After the Ice Age: The Impact of Post-Glacial Dispersal on the Phylogeography of a Small Mammal, Muscardinus avellanarius

We used genetic tools to assess phylogeographic structure of the common dormouse (Muscardinus avellenarius) since the end of the last glacial maximum, to identify post-glacial dispersal routes and to describe population units for conservation. Comparative analysis of mitochondrial genes (Cytochrome b, 704 bp, D-loop, 506 bp) and one nuclear gene (Beta-Fibrinogen, 550 bp) was conducted to reconstruct the recent demographic history within and between UK and continental European populations. Our analysis indicated phylogeographic variation in the UK is similar in magnitude to that found in other regions of continental Europe and suggests a recent population expansion. We present evidence which supports a single post-glacial colonization into the UK. Dispersal time calculations, calibrated with geophysical events, are coincident with the start of the Holocene period, 7.5–11 kya, a time when geological evidence suggests temperatures were stable, woodland habitat was prevalent and a land bridge was present to allow the dispersal of small mammals into the UK. We discuss our findings in the context of the extant geographical genetic structure described here and in relation to conservation management of this threatened species

Upper limb activity in myoelectric prosthesis users is biased towards the intact limb and appears unrelated to goal-directed task performance

Studies of the effectiveness of prosthetic hands involve assessing user performance on functional tasks in the lab/clinic, sometimes combined with self-report of real-world use. In this paper we compare real-world upper limb activity between a group of 20 myoelectric prosthesis users and 20 anatomically intact adults. Activity was measured from wrist-worn accelerometers over a 7-day period. The temporal patterns in upper limb activity are presented and the balance of activity between the two limbs quantified. We also evaluated the prosthesis users’ performance on a goal-directed task, characterised using measures including task success rate, completion time, gaze behaviour patterns, and kinematics (e.g. variability and patterns in hand aperture). Prosthesis users were heavily reliant on their intact limb during everyday life, in contrast to anatomically intact adults who demonstrated similar reliance on both upper limbs. There was no significant correlation between the amount of time a prosthesis was worn and reliance on the intact limb, and there was no significant correlation between either of these measures and any of the assessed kinematic and gaze-related measures of performance. We found participants who had been prescribed a prosthesis for longer to demonstrate more symmetry in their overall upper limb activity, although this was not reflected in the symmetry of unilateral limb use. With the exception of previously published case studies, this is the first report of real world upper limb activity in myoelectric prosthesis users and confirms the widely held belief that users are heavily reliant on their intact limb

WalkMore: a randomized controlled trial of pedometer-based interventions differing on intensity messages

Pedometer-based programs have elicited increased walking behaviors associated with improvements in blood pressure in sedentary/low active postmenopausal women, a population at increased risk of cardiovascular disease. Such programs typically encourage increasing the volume of physical activity with little regard for its intensity. Recent advances in commercially available pedometer technology now permit tracking of both steps/day and time in moderate (or greater) intensity physical activity on a daily basis. It is not known whether the dual message to increase steps/day while also increasing time spent at higher intensity walking will elicit additional improvements in blood pressure relative to a message to only focus on increasing steps/day. The purpose of this paper is to present the rationale, study design, and protocols employed in WalkMore, a 3-arm 3-month blinded and randomized controlled trial (RCT) designed to compare the effects of two community pedometer-based walking interventions (reflecting these separate and combined messages) relative to a control group on blood pressure in sedentary/low active post-menopausal women, a population at increased risk of cardiovascular disease. 120 sedentary/low active post-menopausal women (45-74 years of age) will be randomly assigned (computer-generated) to 1 of 3 groups: A) 10,000 steps/day (with no guidance on walking intensity/speed/cadence; BASIC intervention, n = 50); B) 10,000 steps/day and at least 30 minutes in moderate intensity (i.e., a cadence of at least 100 steps/min; ENHANCED intervention, n = 50); or a Control group (n = 20). An important strength of the study is the strict control and quantification of the pedometer-based physical activity interventions. The primary outcome is systolic blood pressure. Secondary outcomes include diastolic blood pressure, anthropometric measurements, fasting blood glucose and insulin, flow mediated dilation, gait speed, and accelerometer-determined physical activity and sedentary behavior. This study can make important contributions to our understanding of the relative benefits that walking volume and/or intensity may have on blood pressure in a population at risk of cardiovascular disease. ClinicalTrials.gov Record NCT01519583, January 18, 2012

Online versus in-person comparison of Microscale Audit of Pedestrian Streetscapes (MAPS) assessments: reliability of alternate methods

Abstract Background An online version of the Microscale Audit of Pedestrian Streetscapes (Abbreviated) tool was adapted to virtually audit built environment features supportive of physical activity. The current study assessed inter-rater reliability of MAPS Online between in-person raters and online raters unfamiliar with the regions. Methods In-person and online audits were conducted for a total of 120 quarter-mile routes (60 per site) in Phoenix, AZ and San Diego, CA. Routes in each city included 40 residential origins stratified by walkability and SES, and 20 commercial centers. In-person audits were conducted by raters residing in their region. Online audits were conducted by raters in the alternate location using Google Maps (Aerial and Street View) images. The MAPS Abbreviated Online tool consisted of four sections: overall route, street segments, crossings and cul-de-sacs. Items within each section were grouped into subscales, and inter-rater reliability (ICCs) was assessed for subscales at multiple levels of aggregation. Results Online and in-person audits showed excellent agreement for overall positive microscale (ICC = 0.86, 95% CI [0.80, 0.90]) and grand scores (ICC = 0.93, 95% CI [0.89, 0.95]). Substantial to near-perfect agreement was found for 21 of 30 (70%) subscales, valence, and subsection scores, with ICCs ranging from 0.62, 95% CI [0.50, 0.72] to 0.95, 95% CI [0.93, 0.97]. Lowest agreement was found for the aesthetics and social characteristics scores, with ICCs ranging from 0.07, 95% CI [−0.12, 0.24] to 0.27, 95% CI [0.10, 0.43]. Conclusions Results support use of the MAPS Abbreviated Online tool to reliably assess microscale neighborhood features that support physical activity and may be used by raters residing in different geographic regions and unfamiliar with the audit areas

Light-intensity physical activity and cardiometabolic biomarkers in US adolescents

BackgroundThe minimal physical activity intensity that would confer health benefits among adolescents is unknown. The purpose of this study was to examine the associations of accelerometer-derived light-intensity (split into low and high) physical activity, and moderate- to vigorous-intensity physical activity with cardiometabolic biomarkers in a large population-based sample.MethodsThe study is based on 1,731 adolescents, aged 12&ndash;19 years from the 2003/04 and 2005/06 National Health and Nutrition Examination Survey. Low light-intensity activity (100&ndash;799 counts/min), high light-intensity activity (800 counts/min to &lt;4 METs) and moderate- to vigorous-intensity activity (&ge;4 METs, Freedson age-specific equation) were accelerometer-derived. Cardiometabolic biomarkers, including waist circumference, systolic blood pressure, diastolic blood pressure, HDL-cholesterol, and C-reactive protein were measured. Triglycerides, LDL- cholesterol, insulin, glucose, and homeostatic model assessments of &beta;-cell function (HOMA-%B) and insulin sensitivity (HOMA-%S) were also measured in a fasting sub-sample (n=807).ResultsAdjusted for confounders, each additional hour/day of low light-intensity activity was associated with 0.59 (95% CI: 1.18&ndash;0.01) mmHG lower diastolic blood pressure. Each additional hour/day of high light-intensity activity was associated with 1.67 (2.94&ndash;0.39) mmHG lower diastolic blood pressure and 0.04 (0.001&ndash;0.07) mmol/L higher HDL-cholesterol. Each additional hour/day of moderate- to vigorous-intensity activity was associated with 3.54 (5.73&ndash;1.35) mmHG lower systolic blood pressure, 5.49 (1.11&ndash;9.77)% lower waist circumference, 25.87 (6.08&ndash;49.34)% lower insulin, and 16.18 (4.92&ndash;28.53)% higher HOMA-%S.ConclusionsTime spent in low light-intensity physical activity and high light-intensity physical activity had some favorable associations with biomarkers. Consistent with current physical activity recommendations for adolescents, moderate- to vigorous-intensity activity had favorable associations with many cardiometabolic biomarkers. While increasing MVPA should still be a public health priority, further studies are needed to identify dose-response relationships for light-intensity activity thresholds to inform future recommendations and interventions for adolescents.</div

Discrepancies between the medical record and the reports of patients with acute coronary syndrome regarding important aspects of the medical history

<p>Abstract</p> <p>Background</p> <p>Many critical treatment decisions are based on the medical history of patients with an acute coronary syndrome (ACS). Discrepancies between the medical history documented by a health professional and the patient's own report may therefore have important health consequences.</p> <p>Methods</p> <p>Medical histories of 117 patients with an ACS were documented. A questionnaire assessing the patient's health history was then completed by 62 eligible patients. Information about 13 health conditions with relevance to ACS management was obtained from the questionnaire and the medical record. Concordance between these two sources and reasons for discordance were identified.</p> <p>Results</p> <p>There was significant variation in agreement, from very poor in angina (kappa < 0) to almost perfect in diabetes (kappa = 0.94). Agreement was substantial in cerebrovascular accident (kappa = 0.76) and hypertension (kappa = 0.73); moderate in cocaine use (kappa = 0.54), smoking (kappa = 0.46), kidney disease (kappa = 0.52) and congestive heart failure (kappa = 0.54); and fair in arrhythmia (kappa = 0.37), myocardial infarction (kappa = 0.31), other cardiovascular diseases (kappa = 0.37) and bronchitis/pneumonia (kappa = 0.31). The odds of agreement was 42% higher among individuals with at least some college education (OR = 1.42; 95% CI, 1.00 - 2.01, p = 0.053). Listing of a condition in medical record but not in the questionnaire was a common cause of discordance.</p> <p>Conclusion</p> <p>Discrepancies in aspects of the medical history may have important effects on the care of ACS patients. Future research focused on identifying the most effective and efficient means to obtain accurate health information may improve ACS patient care quality and safety.</p

Physical activity guidelines and cardiovascular risk in children: a cross-sectional analysis to determine whether 60 minutes is enough

Background Physical activity reduces cardiovascular mortality and morbidity. The World Health Organisation (WHO) recommends children engage in 60 min daily moderate-to-vigorous physical activity (MVPA). The effect of compliance with this recommendation on childhood cardiovascular risk has not been empirically tested. To evaluate whether achieving recommendations results in reduced composite-cardiovascular risk score (CCVR) in children, and to examine if vigorous PA (VPA) has independent risk-reduction effects. Methods PA was measured using accelerometry in 182 children (9–11 years). Subjects were grouped according to achievement of 60 min daily MVPA (active) or not (inactive). CCVR was calculated (sum of z-scores: DXA body fat %, blood pressure, VO2peak, flow mediated dilation, left ventricular diastolic function; CVR score ≥1SD indicated ‘higher risk’). The cohort was further split into quintiles for VPA and odds ratios (OR) calculated for each quintile. Results Active children (92 (53 boys)) undertook more MVPA (38 ± 11 min, P  0.05). CCVR in the lowest VPA quintile was significantly greater than the highest quintile (3.9 ± 0.6, P < 0.05), and the OR was 4.7 times higher. Conclusion Achievement of current guidelines has positive effects on body composition and cardiorespiratory fitness, but not CCVR. Vigorous physical activity appears to have beneficial effects on CVD risk, independent of moderate PA, implying a more prescriptive approach may be needed for future VPA guidelines

Key signalling nodes in mammary gland development and cancer. Signalling downstream of PI3 kinase in mammary epithelium: a play in 3 Akts

The protein serine/threonine kinase Akt, also known as protein kinase B (PKB), is arguably the most important signalling nexus in the cell. Akt integrates a plethora of extracellular signals to generate diverse outcomes, including proliferation, motility, growth, glucose homeostasis, survival, and cell death. The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is the second most frequently mutated pathway in cancer, after p53, and mutations in components of this pathway are found in around 70% of breast cancers. Thus, understanding how Akt relays input signals to downstream effectors is critically important for the design of therapeutic strategies to combat breast cancer. In this review, we will discuss the various signals upstream of Akt that impact on its activity, how Akt integrates these signals and modulates the activity of downstream targets to control mammary gland development, and how mutations in components of the pathway result in breast cancer

Association of warfarin dose with genes involved in its action and metabolism

We report an extensive study of variability in genes encoding proteins that are believed to be involved in the action and biotransformation of warfarin. Warfarin is a commonly prescribed anticoagulant that is difficult to use because of the wide interindividual variation in dose requirements, the narrow therapeutic range and the risk of serious bleeding. We genotyped 201 patients for polymorphisms in 29 genes in the warfarin interactive pathways and tested them for association with dose requirement. In our study, polymorphisms in or flanking the genes VKORC1, CYP2C9, CYP2C18, CYP2C19, PROC, APOE, EPHX1, CALU, GGCX and ORM1-ORM2 and haplotypes of VKORC1, CYP2C9, CYP2C8, CYP2C19, PROC, F7, GGCX, PROZ, F9, NR1I2 and ORM1-ORM2 were associated with dose (P < 0.05). VKORC1, CYP2C9, CYP2C18 and CYP2C19 were significant after experiment-wise correction for multiple testing (P < 0.000175), however, the association of CYP2C18 and CYP2C19 was fully explained by linkage disequilibrium with CYP2C9*2 and/or *3. PROC and APOE were both significantly associated with dose after correction within each gene. A multiple regression model with VKORC1, CYP2C9, PROC and the non-genetic predictors age, bodyweight, drug interactions and indication for treatment jointly accounted for 62% of variance in warfarin dose. Weaker associations observed for other genes could explain up to ∼10% additional dose variance, but require testing and validation in an independent and larger data set. Translation of this knowledge into clinical guidelines for warfarin prescription will be likely to have a major impact on the safety and efficacy of warfarin. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00439-006-0260-8 and is accessible for authorized users