Impaired glucose tolerance in adults with Duchenne and Becker muscular dystrophy

The aim of this study was to determine the response to an oral glucose tolerance test (OGTT) in adult males with Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD), and to investigate whether body composition contributes to any variance in the glucose response. Twenty-eight adult males with dystrophinopathy (BMD, n = 13; DMD, n = 15) and 12 non-dystrophic controls, ingested 75 g oral anhydrous glucose solution. Fingertip capillary samples were assessed for glucose at 30-min intervals over 2-h post glucose ingestion. Fat free mass relative to body mass (FFM/BM) and body fat (BF%) was assessed using bioelectrical impedance. Vastus lateralis muscle anatomical cross sectional area (VL ACSA) was measured using B-mode ultrasonography. Blood glucose was higher in MD groups than control at 60, 90 and 120 min post ingestion of glucose. Compared to controls, FFM/BM and VL ACSA were lower in MD groups compared to controls (p < 0.001). Glucose tolerance values at 120 min were correlated with FFM/BM and BF% in the BMD group only. Our results suggest that glucose tolerance is impaired following OGTT in adult males with BMD and DMD. It is recommended that adults with BMD and DMD undertake routine glucose tolerance assessments to allow early detection of impaired glucose tolerance

Spatial and Seasonal Distribution of American Whaling and Whales in the Age of Sail

American whalemen sailed out of ports on the east coast of the United States and in California from the 18th to early 20th centuries, searching for whales throughout the world’s oceans. From an initial focus on sperm whales (Physeter macrocephalus) and right whales (Eubalaena spp.), the array of targeted whales expanded to include bowhead whales (Balaena mysticetus), humpback whales (Megaptera novaeangliae), and gray whales (Eschrichtius robustus). Extensive records of American whaling in the form of daily entries in whaling voyage logbooks contain a great deal of information about where and when the whalemen found whales. We plotted daily locations where the several species of whales were observed, both those caught and those sighted but not caught, on world maps to illustrate the spatial and temporal distribution of both American whaling activity and the whales. The patterns shown on the maps provide the basis for various inferences concerning the historical distribution of the target whales prior to and during this episode of global whaling

Whole home exercise intervention for depression in older care home residents (the OPERA study) : a process evaluation

Background: The ‘Older People’s Exercise intervention in Residential and nursing Accommodation’ (OPERA) cluster randomised trial evaluated the impact of training for care home staff together with twice-weekly, physiotherapist-led exercise classes on depressive symptoms in care home residents, but found no effect. We report a process evaluation exploring potential explanations for the lack of effect. Methods: The OPERA trial included over 1,000 residents in 78 care homes in the UK. We used a mixed methods approach including quantitative data collected from all homes. In eight case study homes, we carried out repeated periods of observation and interviews with residents, care staff and managers. At the end of the intervention, we held focus groups with OPERA research staff. We reported our first findings before the trial outcome was known. Results: Homes showed large variations in activity at baseline and throughout the trial. Overall attendance rate at the group exercise sessions was low (50%). We considered two issues that might explain the negative outcome: whether the intervention changed the culture of the homes, and whether the residents engaged with the intervention. We found low levels of staff training, few home champions for the intervention and a culture that prioritised protecting residents from harm over encouraging activity. The trial team delivered 3,191 exercise groups but only 36% of participants attended at least 1 group per week and depressed residents attended significantly fewer groups than those who were not depressed. Residents were very frail and therefore most groups only included seated exercises. Conclusions: The intervention did not change the culture of the homes and, in the case study homes, activity levels did not change outside the exercise groups. Residents did not engage in the exercise groups at a sufficient level, and this was particularly true for those with depressive symptoms at baseline. The physical and mental frailty of care home residents may make it impossible to deliver a sufficiently intense exercise intervention to impact on depressive symptoms

Effectiveness of moving on: an Australian designed generic self-management program for people with a chronic illness

Background: This paper presents the evaluation of “Moving On”, a generic self-management program for people with a chronic illness developed by Arthritis NSW. The program aims to help participants identify their need for behavior change and acquire the knowledge and skills to implement changes that promote their health and quality of life. Method: A prospective pragmatic randomised controlled trial involving two group programs in community settings: the intervention program (Moving On) and a control program (light physical activity). Participants were recruited by primary health care providers across the north-west region of metropolitan Sydney, Australia between June 2009 and October 2010. Patient outcomes were self-reported via pre- and post-program surveys completed at the time of enrolment and sixteen weeks after program commencement. Primary outcomes were change in self-efficacy (Self-efficacy for Managing Chronic Disease 6-Item Scale), self-management knowledge and behaviour and perceived health status (Self-Rated Health Scale and the Health Distress Scale). Results: A total of 388 patient referrals were received, of whom 250 (64.4%) enrolled in the study. Three patients withdrew prior to allocation. 25 block randomisations were performed by a statistician external to the research team: 123 patients were allocated to the intervention program and 124 were allocated to the control program. 97 (78.9%) of the intervention participants commenced their program. The overall attrition rate of 40.5% included withdrawals from the study and both programs. 24.4% of participants withdrew from the intervention program but not the study and 22.6% withdrew from the control program but not the study. A total of 62 patients completed the intervention program and follow-up evaluation survey and 77 patients completed the control program and follow- up evaluation survey. At 16 weeks follow-up there was no significant difference between intervention and control groups in self-efficacy; however, there was an increase in self-efficacy from baseline to follow-up for the intervention participants (t=−1.948, p=0.028). There were no significant differences in self-rated health or health distress scores between groups at follow-up, with both groups reporting a significant decrease in health distress scores. There was no significant difference between or within groups in self-management knowledge and stage of change of behaviours at follow-up. Intervention group attenders had significantly higher physical activity (t=−4.053, p=0.000) and nutrition scores (t=2.315, p= 0.01) at follow-up; however, these did not remain significant after adjustment for covariates. At follow-up, significantly more participants in the control group (20.8%) indicated that they did not have a self-management plan compared to those in the intervention group (8.8%) (X2=4.671, p=0.031). There were no significant changes in other self-management knowledge areas and behaviours after adjusting for covariates at follow-up. Conclusions: The study produced mixed findings. Differences between groups as allocated were diluted by the high proportion of patients not completing the program. Further monitoring and evaluation are needed of the impact and cost effectiveness of the program. Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN1260900029821

Subclonal TP53 copy number is associated with prognosis in multiple myeloma

Multiple myeloma (MM) is a genetically heterogeneous cancer of bone marrow plasma cells with variable outcome. To assess the prognostic relevance of clonal heterogeneity of TP53 copy number, we profiled tumors from 1777 newly diagnosed Myeloma XI trial patients with multiplex ligation-dependent probe amplification (MLPA). Subclonal TP53 deletions were independently associated with shorter overall survival, with a hazard ratio of 1.8 (95% confidence interval, 1.2-2.8; P = .01). Clonal, but not subclonal, TP53 deletions were associated with clinical markers of advanced disease, specifically lower platelet counts (P < .001) and increased lactate dehydrogenase (P < .001), as well as a higher frequency of features indicative of genomic instability, del(13q) (P = .002) or del(1p) (P = .006). Biallelic TP53 loss-of-function by mutation and deletion was rare (2.4%) and associated with advanced disease. We present a framework for identifying subclonal TP53 deletions by MLPA, to improve patient stratification in MM and tailor therapy, enabling management strategies

Long-term passive acoustic recordings track the changing distribution of North Atlantic right whales (Eubalaena glacialis) from 2004 to 2014

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 7 (2017): 13460, doi:10.1038/s41598-017-13359-3.Given new distribution patterns of the endangered North Atlantic right whale (NARW; Eubalaena glacialis) population in recent years, an improved understanding of spatio-temporal movements are imperative for the conservation of this species. While so far visual data have provided most information on NARW movements, passive acoustic monitoring (PAM) was used in this study in order to better capture year-round NARW presence. This project used PAM data from 2004 to 2014 collected by 19 organizations throughout the western North Atlantic Ocean. Overall, data from 324 recorders (35,600 days) were processed and analyzed using a classification and detection system. Results highlight almost year-round habitat use of the western North Atlantic Ocean, with a decrease in detections in waters off Cape Hatteras, North Carolina in summer and fall. Data collected post 2010 showed an increased NARW presence in the mid-Atlantic region and a simultaneous decrease in the northern Gulf of Maine. In addition, NARWs were widely distributed across most regions throughout winter months. This study demonstrates that a large-scale analysis of PAM data provides significant value to understanding and tracking shifts in large whale movements over long time scales.This research was funded and supported by many organizations, specified by projects as follows: Data recordings from region 1 were provided by K. Stafford and this research effort was funded by the National Science Foundation #NSF-ARC 0532611. Region 2 data were provided by D. K. Mellinger and S. Nieukirk, funded by National Oceanic and Atmospheric Agency (NOAA) and the Office of Naval Research (ONR) #N00014–03–1–0099, NOAA #NA06OAR4600100, US Navy #N00244-08-1-0029, N00244-09-1-0079, and N00244-10-1-0047

Impedance Responses Reveal β2-Adrenergic Receptor Signaling Pluridimensionality and Allow Classification of Ligands with Distinct Signaling Profiles

The discovery that drugs targeting a single G protein-coupled receptor (GPCR) can differentially modulate distinct subsets of the receptor signaling repertoire has created a challenge for drug discovery at these important therapeutic targets. Here, we demonstrate that a single label-free assay based on cellular impedance provides a real-time integration of multiple signaling events engaged upon GPCR activation. Stimulation of the β2-adrenergic receptor (β2AR) in living cells with the prototypical agonist isoproterenol generated a complex, multi-featured impedance response over time. Selective pharmacological inhibition of specific arms of the β2AR signaling network revealed the differential contribution of Gs-, Gi- and Gβγ-dependent signaling events, including activation of the canonical cAMP and ERK1/2 pathways, to specific components of the impedance response. Further dissection revealed the essential role of intracellular Ca2+ in the impedance response and led to the discovery of a novel β2AR-promoted Ca2+ mobilization event. Recognizing that impedance responses provide an integrative assessment of ligand activity, we screened a collection of β-adrenergic ligands to determine if differences in the signaling repertoire engaged by compounds would lead to distinct impedance signatures. An unsupervised clustering analysis of the impedance responses revealed the existence of 5 distinct compound classes, revealing a richer signaling texture than previously recognized for this receptor. Taken together, these data indicate that the pluridimensionality of GPCR signaling can be captured using integrative approaches to provide a comprehensive readout of drug activity

Development and validation of the Arizona Cognitive Test Battery for Down syndrome

Neurocognitive assessment in individuals with intellectual disabilities requires a well-validated test battery. To meet this need, the Arizona Cognitive Test Battery (ACTB) has been developed specifically to assess the cognitive phenotype in Down syndrome (DS). The ACTB includes neuropsychological assessments chosen to 1) assess a range of skills, 2) be non-verbal so as to not confound the neuropsychological assessment with language demands, 3) have distributional properties appropriate for research studies to identify genetic modifiers of variation, 4) show sensitivity to within and between sample differences, 5) have specific correlates with brain function, and 6) be applicable to a wide age range and across contexts. The ACTB includes tests of general cognitive ability and prefrontal, hippocampal and cerebellar function. These tasks were drawn from the Cambridge Neuropsychological Testing Automated Battery (CANTAB) and other established paradigms. Alongside the cognitive testing battery we administered benchmark and parent-report assessments of cognition and behavior. Individuals with DS (n = 74, ages 7–38 years) and mental age (MA) matched controls (n = 50, ages 3–8 years) were tested across 3 sites. A subsample of these groups were used for between-group comparisons, including 55 individuals with DS and 36 mental age matched controls. The ACTB allows for low floor performance levels and participant loss. Floor effects were greater in younger children. Individuals with DS were impaired on a number ACTB tests in comparison to a MA-matched sample, with some areas of spared ability, particularly on tests requiring extensive motor coordination. Battery measures correlated with parent report of behavior and development. The ACTB provided consistent results across contexts, including home vs. lab visits, cross-site, and among individuals with a wide range of socio-economic backgrounds and differences in ethnicity. The ACTB will be useful in a range of outcome studies, including clinical trials and the identification of important genetic components of cognitive disability

Response to symptoms of stroke in the UK: a systematic review

<p>Abstract</p> <p>Background</p> <p>The English National Stroke Strategy suggests that there is a need to improve the response of patients and witnesses to the symptoms of acute stroke to increase rapid access to specialist care. We wished to review the evidence base regarding the knowledge, attitudes and behaviours of stroke patients, witnesses and the public to the symptoms of stroke and the need for an urgent response at the onset of symptoms.</p> <p>Methods</p> <p>We conducted a systematic review of UK articles reporting empirical research on a) awareness of and response to the symptoms of acute stroke or TIA, and b) beliefs and attitudes about diagnosis, early treatment and consequences of acute stroke or TIA. Nine electronic databases were searched using a robust search strategy. Citations and abstracts were screened independently by two reviewers. Data were extracted by two researchers independently using agreed criteria.</p> <p>Results</p> <p>11 studies out of 7144 citations met the inclusion criteria. Methods of data collection included: postal survey (n = 2); interview survey (n = 6); review of hospital documentation (n = 2) and qualitative interviews (n = 1). Limited data reveal a good level of knowledge of the two commonest stroke symptoms (unilateral weakness and speech disturbance), and of the need for an emergency response among the general public and at risk patients. Despite this, less than half of patients recognised they had suffered a stroke. Symptom recognition did not reduce time to presentation. For the majority, the first point of contact for medical assistance was a general practitioner.</p> <p>Conclusions</p> <p>There is an assumption that, in the UK, public knowledge of the symptoms of stroke and of the need for an emergency response is lacking, but there is little published research to support this. Public awareness raising campaigns to improve response to the symptoms of stroke therefore may not produce an increase in desired behaviours. Further research is needed to understand why people who experience or witness stroke symptoms frequently do not call emergency services.</p

Ethnic Label Use in Adolescents from Traditional and Non-Traditional Immigrant Communities

Understanding adolescents’ use of ethnic labels is a key developmental issue, particularly given the practical significance of identity and self-definition in adolescents’ lives. Ethnic labeling was examined among adolescents in the traditional immigrant receiving area of Los Angeles (Asian n = 258, Latino n = 279) and the non-traditional immigrant receiving area of North Carolina (Asian n = 165, Latino n = 239). Logistic regressions showed that adolescents from different geographic settings use different ethnic labels, with youth from NC preferring heritage and panethnic labels and youth from LA preferring hyphenated American labels. Second generation youth were more likely than first generation youth to use hyphenated American labels, and less likely to use heritage or panethnic labels. Greater ethnic centrality increased the odds of heritage label use, and greater English proficiency increased the odds of heritage-American label use. These associations significantly mediated the initial effects of setting. Further results examine ethnic differences as well as links between labels and self-esteem. The discussion highlights implications of ethnic labeling and context