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  • Open Access English
    Authors: 
    Davidson, Pavel; Virekunnas, Heikki; Sharma, Dharmendra; Piché, Robert; Cronin, Neil;
    Country: Finland

    This paper describes a single body-mounted sensor that integrates accelerometers, gyroscopes, compasses, barometers, a GPS receiver, and a methodology to process the data for biomechanical studies. The sensor and its data processing system can accurately compute the speed, acceleration, angular velocity, and angular orientation at an output rate of 400 Hz and has the ability to collect large volumes of ecologically-valid data. The system also segments steps and computes metrics for each step. We analyzed the sensitivity of these metrics to changing the start time of the gait cycle. Along with traditional metrics, such as cadence, speed, step length, and vertical oscillation, this system estimates ground contact time and ground reaction forces using machine learning techniques. This equipment is less expensive and cumbersome than the currently used alternatives: Optical tracking systems, in-shoe pressure measurement systems, and force plates. Another advantage, compared to existing methods, is that natural movement is not impeded at the expense of measurement accuracy. The proposed technology could be applied to different sports and activities, including walking, running, motion disorder diagnosis, and geriatric studies. In this paper, we present the results of tests in which the system performed real-time estimation of some parameters of walking and running which are relevant to biomechanical research. Contact time and ground reaction forces computed by the neural network were found to be as accurate as those obtained by an in-shoe pressure measurement system. peerReviewed

  • Publication . Article . Preprint . Other literature type . 2017
    Open Access English
    Authors: 
    Samuel R. Chamberlain; Jonathan Cavanagh; Peter de Boer; Valeria Mondelli; Declan Jones; Wayne C. Drevets; Philip J. Cowen; Neil A. Harrison; Linda Pointon; Carmine M. Pariante; +1 more
    Publisher: Cold Spring Harbor Laboratory
    Country: United Kingdom
    Project: WT | Diagnostically cross-cutt... (110049)

    Research in contextEvidence before this studyDysregulation of the peripheral innate immune system has been implicated in the pathophysiology of major depressive disorder (MDD), and may partly account for why many patients do not experience symptomatic improvement. Elevated CRP has been demonstrated in meta-analysis for MDD compared to healthy volunteers, but little is known about whether this is the case for particular clinical phenotypes of the disorder, as opposed to MDD in general.Added value of this studyThis study recruited a large cohort of MDD patients, stratified by prior exposure to monoamine reuptake inhibitor treatment. MDD participants were carefully screened for physical comorbidity, and were compared to healthy volunteers matched for age, sex, body mass indices, and cigarette smoking status. Using group-wise comparisons and the innovative statistical approach of partial least squares, we demonstrated that elevated CRP was associated with treatment-resistance, childhood adversity, and specific depressive and anxious symptoms.Implications of all the available evidenceCRP is significantly increased “on average” in MDD patients, However, CRP was most abnormally increased in the subgroup of patients with treatment-resistant depression. High BMI, high scores on vegetative symptoms of depression, low scores on calmness, and a history of childhood adversity, were all predictive of increased CRP. In future, stratification of MDD patients using pro-inflammatory biomarkers, like CRP, may be valuable for sample enrichment and targeted treatment interventions.AbstractBackgroundC-reactive protein (CRP) is a candidate biomarker for major depressive disorder (MDD), but it is unclear how peripheral CRP levels relate to the heterogeneous clinical phenotypes of the disorder.MethodsWe recruited 102 treatment-resistant, depressed MDD patients, 48 treatment-responsive, non-depressed MDD patients, 48 depressed but un-medicated patients, and 54 healthy volunteers. High sensitivity CRP in peripheral venous blood, body mass index (BMI), and questionnaire assessments of depression, anxiety, and childhood trauma, were measured. Group differences in CRP were estimated, before and after correction for BMI. Partial least squares (PLS) analysis explored the relationships between CRP and specific clinical phenotypes.OutcomesCompared to healthy volunteers, BMI-corrected CRP was significantly elevated in treatment-resistant patients (P= 0.007; Cohen’s d = 0.47); but not significantly so in the treatment-responsive (d = 0.29) and untreated (d = 0.18) groups. PLS yielded an optimal two factor solution that accounted for 34.7% of variation in clinical measures, and for 36.0% of variation in CRP. The clinical phenotypes most strongly associated with CRP and heavily weighted on the first PLS component were: vegetative depressive symptoms, BMI, state anxiety, and feeling unloved as a child or wishing for a different childhood.InterpretationPeripheral CRP was elevated in MDD, especially in treatment-resistant cases. Other phenotypes associated with elevated CRP included childhood adversity, and specific depressive and anxious symptoms. We suggest that MDD patients stratified for pro-inflammatory biomarkers, like CRP, have a distinctive clinical profile that might be responsive to second-line treatment with anti-inflammatory drugs.FundingWellcome Trust strategy award to the Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium.

  • Open Access English
    Authors: 
    Bliss, CM; Drammeh, A; Bowyer, G; Sanou, GS; Jagne, YJ; Ouedraogo, O; Edwards, NJ; Tarama, C; Ouedraogo, N; Ouedraogo, M; +22 more
    Publisher: Elsevier (Cell Press)
    Country: United Kingdom
    Project: WT | Using the Controlled Huma... (097940), WT | Human and Veterinary Vacc... (084113)

    Heterologous prime-boosting with viral vectors encoding the pre-erythrocytic antigen thrombospondin-related adhesion protein fused to a multiple epitope string (ME-TRAP) induces CD8+ T cell-mediated immunity to malaria sporozoite challenge in European malaria-naive and Kenyan semi-immune adults. This approach has yet to be evaluated in children and infants. We assessed this vaccine strategy among 138 Gambian and Burkinabe children in four cohorts: 2- to 6-year olds in The Gambia, 5- to 17-month-olds in Burkina Faso, and 5- to 12-month-olds and 10-week-olds in The Gambia. We assessed induction of cellular immunity, taking into account the distinctive hematological status of young infants, and characterized the antibody response to vaccination. T cell responses peaked 7 days after boosting with modified vaccinia virus Ankara (MVA), with highest responses in infants aged 10 weeks at priming. Incorporating lymphocyte count into the calculation of T cell responses facilitated a more physiologically relevant comparison of cellular immunity across different age groups. Both CD8+ and CD4+ T cells secreted cytokines. Induced antibodies were up to 20-fold higher in all groups compared with Gambian and United Kingdom (UK) adults, with comparable or higher avidity. This immunization regimen elicited strong immune responses, particularly in young infants, supporting future evaluation of efficacy in this key target age group for a malaria vaccine. An effective malaria vaccine is an urgent global health priority. In these studies, Ewer and colleagues describe strong T cell and antibody responses in children and infants following vaccination with a viral vectored vaccine regime encoding a pre-erythrocytic malaria antigen. This regime has previously demonstrated efficacy in adults and these data support assessment of the efficacy of this vaccine in infants.

  • Open Access English
    Authors: 
    Samra, Rajvinder; Cox, Tom; Gordon, Adam L; Conroy, Simon; Lucassen, Mathijs; Griffiths, Amanda;
    Publisher: Oxford University Press
    Country: United Kingdom

    Background:Studies have sought to identify the possible determinants of medical students’ and doctors’ attitudes towards older patients by examining relationships with a variety of factors: demographic; educational/training; exposure to older people; personality/cognitive; and job/career factors. This review collates and synthesises these findings. \ud Methods: An electronic search of ten databases was performed (ABI/Inform, ASSIA, British Nursing Index, CINAHL, Informa Health, Medline, PsycINFO, Science Direct, Scopus, and Web of Science) through to 7 February 2017. \ud Results: The main search identified 2332 articles; 37 studies met the eligibility criteria set. All included studies analysed self-reported attitudes based on correlational analyses or difference testing, therefore causation could not be determined. However, self-reported positive attitudes towards older patients were related to: (i) intrinsic motivation for studying medicine; (ii) increased preference for working with older patients; and (iii) good previous relationships with older people. Additionally, more positive attitudes were also reported in those with higher knowledge scores but these may relate to the use of a knowledge assessment which is an indirect measure of attitudes (i.e. Palmore’s Facts on Aging Quizzes). Four out of the five high quality studies included in this review reported more positive attitudes in females compared to males. \ud Conclusion:This paper identifies factors associated with medical students’ and doctors’ positive attitudes towards older patients. Future research could bring greater clarity to the relationship between knowledge and attitudes by using a knowledge measure which is distinct from attitudes and also measures knowledge that is relevant to clinical care.

  • Open Access English
    Authors: 
    Shailey Minocha;

    The aim of this tutorial is to present practical guidance for evaluating the effectiveness of educational initiatives involving social software and emerging technologies to support student learning and engagement. Examples of such initiatives are: inclusion of a blog in a course to encourage reflective learning, or having a wiki in a course for fostering team-working skills, or an activity in a 3D virtual world to enable students to learn through simulations, or the use of Delicious for bookmarking resources, or an App on a smartphone. ‘Evaluation’ implies investigating the usability, pedagogical effectiveness (does it meet the learning outcomes?), student experience, and impact on direct stakeholders such as educators and technical support staff (in terms of workload and support required).\ud \ud Educators, practitioners and educational researchers will find this tutorial useful for learning about evaluating initiatives in a systematic manner and yet be able to choose research methods that are not very resource-intensive for themselves and for the participants (primarily students but other direct stakeholders too such as technical support staff). Through examples of social software initiatives, we will discuss a number of data collection and data analysis methods in the tutorial ranging from traditional social science research (e.g. focus groups) to user-centred research methods (e.g. observations, diary studies) and to participatory design methods (e.g. experience sampling, student panels). We will also discuss about ethical considerations of conducting research, specifically, involving social software, where the personal and professional boundaries of user profiles (or identities) sometimes get blurred.

  • Open Access English
    Authors: 
    Tony Robertson; Gayle Beveridge; Catherine Bromley;
    Publisher: Public Library of Science (PLoS)
    Project: UKRI | Scottish Collaboration fo... (MR/K023209/1)

    Allostatic load is a multiple biomarker measure of physiological ‘wear and tear’ that has shown some promise as marker of overall physiological health, but its power as a risk predictor for mortality and morbidity is less well known. This study has used data from the 2003 Scottish Health Survey (SHeS) (nationally representative sample of Scottish population) linked to mortality records to assess how well allostatic load predicts all-cause and cause-specific mortality. From the sample, data from 4,488 men and women were available with mortality status at 5 and 9.5 (rounded to 10) years after sampling in 2003. Cox proportional hazard models estimated the risk of death (all-cause and the five major causes of death in the population) according to allostatic load score. Multiple imputation was used to address missing values in the dataset. Analyses were also adjusted for potential confounders (sex, age and deprivation). There were 258 and 618 deaths over the 5-year and 10-year follow-up period, respectively. In the fully-adjusted model, higher allostatic load (poorer physiological ‘health’) was not associated with an increased risk of all-cause mortality after 5 years (HR = 1.07, 95% CI 0.94 to 1.22; p = 0.269), but it was after 10 years (HR = 1.08, 95% CI 1.01 to 1.16; p = 0.026). Allostatic load was not associated with specific causes of death over the same follow-up period. In conclusions, greater physiological wear and tear across multiple physiological systems, as measured by allostatic load, is associated with an increased risk of death, but may not be as useful as a predictor for specific causes of death.

  • Open Access
    Authors: 
    S. Amodeo; Nicholas Battaglia; Emmanuel Schaan; Simone Ferraro; Emily Moser; Simone Aiola; Jason E. Austermann; James A. Beall; Rachel Bean; Daniel T. Becker; +45 more
    Publisher: American Physical Society (APS)
    Country: United States
    Project: UKRI | A Programme of Technology... (ST/S00033X/1), NSF | ACTPol: The Atacama Cosmo... (0965625), NSF | Collaborative Research wi... (0408698), EC | CMBforward (849169), NSF | Advanced ACTPol (1440226), UKRI | Precision cosmology from ... (ST/M004856/2), NSF | Observations to Constrain... (1910021), NSF | Gravitational Physics fro... (0855887), NSF | Mapping Dark Matter on La... (1907657), NSF | Discovering Properties of... (1513618),...

    The thermal and kinematic Sunyaev-Zel'dovich effects (tSZ, kSZ) probe the thermodynamic properties of the circumgalactic and intracluster medium (CGM and ICM) of galaxies, groups, and clusters, since they are proportional, respectively, to the integrated electron pressure and momentum along the line-of-sight. We present constraints on the gas thermodynamics of CMASS galaxies in the Baryon Oscillation Spectroscopic Survey (BOSS) using new measurements of the kSZ and tSZ signals obtained in a companion paper. Combining kSZ and tSZ measurements, we measure within our model the amplitude of energy injection $\epsilon M_\star c^2$, where $M_\star$ is the stellar mass, to be $\epsilon=(40\pm9)\times10^{-6}$, and the amplitude of the non-thermal pressure profile to be $\alpha_{\rm Nth}<0.2$ (2$\sigma$), indicating that less than 20% of the total pressure within the virial radius is due to a non-thermal component. We estimate the effects of including baryons in the modeling of weak-lensing galaxy cross-correlation measurements using the best fit density profile from the kSZ measurement. Our estimate reduces the difference between the original theoretical model and the weak-lensing galaxy cross-correlation measurements in arXiv:1611.08606 by half, but does not fully reconcile it. Comparing the kSZ and tSZ measurements to cosmological simulations, we find that they under predict the CGM pressure and to a lesser extent the CGM density at larger radii. This suggests that the energy injected via feedback models in the simulations that we compared against does not sufficiently heat the gas at these radii. We do not find significant disagreement at smaller radii. These measurements provide novel tests of current and future simulations. This work demonstrates the power of joint, high signal-to-noise kSZ and tSZ observations, upon which future cross-correlation studies will improve. Comment: Published in Physical Review D. Corrected typos in Sec. 2C and 3C

  • Open Access English
    Authors: 
    Max V. Birk; Ioanna Iacovides; Daniel Johnson; Regan L. Mandryk;
    Country: United Kingdom

    Most of the time games make us happy, but sometimes they are frustrating or make us feel sad. They allow us to experience pleasure, success and joy, but they can also yield feelings of frustration, failure, or sorrow from darker themes. In games, we can experience the full range of emotions -- both positive and negative. While a positive experience is often the goal, there are many ways in which negative affect can enhance play. First, the almost masochistic experience of failure and frustration within play can lead to intense positive feelings when overcome. Second, negative emotional experiences, such as feeling uncomfortable, guilty, or sad can also provide additional emotional range that is valued by players. Third, a number of games have emerged in recent years that encourage players to think about difficult or challenging issues that are unlikely to engender positive emotions. The CHIPLAY 2015 False Dichotomy Workshop focuses on the range of valence in games and invites experts from across fields to contribute to our understanding of the interplay between positive and negative affect within play. The workshop goals are to investigate the interplay between positive and negative affect, identify gaps in our knowledge, determine future research directions, and build the community of people interested in the false dichotomy between positive and negative affect in games. The workshop will consist of a brief introduction game, followed by group brainstorming, small group interaction, and a closing plenary discussion.

  • Open Access
    Authors: 
    Francesco Crea; Lei Sun; L Pikor; Paolo Frumento; Wan L. Lam; Cheryl D. Helgason;
    Publisher: Springer Science and Business Media LLC

    Background: Polycomb group genes (PcGs) are epigenetic effectors implicated in most cancer hallmarks. The mutational status of all PcGs has never been systematically assessed in solid tumours.\ud Methods: We conducted a multi-step analysis on publically available databases and patient samples to identify somatic aberrations of PcGs.\ud Results: Data from more than 1000 cancer patients show for the first time that the PcG member PHC3 is amplified in three epithelial neoplasms (rate: 8–35%). This aberration predicts poorer prognosis in lung and uterine carcinomas (Po0.01). Gene amplification correlates with mRNA overexpression (Po0.01), suggesting a functional role of this aberration.\ud Conclusion: PHC3 amplification may emerge as a biomarker and potential therapeutic target in a relevant fraction of epithelial tumours.

  • Open Access English
    Authors: 
    Laura J Corbin; Vanessa Y Tan; David A. Hughes; Kaitlin H Wade; Dirk S. Paul; Katherine E. Tansey; Frances Butcher; Frank Dudbridge; Joanna M. M. Howson; Momodou W. Jallow; +21 more
    Publisher: Umeå universitet, Medicin
    Countries: United States, United Kingdom, Sweden
    Project: WT | Institutional Strategic S... (105602), UKRI | Causal analyses, statisti... (MC_UU_12013/3), WT | Understanding the genetic... (090532), UKRI | A program of research in ... (G0902313), UKRI | Large-scale integrative s... (MR/L003120/1), NIH | The Impact of Human Gene ... (5R01DK098032-02), WT | Large-scale genomic epide... (202849), UKRI | From Mendelian Randomizat... (MC_UU_12013/1), EC | NASCENT (681742), UKRI | Characterising the shared... (MR/P00167X/1),...

    Detailed phenotyping is required to deepen our understanding of the biological mechanisms behind genetic associations. In addition, the impact of potentially modifiable risk factors on disease requires analytical frameworks that allow causal inference. Here, we discuss the characteristics of Recall-by-Genotype (RbG) as a study design aimed at addressing both these needs. We describe two broad scenarios for the application of RbG: studies using single variants and those using multiple variants. We consider the efficacy and practicality of the RbG approach, provide a catalogue of UK-based resources for such studies and present an online RbG study planner. Recall-by-Genotype (RbG) is an approach to recall participants from genetic studies based on their specific genotype for further, more extensive phenotyping. Here, the authors discuss examples of RbG as well as practical and ethical considerations and provide an online tool to aid in designing RbG studies.

search
Include:
680 Research products, page 1 of 68
  • Open Access English
    Authors: 
    Davidson, Pavel; Virekunnas, Heikki; Sharma, Dharmendra; Piché, Robert; Cronin, Neil;
    Country: Finland

    This paper describes a single body-mounted sensor that integrates accelerometers, gyroscopes, compasses, barometers, a GPS receiver, and a methodology to process the data for biomechanical studies. The sensor and its data processing system can accurately compute the speed, acceleration, angular velocity, and angular orientation at an output rate of 400 Hz and has the ability to collect large volumes of ecologically-valid data. The system also segments steps and computes metrics for each step. We analyzed the sensitivity of these metrics to changing the start time of the gait cycle. Along with traditional metrics, such as cadence, speed, step length, and vertical oscillation, this system estimates ground contact time and ground reaction forces using machine learning techniques. This equipment is less expensive and cumbersome than the currently used alternatives: Optical tracking systems, in-shoe pressure measurement systems, and force plates. Another advantage, compared to existing methods, is that natural movement is not impeded at the expense of measurement accuracy. The proposed technology could be applied to different sports and activities, including walking, running, motion disorder diagnosis, and geriatric studies. In this paper, we present the results of tests in which the system performed real-time estimation of some parameters of walking and running which are relevant to biomechanical research. Contact time and ground reaction forces computed by the neural network were found to be as accurate as those obtained by an in-shoe pressure measurement system. peerReviewed

  • Publication . Article . Preprint . Other literature type . 2017
    Open Access English
    Authors: 
    Samuel R. Chamberlain; Jonathan Cavanagh; Peter de Boer; Valeria Mondelli; Declan Jones; Wayne C. Drevets; Philip J. Cowen; Neil A. Harrison; Linda Pointon; Carmine M. Pariante; +1 more
    Publisher: Cold Spring Harbor Laboratory
    Country: United Kingdom
    Project: WT | Diagnostically cross-cutt... (110049)

    Research in contextEvidence before this studyDysregulation of the peripheral innate immune system has been implicated in the pathophysiology of major depressive disorder (MDD), and may partly account for why many patients do not experience symptomatic improvement. Elevated CRP has been demonstrated in meta-analysis for MDD compared to healthy volunteers, but little is known about whether this is the case for particular clinical phenotypes of the disorder, as opposed to MDD in general.Added value of this studyThis study recruited a large cohort of MDD patients, stratified by prior exposure to monoamine reuptake inhibitor treatment. MDD participants were carefully screened for physical comorbidity, and were compared to healthy volunteers matched for age, sex, body mass indices, and cigarette smoking status. Using group-wise comparisons and the innovative statistical approach of partial least squares, we demonstrated that elevated CRP was associated with treatment-resistance, childhood adversity, and specific depressive and anxious symptoms.Implications of all the available evidenceCRP is significantly increased “on average” in MDD patients, However, CRP was most abnormally increased in the subgroup of patients with treatment-resistant depression. High BMI, high scores on vegetative symptoms of depression, low scores on calmness, and a history of childhood adversity, were all predictive of increased CRP. In future, stratification of MDD patients using pro-inflammatory biomarkers, like CRP, may be valuable for sample enrichment and targeted treatment interventions.AbstractBackgroundC-reactive protein (CRP) is a candidate biomarker for major depressive disorder (MDD), but it is unclear how peripheral CRP levels relate to the heterogeneous clinical phenotypes of the disorder.MethodsWe recruited 102 treatment-resistant, depressed MDD patients, 48 treatment-responsive, non-depressed MDD patients, 48 depressed but un-medicated patients, and 54 healthy volunteers. High sensitivity CRP in peripheral venous blood, body mass index (BMI), and questionnaire assessments of depression, anxiety, and childhood trauma, were measured. Group differences in CRP were estimated, before and after correction for BMI. Partial least squares (PLS) analysis explored the relationships between CRP and specific clinical phenotypes.OutcomesCompared to healthy volunteers, BMI-corrected CRP was significantly elevated in treatment-resistant patients (P= 0.007; Cohen’s d = 0.47); but not significantly so in the treatment-responsive (d = 0.29) and untreated (d = 0.18) groups. PLS yielded an optimal two factor solution that accounted for 34.7% of variation in clinical measures, and for 36.0% of variation in CRP. The clinical phenotypes most strongly associated with CRP and heavily weighted on the first PLS component were: vegetative depressive symptoms, BMI, state anxiety, and feeling unloved as a child or wishing for a different childhood.InterpretationPeripheral CRP was elevated in MDD, especially in treatment-resistant cases. Other phenotypes associated with elevated CRP included childhood adversity, and specific depressive and anxious symptoms. We suggest that MDD patients stratified for pro-inflammatory biomarkers, like CRP, have a distinctive clinical profile that might be responsive to second-line treatment with anti-inflammatory drugs.FundingWellcome Trust strategy award to the Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium.

  • Open Access English
    Authors: 
    Bliss, CM; Drammeh, A; Bowyer, G; Sanou, GS; Jagne, YJ; Ouedraogo, O; Edwards, NJ; Tarama, C; Ouedraogo, N; Ouedraogo, M; +22 more
    Publisher: Elsevier (Cell Press)
    Country: United Kingdom
    Project: WT | Using the Controlled Huma... (097940), WT | Human and Veterinary Vacc... (084113)

    Heterologous prime-boosting with viral vectors encoding the pre-erythrocytic antigen thrombospondin-related adhesion protein fused to a multiple epitope string (ME-TRAP) induces CD8+ T cell-mediated immunity to malaria sporozoite challenge in European malaria-naive and Kenyan semi-immune adults. This approach has yet to be evaluated in children and infants. We assessed this vaccine strategy among 138 Gambian and Burkinabe children in four cohorts: 2- to 6-year olds in The Gambia, 5- to 17-month-olds in Burkina Faso, and 5- to 12-month-olds and 10-week-olds in The Gambia. We assessed induction of cellular immunity, taking into account the distinctive hematological status of young infants, and characterized the antibody response to vaccination. T cell responses peaked 7 days after boosting with modified vaccinia virus Ankara (MVA), with highest responses in infants aged 10 weeks at priming. Incorporating lymphocyte count into the calculation of T cell responses facilitated a more physiologically relevant comparison of cellular immunity across different age groups. Both CD8+ and CD4+ T cells secreted cytokines. Induced antibodies were up to 20-fold higher in all groups compared with Gambian and United Kingdom (UK) adults, with comparable or higher avidity. This immunization regimen elicited strong immune responses, particularly in young infants, supporting future evaluation of efficacy in this key target age group for a malaria vaccine. An effective malaria vaccine is an urgent global health priority. In these studies, Ewer and colleagues describe strong T cell and antibody responses in children and infants following vaccination with a viral vectored vaccine regime encoding a pre-erythrocytic malaria antigen. This regime has previously demonstrated efficacy in adults and these data support assessment of the efficacy of this vaccine in infants.

  • Open Access English
    Authors: 
    Samra, Rajvinder; Cox, Tom; Gordon, Adam L; Conroy, Simon; Lucassen, Mathijs; Griffiths, Amanda;
    Publisher: Oxford University Press
    Country: United Kingdom

    Background:Studies have sought to identify the possible determinants of medical students’ and doctors’ attitudes towards older patients by examining relationships with a variety of factors: demographic; educational/training; exposure to older people; personality/cognitive; and job/career factors. This review collates and synthesises these findings. \ud Methods: An electronic search of ten databases was performed (ABI/Inform, ASSIA, British Nursing Index, CINAHL, Informa Health, Medline, PsycINFO, Science Direct, Scopus, and Web of Science) through to 7 February 2017. \ud Results: The main search identified 2332 articles; 37 studies met the eligibility criteria set. All included studies analysed self-reported attitudes based on correlational analyses or difference testing, therefore causation could not be determined. However, self-reported positive attitudes towards older patients were related to: (i) intrinsic motivation for studying medicine; (ii) increased preference for working with older patients; and (iii) good previous relationships with older people. Additionally, more positive attitudes were also reported in those with higher knowledge scores but these may relate to the use of a knowledge assessment which is an indirect measure of attitudes (i.e. Palmore’s Facts on Aging Quizzes). Four out of the five high quality studies included in this review reported more positive attitudes in females compared to males. \ud Conclusion:This paper identifies factors associated with medical students’ and doctors’ positive attitudes towards older patients. Future research could bring greater clarity to the relationship between knowledge and attitudes by using a knowledge measure which is distinct from attitudes and also measures knowledge that is relevant to clinical care.

  • Open Access English
    Authors: 
    Shailey Minocha;

    The aim of this tutorial is to present practical guidance for evaluating the effectiveness of educational initiatives involving social software and emerging technologies to support student learning and engagement. Examples of such initiatives are: inclusion of a blog in a course to encourage reflective learning, or having a wiki in a course for fostering team-working skills, or an activity in a 3D virtual world to enable students to learn through simulations, or the use of Delicious for bookmarking resources, or an App on a smartphone. ‘Evaluation’ implies investigating the usability, pedagogical effectiveness (does it meet the learning outcomes?), student experience, and impact on direct stakeholders such as educators and technical support staff (in terms of workload and support required).\ud \ud Educators, practitioners and educational researchers will find this tutorial useful for learning about evaluating initiatives in a systematic manner and yet be able to choose research methods that are not very resource-intensive for themselves and for the participants (primarily students but other direct stakeholders too such as technical support staff). Through examples of social software initiatives, we will discuss a number of data collection and data analysis methods in the tutorial ranging from traditional social science research (e.g. focus groups) to user-centred research methods (e.g. observations, diary studies) and to participatory design methods (e.g. experience sampling, student panels). We will also discuss about ethical considerations of conducting research, specifically, involving social software, where the personal and professional boundaries of user profiles (or identities) sometimes get blurred.

  • Open Access English
    Authors: 
    Tony Robertson; Gayle Beveridge; Catherine Bromley;
    Publisher: Public Library of Science (PLoS)
    Project: UKRI | Scottish Collaboration fo... (MR/K023209/1)

    Allostatic load is a multiple biomarker measure of physiological ‘wear and tear’ that has shown some promise as marker of overall physiological health, but its power as a risk predictor for mortality and morbidity is less well known. This study has used data from the 2003 Scottish Health Survey (SHeS) (nationally representative sample of Scottish population) linked to mortality records to assess how well allostatic load predicts all-cause and cause-specific mortality. From the sample, data from 4,488 men and women were available with mortality status at 5 and 9.5 (rounded to 10) years after sampling in 2003. Cox proportional hazard models estimated the risk of death (all-cause and the five major causes of death in the population) according to allostatic load score. Multiple imputation was used to address missing values in the dataset. Analyses were also adjusted for potential confounders (sex, age and deprivation). There were 258 and 618 deaths over the 5-year and 10-year follow-up period, respectively. In the fully-adjusted model, higher allostatic load (poorer physiological ‘health’) was not associated with an increased risk of all-cause mortality after 5 years (HR = 1.07, 95% CI 0.94 to 1.22; p = 0.269), but it was after 10 years (HR = 1.08, 95% CI 1.01 to 1.16; p = 0.026). Allostatic load was not associated with specific causes of death over the same follow-up period. In conclusions, greater physiological wear and tear across multiple physiological systems, as measured by allostatic load, is associated with an increased risk of death, but may not be as useful as a predictor for specific causes of death.

  • Open Access
    Authors: 
    S. Amodeo; Nicholas Battaglia; Emmanuel Schaan; Simone Ferraro; Emily Moser; Simone Aiola; Jason E. Austermann; James A. Beall; Rachel Bean; Daniel T. Becker; +45 more
    Publisher: American Physical Society (APS)
    Country: United States
    Project: UKRI | A Programme of Technology... (ST/S00033X/1), NSF | ACTPol: The Atacama Cosmo... (0965625), NSF | Collaborative Research wi... (0408698), EC | CMBforward (849169), NSF | Advanced ACTPol (1440226), UKRI | Precision cosmology from ... (ST/M004856/2), NSF | Observations to Constrain... (1910021), NSF | Gravitational Physics fro... (0855887), NSF | Mapping Dark Matter on La... (1907657), NSF | Discovering Properties of... (1513618),...

    The thermal and kinematic Sunyaev-Zel'dovich effects (tSZ, kSZ) probe the thermodynamic properties of the circumgalactic and intracluster medium (CGM and ICM) of galaxies, groups, and clusters, since they are proportional, respectively, to the integrated electron pressure and momentum along the line-of-sight. We present constraints on the gas thermodynamics of CMASS galaxies in the Baryon Oscillation Spectroscopic Survey (BOSS) using new measurements of the kSZ and tSZ signals obtained in a companion paper. Combining kSZ and tSZ measurements, we measure within our model the amplitude of energy injection $\epsilon M_\star c^2$, where $M_\star$ is the stellar mass, to be $\epsilon=(40\pm9)\times10^{-6}$, and the amplitude of the non-thermal pressure profile to be $\alpha_{\rm Nth}<0.2$ (2$\sigma$), indicating that less than 20% of the total pressure within the virial radius is due to a non-thermal component. We estimate the effects of including baryons in the modeling of weak-lensing galaxy cross-correlation measurements using the best fit density profile from the kSZ measurement. Our estimate reduces the difference between the original theoretical model and the weak-lensing galaxy cross-correlation measurements in arXiv:1611.08606 by half, but does not fully reconcile it. Comparing the kSZ and tSZ measurements to cosmological simulations, we find that they under predict the CGM pressure and to a lesser extent the CGM density at larger radii. This suggests that the energy injected via feedback models in the simulations that we compared against does not sufficiently heat the gas at these radii. We do not find significant disagreement at smaller radii. These measurements provide novel tests of current and future simulations. This work demonstrates the power of joint, high signal-to-noise kSZ and tSZ observations, upon which future cross-correlation studies will improve. Comment: Published in Physical Review D. Corrected typos in Sec. 2C and 3C

  • Open Access English
    Authors: 
    Max V. Birk; Ioanna Iacovides; Daniel Johnson; Regan L. Mandryk;
    Country: United Kingdom

    Most of the time games make us happy, but sometimes they are frustrating or make us feel sad. They allow us to experience pleasure, success and joy, but they can also yield feelings of frustration, failure, or sorrow from darker themes. In games, we can experience the full range of emotions -- both positive and negative. While a positive experience is often the goal, there are many ways in which negative affect can enhance play. First, the almost masochistic experience of failure and frustration within play can lead to intense positive feelings when overcome. Second, negative emotional experiences, such as feeling uncomfortable, guilty, or sad can also provide additional emotional range that is valued by players. Third, a number of games have emerged in recent years that encourage players to think about difficult or challenging issues that are unlikely to engender positive emotions. The CHIPLAY 2015 False Dichotomy Workshop focuses on the range of valence in games and invites experts from across fields to contribute to our understanding of the interplay between positive and negative affect within play. The workshop goals are to investigate the interplay between positive and negative affect, identify gaps in our knowledge, determine future research directions, and build the community of people interested in the false dichotomy between positive and negative affect in games. The workshop will consist of a brief introduction game, followed by group brainstorming, small group interaction, and a closing plenary discussion.

  • Open Access
    Authors: 
    Francesco Crea; Lei Sun; L Pikor; Paolo Frumento; Wan L. Lam; Cheryl D. Helgason;
    Publisher: Springer Science and Business Media LLC

    Background: Polycomb group genes (PcGs) are epigenetic effectors implicated in most cancer hallmarks. The mutational status of all PcGs has never been systematically assessed in solid tumours.\ud Methods: We conducted a multi-step analysis on publically available databases and patient samples to identify somatic aberrations of PcGs.\ud Results: Data from more than 1000 cancer patients show for the first time that the PcG member PHC3 is amplified in three epithelial neoplasms (rate: 8–35%). This aberration predicts poorer prognosis in lung and uterine carcinomas (Po0.01). Gene amplification correlates with mRNA overexpression (Po0.01), suggesting a functional role of this aberration.\ud Conclusion: PHC3 amplification may emerge as a biomarker and potential therapeutic target in a relevant fraction of epithelial tumours.

  • Open Access English
    Authors: 
    Laura J Corbin; Vanessa Y Tan; David A. Hughes; Kaitlin H Wade; Dirk S. Paul; Katherine E. Tansey; Frances Butcher; Frank Dudbridge; Joanna M. M. Howson; Momodou W. Jallow; +21 more
    Publisher: Umeå universitet, Medicin
    Countries: United States, United Kingdom, Sweden
    Project: WT | Institutional Strategic S... (105602), UKRI | Causal analyses, statisti... (MC_UU_12013/3), WT | Understanding the genetic... (090532), UKRI | A program of research in ... (G0902313), UKRI | Large-scale integrative s... (MR/L003120/1), NIH | The Impact of Human Gene ... (5R01DK098032-02), WT | Large-scale genomic epide... (202849), UKRI | From Mendelian Randomizat... (MC_UU_12013/1), EC | NASCENT (681742), UKRI | Characterising the shared... (MR/P00167X/1),...

    Detailed phenotyping is required to deepen our understanding of the biological mechanisms behind genetic associations. In addition, the impact of potentially modifiable risk factors on disease requires analytical frameworks that allow causal inference. Here, we discuss the characteristics of Recall-by-Genotype (RbG) as a study design aimed at addressing both these needs. We describe two broad scenarios for the application of RbG: studies using single variants and those using multiple variants. We consider the efficacy and practicality of the RbG approach, provide a catalogue of UK-based resources for such studies and present an online RbG study planner. Recall-by-Genotype (RbG) is an approach to recall participants from genetic studies based on their specific genotype for further, more extensive phenotyping. Here, the authors discuss examples of RbG as well as practical and ethical considerations and provide an online tool to aid in designing RbG studies.

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