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1دورية أكاديمية
المؤلفون: Catherine Huntley, Lucy Loong, Corinne Mallinson, Rachel Bethell, Tameera Rahman, Neelam Alhaddad, Oliver Tulloch, Xue Zhou, Jason Lee, Paul Eves, Fiona McRonald, Bethany Torr, John Burn, Adam Shaw, Eva J.A. Morris, Kevin Monahan, Steven Hardy, Clare Turnbull, Jacqueline Cook, Ruth Armstrong, Munaza Ahmed, Terri McVeigh, Bianca DeSouza, Anjana Kulkarni, Heirdre Bezuidenhout, Richard Martin, Debbie Holliday, Rachel Hart, Fiona Lalloo, Alan Donaldson, Ruth Cleaver, Catherine Willis, Victoria Kiesel, Marie-Anne O'Reilly, Dorothy Halliday, Joyce Solomons, Kai Ren Ong
المصدر: EClinicalMedicine, Vol 69, Iss , Pp 102465- (2024)
مصطلحات موضوعية: Lynch syndrome, Registry, Genomics, Data, Medicine (General), R5-920
الوصف: Summary: Background: Lynch Syndrome (LS) is a cancer predisposition syndrome caused by constitutional pathogenic variants in the mismatch repair (MMR) genes. To date, fragmentation of clinical and genomic data has restricted understanding of national LS ascertainment and outcomes, and precluded evaluation of NICE guidance on testing and management. To address this, via collaboration between researchers, the National Disease Registration Service (NDRS), NHS Genomic Medicine Service Alliances (GMSAs), and NHS Regional Clinical Genetics Services, a comprehensive registry of LS carriers in England has been established. Methods: For comprehensive ascertainment of retrospectively identified MMR pathogenic variant (PV) carriers (diagnosed prior to January 1, 2023), information was retrieved from all clinical genetics services across England, then restructured, amalgamated, and validated via a team of trained experts in NDRS. An online submission portal was established for prospective ascertainment from January 1, 2023. The resulting data, stored in a secure database in NDRS, were used to investigate the demographic and genetic characteristics of the cohort, censored at July 25, 2023. Cancer outcomes were investigated via linkage to the National Cancer Registration Dataset (NCRD). Findings: A total of 11,722 retrospective and 570 prospective data submissions were received, resulting in a comprehensive English National Lynch Syndrome Registry (ENLSR) comprising 9030 unique individuals. The most frequently identified pathogenic MMR genes were MSH2 and MLH1 at 37.2% (n = 3362) and 29.1% (n = 2624), respectively. 35.9% (n = 3239) of the ENLSR cohort received their LS diagnosis before their first cancer diagnosis (presumptive predictive germline test). Of these, 6.3% (n = 204) developed colorectal cancer, at a median age of initial diagnosis of 51 (IQR 40–62), compared to 73 years (IQR 64–80) in the general population (p
وصف الملف: electronic resource
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المؤلفون: James A. G. Whitworth, Hannah West, Emma R. Woodward, R. Gordon Hislop, Carol Gardiner, Derek H K Lim, Jacqueline Cook, Eamonn R. Maher, Marc Tischkowitz, Emily Murray, Philip Smith, Patrick J. Morrison, Anne Y. Warren
المصدر: Genes, Chromosomes & Cancer
مصطلحات موضوعية: Adult, Male, renal cell carcinoma, Cancer Research, translocation, Translocation Breakpoint, Chromosomal translocation, Protein Serine-Threonine Kinases, Biology, urologic and male genital diseases, Chromosome Breakpoints, 03 medical and health sciences, 0302 clinical medicine, FHIT, Proto-Oncogene Proteins, Genetics, Humans, Genetic Testing, Folliculin, Carcinoma, Renal Cell, Gene, Research Articles, Aged, Chromosome Aberrations, whole genome sequencing, Tumor Suppressor Proteins, Breakpoint, Chromosome, Sequence Analysis, DNA, Middle Aged, Kidney Neoplasms, Acid Anhydride Hydrolases, Neoplasm Proteins, Chromosome 3, 030220 oncology & carcinogenesis, Female, ras Guanine Nucleotide Exchange Factors, Chromosomes, Human, Pair 3, Research Article
الوصف: Constitutional translocations, typically involving chromosome 3, have been recognized as a rare cause of inherited predisposition to renal cell carcinoma (RCC) for four decades. However, knowledge of the molecular basis of this association is limited. We have characterized the breakpoints by genome sequencing (GS) of constitutional chromosome abnormalities in five individuals who presented with RCC. In one individual with constitutional t(10;17)(q11.21;p11.2), the translocation breakpoint disrupted two genes: the known renal tumor suppressor gene (TSG) FLCN (and clinical features of Birt‐Hogg‐Dubé syndrome were detected) and RASGEF1A. In four cases, the rearrangement breakpoints did not disrupt known inherited RCC genes. In the second case without chromosome 3 involvement, the translocation breakpoint in an individual with a constitutional t(2;17)(q21.1;q11.2) mapped 12 Kb upstream of NLK. Interestingly, NLK has been reported to interact indirectly with FBXW7 and a previously reported RCC‐associated translocation breakpoint disrupted FBXW7. In two cases of constitutional chromosome 3 translocations, no candidate TSGs were identified in the vicinity of the breakpoints. However, in an individual with a constitutional chromosome 3 inversion, the 3p breakpoint disrupted the FHIT TSG (which has been reported previously to be disrupted in two apparently unrelated families with an RCC‐associated t(3;8)(p14.2;q24.1). These findings (a) expand the range of constitutional chromosome rearrangements that may be associated with predisposition to RCC, (b) confirm that chromosome rearrangements not involving chromosome 3 can predispose to RCC, (c) suggest that a variety of molecular mechanisms are involved the pathogenesis of translocation‐associated RCC, and (d) demonstrate the utility of GS for investigating such cases.
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المؤلفون: Muhammad Fahad Arshad, Sabapathy P. Balasubramanian, Richard Eastell, Edmund Rab, Jacqueline Cook, James McAllister, Azhar Merchant
المصدر: Postgraduate medical journal. 97(1151)
مصطلحات موضوعية: Male, medicine.medical_specialty, endocrine system diseases, Demographics, Urinary system, 030209 endocrinology & metabolism, 03 medical and health sciences, 0302 clinical medicine, Electronic records, Internal medicine, medicine, Humans, In patient, Familial hypocalciuric hypercalcaemia, 030304 developmental biology, Aged, 0303 health sciences, business.industry, Reproducibility of Results, General Medicine, Middle Aged, medicine.disease, Hyperparathyroidism, Primary, Urinary calcium, Treatment Outcome, Case-Control Studies, Hypercalcemia, Calcium, Female, Differential diagnosis, business, Primary hyperparathyroidism
الوصف: Aim Primary hyperparathyroidism (PHPT) is much more common than familial hypocalciuric hypercalcaemia (FHH), but there is considerable overlap in biochemical features. Urine calcium indices help with the differential diagnosis, but their reliability in making this distinction is not clear. The aim of this study was to compare urinary calcium values in patients with PHPT and FHH. Methods This was a case–control study of patients with PHPT who had successful surgery and genetically proven FHH between 2011 and 2016. Due to low FHH numbers, patients from neighbouring hospitals and outside study period (2017–2019) were allowed to improve power. Data on demographics and urinary calcium were obtained from electronic records and compared between the two groups. Results During the study period, 250 patients underwent successful PHPT surgery, while in the FHH arm, 19 genetically proven cases were included. The median (IQR) 24-hour urine calcium excretion (UCE) in the PHPT group was 8.3 (5.6–11.2) mmol/24 hours compared with 3.2 (2.1–6.1) mmol/24 hour in the FHH group (p0.02). The specificity of the urinary tests for FHH was 29.4% for UCE (cut-off Conclusions 24-hour UCE is more sensitive in diagnosing PHPT; however, it is less specific in ruling out FHH as compared with CCCR, when the cut-offs suggested by the International guidelines from the fourth international workshop are used. A significant proportion of patients with PHPT would have also required genetic studies if the guidelines were followed.
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المؤلفون: Jacqueline Cook
المصدر: Contents of Commercial Contracts
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::b4991a7377d2083c32f68f473984a85d
https://doi.org/10.5040/9781509930524.ch-021 -
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المصدر: Molecular Phylogenetics and Evolution. 112:194-208
مصطلحات موضوعية: 0106 biological sciences, 0301 basic medicine, Species complex, Chloroplasts, Zoology, Biology, Tribe (biology), 010603 evolutionary biology, 01 natural sciences, Evolution, Molecular, 03 medical and health sciences, Genus, Polyphyly, Genetics, Clade, Molecular Biology, Phylogeny, Ecology, Evolution, Behavior and Systematics, Base Sequence, Phylogenetic tree, DNA, Chloroplast, Disjunct distribution, Bayes Theorem, biology.organism_classification, Phenotype, 030104 developmental biology, Zaluzianskya, Scrophulariaceae
الوصف: The genus Zaluzianskya (Scrophulariaceae s.s.) encompasses a diversity of floral and ecological traits. However, this diversity, as described by the current taxonomic circumscription of Zaluzianskya, is an underestimate. We present molecular data suggesting that this genus requires expansion via incorporation of species from other genera and recognition of unnamed cryptic species. This study advances prior molecular phylogenies of the southern African genus through the addition of DNA regions and 51 populations that had not previously been sampled in a published phylogeny. A total of 82 species of Zaluzianskya and related genera are included, adding 48 to those previously sampled. Results are presented from analyses of five DNA regions, including nuclear ITS and four rapidly evolving chloroplast regions (trnL-trnF, rpl16, rps16, and trnS-trnfM). Our primary finding is that the genus Phyllopodium is polyphyletic as currently circumscribed, with some species placed within Zaluzianskya and others grouping with Polycarena, indicating the need for further phylogenetic work on these genera. Preliminary support for the incorporation of Reyemia into Zaluzianskya is reinforced here by the first molecular analysis to include both species of Reyemia and a strong sampling of species across Zaluzianskya and major clades of tribe Limoselleae. The two disjunct, tropical African species of Zaluzianskya are also confirmed as members of this genus. Finally, a broad sampling of 21 populations of Z. microsiphon establishes their phylogenetic division into two to five separate lineages. Hybridization, coevolution, and cryptic speciation may each play a role in the evolution of Z. microsiphon. Further resolution within a clade comprising sections Nycterinia and Macrocalyx is needed to better understand their relationships.
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المؤلفون: Jacqueline Cook, Richard Eastell, Azhar Merchant, Edmund Rab, Muhammad Fahad Arshad, James McAllister, Saba P. Balasubramanian
المصدر: Journal of the Endocrine Society
مصطلحات موضوعية: medicine.medical_specialty, endocrine system diseases, business.industry, Bone and Mineral Metabolism, Endocrinology, Diabetes and Metabolism, medicine.disease, Gastroenterology, Urinary calcium, Internal medicine, medicine, Parathyroid Hormone: Clinical Disorders and Basic Insights, Familial hypocalciuric hypercalcaemia, business, Primary hyperparathyroidism
الوصف: Introduction: Primary hyperparathyroidism (PHPT) has a prevalence of around 1% and requires surgery for definite treatment. On the other hand, familial hypocalciuric hypercalcaemia (FHH) is much rarer and does not need specific treatment. There may be considerable overlap in biochemical features in these conditions. Urine calcium indices are used to help with the differential diagnosis, but their reliability in making this distinction is not clear. The aim of this retrospective cohort study was to review urinary calcium values in patients with proven PHPT and those with genetically proven FHH. Methods: Over six years (2011-2016), 265 patients with PHPT underwent surgery. Of these, 14 patients with intermittent or persistent hypercalcaemia within 6 months after surgery were excluded leaving 251 patients (female to male ratio 5:1) for final analysis. In the FHH arm, only genetically proven cases (n = 10) were included. Results: In the PHPT arm, pre-operative data was available for 24 hr urine calcium excretion (UCE) and fractional excretion of calcium (FeCa) in 93 patients; 24 hr UCE only in 95 patients; and FeCa only in 43 patients. 24 hr UCE was low (i.e.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::65adafe81bf05927e3fff15e3ab77188
https://doi.org/10.1210/js.2019-mon-532 -
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المؤلفون: Jacqueline Cook, Tristan Hopper, Andrew Ritcey, Kristine Webber, Andrea King, Jerome F. Singleton
المصدر: Activities, Adaptation & Aging. 40:150-163
مصطلحات موضوعية: Gerontology, 030506 rehabilitation, Exploratory research, Health Professions (miscellaneous), Social relation, Leisure satisfaction, 03 medical and health sciences, Patient population, 0302 clinical medicine, Day hospital, Social determinants of health, Geriatrics and Gerontology, 0305 other medical science, Psychology, Recreation, Competence (human resources), 030217 neurology & neurosurgery, Clinical psychology
الوصف: This research explored the effectiveness of a leisure education program on participants’ overall leisure functioning. The study took place within a Geriatric Day Hospital (GDH) where the goals are to treat and ameliorate patients’ symptoms and conditions, while also ensuring promotion of a healthy lifestyle.At the time of the study there were no recreation therapy services provided to the GDH patients. The literature reviewed suggested that a formalized service including leisure education to address leisure awareness, social interaction skills, leisure resources, leisure activity skills, and recreation participation may have significant impact on GDH patients’ physical, psychological, and social health. The study design therefore focused on participants’ motivation and competence to engage in leisure activities and their personal leisure satisfaction.No significant differences were found between the experimental and control group related to leisure satisfaction and leisure motivation. However, interesting...
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المؤلفون: Adam A. Scaife, Jonathan D. Mackay, Jacqueline Cook, Rob Ward, Christopher R. Jackson, Anca Brookshaw
المصدر: Journal of Hydrology. 530:815-828
مصطلحات موضوعية: geography, geography.geographical_feature_category, Ensemble forecasting, Meteorology, Weather forecasting, Forecast skill, Aquifer, computer.software_genre, Climatology, Quantitative precipitation forecast, Environmental science, Tropical cyclone forecast model, Groundwater model, computer, Groundwater, Water Science and Technology
الوصف: Summary To date, the majority of hydrological forecasting studies have focussed on using medium-range (3–15 days) weather forecasts to drive hydrological models and make predictions of future river flows. With recent developments in seasonal (1–3 months) weather forecast skill, such as those from the latest version of the UK Met Office global seasonal forecast system (GloSea5), there is now an opportunity to use similar methodologies to forecast groundwater levels in more slowly responding aquifers on seasonal timescales. This study uses seasonal rainfall forecasts and a lumped groundwater model to simulate groundwater levels at 21 locations in the United Kingdom up to three months into the future. The results indicate that the forecasts have skill; outperforming a persistence forecast and demonstrating reliability, resolution and discrimination. However, there is currently little to gain from using seasonal rainfall forecasts over using site climatology for this type of application. Furthermore, the forecasts are not able to capture extreme groundwater levels, primarily because of inadequacies in the driving rainfall forecasts. The findings also show that the origin of forecast skill, be it from the meteorological input, groundwater model or initial condition, is site specific and related to the groundwater response characteristics to rainfall and antecedent hydro-meteorological conditions.
وصف الملف: text
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9دورية أكاديمية
المؤلفون: Arkka Bhattacharyya, Carl Peterson, Takeki Itoh, Saurav Roy, Jacqueline Cooke, Steve Rebollo, Praneeth Ranga, Berardi Sensale-Rodriguez, Sriram Krishnamoorthy
المصدر: APL Materials, Vol 11, Iss 2, Pp 021110-021110-10 (2023)
مصطلحات موضوعية: Biotechnology, TP248.13-248.65, Physics, QC1-999
الوصف: We demonstrate a new substrate cleaning and buffer growth scheme in β-Ga2O3 epitaxial thin films using metal–organic vapor phase epitaxy (MOVPE). For the channel structure, a low-temperature (LT, 600 °C) un-doped Ga2O3 buffer was grown, followed by a transition layer to a high-temperature (HT, 810 °C) Si-doped Ga2O3 channel layers without growth interruption. The (010) Ga2O3 Fe-doped substrate cleaning uses solvent cleaning, followed by additional hydrofluoric acid (49% in water) treatment for 30 min before the epilayer growth. This step is shown to compensate the parasitic Si channel at the epilayer–substrate interface that originates from the substrate polishing process or contamination from the ambient. From secondary ion mass spectroscopy (SIMS) analysis, the Si peak atomic density at the substrate interface is found to be several times lower than the Fe atomic density in the substrate—indicating full compensation. The elimination of the parasitic electron channel at the epi–substrate interface was also verified by electrical (capacitance–voltage profiling) measurements. In the LT-grown (600 °C) buffer layers, it is seen that the Fe forward decay tail from the substrate is very sharp, with a decay rate of ∼9 nm/dec. X-ray off-axis rocking curve ω-scans show very narrow full width at half maximum (FWHM) values, similar to the as-received substrates. These channels show record high electron mobility in the range of 196–85 cm2/V⋅s in unintentionally doped and Si-doped films in the doping range of 2 × 1016–1 × 1020 cm−3. Si delta-doped channels were also grown utilizing this substrate cleaning and the hybrid LT buffers. Record high electron Hall mobility of 110 cm2/V⋅s was measured for sheet charge density of 9.2 × 1012 cm−2. This substrate cleaning, combined with the LT buffer scheme, shows the potential of designing Si-doped β-Ga2O3 channels with exceptional transport properties for high-performance Ga2O3-based electron devices.
وصف الملف: electronic resource
Relation: https://doaj.org/toc/2166-532X
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10دورية أكاديمية
المؤلفون: Jacqueline Cooke, Praneeth Ranga, Jani Jesenovec, John S. McCloy, Sriram Krishnamoorthy, Michael A. Scarpulla, Berardi Sensale-Rodriguez
المصدر: Scientific Reports, Vol 12, Iss 1, Pp 1-10 (2022)
الوصف: Abstract In this work, a systematic photoluminescence (PL) study on three series of gallium oxide/aluminum gallium oxide films and bulk single crystals is performed including comparing doping, epitaxial substrates, and aluminum concentration. It is observed that blue/green emission intensity strongly correlates with extended structural defects rather than the point defects frequently assumed. Bulk crystals or Si-doped films homoepitaxially grown on (010) β-Ga2O3 yield an intense dominant UV emission, while samples with extended structural defects, such as gallium oxide films grown on either (-201) β-Ga2O3 or sapphire, as well as thick aluminum gallium oxide films grown on either (010) β-Ga2O3 or sapphire, all show a very broad PL spectrum with intense dominant blue/green emission. PL differences between samples and the possible causes of these differences are analyzed. This work expands previous reports that have so far attributed blue and green emissions to point defects and shows that in the case of thin films, extended defects might have a prominent role in emission properties.
وصف الملف: electronic resource
Relation: https://doaj.org/toc/2045-2322
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