A composite immune signature parallels disease progression across T1D subjects

At diagnosis, most people with type 1 diabetes (T1D) produce measurable levels of endogenous insulin, but the rate at which insulin secretion declines is heterogeneous. To explain this heterogeneity, we sought to identify a composite signature predictive of insulin secretion, using a collaborative assay evaluation and analysis pipeline that incorporated multiple cellular and serum measures reflecting beta cell health and immune system activity. The ability to predict decline in insulin secretion would be useful for patient stratification for clinical trial enrollment or therapeutic selection. Analytes from 12 qualified assays were measured in shared samples from subjects newly diagnosed with T1D. We developed a computational tool to identify a composite panel associated with decline in insulin secretion over 2 years after diagnosis. The tool employs multiple filtering steps to reduce data dimensionality, incorporates error-estimation techniques including cross-validation and sensitivity analysis, and is flexible to assay type, clinical outcome and disease setting. Using this novel analytical tool, we identified a panel of immune markers that, in combination, are highly associated with loss of insulin secretion. The methods used here represent a novel process for identifying combined immune signatures that predict outcomes relevant for complex and heterogeneous diseases like T1D

We are all one together : peer educators\u27 views about falls prevention education for community-dwelling older adults - a qualitative study

Background: Falls are common in older people. Despite strong evidence for effective falls prevention strategies, there appears to be limited translation of these strategies from research to clinical practice. Use of peers in delivering falls prevention education messages has been proposed to improve uptake of falls prevention strategies and facilitate translation to practice. Volunteer peer educators often deliver educational presentations on falls prevention to community-dwelling older adults. However, research evaluating the effectiveness of peer-led education approaches in falls prevention has been limited and no known study has evaluated such a program from the perspective of peer educators involved in delivering the message. The purpose of this study was to explore peer educators’ perspective about their role in delivering peer-led falls prevention education for community-dwelling older adults. Methods: A two-stage qualitative inductive constant comparative design was used.In stage one (core component) focus group interviews involving a total of eleven participants were conducted. During stage two (supplementary component) semi-structured interviews with two participants were conducted. Data were analysed thematically by two researchers independently. Key themes were identified and findings were displayed in a conceptual framework. Results: Peer educators were motivated to deliver educational presentations and importantly, to reach an optimal peer connection with their audience. Key themes identified included both personal and organisational factors that impact on educators’ capacity to facilitate their peers’ engagement with the message. Personal factors that facilitated message delivery and engagement included peer-to-peer connection and perceived credibility, while barriers included a reluctance to accept the message that they were at risk of falling by some members in the audience. Organisational factors, including ongoing training for peer educators and formative feedback following presentations, were perceived as essential because they affect successful message delivery. Conclusions: Peer educators have the potential to effectively deliver falls prevention education to older adults and influence acceptance of the message as they possess the peer-to-peer connection that facilitates optimal engagement. There is a need to consider incorporating learnings from this research into a formal large scale evaluation of the effectiveness of the peer education approach in reducing falls in older adults

Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120

BACKGROUND: Cellulose acetate phthalate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was shown to inhibit infection by the human immunodeficiency virus type 1 (HIV-1) and several herpesviruses. CAP formulations inactivated HIV-1, herpesvirus types 1 (HSV-1) and 2 (HSV-2) and the major nonviral sexually transmitted disease (STD) pathogens and were effective in animal models for vaginal infection by HSV-2 and simian immunodeficiency virus. METHODS: Enzyme-linked immunoassays and flow cytometry were used to demonstrate CAP binding to HIV-1 and to define the binding site on the virus envelope. RESULTS: 1) CAP binds to HIV-1 virus particles and to the envelope glycoprotein gp120; 2) this leads to blockade of the gp120 V3 loop and other gp120 sites resulting in diminished reactivity with HIV-1 coreceptors CXCR4 and CCR5; 3) CAP binding to HIV-1 virions impairs their infectivity; 4) these findings apply to both HIV-1 IIIB, an X4 virus, and HIV-1 BaL, an R5 virus. CONCLUSIONS: These results provide support for consideration of CAP as a topical microbicide of choice for prevention of STDs, including HIV-1 infection

Cross-sectional and longitudinal associations between the 24-hour movement behaviours, including muscle and bone strengthening activity, with bone and lean mass from childhood to adolescence.

This is the final version. Available from BMC via the DOI in this record. Availability of data and materials: The data that support the findings of this study are available from University of Eastern Finland but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of University of Eastern Finland and PANIC study Principal Investigator ([email protected]).BACKGROUND: This study aimed to assess whether moderate-to-vigorous physical activity (MVPA), sport and exercise as a proxy measure of muscle and bone strengthening activity, sedentary behaviour, and sleep were associated with total-body-less-head (TBLH) bone mineral content (BMC) and TBLH lean mass cross-sectionally and longitudinally from age 6 to 9 years and age 9 to 11 years to age 15 to 17 years. METHODS: We used longitudinal data from a population sample of Finnish children from the Physical Activity and Nutrition in Children study (age 6 to 9 years: n = 478, 229 females; age 9 to 11 years: n = 384, 197 females; age 15 to 17 years: n = 222, 103 females). Linear regression analysed the cross-sectional and longitudinal associations between accelerometer-assessed MVPA, sedentary time and sleep, and questionnaire-assessed sport and exercise participation and screen time with dual-energy X-ray absorptiometry-assessed TBLH BMC and lean mass. RESULTS: In females, MVPA at age 6 to 9 years was positively associated with TBLH BMC at age 15 to 17 years (β = 0.008, p = 0.010). Sport and exercise at age 9 to 11 years was positively associated with TBLH BMC (β = 0.020, p = 0.002) and lean mass (β = 0.343, p = 0.040) at age 15 to 17 years. MVPA at age 9 to 11 years was positively associated with TBLH lean mass (β = 0.272, p = 0.004) at age 15 to 17 years. In males, sleep at age 6 to 9 years was positively associated with TBLH lean mass (β = 0.382, p = 0.003) at age 15 to 17 years. Sport and exercise at age 9 to 11 years was positively associated with TBLH BMC (β = 0.027, p = 0.012) and lean mass (β = 0.721, p < 0.001) at age 15 to 17 years. CONCLUSIONS: Promoting engagement in the 24-hour movement behaviours in childhood, particularly sport and exercise to strengthen muscle and bone, is important in supporting bone and lean mass development in adolescence. TRIAL REGISTRATION: NCT01803776; first trial registration date: 04/03/2013.Kuopio University HospitalMedical Research CouncilMedical Research CouncilNational Institute for Health ResearchMinistry of Education and Culture of FinlandAcademy of FinlandMinistry of Social Affairs and Health of FinlandFinnish Innovation Fund SitraSocial Insurance Institution of FinlandFinnish Cultural FoundationJuho Vainio FoundationFoundation for Paediatric ResearchDoctoral Programs in Public Health, Paavo Nurmi FoundationPaulo FoundationDiabetes Research FoundationThe Finnish Medical Society DuodecimOrion Research Foundatio

Does General Parenting Context Modify Adolescents' Appraisals and Coping with a Situation of Parental Regulation? The Case of Autonomy-Supportive Parenting

Theory and research suggest that adolescents differ in their appraisals and coping reactions in response to parental regulation. Less is known, however, about factors that determine these differences in adolescents’ responses. In this study, we examined whether adolescents' appraisals and coping reactions depend upon parents’ situation-specific autonomy-supportive or controlling communication style (i.e., the situation) in interaction with adolescents’ past experiences with general autonomy-supportive parenting (i.e., the parenting context). Whereas in Study 1 (N = 176) adolescents’ perceived general autonomy-supportive parenting context was assessed at one point in time, in Study 2 (N = 126) it was assessed multiple times across a 6-year period, allowing for an estimation of trajectories of perceived autonomy-supportive parenting context. In each study, adolescents read a vignette-based scenario depicting a situation of maternal regulation (i.e., a request to study more), which was communicated in either an autonomy-supportive or a controlling way. Following this scenario, they reported upon their appraisals and their anticipated coping reactions. Results of each study indicated that both the autonomy-supportive (relative to the controlling) situation and the perceived autonomy-supportive parenting context generally related to more positive appraisals (i.e., more autonomy need satisfaction, less autonomy need frustration), as well as to more constructive coping responses (i.e., less oppositional defiance and submission, more negotiation and accommodation). In addition, situation × context interactions were found, whereby adolescents growing up in a more autonomy-supportive context seemed to derive greater benefits from the exposure to an autonomy-supportive situation and reacted more constructively to a controlling situation

Punica granatum (Pomegranate) juice provides an HIV-1 entry inhibitor and candidate topical microbicide

BACKGROUND: For ≈ 24 years the AIDS pandemic has claimed ≈ 30 million lives, causing ≈ 14,000 new HIV-1 infections daily worldwide in 2003. About 80% of infections occur by heterosexual transmission. In the absence of vaccines, topical microbicides, expected to block virus transmission, offer hope for controlling the pandemic. Antiretroviral chemotherapeutics have decreased AIDS mortality in industrialized countries, but only minimally in developing countries. To prevent an analogous dichotomy, microbicides should be: acceptable; accessible; affordable; and accelerative in transition from development to marketing. Already marketed pharmaceutical excipients or foods, with established safety records and adequate anti-HIV-1 activity, may provide this option. METHODS: Fruit juices were screened for inhibitory activity against HIV-1 IIIB using CD4 and CXCR4 as cell receptors. The best juice was tested for inhibition of: (1) infection by HIV-1 BaL, utilizing CCR5 as the cellular coreceptor; and (2) binding of gp120 IIIB and gp120 BaL, respectively, to CXCR4 and CCR5. To remove most colored juice components, the adsorption of the effective ingredient(s) to dispersible excipients and other foods was investigated. A selected complex was assayed for inhibition of infection by primary HIV-1 isolates. RESULTS: HIV-1 entry inhibitors from pomegranate juice adsorb onto corn starch. The resulting complex blocks virus binding to CD4 and CXCR4/CCR5 and inhibits infection by primary virus clades A to G and group O. CONCLUSION: These results suggest the possibility of producing an anti-HIV-1 microbicide from inexpensive, widely available sources, whose safety has been established throughout centuries, provided that its quality is adequately standardized and monitored

Kernel-based methods for combining information of several frame surveys

A sample selected from a single sampling frame may not represent adequatly the entire population. Multiple frame surveys are becoming increasingly used and popular among statistical agencies and private organizations, in particular in situations where several sampling frames may provide better coverage or can reduce sampling costs for estimating population quantities of interest. Auxiliary information available at the population level is often categorical in nature, so that incorporating categorical and continuous information can improve the efficiency of the method of estimation. Nonparametric regression methods represent a widely used and flexible estimation approach in the survey context. We propose a kernel regression estimator for dual frame surveys that can handle both continuous and categorical data. This methodology is extended to multiple frame surveys. We derive theoretical properties of the proposed methods and numerical experiments indicate that the proposed estimator perform well in practical settings under different scenarios.Ministerio de Economía y CompetitividadConsejería de Economía, Innovación, Ciencia y Emple

Physical activity volume and intensity distribution in relation to bone, lean and fat mass in children

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: The datasets analyzed during the current study are not publicly available due to research ethical reasons and because the owner of the data is the University of Eastern Finland and not the research group. Requests to access the datasets should be directed to www.panicstudy.fi/en/etusivu.Considering physical activity (PA) volume and intensity may provide novel insights into the relationships of PA with bone, lean, and fat mass. This study aimed to assess the associations of PA volume, PA intensity distribution, including moderate-to-vigorous PA (MVPA) with total-body-less-head bone mineral content (BMC), lean, and fat mass in children. A population sample of 290 Finnish children (158 females) aged 9 to 11 years from the Physical Activity and Nutrition in Children (PANIC) Study was studied. PA, including MVPA, was assessed with a combined heart rate and movement sensor, and the uniaxial acceleration was used to calculate average-acceleration (a proxy metric for PA volume) and intensity-gradient (reflective of PA intensity distribution). Linear regression analysed the associations of PA volume, PA intensity and MVPA with BMC, lean mass, and fat mass assessed by dual-energy X-ray absorptiometry. PA volume was positively associated with BMC in females (unstandardised regression coefficient (ß) = 0.26) and males (ß = 0.47), and positively associated with lean (ß = 7.33) and negatively associated with fat mass in males (ß = -20.62). PA intensity was negatively associated with BMC in males (ß = -0.13). MVPA was positively associated with lean mass in females and males (ß = 0.007 to 0.012), negatively associated with fat mass in females and males (ß = -0.030 to -0.029). PA volume may be important for improving BMC in females and males, and increasing lean and reducing fat mass in males, whereas MVPA may be important for favourable lean and fat outcomes in both sexes.Ministry of Education and Culture of FinlandMinistry of Social Affairs and Health of FinlandFinnish Innovation Fund SitraSocial Insurance Institution of FinlandFinnish Cultural FoundationJuho Vainio FoundationFoundation for Pediatric ResearchPaavo Nurmi FoundationPaulo FoundationDiabetes Research FoundationFinnish Medical Society DuodecimOrion Research FoundationKuopio University HospitalCity of KuopioMedical Research Council (MRC)National Institute for Health Research (NIHR

Stand Out in Class: restructuring theclassroom environment to reducesedentary behaviour in 9–10-year-olds—study protocol for a pilot clusterrandomised controlled trial

Background: Sedentary behaviour (sitting) is a highly prevalent negative health behaviour, with individuals of allages exposed to environments that promote prolonged sitting. Excessive sedentary behaviour adversely affects health inchildren and adults. As sedentary behaviour tracks from childhood into adulthood, the reduction of sedentary time inyoung people is key for the prevention of chronic diseases that result from excessive sitting in later life. The sedentaryschool classroom represents an ideal setting for environmentalchange, through the provision of sit-stand desks. Whilstthe use of sit-stand desks in classrooms demonstrates positiveeffects in some key outcomes, evidence is currently limitedby small samples and/or short intervention durations, withfewstudiesadoptingrandomisedcontrolledtrial(RCT)designs. This paper describes the protocol of a pilot cluster RCT of a sit-stand desk interventioninprimaryschoolclassrooms.Methods/Design:A two-arm pilot cluster RCT will be conducted in eight primary schools (four intervention, four control)with at least 120 year 5 children (aged 9–10 years). Sit-stand desks will replace six standard desks in the interventionclassrooms. Teachers will be encouraged to ensure all pupils are exposed to the sit-stand desks for at least 1 h/dayon average using a rotation system. Schools assigned to the control arm will continue with their usual practice, noenvironmental changes will be made to their classrooms. Measurements will be taken at baseline, beforerandomisation, and at the end of the schools’academic year. In this study, the primary outcomes of interest will beschool and participant recruitment and attrition, acceptability of the intervention, and acceptability and complianceto the proposed outcome measures (including activPAL-measured school-time and school-day sitting, accelerometer-measured physical activity, adiposity, blood pressure, cognitive function, academic progress, engagement, andbehaviour) for inclusion in a definitive trial. A full process evaluation and an exploratory economic evaluation willalso be conducted to further inform a definitive tria

A mobile telehealth intervention for adults with insulin-requiring diabetes: early results of a mixed-methods randomized controlled trial

BACKGROUND: The role of technology in health care delivery has grown rapidly in the last decade. The potential of mobile telehealth (MTH) to support patient self-management is a key area of research. Providing patients with technological tools that allow for the recording and transmission of health parameters to health care professionals (HCPs) may promote behavior changes that result in improved health outcomes. Although for some conditions the evidence of the effectiveness of MTH is clear, to date the findings on the effects of MTH on diabetes management remain inconsistent. OBJECTIVE: This study aims to evaluate an MTH intervention among insulin-requiring adults with diabetes to establish whether supplementing standard care with MTH results in improved health outcomes-glycated hemoglobin (HbA1c), blood pressure (BP), health-related quality of life (HRQoL), diabetes self-management behaviors, diabetes health care utilization, and diabetes self-efficacy and illness beliefs. An additional objective was to explore the acceptability of MTH and patients' perceptions of, and experience, using it. METHODS: A mixed-method design consisting of a 9-month, two-arm, parallel randomized controlled trial (RCT) was used in combination with exit qualitative interviews. Quantitative data was collected at baseline, 3 months, and 9 months. Additional intervention fidelity data, such as participants' MTH transmissions and contacts with the MTH nurse during the study, were also recorded. RESULTS: Data collection for both the quantitative and qualitative components of this study has ended and data analysis is ongoing. A total of 86 participants were enrolled into the study. Out of 86 participants, 45 (52%) were randomized to the intervention group and 36 (42%) to the control group. Preliminary data on MTH training sessions and MTH usage by intervention participants are presented in this paper. We expect to publish complete study results in 2015. CONCLUSIONS: The range of data collected in this study will allow for a comprehensive evaluation of processes and outcomes. The early results presented suggest that MTH usage decreases over time and that MTH participants would benefit from attending more than one training session. TRIAL REGISTRATION: ClinicalTrials.gov NCT00922376; http://clinicaltrials.gov/ct2/show/NCT00922376 (Archived by WebCite at http://www.webcitation.org/6Vu4nhLI6)