significantly from control and pre-training schools. Students presenting to services from these schools were younger, from single parent families; were referred more because of adjustment and learning/attention problems; had complex social/family issues; thought disturbances, and harmful behavior/thoughts towards others. While they waited longer to be admitted they stayed longer in services; had more provisional comorbid diagnoses and demonstrated positive treatment outcomes. CONCLUSIONS: The Go-To Educator training may be an effective intervention helping educators identify students at risk of mental disorders and in substantial need of mental health services, demonstrating improved linkages between education and health sectors.

Evaluation of the mental health impacts of Universal Credit: protocol for a mixed methods study.

INTRODUCTION: The UK social security system is being transformed by the implementation of Universal Credit (UC), which combines six existing benefits and tax credits into a single payment for low-income households. Despite extensive reports of hardship associated with the introduction of UC, no previous studies have comprehensively evaluated its impact on mental health. Because payments are targeted at low-income households, impacts on mental health will have important consequences for health inequalities. METHODS AND ANALYSIS: We will conduct a mixed methods study. Work package (WP) 1 will compare health outcomes for new recipients of UC with outcomes for legacy benefit recipients in two large population surveys, using the phased rollout of UC as a natural experiment. We will also analyse the relationship between the proportion of UC claimants in small areas and a composite measure of mental health. WP2 will use data collected by Citizen's Advice to explore the sociodemographic and health characteristics of people who seek advice when claiming UC and identify features of the claim process that prompt advice-seeking. WP3 will conduct longitudinal in-depth interviews with up to 80 UC claimants in England and Scotland to explore reasons for claiming and experiences of the claim process. Up to 30 staff supporting claimants will also be interviewed. WP4 will use a dynamic microsimulation model to simulate the long-term health impacts of different implementation scenarios. WP5 will undertake cost-consequence analysis of the potential costs and outcomes of introducing UC and cost-benefit analyses of mitigating actions. ETHICS AND DISSEMINATION: We obtained ethical approval for the primary data gathering from the University of Glasgow, College of Social Sciences Research Ethics Committee, application number 400200244. We will use our networks to actively disseminate findings to UC claimants, the public, practitioners and policy-makers, using a range of methods and formats. TRIAL REGISTRATION NUMBER: The study is registered with the Research Registry: researchregistry6697.

Identification and Optimization of a Ligand-Efficient Benzoazepinone Bromodomain and Extra Terminal (BET) Family Acetyl-Lysine Mimetic into the Oral Candidate Quality Molecule I-BET432.

The bromodomain and extra terminal (BET) family of proteins are an integral part of human epigenome regulation, the dysregulation of which is implicated in multiple oncology and inflammatory diseases. Disrupting the BET family bromodomain acetyl-lysine (KAc) histone protein-protein interaction with small-molecule KAc mimetics has proven to be a disease-relevant mechanism of action, and multiple molecules are currently undergoing oncology clinical trials. This work describes an efficiency analysis of published GSK pan-BET bromodomain inhibitors, which drove a strategic choice to focus on the identification of a ligand-efficient KAc mimetic with the hypothesis that lipophilic efficiency could be drastically improved during optimization. This focus drove the discovery of the highly ligand-efficient and structurally distinct benzoazepinone KAc mimetic. Following crystallography to identify suitable growth vectors, the benzoazepinone core was optimized through an explore-exploit structure-activity relationship (SAR) approach while carefully monitoring lipophilic efficiency to deliver I-BET432 (41) as an oral candidate quality molecule.