2,642 research outputs found

    Linkage analysis merging replicate phenotypes: an application to three quantitative phenotypes in two African samples

    Get PDF
    We report two approaches for linkage analysis of data consisting of replicate phenotypes. The first approach is specifically designed for the unusual (in human data) replicate structure of the Genetic Analysis Workshop 17 pedigree data. The second approach consists of a standard linkage analysis that, although not specifically tailored to data consisting of replicate genotypes, was envisioned as providing a sounding board against which our novel approach could be assessed. Both approaches are applied to the analysis of three quantitative phenotypes (Q1, Q2, and Q4) in two sets of African families. All analyses were carried out blind to the generating model (i.e., the “answers”). Using both methods, we found numerous significant linkage signals for Q1, although population colocalization was absent for most of these signals. The linkage analysis of Q2 and Q4 failed to reveal any strong linkage signals

    Serum 25-hydroxyvitamin D and cognitive decline in the very old: the Newcastle 85+ Study.

    Get PDF
    This is the final version of the article. Available from Wiley via the DOI in this record.BACKGROUND AND PURPOSE: Studies investigating the association between 25-hydroxyvitamin D [25(OH)D] and cognition in the very old (85+) are lacking. METHODS: Cross-sectional (baseline) and prospective data (up to 3 years follow-up) from 775 participants in the Newcastle 85+ Study were analysed for global (measured by the Standardized Mini-Mental State Examination) and attention-specific (measured by the attention battery of the Cognitive Drug Research test) cognitive performance in relation to season-specific 25(OH)D quartiles. RESULTS: Those in the lowest and highest season-specific 25(OH)D quartiles had an increased risk of impaired prevalent (1.66, 95% confidence interval 1.06-2.60, P = 0.03; 1.62, 95% confidence interval 1.02-2.59, P = 0.04, respectively) but not incident global cognitive functioning or decline in functioning compared with those in the middle quartiles adjusted for sociodemographic, health and lifestyle confounders. Random effects models showed that participants belonging to the lowest and highest 25(OH)D quartiles, compared with those in the middle quartiles, had overall slower (log-transformed) attention reaction times for Choice Reaction Time (lowest, ÎČ = 0.023, P = 0.01; highest, ÎČ = 0.021, P = 0.02), Digit Vigilance Task (lowest, ÎČ = 0.009, P = 0.05; highest, ÎČ = 0.01, P = 0.02) and Power of Attention (lowest, ÎČ = 0.017, P = 0.02; highest, ÎČ = 0.022, P = 0.002) and greater Reaction Time Variability (lowest, ÎČ = 0.021, P = 0.02; highest, ÎČ = 0.02, P = 0.03). The increased risk of worse global cognition and attention amongst those in the highest quartile was not observed in non-users of vitamin D supplements/medication. CONCLUSION: Low and high season-specific 25(OH)D quartiles were associated with prevalent cognitive impairment and poorer overall performance in attention-specific tasks over 3 years in the very old, but not with global cognitive decline or incident impairment.This work was supported by the National Institute for Health Research Newcastle Biomedical Research Centre based at Newcastle Hospitals Foundation Trust and Newcastle University (AG). The Newcastle 85+ Study has been funded by the Medical Research Council, Biotechnology and Biological Sciences Research Council and the Dunhill Medical Trust. Additional work has also been funded by the British Heart Foundation, Unilever Corporate Research, Newcastle University and National Health Service (NHS) North of Tyne (Newcastle Primary Care Trust). The views expressed in this paper are those of the authors and not necessarily those of the National Health Service, UK. We acknowledge the operational support of NHS North of Tyne, the local general practitioners and their staff, the research nurses, laboratory technicians, data management and clerical team, as well as many colleagues for their expert advice. Thanks are due especially to the study participants

    Identification of plastic constitutive parameters at large deformations from three dimensional displacement fields

    Get PDF
    The aim of this paper is to provide a general procedure to extract the constitutive parameters of a plasticity model starting from displacement measurements and using the Virtual Fields Method. This is a classical inverse problem which has been already investigated in the literature, however several new features are developed here. First of all the procedure applies to a general three-dimensional displacement field which leads to large plastic deformations, no assumptions are made such as plane stress or plane strain although only pressure-independent plasticity is considered. Moreover the equilibrium equation is written in terms of the deviatoric stress tensor that can be directly computed from the strain field without iterations. Thanks to this, the identification routine is much faster compared to other inverse methods such as finite element updating. The proposed method can be a valid tool to study complex phenomena which involve severe plastic deformation and where the state of stress is completely triaxial, e.g. strain localization or necking occurrence. The procedure has been validated using a three dimensional displacement field obtained from a simulated experiment. The main potentialities as well as a first sensitivity study on the influence of measurement errors are illustrated

    Early menopause, association with tobacco smoking, coffee consumption and other lifestyle factors: a cross-sectional study

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Early onset of menopause is a risk factor for several health problems. The objective was primarily to investigate the association between early menopause and current, past active and passive smoking. A second aim was to investigate the association between coffee and alcohol consumption and early menopause.</p> <p>Methods</p> <p>The present population-based cross-sectional study included a sub-sample of 2123 postmenopausal women born in 1940–41 who participated in the Oslo Health Study. Early menopause was defined as menopause occurring at an age of less than 45 years. We applied logistic regression analyses (crude and adjusted odds ratio (OR)) to examine the association between early menopause and selected lifestyle factors.</p> <p>Results</p> <p>Current smoking was significantly associated with early menopause (adj. OR, 1.59; 95% CI, 1.11–2.28). Stopping smoking more than 10 years before menopause considerably reduced the risk of early menopause (adj. OR, 0.13; 95% CI, 0.05–0.33). Total exposure to smoking (the product of number of cigarettes per day and time as a smoker) was positively related to early menopause and, at the highest doses, nearly doubled the odds (adj. OR, 1.93; 95% CI, 1.12–3.30). These data suggest a possible dose-response relationship between total exposure to smoking and early menopause, but no dose-response relationship was detected for the other variables examined. We found no significant association of coffee or alcohol consumption with early menopause. Of the lifestyle factors tested, high educational level (adj. OR, 0.50; 95% CI, 0.34–0.72) and high social participation (adj. OR, 0.60, 95% CI, 0.39–0.98) were negatively associated with early menopause.</p> <p>Conclusion</p> <p>This cross-sectional study shows an association between current smoking and early menopause. The data also suggest that the earlier a woman stops smoking the more protected she is from early menopause. Early menopause was not significantly associated with passive smoking, or alcohol or coffee consumption.</p

    Advances in small lasers

    Get PDF
    M.T.H was supported by an Australian Research council Future Fellowship research grant for this work. M.C.G. is grateful to the Scottish Funding Council (via SUPA) for financial support.Small lasers have dimensions or modes sizes close to or smaller than the wavelength of emitted light. In recent years there has been significant progress towards reducing the size and improving the characteristics of these devices. This work has been led primarily by the innovative use of new materials and cavity designs. This Review summarizes some of the latest developments, particularly in metallic and plasmonic lasers, improvements in small dielectric lasers, and the emerging area of small bio-compatible or bio-derived lasers. We examine the different approaches employed to reduce size and how they result in significant differences in the final device, particularly between metal- and dielectric-cavity lasers. We also present potential applications for the various forms of small lasers, and indicate where further developments are required.PostprintPeer reviewe

    HERMES-24 Score Derivation and Validation for Simple and Robust Outcome Prediction After Large Vessel Occlusion Treatment

    Get PDF
    \ua9 2024 American Heart Association, Inc. BACKGROUND: Clinicians need simple and highly predictive prognostic scores to assist practical decision-making. We aimed to develop a simple outcome prediction score applied 24 hours after anterior circulation acute ischemic stroke treatment with endovascular thrombectomy and validate it in patients treated both with and without endovascular thrombectomy. METHODS: Using the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration data set (n=1764), patients in the endovascular thrombectomy arm were divided randomly into a derivation cohort (n=430) and a validation cohort (n=441). From a set of candidate predictors, logistic regression modeling using forward variable selection was used to select a model that was both parsimonious and highly predictive for modified Rankin Scale (mRS) ≀2 at 90 days. The score was validated in validation cohort, control arm (n=893), and external validation cohorts from the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke; n=1066) and INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography; n=614). RESULTS: In the derivation cohort, we selected 2 significant predictors of mRS ≀2 (National Institutes of Health Stroke Scale score at 24 hours and age [ÎČ-coefficient, 0.34 and 0.06]) and derived the HERMES-24 score: age (years)/10+National Institutes of Health Stroke Scale score at 24 hours. The HERMES-24 score was highly predictive for mRS ≀2 (c-statistic 0.907 [95% CI, 0.879–0.935]) in the derivation cohort. In the validation cohort and the control arm, the HERMES-24 score predicts mRS ≀2 (c-statistic, 0.914 [95% CI, 0.886–0.944] and 0.909 [95% CI, 0.887–0.930]). Observed provability of mRS ≀2 ranged between 3.1% and 3.4% when HERMES-24 score ≄25, while it ranged between 90.6% and 93.0% when HERMES-24 score &lt;10 in the derivation cohort, validation cohort, and control arm. The HERMES-24 score also showed c-statistics of 0.894 and 0.889 for mRS ≀2 in the ESCAPE-NA1 and INTERRSeCT populations. CONCLUSIONS: The post-treatment HERMES-24 score is a simple validated score that predicts a 3-month outcome after anterior circulation large vessel occlusion stroke regardless of intervention, which helps prognostic discussion with families on day 2

    Increasing response to a postal survey of sedentary patients – a randomised controlled trial [ISRCTN45665423]

    Get PDF
    BACKGROUND: A systematic review identified a range of methods, which can influence response rates. However, analysis specific to a healthcare setting, and in particular, involving people expected to be poor responders, was missing, We examined the effect of pre-warning letters on response rates to a postal survey of sedentary patients whom we expected a low rate of response. METHODS: Participants were randomised to receive a pre-warning letter or no pre-warning letter, seven days before sending the main questionnaire. The main questionnaire included a covering letter and pre-paid return envelope. After seven days, non-responders were sent a reminder letter and seven days later, another reminder letter with a further copy of the questionnaire and return envelope. RESULTS: 627 adults, with a mean age of 48 years (SD 13, range 18 to 78) of whom 69.2% (434/627) were women, were randomised. 49.0% (307/627) of patients were allocated to receive a pre-warning letter and 51.0% (320/627) no pre-warning letter, seven days in advance of posting the main questionnaire. The final response rate to the main questionnaire was 30.0% (92/307) amongst those sent a pre-warning letter and 20.9% (67/320) not sent a pre-warning letter, with an adjusted odds ratio of 1.60 (95% CI 1.1, 2.30). CONCLUSIONS: The relatively low cost method of sending a pre-warning letter had a modest impact on increasing response rates to a postal questionnaire sent to a group of patients for whom a low response rate was anticipated. Investigators should consider incorporating this simple intervention when conducting postal surveys, to reduce the potential for nonresponse bias and to increase the study power. Methods other than postal surveys may be needed however when a low response rate to postal surveys is likely

    Effects of experiment start time and duration on measurement of standard physicological variables

    Get PDF
    Duration and start time of respirometry experiments have significant effects on the measurement of basal values for several commonly measured physiological variables (metabolic rate, evaporative water loss and body temperature). A longer measurement duration reduced values for all variables for all start times, and this was an effect of reduced animal activity rather than random sampling. However, there was also an effect of circadian rhythm on the timing of minimal physiological values. Experiment start time had a significant effect on time taken to reach minimal values for all variables, ranging from 4:00 h ± 38 min (body temperature, start time 23:00 h) to 8:54 h ± 52 min (evaporative water loss, start time 17:00 h). It also influenced the time of day that minimal values were obtained, ranging from 22:24 h ± 40 min (carbon dioxide production, start time 15:00 h) to 06:00 h ± 57 min (oxygen consumption, start time 23:00 h), and the minimum values measured. Consequently both measurement duration and experiment start time should be considered in experimental design to account for both a handling and a circadian effect on the animal’s physiology. We suggest that experiments to measure standard physiological variables for small diurnal birds should commence between 17:00 h and 21:00 h, and measurement duration should be at least 9 h
    • 

    corecore