Causes, Solutions and Health Inequalities: Comparing Perspectives of Professional Stakeholders and Community Participants Experiencing Low Income and Poor Health in London.

Background: Engaging with the public can influence policy decisions, particularly towards more radical policy change. While established research exists exploring public perceptions on causes of health inequalities, much less exists on how to tackle health inequalities in the UK. Despite an emphasis on 'lived experience', currently no study has focused on how individuals with very poor health conceive of both causes of, and solutions to, health inequalities.

Meta-analyses uncover the genetic architecture of Idiopathic Inflammatory Myopathies.

Objective: Idiopathic inflammatory myopathies (myositis, IIMs) are rare, systemic autoimmune disorders that lead to muscle inflammation, weakness, and extra-muscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome-wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome-wide myositis studies and analyzed the largest myositis dataset to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes.

Preventing acute neurotoxicity of CNS therapeutic oligonucleotides with the addition of Ca and Mg in the formulation.

Oligonucleotide therapeutics (ASOs and siRNAs) have been explored for modulation of gene expression in the central nervous system (CNS), with several drugs approved and many in clinical evaluation. Administration of highly concentrated oligonucleotides to the CNS can induce acute neurotoxicity. We demonstrate that delivery of concentrated oligonucleotides to the CSF in awake mice induces acute toxicity, observable within seconds of injection.

Anti-Sp4 and Anti-CCAR1 autoantibodies in UK vs. US patients with adult and juvenile-onset anti-TIF1Æ´-positive myositis.

Objectives: Anti-TIF1γ autoantibodies are associated with malignancy in adult-onset idiopathic inflammatory myopathy (IIM) and this risk is attenuated if patients are also positive for anti-specificity protein 4 (Sp4) or anti-cell division cycle apoptosis regulator protein 1 (CCAR1). In anti-TIF1γ positive US dermatomyositis (DM) patients, anti-Sp4 and anti-CCAR1 autoantibody frequencies are reported as 32% and 43% in adults and 9% and 19% in juveniles, respectively. This study aims to identify the frequency of anti-Sp4 and anti-CCAR1 in adult and juvenile UK anti-TIF1ƴ-positive myositis populations and report clinical associations.

The Healthy and Active Fund: Lessons From the Evaluation Experiences of Community-Based Physical Activity Projects in Wales.

Background: The "Healthy and Active Fund" involved 17 community-based projects focused on the delivery of physical activity interventions, led by a variety of public and third sector organizations. As a novel, direct approach to capturing impact at this level, these organizations were encouraged to robustly evaluate and monitor their own project's outcomes, with core funds allocated to this process. This study aimed to explore project experiences of planning and completing evaluation activities, to better understand how to support community-based practice improvement.

An update on myositis autoantibodies and insights into pathogenesis.

Myositis-specific autoantibodies (MSAs) are hallmarks of idiopathic inflammatory myopathies (IIMs) and have become increasing valuable in disease diagnosis, phenotyping, and classification. In addition to their clinical utility, emerging data, including findings from several animal studies, suggest that MSAs and autoreactive T cells substantially contribute to the etiopathogenesis of IIMs. This review aims to provide an updated perspective on myositis autoantibodies by focusing on relevant clinical and translational studies.

Topical Anesthesia in Cutaneous Head and Neck Surgery: A Randomized Controlled Trial.

Objective: Cutaneous head and neck surgery can safely and effectively be performed using local anesthetic (LA). However, optimizing pain management during LA administration is paramount for patient comfort and procedural efficacy. The primary objective of this study was to investigate the comparative effectiveness of EMLA cream and ethyl chloride (EC) spray in mitigating pain associated with LA administration in cutaneous head and neck surgery.

Search for Time-Dependent CP Violation in D^{0}→π^{+}π^{-}π^{0} Decays.

A measurement of time-dependent CP violation in D^{0}→π^{+}π^{-}π^{0} decays using a pp collision data sample collected by the LHCb experiment in 2012 and from 2015 to 2018, corresponding to an integrated luminosity of 7.7  fb^{-1}, is presented. The initial flavor of each D^{0} candidate is determined from the charge of the pion produced in the D^{*}(2010)^{+}→D^{0}π^{+} decay.

Incidence of Psoriatic Arthritis in a Primary Care Psoriasis Population in the United Kingdom.

Objective: To determine the annual incidence of psoriatic arthritis (PsA) in a United Kingdom primary care population with preexisting psoriasis (PsO) followed prospectively over 2 years after excluding baseline prevalence of existing disease.

Methods: Total Burden of Psoriasis (TUDOR; ISRCTN registry: ISRCTN38877516) was a multicenter, prospective, 2-arm parallel-group cluster randomized controlled trial of the early identification of PsA by annual rheumatological assessment (termed "Enhanced Surveillance") vs standard care in people with PsO identified in primary care. Incidence of PsA is reported at 12 months and 24 months using patients from the Enhanced Surveillance arm, which allows for the exclusion of patients with prevalent PsA at baseline.

Systemic sclerosis and cancer in the UK: An epidemiological analysis using the Clinical Practice Research Datalink.

Background: Cancer can cause mortality in systemic sclerosis (SSc). We investigated the association between cancer and SSc using the Clinical Practice Research Datalink (CPRD).

Methods: A validated case-ascertainment strategy identified SSc patients in the CPRD.

Enhancing siRNA efficacy in vivo with extended nucleic acid backbones.

Therapeutic small interfering RNA (siRNA) requires sugar and backbone modifications to inhibit nuclease degradation. However, metabolic stabilization by phosphorothioate (PS), the only backbone chemistry used clinically, may be insufficient for targeting extrahepatic tissues. To improve oligonucleotide stabilization, we report the discovery, synthesis and characterization of extended nucleic acid (exNA) consisting of a methylene insertion between the 5'-C and 5'-OH of a nucleoside.

Changes in the incidence and prevalence of systemic lupus erythematosus between 1990 and 2020: an observational study using the Clinical Practice Research Datalink (CPRD).

Objective: To obtain updated estimates on the incidence and prevalence of systemic lupus erythematosus (SLE) in the UK, over the period 1990-2020, using the Clinical Practice Research Datalink (CPRD).

Methods: This was a retrospective cohort study using the CPRD covering the period 1990-2020. A case ascertainment algorithm was developed in line with best practice recommendations for observational research.

Enhanced surveillance for the detection of psoriatic arthritis in a UK primary care psoriasis population: results from the TUDOR trial.

Background: Our objective was to determine whether early detection of undiagnosed psoriatic arthritis (PsA) in a primary care psoriasis population improves outcome in physical function at 24 months post-registration.

Methods: A multicentre, prospective, parallel group cluster randomised controlled trial in patients with psoriasis was conducted. Participants with suspected inflammatory arthritis on screening were referred for an assessment of PsA (enhanced surveillance (ES) arm: at baseline, 12 and 24 months; standard care (SC) arm: at 24 months).

mRNA Nuclear Clustering Leads to a Difference in Mutant Huntingtin mRNA and Protein Silencing by siRNAs .

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by CAG repeat expansion in the first exon of the huntingtin gene (). Oligonucleotide therapeutics, such as short interfering RNA (siRNA), reduce levels of huntingtin mRNA and protein and are considered a viable therapeutic strategy. However, the extent to which they silence huntingtin mRNA in the nucleus is not established.

Modification of χ_{c1}(3872) and ψ(2S) Production in pPb Collisions at sqrt[s_{NN}]=8.16  TeV.

The LHCb Collaboration measures production of the exotic hadron χ_{c1}(3872) in proton-nucleus collisions for the first time. Comparison with the charmonium state ψ(2S) suggests that the exotic χ_{c1}(3872) experiences different dynamics in the nuclear medium than conventional hadrons, and comparison with data from proton-proton collisions indicates that the presence of the nucleus may modify χ_{c1}(3872) production rates. This is the first measurement of the nuclear modification factor of an exotic hadron.

Living on low-incomes with multiple long-term health conditions: A new method to explore the complex interaction between finance and health.

People on low-incomes in the UK develop multiple long-term health conditions over 10 years earlier than affluent individuals. Financial diaries -new to public health- are used to explore the lived experiences of financially-vulnerable individuals, diagnosed with at least one long-term condition, living in two inner-city London Boroughs. Findings show that the health status of these individuals is a key barrier to work opportunities, undermining their income.

Preventing acute neurotoxicity of CNS therapeutic oligonucleotides with the addition of Ca and Mg in the formulation.

Oligonucleotide therapeutics (ASOs and siRNAs) have been explored for modulation of gene expression in the central nervous system (CNS), with several drugs approved and many in clinical evaluation. Administration of highly concentrated oligonucleotides to the CNS can induce acute neurotoxicity. We demonstrate that delivery of concentrated oligonucleotides to the CSF in awake mice induces acute toxicity, observable within seconds of injection.

mRNA nuclear clustering leads to a difference in mutant huntingtin mRNA and protein silencing by siRNAs .

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by CAG repeat expansion in the first exon of the huntingtin gene (). Oligonucleotide therapeutics, such as short interfering RNA (siRNA), reduce levels of huntingtin mRNA and protein and are considered a viable therapeutic strategy. However, the extent to which they silence HTT mRNA in the nucleus is not established.

From polarity to plurality: Perceptions of COVID-19 and policy measures in England and Scotland.

Aim: The aim of this study was to uncover perspectives on the COVID-19 pandemic and the responses implemented by the UK and Scottish Governments to help control the spread of infection. Such understanding could help to inform future responses to pandemics at individual, community and national levels.

Method: Q methodology was used to elicit perspectives from people in England and Scotland with different experiences of the pandemic including public health officials, key workers, those on furlough, those who were unvaccinated or vaccinated to different levels, those who were 'shielding' because they were at higher risk and people with different scientific expertise.