Balancing the dilution and oddity effects: Decisions depend on body size

Background Grouping behaviour, common across the animal kingdom, is known to reduce an individual's risk of predation; particularly through dilution of individual risk and predator confusion (predator inability to single out an individual for attack). Theory predicts greater risk of predation to individuals more conspicuous to predators by difference in appearance from the group (the ‘oddity’ effect). Thus, animals should choose group mates close in appearance to themselves (eg. similar size), whilst also choosing a large group. Methodology and Principal Findings We used the Trinidadian guppy (Poecilia reticulata), a well known model species of group-living freshwater fish, in a series of binary choice trials investigating the outcome of conflict between preferences for large and phenotypically matched groups along a predation risk gradient. We found body-size dependent differences in the resultant social decisions. Large fish preferred shoaling with size-matched individuals, while small fish demonstrated no preference. There was a trend towards reduced preferences for the matched shoal under increased predation risk. Small fish were more active than large fish, moving between shoals more frequently. Activity levels increased as predation risk decreased. We found no effect of unmatched shoal size on preferences or activity. Conclusions and Significance Our results suggest that predation risk and individual body size act together to influence shoaling decisions. Oddity was more important for large than small fish, reducing in importance at higher predation risks. Dilution was potentially of limited importance at these shoal sizes. Activity levels may relate to how much sampling of each shoal was needed by the test fish during decision making. Predation pressure may select for better decision makers to survive to larger size, or that older, larger fish have learned to make shoaling decisions more efficiently, and this, combined with their size relative to shoal-mates, and attractiveness as prey items influences shoaling decisions

Role of the Subunits Interactions in the Conformational Transitions in Adult Human Hemoglobin: an Explicit Solvent Molecular Dynamics Study

Hemoglobin exhibits allosteric structural changes upon ligand binding due to the dynamic interactions between the ligand binding sites, the amino acids residues and some other solutes present under physiological conditions. In the present study, the dynamical and quaternary structural changes occurring in two unligated (deoxy-) T structures, and two fully ligated (oxy-) R, R2 structures of adult human hemoglobin were investigated with molecular dynamics. It is shown that, in the sub-microsecond time scale, there is no marked difference in the global dynamics of the amino acids residues in both the oxy- and the deoxy- forms of the individual structures. In addition, the R, R2 are relatively stable and do not present quaternary conformational changes within the time scale of our simulations while the T structure is dynamically more flexible and exhibited the T\rightarrow R quaternary conformational transition, which is propagated by the relative rotation of the residues at the {\alpha}1{\beta}2 and {\alpha}2{\beta}1 interface.Comment: Reprinted (adapted) with permission from J. Phys. Chem. B DOI:10.1021/jp3022908. Copyright (2012) American Chemical Societ

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Core Outcomes for Colorectal Cancer Surgery: A Consensus Study

Background: Colorectal cancer (CRC) is a major cause of worldwide morbidity and mortality. Surgical treatment is common, and there is a great need to improve the delivery of such care. The gold standard for evaluating surgery is within well-designed randomized controlled trials (RCTs); however, the impact of RCTs is diminished by a lack of coordinated outcome measurement and reporting. A solution to these issues is to develop an agreed standard “core” set of outcomes to be measured in all trials to facilitate cross-study comparisons, meta-analysis, and minimize outcome reporting bias. This study defines a core outcome set for CRC surgery. Methods and Findings: The scope of this COS includes clinical effectiveness trials of surgical interventions for colorectal cancer. Excluded were nonsurgical oncological interventions. Potential outcomes of importance to patients and professionals were identified through systematic literature reviews and patient interviews. All outcomes were transcribed verbatim and categorized into domains by two independent researchers. This informed a questionnaire survey that asked stakeholders (patients and professionals) from United Kingdom CRC centers to rate the importance of each domain. Respondents were resurveyed following group feedback (Delphi methods). Outcomes rated as less important were discarded after each survey round according to predefined criteria, and remaining outcomes were considered at three consensus meetings; two involving international professionals and a separate one with patients. A modified nominal group technique was used to gain the final consensus. Data sources identified 1,216 outcomes of CRC surgery that informed a 91 domain questionnaire. First round questionnaires were returned from 63 out of 81 (78%) centers, including 90 professionals, and 97 out of 267 (35%) patients. Second round response rates were high for all stakeholders (>80%). Analysis of responses lead to 45 and 23 outcome domains being retained after the first and second surveys, respectively. Consensus meetings generated agreement on a 12 domain COS. This constituted five perioperative outcome domains (including anastomotic leak), four quality of life outcome domains (including fecal urgency and incontinence), and three oncological outcome domains (including long-term survival). Conclusion: This study used robust consensus methodology to develop a core outcome set for use in colorectal cancer surgical trials. It is now necessary to validate the use of this set in research practice

Age-related changes to motor synergies in multi-joint and multi-finger manipulative skills: a meta-analysis

Purpose The aim of the current meta-analysis was to examine the extent to which there are differences in upper extremity motor synergies across different age groups in manipulative tasks. Methods The studies that used the uncontrolled manifold method to examine the effect of age on motor synergies in multijoint and multi-finger tasks were selected. Sixteen relevant studies from 1154 articles were selected for the meta-analysis—4 and 12 studies considered multi-joint kinematics and multi-finger kinetic tasks respectively. Results The results of the meta-analysis suggested reduced strength of synergies in multi-finger task in older adults, but this was not the case for synergies in multi-joint task. Part of this age-related difference in finger function is related to the increased variability in total force in grasping tasks. However, reductions in the strength of multi-finger synergies in hand functions following ageing appear to depend on the characteristics of the task. Conclusions These findings indicate that the cooperation among fingers to stabilise the total required force to apply for grasping and other fine motor skills is less efficient in older adults that might affect the quality of manipulative tasks

Dynamic data-driven meta-analysis for prioritisation of host genes implicated in COVID-19

The increasing body of literature describing the role of host factors in COVID-19 pathogenesis demonstrates the need to combine diverse, multi-omic data toevaluate and substantiate the most robust evidence and inform development oftherapies.Here we present a dynamic ranking of host genes implicated in human betacoronavirus infection (SARS-CoV-2, SARS-CoV, MERS-CoV, seasonal coronaviruses).We conducted an extensive systematic review of experiments identifying potential host factors. Gene lists from diverse sources were integrated using Meta-Analysis by Information Content (MAIC). This previously described algorithm uses data-driven gene list weightings to produce a comprehensive ranked list of implicated host genes.From 32 datasets, the top ranked gene was PPIA, encoding cyclophilin A, a druggable target using cyclosporine.Other highly-ranked genes included proposed prognostic factors (CXCL10, CD4, CD3E) and investigational therapeutic targets (IL1A) for COVID-19. Gene rankings also inform the interpretation of COVID-19 GWAS results, implicating FYCO1 over other nearby genes in a disease-associated locus on chromosome 3.Researchers can search and review the ranked genes and thecontribution of different experimental methods to gene rank athttps://baillielab.net/maic/covid19. As new data are published we willregularly update list of genes as a resource to inform and prioritise futurestudies

Elucidating knowledge and beliefs about obesity and eating disorders among key stakeholders : paving the way for an integrated approach to health promotion

Background: Understanding the knowledge and beliefs of key stakeholders is crucial in developing effective public health interventions. Knowledge and beliefs about obesity and eating disorders (EDs) have rarely been considered, despite increasing awareness of the need for integrated health promotion programs. We investigated key aspects of knowledge and beliefs about obesity and EDs among key stakeholders in Australia. Methods: Using a semi-structured question guide, eight focus groups and seven individual interviews were conducted with 62 participants including health professionals, personal trainers, teachers and consumer group representatives. An inductive thematic approach was used for data analysis. Results: The findings suggest that, relative to obesity, EDs are poorly understood among teachers, personal trainers, and certain health professionals. Areas of commonality and distinction between the two conditions were identified. Integrated health promotion efforts that focus on shared risk (e.g., low self-esteem, body dissatisfaction) and protective (e.g., healthy eating, regular exercise) factors were supported. Suggested target groups for such efforts included young children, adolescents and parents. Conclusions: The findings indicate areas where the EDs and obesity fields have common ground and can work together in developing integrated health promotion programs

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings: In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Health impact, and economic value, of meeting housing quality standards: a retrospective longitudinal data linkage study

Background Poor-quality housing adversely affects residents’ health but there is a paucity of high-quality evidence to support this. Objective This research investigated the health impact of bringing housing to a national quality standard. Design A natural experiment of improvements to housing quality analysed using repeated measures of health-care utilisation and economic outcomes at an individual person level. Setting Carmarthenshire, UK. Participants A total of 32,009 residents registered for a minimum of 60 days at 8558 social homes that received housing improvements between January 2005 and March 2015. Interventions Multiple internal and external housing improvements, including wall and loft insulation, windows and doors, heating system upgrades, new kitchens and bathrooms, garden path safety improvements and electrical system upgrades (adding power sockets, and extractor fans in kitchens and bathrooms). Main outcome measures Emergency hospital admissions for cardiorespiratory conditions and injuries. Primary health-care utilisation for respiratory and common mental health disorders, emergency department injury attendances and health-care utilisation costs. Data sources Carmarthenshire County Council home address and intervention records were anonymously linked within the Secure Anonymous Information Linkage databank to demographic information from the Welsh Demographic Service data set; hospital admission data from the Patient Episode Dataset for Wales; primary care contacts and prescribed medications from general practice data; emergency department attendances from the Emergency Department Data Set; and deaths from the Office for National Statistics mortality register. Methods The study used a longitudinal panel design to examine changes in standard of eight housing cointervention from intervention records, and linked to individuals registered at intervention homes. Health outcomes were obtained retrospectively for each individual in a dynamic cohort and were captured for up to 123 consecutive months. An additional local authority region could not be utilised as a comparator owing to different reporting pressures resulting in the recording of a different intervention. The exposure group for each cointervention was compared with an internal reference group of people living in homes that did not receive the cointervention during their tenancy. A multilevel modelling approach was used to account for repeated observations for individuals living in intervention homes. Counts of health outcomes were analysed using negative binomial regression models to determine the effect of each cointervention that reached housing quality standards during an individual’s period of tenancy, compared with those living in properties that did not. We adjusted for potential confounding factors and for background trends in the regional general population. A cost–consequences analysis was conducted as part of the health economic evaluation. Results Residents aged ≥ 60 years living in homes in which electrical systems were upgraded were associated with 39% fewer admissions than those living in homes in which they were not [incidence rate ratio (IRR) 0.61, 95% confidence interval (CI) 0.53 to 0.72; p < 0.01]. Reduced admissions were also associated with windows and doors (IRR 0.71, 95% CI 0.63 to 0.81; p < 0.01), wall insulation (IRR 0.75, 95% CI 0.67 to 0.84; p < 0.01) and gardens and estates (IRR 0.73, 95% CI 0.64 to 0.83; p < 0.01) for those living in homes in which these cointervention were upgraded. There were no associations of change in emergency admissions with upgrading heating (IRR 0.91, 95% CI 0.82 to 1.01; p = 0.072), loft insulation (IRR 0.98, 95% CI 0.86 to 1.11; p = 0.695), kitchens (IRR 0.98, 95% CI 0.83 to 1.17; p = 0.843) or bathrooms (IRR 0.93, 95% CI 0.81 to 1.06; p = 0.287). Limitations There was no randomisation, there were incomplete data on the scale of the intervention for individual households and there were no estimates for the impact of the whole programme. Conclusions This complex interdisciplinary study found that hospital admissions could be avoided through improving housing quality standards