Nature and prevalence of long-term conditions in people with intellectual disability: retrospective longitudinal population-based study.

Objective: Explore the nature and prevalence of long-term conditions in individuals with intellectual disability.

Design: Retrospective longitudinal population-based study.

Setting: Primary and secondary care data across the population of Wales with the Secure Anonymised Information Linkage (SAIL) Databank.

Chemical and temporal manipulation of early steps in protein assembly tunes the structure and intermolecular interactions of protein-based materials.

The Drosophila intrinsically disordered protein Ultrabithorax (Ubx) undergoes a series of phase transitions, beginning with noncovalent interactions between apparently randomly organized monomers, and evolving over time to form increasingly ordered coacervates. This assembly process ends when specific dityrosine covalent bonds lock the monomers in place, forming macroscale materials. Inspired by this hierarchical, multistep assembly process, we analyzed the impact of protein concentration, assembly time, and subphase composition on the early, noncovalent stages of Ubx assembly, which are extremely sensitive to their environment.

Metabolic and Hormonal Responses to Isomaltulose Ingestion Before or During Sustained Submaximal Exercise in Adults with Type 1 Diabetes Using Automated Insulin Delivery Systems.

Objectives: This article compares metabolic, pancreatic, and gut-derived hormone responses to isomaltulose ingestion, before versus during submaximal sustained exercise, in adults with type 1 diabetes (T1D) using automated insulin delivery systems.

Methods: In a randomized, cross-over trial, eight participants with T1D being treated with automated insulin pumps (five females, age: 47 ± 16 years, BMI: 27.5 ± 3.

Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma.

Background: Previous results from this trial showed longer overall survival after treatment with nivolumab plus ipilimumab or with nivolumab monotherapy than with ipilimumab monotherapy in patients with advanced melanoma. Given that patients with advanced melanoma are living longer than 7.5 years, longer-term data were needed to address new clinically relevant questions.

Impact of the COVID-19 Pandemic on Influenza Hospital Admissions and Deaths in Wales: Descriptive National Time Series Analysis.

Background: The COVID-19 pandemic and the ensuing implementation of control measures caused widespread societal disruption. These disruptions may also have affected community transmission and seasonal circulation patterns of endemic respiratory viruses.

Objective: We aimed to investigate the impact of COVID-19-related disruption on influenza-related emergency hospital admissions and deaths in Wales in the first 2 years of the pandemic.

Insights into E. coli Cyclopropane Fatty Acid Synthase (CFAS) Towards Enantioselective Carbene Free Biocatalytic Cyclopropanation.

Cyclopropane fatty acid synthases (CFAS) are a class of S-adenosylmethionine (SAM) dependent methyltransferase enzymes able to catalyse the cyclopropanation of unsaturated phospholipids. Since CFAS enzymes employ SAM as a methylene source to cyclopropanate alkene substrates, they have the potential to be mild and more sustainable biocatalysts for cyclopropanation transformations than current carbene-based approaches. This work describes the characterisation of E.

Dbh catecholaminergic cardiomyocytes contribute to the structure and function of the cardiac conduction system in murine heart.

The heterogeneity of functional cardiomyocytes arises during heart development, which is essential to the complex and highly coordinated cardiac physiological function. Yet the biological and physiological identities and the origin of the specialized cardiomyocyte populations have not been fully comprehended. Here we report a previously unrecognised population of cardiomyocytes expressing Dbhgene encoding dopamine beta-hydroxylase in murine heart.

Dimensions of equality in uptake of COVID-19 vaccination in Wales, UK: A multivariable linked data population analysis.

Vaccination has proven to be effective at preventing severe outcomes of COVID-19 infection, and uptake in the population has been high in Wales. However, there is a risk that high-level vaccination coverage statistics may mask hidden inequalities in under-served populations, many of whom may be at increased risk of severe outcomes of COVID-19 infection. The study population included 1,436,229 individuals aged 18 years and over, alive and residence in Wales as at 31st July 2022, and excluded immunosuppressed or care home residents.

Ambient greenness, access to local green spaces, and subsequent mental health: a 10-year longitudinal dynamic panel study of 2·3 million adults in Wales.

Background: Living in greener areas, or close to green and blue spaces (GBS; eg, parks, lakes, or beaches), is associated with better mental health, but longitudinal evidence when GBS exposures precede outcomes is less available. We aimed to analyse the effect of living in or moving to areas with more green space or better access to GBS on subsequent adult mental health over time, while explicitly considering health inequalities.

Methods: A cohort of the people in Wales, UK (≥16 years; n=2 341 591) was constructed from electronic health record data sources from Jan 1, 2008 to Oct 31, 2019, comprising 19 141 896 person-years of follow-up.

Data linkage can reduce the burden and increase the opportunities in the implementation of Value-Based Health Care policy: a study in patients with ulcerative colitis (PROUD-UC Study).

Introduction: Healthcare systems face rising demand and unsustainable cost pressures. In response, health policymakers are adopting Value-Based Health Care (VBHC), targeting available resources to achieve the best possible patient outcomes at the lowest possible cost and actively disinvesting in care of low-value. This requires the evaluation of longitudinal clinical and patient reported outcome measures (PROMs) at an individual-level and population-scale, which can create significant data challenges.

The impact of the COVID-19 pandemic on community prescription of opioid and antineuropathic analgesics for cancer patients in Wales, UK.

Purpose: Public health measures instituted at the onset of the COVID-19 pandemic in the UK in 2020 had profound effects on the cancer patient pathway. We hypothesise that this may have affected analgesic prescriptions for cancer patients in primary care.

Methods: A whole-nation retrospective, observational study of opioid and antineuropathic analgesics prescribed in primary care for two cohorts of cancer patients in Wales, using linked anonymised data to evaluate the impact of the pandemic and variation between different demographic backgrounds.

Health care utilization outcomes in patients with blunt chest wall trauma following discharge from the emergency department: A retrospective, observational data-linkage study.

Background: Although much is published reporting clinical outcomes in the patients with blunt chest wall trauma who are admitted to hospital from the ED, less is known about the patients' recovery when they are discharged directly without admission. The aim of this study was to investigate the health care utilization outcomes in adult patients with blunt chest wall trauma, discharged directly from ED in a trauma unit in the United Kingdom.

Methods: This was a longitudinal, retrospective, single-center, observational study incorporating analysis of linked datasets, using the Secure Anonymised Information Linkage databank for admissions to a trauma unit in the Wales, between January 1, 2016, and December 31, 2020.

Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous Insulin.

Background: Insulin icodec is an investigational once-weekly basal insulin analogue for diabetes management.

Methods: We conducted a 78-week randomized, open-label, treat-to-target phase 3a trial (including a 52-week main phase and a 26-week extension phase, plus a 5-week follow-up period) involving adults with type 2 diabetes (glycated hemoglobin level, 7 to 11%) who had not previously received insulin. Participants were randomly assigned in a 1:1 ratio to receive once-weekly insulin icodec or once-daily insulin glargine U100.

The dietary sweetener sucralose is a negative modulator of T cell-mediated responses.

Artificial sweeteners are used as calorie-free sugar substitutes in many food products and their consumption has increased substantially over the past years. Although generally regarded as safe, some concerns have been raised about the long-term safety of the consumption of certain sweeteners. In this study, we show that the intake of high doses of sucralose in mice results in immunomodulatory effects by limiting T cell proliferation and T cell differentiation.

Am I being dehumanized? Development and validation of the experience of dehumanization measurement.

Scholarly interest in the experience of dehumanization, the perception that one is being dehumanized, has increased significantly in recent years, yet the construct lacks a validated measurement. The purpose of this research is therefore to develop and validate a theoretically grounded experience of dehumanization measurement (EDHM) using item response theory. Evidence from five studies using data collected from participants in the United Kingdom (N = 2082) and Spain (N = 1427), shows that (a) a unidimensional structure replicates and fits well; (b) the measurement demonstrates high precision and reliability across a broad range of the latent trait; (c) the measurement demonstrates evidence for nomological and discriminant validity with constructs in the experience of dehumanization nomological network; (d) the measurement is invariant across gender and cultures; (e) the measurement demonstrates incremental validity in the prediction of important outcomes over and above conceptually overlapping constructs and prior measurements.

Hexapeptides from mammalian inhibitory hormone hunt activate and inactivate nematode reproduction.

Background: Biopurification has been used to disclose an evolutionarily conserved inhibitory reproductive hormone involved in tissue mass determination. A (rat) bioassay-guided physicochemical fractionation using ovine materials yielded via Edman degradation a 14-residue amino acid (aa) sequence. As a 14mer synthetic peptide (EPL001) this displayed antiproliferative and reproduction-modulating activity, while representing only a part of the native polypeptide.

One Dimensional Twisted Van der Waals Structures Constructed by Self-Assembling Graphene Nanoribbons on Carbon Nanotubes.

Twisted van der Waals heterostructures were recently found to possess unique physical properties, such as superconductivity in magic angle bilayer graphene. Owing to the nonhomogeneous stacking, the energy of twisted van der Waals heterostructures are often higher than their AA or AB stacking counterpart, therefore, fabricating such structures remains a great challenge in experiments. On the other hand, one dimensional (1D) coaxial van der Waals structures has less freedom to undergo phase transition, thus offer opportunity for fabricating the 1D cousin of twisted bilayer graphene.

Effects of the COVID-19 pandemic on secondary care for cardiovascular disease in the UK: an electronic health record analysis across three countries.

Background: Although morbidity and mortality from COVID-19 have been widely reported, the indirect effects of the pandemic beyond 2020 on other major diseases and health service activity have not been well described.

Methods And Results: Analyses used national administrative electronic hospital records in England, Scotland, and Wales for 2016-21. Admissions and procedures during the pandemic (2020-21) related to six major cardiovascular conditions [acute coronary syndrome (ACS), heart failure (HF), stroke/transient ischaemic attack (TIA), peripheral arterial disease (PAD), aortic aneurysm (AA), and venous thromboembolism(VTE)] were compared with the annual average in the pre-pandemic period (2016-19).

A Hybrid Architecture (CO-CONNECT) to Facilitate Rapid Discovery and Access to Data Across the United Kingdom in Response to the COVID-19 Pandemic: Development Study.

Background: COVID-19 data have been generated across the United Kingdom as a by-product of clinical care and public health provision, as well as numerous bespoke and repurposed research endeavors. Analysis of these data has underpinned the United Kingdom's response to the pandemic, and informed public health policies and clinical guidelines. However, these data are held by different organizations, and this fragmented landscape has presented challenges for public health agencies and researchers as they struggle to find relevant data to access and interrogate the data they need to inform the pandemic response at pace.

Assessment of cholesterol homeostasis in the living human brain.

Alterations in brain cholesterol homeostasis have been broadly implicated in neurological disorders. Notwithstanding the complexity by which cholesterol biology is governed in the mammalian brain, excess neuronal cholesterol is primarily eliminated by metabolic clearance via cytochrome P450 46A1 (CYP46A1). No methods are currently available for visualizing cholesterol metabolism in the living human brain; therefore, a noninvasive technology that quantitatively measures the extent of brain cholesterol metabolism via CYP46A1 could broadly affect disease diagnosis and treatment options using targeted therapies.

Association of COVID-19 With Major Arterial and Venous Thrombotic Diseases: A Population-Wide Cohort Study of 48 Million Adults in England and Wales.

Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a prothrombotic state, but long-term effects of COVID-19 on incidence of vascular diseases are unclear.

Methods: We studied vascular diseases after COVID-19 diagnosis in population-wide anonymized linked English and Welsh electronic health records from January 1 to December 7, 2020. We estimated adjusted hazard ratios comparing the incidence of arterial thromboses and venous thromboembolic events (VTEs) after diagnosis of COVID-19 with the incidence in people without a COVID-19 diagnosis.

Design, Synthesis and Biological Investigation of 2-Anilino Triazolopyrimidines as Tubulin Polymerization Inhibitors with Anticancer Activities.

A further investigation aiming to generate new potential antitumor agents led us to synthesize a new series of twenty-two compounds characterized by the presence of the 7-(3',4',5'-trimethoxyphenyl)-[1,2,4]triazolo[1,5-]pyrimidine pharmacophore modified at its 2-position. Among the synthesized compounds, three were significantly more active than the others. These bore the substituents -toluidino (), -ethylanilino () and 3',4'-dimethylanilino (), and these compounds had IC values of 30-43, 160-240 and 67-160 nM, respectively, on HeLa, A549 and HT-29 cancer cells.