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排序方式: 共有9028条查询结果,搜索用时 12 毫秒
81.
Bettina Kuschel Georgia Chenevix-Trench Amanda B Spurdle Xiaoqing Chen John L Hopper Graham G Giles Margret McCredie Jenny Chang-Claude Catherine S Gregory Nick E Day Douglas F Easton Bruce A J Ponder Alison M Dunning Paul D P Pharoah 《Cancer epidemiology, biomarkers & prevention》2005,14(7):1828-1831
A substantial proportion of the familial risk of breast cancer may be due to genetic variants, each contributing a small effect. The protein encoded by ERCC2 is a key enzyme involved in nucleotide excision repair, in which gene defects could lead to cancer prone syndromes such as Xeroderma pigmentosum D. We have examined the association between single nucleotide polymorphisms in the ERCC2 gene and the incidence of invasive breast cancer in three case-control series, with a maximum of 3,634 patients and of 3,340 controls. None of the three single nucleotide polymorphisms were significantly associated with the incidence of breast cancer. 相似文献
82.
Michal Hledík Nick Barton Gaper Tka
ik 《Proceedings of the National Academy of Sciences of the United States of America》2022,119(36)
Selection accumulates information in the genome—it guides stochastically evolving populations toward states (genotype frequencies) that would be unlikely under neutrality. This can be quantified as the Kullback–Leibler (KL) divergence between the actual distribution of genotype frequencies and the corresponding neutral distribution. First, we show that this population-level information sets an upper bound on the information at the level of genotype and phenotype, limiting how precisely they can be specified by selection. Next, we study how the accumulation and maintenance of information is limited by the cost of selection, measured as the genetic load or the relative fitness variance, both of which we connect to the control-theoretic KL cost of control. The information accumulation rate is upper bounded by the population size times the cost of selection. This bound is very general, and applies across models (Wright–Fisher, Moran, diffusion) and to arbitrary forms of selection, mutation, and recombination. Finally, the cost of maintaining information depends on how it is encoded: Specifying a single allele out of two is expensive, but one bit encoded among many weakly specified loci (as in a polygenic trait) is cheap.Throughout evolution, selection accumulates information in the genome. It guides evolving populations toward fitter phenotypes, genotypes, and genotype frequencies, which would be highly unlikely to arise by chance. This information—the degree to which selection can control the stochastic process of evolution—has been a long-standing subject of research (1–7), and relates to basic questions in evolutionary biology and genetics. 相似文献
83.
Tjede Funk Francesco Innocenti Joana Gomes Dias Lina Nerlander Tanya Melillo Charmaine Gauci Jackie M Melillo Patrik Lenz Helena Sebestova Pavel Slezak Iva Vlckova Jacob Dag Berild Camilla Mauroy Elina Seppl Ragnhild Tnnessen Anne Vergison Joël Mossong Silvana Masi Laetitia Huiart Gillian Cullen Niamh Murphy Lois OConnor Joan ODonnell Piers Mook Richard G Pebody Nick Bundle 《Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin》2022,27(35)
BackgroundUnderlying conditions are risk factors for severe COVID-19 outcomes but evidence is limited about how risks differ with age.AimWe sought to estimate age-specific associations between underlying conditions and hospitalisation, death and in-hospital death among COVID-19 cases.MethodsWe analysed case-based COVID-19 data submitted to The European Surveillance System between 2 June and 13 December 2020 by nine European countries. Eleven underlying conditions among cases with only one condition and the number of underlying conditions among multimorbid cases were used as exposures. Adjusted odds ratios (aOR) were estimated using 39 different age-adjusted and age-interaction multivariable logistic regression models, with marginal means from the latter used to estimate probabilities of severe outcome for each condition–age group combination.ResultsCancer, cardiac disorder, diabetes, immunodeficiency, kidney, liver and lung disease, neurological disorders and obesity were associated with elevated risk (aOR: 1.5–5.6) of hospitalisation and death, after controlling for age, sex, reporting period and country. As age increased, age-specific aOR were lower and predicted probabilities higher. However, for some conditions, predicted probabilities were at least as high in younger individuals with the condition as in older cases without it. In multimorbid patients, the aOR for severe disease increased with number of conditions for all outcomes and in all age groups.ConclusionWhile supporting age-based vaccine roll-out, our findings could inform a more nuanced, age- and condition-specific approach to vaccine prioritisation. This is relevant as countries consider vaccination of younger people, boosters and dosing intervals in response to vaccine escape variants. 相似文献
84.
Kate Sellen Nick Goso Laura Halleran Alison MulvaleFletcher Felipe Sarmiento Filipe Ligabue Curtis Handford Michelle Klaiman Geoffrey Milos Amy Wright Mercy Charles Ruby Sniderman Richard Hunt Janet A. Parsons Pamela Leece Shaun Hopkins Rita Shahin Peter Jüni Laurie Morrison Douglas M. Campbell Carol Strike Aaron Orkin SOONER Investigators 《Health expectations》2022,25(5):2440
IntroductionOverdose education and naloxone distribution (OEND) programmes equip and train people who are likely to witness an opioid overdose to respond with effective first aid interventions. Despite OEND expansion across North America, overdose rates are increasing, raising questions about how to improve OEND programmes. We conducted an iterative series of codesign stakeholder workshops to develop a prototype for take‐home naloxone (THN)‐kit (i.e., two doses of intranasal naloxone and training on how to administer it).MethodsWe recruited people who use opioids, frontline healthcare providers and public health representatives to participate in codesign workshops covering questions related to THN‐kit prototypes, training on how to use it, and implementation, including refinement of design artefacts using personas and journey maps. Completed over 9 months, the workshops were audio‐recorded and transcribed with visible results of the workshops (i.e., sticky notes, sketches) archived. We used thematic analyses of these materials to identify design requirements for THN‐kits and training.ResultsWe facilitated 13 codesign workshops to identify and address gaps in existing opioid overdose education training and THN‐kits and emphasize timely response and stigma in future THN‐kit design. Using an iterative process, we created 15 prototypes, 3 candidate prototypes and a final prototype THN‐kit from the synthesis of the codesign workshops.ConclusionThe final prototype is available for a variety of implementation and evaluation processes. The THN‐kit offers an integrated solution combining ultra‐brief training animation and physical packaging of nasal naloxone to be distributed in family practice clinics, emergency departments, addiction medicine clinics and community settings.Patient or Public ContributionThe codesign process was deliberately structured to involve community members (the public), with multiple opportunities for public contribution. In addition, patient/public participation was a principle for the management and structuring of the research team. 相似文献
85.
Aaron Schokman Yu Sun Bin Diana Naehrig Janet M Y Cheung Kristina Kairaitis Nick Glozier 《Sleep》2022,45(10)
Study ObjectivesTo systematically determine subjective and objective outcome measures used to measure the efficacy of narcolepsy interventions in randomized controlled trials (RCTs) in adults and children and assess psychometric properties of patient-reported outcome measures (PROMs) used.MethodsWe searched bibliographical databases and clinical trial registries for narcolepsy RCTs and extracted objective and subjective outcome measures. If PROMs were used, we searched for psychometric studies conducted in a narcolepsy population using bibliographical databases and appraised using Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines.ResultsIn total, 80 different outcome measures were used across 100 RCTs. Epworth Sleepiness Scale (ESS) (n = 49) and Maintenance of Wakefulness Test (n = 47) were the most frequently used outcome measures. We found 19 validation studies of 10 PROMs in narcolepsy populations. There was limited evidence for validity or responsiveness of the ESS; yet sufficient reliability (pooled ICC: 0.81–0.87). Narcolepsy Severity Scale (NSS) had sufficient reliability (pooled ICC: 0.71–0.92) and both adult and pediatric versions had sufficient discriminant validity (treated/untreated). Content validity was only evaluated in pediatric populations for ESS-CHAD and NSS-P and rated inconclusive. Quality of evidence of the psychometric studies for all scales ranged from very low to low.ConclusionsAlthough recognized by regulatory bodies and widely used as primary outcome measures in trials, there is surprisingly little evidence for the validity, reliability, and responsiveness of PROMs frequently used to assess treatment efficacy in narcolepsy. The field needs to establish patient-centered minimal clinically important differences for the PROMs used in these trials. 相似文献
86.
Pamela T. Soliman David Iglesias Mark F. Munsell Michael Frumovitz Shannon N. Westin Alpa M. Nick Kathleen M. Schmeler Pedro T. Ramirez 《Gynecologic oncology》2013
Background
The increasing role of robotic surgery in gynecologic oncology may impact fellowship training. The purpose of this study was to review the proportion of robotic procedures performed by fellows at the console, and compare operative times and lymph node yields to faculty surgeons.Methods
A prospective database of women undergoing robotic gynecologic surgery has been maintained since 2008. Intra-operative datasheets completed include surgical times and primary surgeon at the console. Operative times were compared between faculty and fellows for simple hysterectomy (SH), bilateral salpingo-oophorectomy (BSO), pelvic (PLND) and paraaortic lymph node dissection (PALND) and vaginal cuff closure (VCC). Lymph nodes counts were also compared.Results
Times were recorded for 239 SH, 43 BSOs, 105 right PLNDs, 104 left PLNDs, 34 PALND and 269 VCC. Comparing 2008 to 2011, procedures performed by the fellow significantly increased; SH 16% to 83% (p < 0.001), BSO 7% to 75% (p = 0.005), right PLND 4% to 44% (p < 0.001), left PLND 0% to 56% (p < 0.001), and VCC 59% to 82% (p = 0.024). Console times (min) were similar for SH (60 vs. 63, p = 0.73), BSO (48 vs. 43, p = 0.55), and VCC (20 vs. 22, p = 0.26). Faculty times (min) were shorter for PLND (right 26 vs. 30, p = 0.04, left 23 vs. 27, p = 0.02). Nodal counts were not significantly different (right 7 vs. 8, p = 0.17 or left 7 vs. 7, p = 0.87).Conclusions
Robotic surgery can be successfully incorporated into gynecologic oncology fellowship training. With increased exposure to robotic surgery, fellows had similar operative times and lymph node yields as faculty surgeons. 相似文献87.
The influence of children's self-report trait anxiety and depression on visual search for emotional faces 总被引:2,自引:0,他引:2
Hadwin JA Donnelly N French CC Richards A Watts A Daley D 《Journal of child psychology and psychiatry, and allied disciplines》2003,44(3):432-444
BACKGROUND: This study presents two experiments that investigated the relationship between 7- and 10-year-olds' levels of self-report trait anxiety and depression and their visual search for threatening (angry faces) and non-threatening (happy and neutral faces) stimuli. METHOD: In both experiments a visual search paradigm was used to measure participants' reaction times to detect the presence or absence of angry, happy or neutral schematic faces (Experiment 1) or cartoon drawings (Experiment 2). On target present trials, a target face was displayed alongside three, five or seven distractor items. On target absent trials all items were distractors. RESULTS: Both experiments demonstrated that on target absent (but not present) trials, increased levels of anxiety produced significantly faster search times in the angry face condition, but not in the neutral condition. In Experiment 2 there was some trend towards significance between anxiety and searches for happy faces in absent trials. There were no effects of depression on search times in any condition. CONCLUSION: The results support previous work highlighting a specific link between anxiety and attention to threat in childhood. 相似文献
88.
Thomas Creasey Emilio Barretta Sarra L. Ryan Ellie Butler Amy A. Kirkwood Daniel Leongamornlert Elli Papaemmanuil Pip Patrick Laura Clifton-Hadley Bela Patel Tobias Menne Andrew K. McMillan Christine J. Harrison Clare J. Rowntree Nick Morley David I. Marks Adele K. Fielding Anthony V. Moorman 《Haematologica》2022,107(9):2051
Despite being predominantly a childhood disease, the incidence of acute lymphoblastic leukemia (ALL) has a second peak in adults aged 60 years and over. These older adults fare extremely poorly with existing treatment strategies and very few studies have undertaken a comprehensive genetic and genomic characterization to improve prognosis in this age group. We performed cytogenetic, single nucleotide polymorphism (SNP) array and next-generation sequencing (NGS) analyses on samples from 210 patients aged ≥60 years from the UKALL14 and UKALL60+ clinical trials. BCR-ABL1-positive disease was present in 26% (55/210) of patients, followed by low hypodiploidy/near triploidy in 13% (28/210). Cytogenetically cryptic rearrangements in CRLF2, ZNF384 and MEF2D were detected in 5%, 1% and <1% of patients, respectively. Copy number abnormalities were common and deletions in ALL driver genes were seen in 77% of cases. IKZF1 deletion was present in 51% (40/78) of samples tested and the IKZF1plus profile was identified in over a third (28/77) of cases of B-cell precursor ALL. The genetic good-risk abnormalities high hyperdiploidy (n=2), ETV6-RUNX1 (no cases) and ERG deletion (no cases) were exceptionally rare in this cohort. RAS pathway mutations were seen in 17% (4/23) of screened samples. KDM6A abnormalities, including biallelic deletions, were discovered in 5% (4/78) of SNP arrays and 9% (2/23) of NGS samples, and represent novel, potentially therapeutically actionable lesions using EZH2 inhibitors. Outcome remained poor with 5-year event-free and overall survival rates of 17% and 24%, respectively, across the cohort, indicating a need for novel therapeutic strategies. 相似文献
89.
We aimed to develop a novel and effective technique for creating a smooth deep lamellar dissection of the cornea using a femtosecond (FS) laser for deep anterior lamellar keratoplasty (DALK), we conducted a retrospective eye bank study. Thirteen fresh human corneas were mounted on an artificial anterior chamber, and deep lamellar cuts were made with a 500-kHz VisuMax FS laser at a level of 50–80 mm anterior to the Descemet’s membrane (DM). A posterior diameter of 8 mm with a side cut angle of 110° was used for the anterior penetrating side cut. The anterior lamellar tissue was bluntly dissected. The residual posterior stromal beds and side cuts were examined with microscopy and intraoperative optical coherence tomography (OCT) and post-cut endothelial cell evaluations. All corneas revealed a smooth residual posterior stromal bed without any visible irregularities or ridges by microscopy and OCT imaging. Six corneas were suitable for post-cut endothelial cell evaluation 2 days after laser cut, with no significant endothelial cell loss post-laser and blunt dissection of the posterior stroma. FS laser deep lamellar keratoplasty utilizing an ultrafast laser to produce a smooth deep stromal dissection followed by blunt dissection and removal of the anterior stromal tissue yields a consistent and smooth residual stromal bed. The creation of a smooth lamellar dissection in the deep posterior cornea may result in more consistent DALK without the need for air bubble or manual baring of DM that has the risk for DM perforation. 相似文献
90.