A5027517883- Genomics and Rare Diseases
- Ion channel regulation and function
- Cancer Genomics and Diagnostics
- Climate variability and models
- Genetic factors in colorectal cancer
- BRCA gene mutations in cancer
- Molecular Biology Techniques and Applications
- Influenza Virus Research Studies
- Meteorological Phenomena and Simulations
- Hydrology and Drought Analysis
- Pneumonia and Respiratory Infections
- Cardiac electrophysiology and arrhythmias
- Chemical Reactions and Mechanisms
- Cancer, Hypoxia, and Metabolism
- Adrenal and Paraganglionic Tumors
- Colorectal Cancer Screening and Detection
- Hydrology and Watershed Management Studies
- Synthesis and Catalytic Reactions
- Genetic Associations and Epidemiology
- Chromosomal and Genetic Variations
- Beetle Biology and Toxicology Studies
- Blood Pressure and Hypertension Studies
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Respiratory viral infections research
NOAA Physical Sciences Laboratory
2023-2025
Cooperative Institute for Research in Environmental Sciences
2023-2025
University of Colorado Boulder
2023-2025
Leeds Teaching Hospitals NHS Trust
2019-2024
Augusta University Health
2023
SRM Institute of Science and Technology
2023
University of North Carolina at Charlotte
2023
Wessex Regional Genetics Laboratory
2023
NOAA Earth System Research Laboratory
2023
St James's University Hospital
2003-2022
PurposeWhere multiple in silico tools are concordant, the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) framework affords supporting evidence toward pathogenicity or benignity, equivalent to a likelihood ratio ~2. However, limited availability "clinical truth sets" prior use tool training limits their utility evaluation performance.MethodsWe created set 9,436 missense variants classified as deleterious tolerated clinically validated...
Aims and Objectives: It has been hypothesised that vestibular stimulation may have a modulatory effect on anxiety. The aim of this randomised, double blind, sham-controlled trial was to determine the efficacy safety non-invasive electrical nerve (VeNS) device as treatment for anxiety compared sham device. Materials methods: A total 60 participants (mean age [SD]: 35.6 [8.1]) with generalized disorder assessment (GAD-7) score ≥10 were randomised receive either an active VeNS (n = 34) or...
Advances in technology have led to a massive expansion the capacity for genomic analysis, with commensurate fall costs. The clinical indications testing evolved markedly; volume of sequencing has increased dramatically; and range professionals involved process broadened. There is general acceptance that our early dichotomous paradigms variants being pathogenic–high risk benign–no are overly simplistic. increasing recognition interpretation data requires significant expertise...
Accurate classification of variants in cancer susceptibility genes (CSGs) is key for correct estimation risk and management patients. Consistency the weighting assigned to individual elements evidence has been much improved by American College Medical Genetics (ACMG) 2015 framework variant classification, UK Association Clinical Genomic Science (UK-ACGS) Best Practice Guidelines subsequent Cancer Variant Interpretation Group (CanVIG-UK) consensus specification CSGs. However, considerable...
Abstract Hereditary Breast and Ovarian Cancer (HBOC) is a genetic condition associated with increased risk of cancers. The past decade has brought about significant changes to hereditary breast ovarian cancer diagnostic testing new treatments, methods strategies, evolving information on associations. These best practice guidelines have been produced assist clinical laboratories in effectively addressing the complexities HBOC testing, while taking into account advancements since last were...
Advances in technology have made possible Multiplex Assays of Variant Effect (MAVEs), systematically generating functional data for many thousands genetic variants. Robust clinical validation and accessible online resources MAVE previously been identified as barriers to adoption new MAVEs. We delivered a survey during the November 2024 Cancer Interpretation Group (CanVIG-UK) meeting comprising NHS scientists geneticists, received 46 responses from individuals regularly performing variant...
Purpose Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is a rare cancer susceptibility syndrome exclusively attributable to pathogenic variants in FH. This paper quantitatively weights the phenotypic context (PP4/PS4) of such very Methods We collated clinical diagnostic testing data on germline FH from 387 individuals with HLRCC 1,780 renal cancer, compared frequency 'very rare' each cohort against 562,295 population controls. generated pan-gene variant likelihood ratios...
Multiplex assays of variant effect (MAVEs) provide promising new sources functional evidence, potentially empowering improved classification germline genomic variants, particularly rare missense which are commonly assigned as VUS (variants uncertain significance). However, paradoxically, quantification clinically applicable evidence strengths for MAVEs requires construction truthsets comprising variants already robustly classified pathogenic and benign. In this study, we demonstrate how...
Photolysis of beta-azido propiophenone derivatives, 1, with built-in sensitizer units, leads to selective formation triplet alkyl nitrenes 2 that were detected directly laser flash photolysis (lambdamax = 325 nm, tau 27 ms) and ESR spectroscopy (|D/hc| 1.64 cm-1, |E/hc| 0.004 cm-1). Nitrenes further characterized argon matrix isolation, isotope labeling, molecular modeling. The are persistent intermediates do not abstract H-atoms from the solvent but decay by dimerizing another nitrene form...
Abstract. Saturation vapor pressure deficit (VPD), a measure of the difference between how much moisture atmosphere can hold versus is present, highly correlated with annual mean area burned by wildland fires in western United States. The present analysis uses linear inverse models (LIMs) to forecast seasonal VPD and decompose skill into contributions from nonlinear trend, coupled sea surface temperature (SST)-VPD variability, VPD-only variability. Subregions US are considered using...
ABSTRACT Despite forecasts to the contrary, Southwest Asia precipitation was unexpectedly below normal in October–December 2023, which extended an ongoing three‐year drought that responsible for water shortages and acute food insecurity. Expectations above‐normal this season were based on predictions made prior September from initialized forecast systems, indicated a greater than 60% chance of such occurrence. Confident predictions, making 2023 apparent opportunity, due attendant El Niño...
Abstract Introduction The bi-directional relationship between sleep and depression is well reported, with up to 70% of individuals major depressive disorder (MDD) experiencing insomnia, pre-existing insomnia doubling the risk developing depression. aim was explore impact an electrical vestibular nerve stimulation (VeNS) treatment for on symptoms. Methods study a double-blind randomised, sham-controlled trial (RCT) that evaluated efficacy safety VeNS MDD. undertaken in Andhra Pradesh, India...
Recessive Fanconi anemia (FA) phenotype is used in classification of BRCA1/FANCS, BRCA2/FANCD1 and PALB2/FANCN variants with respect to dominant hereditary breast-ovarian cancer syndrome. We assessed its utility by examining the spectrum phenotypes observed individuals biallelic for BRCA1, BRCA2 or PALB2 pathogenic variants, exploring relationship between presentation allele severity score based on variant molecular features. A data collection instrument comprising 158 Human Phenotype...
We report the first detection of triplet alkyl nitrenes in fluid solution by laser flash photolysis alpha-azido acetophenone derivatives, 1. Alphazides 1 contain an intramolecular sensitizer, which ensures formation nitrene bypassing singlet intermediate. At room temperature, azides cleave to form benzoyl and methyl azide radicals competition with energy transfer nitrene. The major photoproduct 3 arises from interception radicals. intermediates are also trapped molecular oxygen yield...
Abstract Genetic testing for cancer predisposition has been curtailed by the cost of sequencing, and restricted eligibility criteria. As sequencing decreases, question expanding multi-gene panels to a broader population arises. We evaluated how many additional actionable genetic variants are returned unrestricted panel in private sector compared those which would be adhering current NHS reviewed 152 patients referred between 2014 2016. counselling disclosure all results was standard care...
We have designed molecules which release alcohols upon exposure to UV light independent of the reaction media, making it possible liberate in a controlled manner applications. Photolysis 2-(2-isopropylbenzoyl)benzoate ester derivatives 4 various solvents and thin films results liberation alcohol moiety from ester. The mechanism for has been elucidated by time-resolved laser flash photolysis. Upon irradiation triplet excited state ketone, is formed, its lifetime can be estimated between 0.08...
Malignant hyperthermia (MH) is an autosomal dominant genetic condition that presents in susceptible people undergoing general anaesthesia. The clinical disorder a major cause of anaesthetic morbidity and mortality. UK Hyperthermia Group has performed linkage analysis on 20 large, well defined malignant families, using hypervariable markers chromosome 19q13.1, including the candidate MH gene RYR1, coding for skeletal muscle ryanodine receptor protein. results were analysed LINKAGE to perform...
Colorectal cancer (CRC) is common with 3% of cases associated germline mutations in the mismatch repair pathway characteristic Lynch syndrome (LS). The UK National Institute for Health and Care Excellence recommends screening LS all patients newly diagnosed CRC, irrespective age. Yorkshire Cancer Research Bowel Improvement Programme includes a regional service new diagnoses CRC. In first 829 screened, 80 showed deficient (dMMR) including four showing areas loss expression proteins by...