Influenza transmission in a cohort of households with children: 2010-2011

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Comparing computer-generated and pathologist-generated tumour segmentations for immunohistochemical scoring of breast tissue microarrays

BACKGROUND: Tissue microarrays (TMAs) have become a valuable resource for biomarker expression in translational research. Immunohistochemical (IHC) assessment of TMAs is the principal method for analysing large numbers of patient samples, but manual IHC assessment of TMAs remains a challenging and laborious task. With advances in image analysis, computer-generated analyses of TMAs have the potential to lessen the burden of expert pathologist review. METHODS: In current commercial software computerised oestrogen receptor (ER) scoring relies on tumour localisation in the form of hand-drawn annotations. In this study, tumour localisation for ER scoring was evaluated comparing computer-generated segmentation masks with those of two specialist breast pathologists. Automatically and manually obtained segmentation masks were used to obtain IHC scores for thirty-two ER-stained invasive breast cancer TMA samples using FDA-approved IHC scoring software. RESULTS: Although pixel-level comparisons showed lower agreement between automated and manual segmentation masks (κ=0.81) than between pathologists' masks (κ=0.91), this had little impact on computed IHC scores (Allred; [Image: see text]=0.91, Quickscore; [Image: see text]=0.92). CONCLUSIONS: The proposed automated system provides consistent measurements thus ensuring standardisation, and shows promise for increasing IHC analysis of nuclear staining in TMAs from large clinical trials

Breast cancer risk reduction:is it feasible to initiate a randomised controlled trial of a lifestyle intervention programme (ActWell) within a national breast screening programme?

BackgroundBreast cancer is the most commonly diagnosed cancer and the second cause of cancer deaths amongst women in the UK. The incidence of the disease is increasing and is highest in women from least deprived areas. It is estimated that around 42% of the disease in post-menopausal women could be prevented by increased physical activity and reductions in alcohol intake and body fatness. Breast cancer control endeavours focus on national screening programmes but these do not include communications or interventions for risk reductionThis study aimed to assess the feasibility of delivery, indicative effects and acceptability of a lifestyle intervention programme initiated within the NHS Scottish Breast Screening Programme (NHSSBSP).MethodsA 1:1 randomised controlled trial (RCT) of the 3 month ActWell programme (focussing on body weight, physical activity and alcohol) versus usual care conducted in two NHSSBSP sites between June 2013 and January 2014. Feasibility assessments included recruitment, retention, and fidelity to protocol. Indicative outcomes were measured at baseline and 3 month follow-up (body weight, waist circumference, eating and alcohol habits and physical activity. At study end, a questionnaire assessed participant satisfaction and qualitative interviews elicited women¿s, coaches and radiographers¿ experiences. Statistical analysis used Chi squared tests for comparisons in proportions and paired t tests for comparisons of means. Linear regression analyses were performed, adjusted for baseline values, with group allocation as a fixed effectResultsA pre-set recruitment target of 80 women was achieved within 12 weeks and 65 (81%) participants (29 intervention, 36 control) completed 3 month assessments. Mean age was 58¿±¿5.6 years, mean BMI was 29.2¿±¿7.0 kg/m2 and many (44%) reported a family history of breast cancer.The primary analysis (baseline body weight adjusted) showed a significant between group difference favouring the intervention group of 2.04 kg (95%CI ¿3.24 kg to ¿0.85 kg). Significant, favourable between group differences were also detected for BMI, waist circumference, physical activity and sitting time. Women rated the programme highly and 70% said they would recommend it to others.ConclusionsRecruitment, retention, indicative results and participant acceptability support the development of a definitive RCT to measure long term effects.Trial registrationThe trial was registered with Current Controlled Trials (ISRCTN56223933)

Nonlinear Analysis of Irregular Variables

The Fourier spectral techniques that are common in Astronomy for analyzing periodic or multi-periodic light-curves lose their usefulness when they are applied to unsteady light-curves. We review some of the novel techniques that have been developed for analyzing irregular stellar light or radial velocity variations, and we describe what useful physical and astronomical information can be gained from their use.Comment: 31 pages, to appear as a chapter in `Nonlinear Stellar Pulsation' in the Astrophysics and Space Science Library (ASSL), Editors: M. Takeuti & D. Sasselo

Born to yawn? Understanding yawning as a warning of the rise in cortisol levels: Randomized trial

Background: Yawning consistently poses a conundrum to the medical profession and neuroscientists. Despite neurological evidence such as parakinesia brachialis oscitans in stroke patients and thermo-irregulation in multiple sclerosis patients, there is considerable debate over the reasons for yawning with the mechanisms and hormonal pathways still not fully understood. Cortisol is implicated during yawning and may link many neurological disorders. Evidence was found in support of the Thompson cortisol hypothesis that proposes cortisol levels are elevated during yawning just as they tend to rise during stress and fatigue. Objectives: To investigate whether saliva cortisol levels rise during yawning and, therefore, support the Thompson cortisol hypothesis. Methods: We exposed 20 male and female volunteers aged between 18 and 53 years to conditions that provoked a yawning response in a randomized controlled trial. Saliva samples were collected at the start and again after the yawning response, or at the end of the stimuli presentations if the participant did not yawn. In addition, we collected electromyographic data of the jaw muscles to determine rest and yawning phases of neural activity. Yawning susceptibility scale, Hospital Anxiety and Depression Scale, General Health Questionnaire, and demographic and health details were also collected from each participant. A comprehensive data set allowed comparison between yawners and nonyawners, as well as between rest and yawning phases. Collecting electromyographic data from the yawning phase is novel, and we hope this will provide new information about neuromuscular activity related to cortisol levels. Exclusion criteria included chronic fatigue, diabetes, fibromyalgia, heart conditions, high blood pressure, hormone replacement therapy, multiple sclerosis, and stroke. We compared data between and within participants. Results: In the yawning group, there was a significant difference between saliva cortisol samples (t = -3.071, P = .01). Power and effect size were computed based on repeated-measures t tests for both the yawning and nonyawning groups. There was a medium effect size for the nonyawners group (r = .467) but low power (36%). Results were similar for the yawners group: medium effect size (r = .440) and low power (33%). Conclusions: There was significant evidence in support of the Thompson cortisol hypothesis that suggests cortisol levels are elevated during yawning. A further longitudinal study is planned to test neurological patients. We intend to devise a diagnostic tool based on changes in cortisol levels that may assist in the early diagnosis of neurological disorders based on the data collected. Trial Registration: International Standard Randomized Controlled Trial Number (ISRCTN): 61942768; http://www.controlled-trials.com/ISRCTN61942768/61942768 (Archived by WebCite at http://www.webcitation.org/6A75ZNYvr)

Sedentary time and markers of inflammation in people with newly diagnosed type 2 diabetes

This is the final version. Available on open access from Elsevier via the DOI in this recordBACKGROUND AND AIMS: We investigated whether objectively measured sedentary time was associated with markers of inflammation in adults with newly diagnosed type 2 diabetes. METHODS AND RESULTS: We studied 285 adults (184 men, 101 women, mean age 59.0 ± 9.7) who had been recruited to the Early ACTivity in Diabetes (Early ACTID) randomised controlled trial. C-reactive protein (CRP), adiponectin, soluble intracellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), and accelerometer-determined sedentary time and moderate-vigorous physical activity (MVPA) were measured at baseline and after six-months. Linear regression analysis was used to investigate the independent cross-sectional and longitudinal associations of sedentary time with markers of inflammation. At baseline, associations between sedentary time and IL-6 were observed in men and women, an association that was attenuated following adjustment for waist circumference. After 6 months of follow-up, sedentary time was reduced by 0.4 ± 1.2 h per day in women, with the change in sedentary time predicting CRP at follow-up. Every hour decrease in sedentary time between baseline and six-months was associated with 24% (1, 48) lower CRP. No changes in sedentary time between baseline and 6 months were seen in men. CONCLUSIONS: Higher sedentary time is associated with IL-6 in men and women with type 2 diabetes, and reducing sedentary time is associated with improved levels of CRP in women. Interventions to reduce sedentary time may help to reduce inflammation in women with type 2 diabetes.National Institute for Health Research (NIHR

Peripheral neuropathy in HIV patients in sub-Saharan Africa failing first-line therapy and the response to second-line ART in the EARNEST trial.

Sensory peripheral neuropathy (PN) remains a common complication in HIV-positive patients despite effective combination anti-retroviral therapy (ART). Data on PN on second-line ART is scarce. We assessed PN using a standard tool in patients failing first-line ART and for 96 weeks following a switch to PI-based second-line ART in a large Randomised Clinical Trial in Sub-Saharan Africa. Factors associated with PN were investigated using logistic regression. Symptomatic PN (SPN) prevalence was 22 % at entry (N = 1,251) and was associated (p < 0.05) with older age (OR = 1.04 per year), female gender (OR = 1.64), Tuberculosis (TB; OR = 1.86), smoking (OR = 1.60), higher plasma creatinine (OR = 1.09 per 0.1 mg/dl increase), CD4 count (OR = 0.83 per doubling) and not consuming alcohol (OR = 0.55). SPN prevalence decreased to 17 % by week 96 (p = 0.0002) following similar trends in all study groups (p = 0.30). Asymptomatic PN (APN) increased over the same period from 21 to 29 % (p = 0.0002). Signs suggestive of PN (regardless of symptoms) returned to baseline levels by week 96. At weeks 48 and 96, after adjusting for time-updated associations above and baseline CD4 count and viral load, SPN was strongly associated with TB (p < 0.0001). In summary, SPN prevalence was significantly reduced with PI-based second-line therapy across all treatment groups, but we did not find any advantage to the NRTI-free regimens. The increase of APN and stability of PN-signs regardless of symptoms suggest an underlying trend of neuropathy progression that may be masked by reduction of symptoms accompanying general health improvement induced by second-line ART. SPN was strongly associated with isoniazid given for TB treatment

Internal twist drill coolant channel modelling using computational fluid dynamics

Coolant technologies have become increasingly used within twist-drill machining. Internal helical coolant channels are a common means of delivering high-pressure coolant directly to the cutting edge to increase the transfer of heat away from the cutting edge and to aid with chip evacuation. However, the complex behaviour of Coriolis and centrifugal forces generated by large angular velocities and the curvature of the coiled channel govern the highly turbulent flow of coolant. This research uses Computational Fluid Dynamics (CFD) to study the design of internal coolant channels across the internal section of the drill bit