Roger Reeves

IMPORTANCE: Most neovascular age-related macular degeneration (nAMD) treatments involve long-term follow-up of disease activity. Home-monitoring would reduce the burden on patients and their caregivers and release clinic capacity. OBJECTIVE: To evaluate 3 vision home-monitoring tests for patients to use to detect active nAMD compared with diagnosing active nAMD at hospital follow-up during the after-treatment monitoring phase. DESIGN, SETTING, AND PARTICIPANTS: This was a diagnostic test accuracy study wherein the reference standard was detection of active nAMD by an ophthalmologist at hospital follow-up...

OBJECTIVES: Remote monitoring of health has the potential to reduce the burden to patients of face-to-face appointments and make healthcare more efficient. Apps are available for patients to self-monitor vision at home, for example, to detect reactivation of age-related macular degeneration (AMD). Describing the challenges when implementing apps for self-monitoring of vision at home was an objective of the MONARCH study to evaluate two vision-monitoring apps on an iPod Touch (Multibit and MyVisionTrack)...

PURPOSE: To describe inequalities in the Monitoring for Neovascular Age-related Macular Degeneration Reactivation at Home (MONARCH) diagnostic test accuracy study for: recruitment; participants' ability to self-test; and adherence to testing using digital applications during follow-up. METHODS: Home-monitoring vision tests included two tests implemented as software applications (apps: MyVisionTrack and MultiBit) on an iPod Touch device. Patients were provided with all hardware required to participate (iPod and MIFI device) and trained to use the apps...

INTRODUCTION: Adalimumab is an effective treatment for autoimmune non-infectious uveitis (ANIU), but it is currently only funded for a minority of patients with ANIU in the UK as it is restricted by the National Institute for Health and Care Excellence guidance. Ophthalmologists believe that adalimumab may be effective in a wider range of patients. The Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness (ASTUTE) trial will recruit patients with ANIU who do and do not meet funding criteria and will evaluate the effectiveness and cost-effectiveness of adalimumab versus placebo as an add-on therapy to standard care...

Mouse models are central to studying and understanding the genotypic-to-phenotypic outcomes of Down syndrome (DS), a complex condition caused by an extra copy of the long arm of human chromosome 21. The recently developed TcMAC21-a transchromosomic mouse strain with comparable gene dosage to human chromosome 21 (Hsa21)-includes more Hsa21 genes than any other model of DS. Recent studies on TcMAC21 have provided valuable insight into the molecular, physiological, and neuroanatomical aspects of the model. However, relatively little is known about the craniofacial phenotype of TcMAC21 mice, particularly as it compares to the widely studied Ts65Dn model...

Key innovations are fundamental to biological diversification, but their genetic basis is poorly understood. A recent transition from egg-laying to live-bearing in marine snails ( Littorina spp.) provides the opportunity to study the genetic architecture of an innovation that has evolved repeatedly across animals. Individuals do not cluster by reproductive mode in a genome-wide phylogeny, but local genealogical analysis revealed numerous small genomic regions where all live-bearers carry the same core haplotype...

The post-translational modification of intracellular proteins by O-linked β-GlcNAc (O-GlcNAc) has emerged as a critical regulator of cardiac function. Enhanced O-GlcNAcylation activates cytoprotective pathways in cardiac models of ischemia-reperfusion (I/R) injury; however, the mechanisms underpinning O-GlcNAc cycling in response to I/R injury have not been comprehensively assessed. The cycling of O-GlcNAc is regulated by the collective efforts of two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which catalyze the addition and hydrolysis of O-GlcNAc, respectively...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA generally becomes undetectable in upper airways after a few days or weeks postinfection. Here we used a model of viral infection in macaques to address whether SARS-CoV-2 persists in the body and which mechanisms regulate its persistence. Replication-competent virus was detected in bronchioalveolar lavage (BAL) macrophages beyond 6 months postinfection. Viral propagation in BAL macrophages occurred from cell to cell and was inhibited by interferon-γ (IFN-γ)...

Inversions are thought to play a key role in adaptation and speciation, suppressing recombination between diverging populations. Genes influencing adaptive traits cluster in inversions, and changes in inversion frequencies are associated with environmental differences. However, in many organisms, it is unclear if inversions are geographically and taxonomically widespread. The intertidal snail, Littorina saxatilis, is one such example. Strong associations between putative polymorphic inversions and phenotypic differences have been demonstrated between two ecotypes of L...

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a lifelong diagnosis that involves immune-mediated damage of pancreatic beta cells and subsequent hyperglycemia, manifesting as: polyuria, polydipsia, polyphagia, and weight loss. Treatment of type 1 diabetes centers on insulin administration to replace or supplement the body's own insulin with the goal of achieving euglycemia and preventing or minimizing complications. Patients with T1DM are at risk for developing other autoimmune conditions, most commonly thyroid or celiac disease...

Thousands of mammalian intracellular proteins are dynamically modified by O-linked β-N-acetylglucosamine (O-GlcNAc). Global changes in O-GlcNAcylation have been associated with the development of cardiomyopathy, heart failure, hypertension, and neurodegenerative disease. Levels of O-GlcNAc in cells and tissues can be detected using numerous approaches; however, immunoblotting using GlcNAc-specific antibodies and lectins is commonplace. The goal of this study was to optimize the detection of O-GlcNAc in heart lysates by immunoblotting...

BACKGROUND: Bleeding among populations undergoing percutaneous coronary intervention or coronary artery bypass grafting and among conservatively managed patients with acute coronary syndrome exposed to different dual antiplatelet therapy and triple therapy (i.e. dual antiplatelet therapy plus an anticoagulant) has not been previously quantified. OBJECTIVES: The objectives were to estimate hazard ratios for bleeding for different antiplatelet and triple therapy regimens, estimate resources and the associated costs of treating bleeding events, and to extend existing economic models of the cost-effectiveness of dual antiplatelet therapy...

Broadly neutralizing antibodies (bNAbs) may provide an alternative to standard antiretroviral treatment (ART) for controlling HIV-1 replication and may have immunotherapeutic effects against HIV-1 reservoirs. We conducted a prospective clinical trial with two HIV-1 bNAbs (VRC01LS and 10-1074) in children ( n = 25) who had previously initiated small-molecule ART treatment before 7 days of age and who continued treatment for at least 96 weeks. Both bNAbs were dosed intravenously every 4 weeks, overlapping with ART for at least 8 weeks and then continued for up to 24 weeks or until detectable viremia of HIV-1 RNA rose above 400 copies per milliliter in the absence of ART...

Children with Down syndrome (DS, trisomy of chromosome 21) have an increased risk of infantile spasms (IS). As an epileptic encephalopathy, IS may further impair cognitive function and exacerbate neurodevelopmental delays already present in children with DS. To investigate the pathophysiology of IS in DS, we induced IS-like epileptic spasms in a genetic mouse model of DS that carries human chromosome 21q, TcMAC21, the animal model most closely representing gene dosage imbalance in DS. Repetitive extensor/flexor spasms were induced by the GABAB receptor agonist γ-butyrolactone (GBL) and occurred predominantly in young TcMAC21 mice (85%) but also in some euploid mice (25%)...

OBJECTIVES: To assess the effectiveness of injectable tissue pulmonary valve compared with standard pulmonary valve in patients requiring pulmonary valve replacement surgery. DESIGN: A multicentre, single-blind, parallel two-group randomised controlled trial. Participants were blind to their allocation. Follow-up continued for 6 months. Randomised allocations were generated by a computer using block randomisation, stratified by centre. SETTING: Two National Health Service secondary care centres in the UK...

The consequences of aneuploidy have traditionally been studied in cell and animal models in which the extrachromosomal DNA is from the same species. Here, we explore a fundamental question concerning the impact of aneuploidy on systemic metabolism using a non-mosaic transchromosomic mouse model (TcMAC21) carrying a near-complete human chromosome 21. Independent of diets and housing temperatures, TcMAC21 mice consume more calories, are hyperactive and hypermetabolic, remain consistently lean and profoundly insulin sensitive, and have a higher body temperature...

Nanotechnology has delivered an amazing range of new materials such as nanowires, tubes, ribbons, belts, cages, flowers, and sheets. However, these are usually circular, cylindrical, or hexagonal in nature, while nanostructures with square geometries are comparatively rare. Here, a highly scalable method is reported for producing vertically aligned Sb-doped SnO2 nanotubes with perfectly-square geometries on Au nanoparticle covered m-plane sapphire using mist chemical vapor deposition. Their inclination can be varied using r- and a-plane sapphire, while unaligned square nanotubes of the same high structural quality can be grown on silicon and quartz...

BACKGROUND: Psychosis in Parkinson's disease includes hallucinations and delusions. Other non-psychotic neuropsychiatric features include depression, anxiety and apathy. There is currently controversy over whether psychosis in Parkinson's is an intrinsic part of the disorder or the result of dopaminergic medications. This study aimed to examine a historical cohort of individuals with Parkinson's prior to the use of dopaminergic therapy to assess the prevalence of psychotic and other neuropsychiatric features...

Trisomy 21 and mutations in the Sonic hedgehog (SHH) signaling pathway cause overlapping and pleiotropic phenotypes including cerebellar hypoplasia, craniofacial abnormalities, congenital heart defects, and Hirschsprung disease. Trisomic cells derived from individuals with Down syndrome possess deficits in SHH signaling, suggesting that overexpression of chromosome 21 genes may contribute to SHH-associated phenotypes by disrupting normal SHH signaling during development. However, chromosome 21 does not encode any known components of the canonical SHH pathway...

OBJECTIVES: Intermittent cold blood cardioplegia is commonly used in children whereas intermittent warm blood cardioplegia is widely used in adults. We aimed to compare clinical and biochemical outcomes with these two methods. METHODS: A single centre, randomized controlled trial was conducted to compare the effectiveness of warm (≥34°C) versus cold (4-6°C) antegrade cardioplegia in children. The primary outcome was cardiac troponin T over the first 48 postoperative hours...