The effect of alpha(+)-thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya

BACKGROUND: The alpha-thalassaemias are the commonest genetic disorders of humans. It is generally believed that this high frequency reflects selection through a survival advantage against death from malaria; nevertheless, the epidemiological description of the relationships between alpha-thalassaemia, malaria, and other common causes of child mortality remains incomplete. METHODS AND FINDINGS: We studied the alpha+-thalassaemia-specific incidence of malaria and other common childhood diseases in two cohorts of children living on the coast of Kenya. We found no associations between alpha+-thalassaemia and the prevalence of symptomless Plasmodium falciparum parasitaemia, the incidence of uncomplicated P. falciparum disease, or parasite densities during mild or severe malaria episodes. However, we found significant negative associations between alpha+-thalassaemia and the incidence rates of severe malaria and severe anaemia (haemoglobin concentration < 50 g/l). The strongest associations were for severe malaria anaemia (> 10,000 P. falciparum parasites/mul) and severe nonmalaria anaemia; the incidence rate ratios and 95% confidence intervals (CIs) for alpha+-thalassaemia heterozygotes and homozygotes combined compared to normal children were, for severe malaria anaemia, 0.33 (95% CI, 0.15,0.73; p = 0.006), and for severe nonmalaria anaemia, 0.26 (95% CI, 0.09,0.77; p = 0.015). CONCLUSIONS: Our observations suggest, first that selection for alpha+-thalassaemia might be mediated by a specific effect against severe anaemia, an observation that may lead to fresh insights into the aetiology of this important condition. Second, although alpha+-thalassaemia is strongly protective against severe and fatal malaria, its effects are not detectable at the level of any other malaria outcome; this result provides a cautionary example for studies aimed at testing malaria interventions or identifying new malaria-protective genes

Underperforming policy networks : the biopesticides network in the United Kingdom

Loosely integrated and incomplete policy networks have been neglected in the literature. They are important to consider in terms of understanding network underperformance. The effective delivery and formulation of policy requires networks that are not incomplete or underperforming. The biopesticides policy network in the United Kingdom is considered and its components identified with an emphasis on the lack of integration of retailers and environmental groups. The nature of the network constrains the actions of its agents and frustrates the achievement of policy goals. A study of this relatively immature policy network also allows for a focus on network formation. The state, via an external central government department, has been a key factor in the development of the network. Therefore, it is important to incorporate such factors more systematically into understandings of network formation. Feedback efforts from policy have increased interactions between productionist actors but the sphere of consumption remains insufficiently articulated

What can patients tell us about the quality and safety of hospital care? Findings from a UK multicentre survey study

Background Patient safety measurement remains a global challenge. Patients are an important but neglected source of learning; however, little is known about what patients can add to our understanding of safety. We sought to understand the incidence and nature of patient-reported safety concerns in hospital. Methods Feedback about the experience of safety within hospital was gathered from 2471 inpatients as part of a multicentre, waitlist cluster randomised controlled trial of an intervention, undertaken within 33 wards across three English NHS Trusts, between May 2013 and September 2014. Patient volunteers, supported by researchers, developed a classification framework of patient-reported safety concerns from a random sample of 231 reports. All reports were then classified using the patient-developed categories. Following this, all patient-reported safety concerns underwent a two-stage clinical review process for identification of patient safety incidents. Results Of the 2471 inpatients recruited, 579 provided 1155 patient-reported incident reports. 14 categories were developed for classification of reports, with communication the most frequently occurring (22%), followed by staffing issues (13%) and problems with the care environment (12%). 406 of the total 1155 patient incident reports (35%) were classified by clinicians as a patient safety incident according to the standard definition. 1 in 10 patients (264 patients) identified a patient safety incident, with medication errors the most frequently reported incident. Conclusions Our findings suggest that patients can provide insight about safety that complements existing patient safety measurement, with a frequency of reported patient safety incidents that is similar to those obtained via case note review. However, patients provide a unique perspective about hospital safety which differs from and adds to current definitions of patient safety incidents

S2P3-R v2.0: computationally efficient modelling of shelf seas on regional to global scales

This is the final version. Available on open access from the European Geosciences Union via the DOI in this recordCode availability: S2P3Rv2.0 is available on GitHub: https://github.com/PaulHalloran/S2P3Rv2.0 (last access: 21 September 2021). The release associated with this paper (https://github.com/PaulHalloran/S2P3Rv2.0/releases/tag/v1.0.1, last access: 21 September 2021​​​​​​​) has been archived on Zenodo with the following DOI: https://doi.org/10.5281/zenodo.4147559 (Halloran, 2020a). The readme file available on GitHub or via the DOI link provides step-by-step instructions for how to install, set up and run the model, and it provides a basic script for analysing the model output. At the bottom of the readme, a worked example is provided to help the user go through the full process from generating model forcing files, running the model and displaying the output with some example data.Data availability: The model minus satellite SST data from the global (65∘ S–65∘ N) simulation averaged between 2006 and 2016, from which the global validation has been undertaken in this paper, is archived as NetCDF and csv files to allow potential users to undertake bespoke assessment of the model http://doi.org/10.5281/zenodo.4018815 (Halloran, 2020b).The marine impacts of climate change on our societies will be largely felt through coastal waters and shelf seas. These impacts involve sectors as diverse as tourism, fisheries and energy production. Projections of future marine climate change come from global models. Modelling at the global scale is required to capture the feedbacks and large-scale transport of physical properties such as heat, which occur within the climate system, but global models currently cannot provide detail in the shelf seas. Version 2 of the regional implementation of the Shelf Sea Physics and Primary Production (S2P3-R v2.0) model bridges the gap between global projections and local shelf-sea impacts. S2P3-R v2.0 is a highly simplified coastal shelf model, computationally efficient enough to be run across the shelf seas of the whole globe. Despite the simplified nature of the model, it can display regional skill comparable to state-of-the-art models, and at the scale of the global (excluding high latitudes) shelf seas it can explain >50 % of the interannual sea surface temperature (SST) variability in ∼60 % of grid cells and >80 % of interannual variability in ∼20 % of grid cells. The model can be run at any resolution for which the input data can be supplied, without expert technical knowledge, and using a modest off-the-shelf computer. The accessibility of S2P3-R v2.0 places it within reach of an array of coastal managers and policy makers, allowing it to be run routinely once set up and evaluated for a region under expert guidance. The computational efficiency and relative scientific simplicity of the tool make it ideally suited to educational applications. S2P3-R v2.0 is set up to be driven directly with output from reanalysis products or daily atmospheric output from climate models such as those which contribute to the sixth phase of the Climate Model Intercomparison Project, making it a valuable tool for semi-dynamical downscaling of climate projections. The updates introduced into version 2.0 of this model are primarily focused around the ability to geographical relocate the model, model usability and speed but also scientific improvements. The value of this model comes from its computational efficiency, which necessitates simplicity. This simplicity leads to several limitations, which are discussed in the context of evaluation at regional and global scales.Natural Environment Research Council (NERC)European Union Horizon 2020NOA

Expecting to lift a box together makes the load look lighter

The action abilities of an individual observer modulate his or her perception of spatial properties of the environment and of objects. The present study investigated how joint action abilities shape perception. Four experiments examined how the intention to lift an object with another individual affects perceived weight. In Experiments 1, 2a, and 2b, participants judged the perceived weight of boxes while expecting to lift them either alone or with a co-actor. In Experiment 3, the co-actor was healthy or injured. Participants intending to lift a box with a co-actor perceived the box as lighter than participants intending to lift the same box alone, provided that the co-actor appeared healthy and therefore capable of helping. These findings suggest that anticipated effort modulates the perception of object properties in the context of joint action. We discuss implications for the role of action prediction and action simulation processes in social interaction

Isotocin neuronal phenotypes differ among social systems in cichlid fishes

Social living has evolved numerous times across a diverse array of animal taxa. An open question is how the transition to a social lifestyle has shaped, and been shaped by, the underlying neurohormonal machinery of social behaviour. The nonapeptide neurohormones, implicated in the regulation of social behaviours, are prime candidates for the neuroendocrine substrates of social evolution. Here, we examined the brains of eight cichlid fish species with divergent social systems, comparing the number and size of preoptic neurons that express the nonapeptides isotocin and vasotocin. While controlling for the influence of phylogeny and body size, we found that the highly social cooperatively breeding species (n = 4) had fewer parvocellular isotocin neurons than the less social independently breeding species (n = 4), suggesting that the evolutionary transition to group living and cooperative breeding was associated with a reduction in the number of these neurons. In a complementary analysis, we found that the size and number of isotocin neurons significantly differentiated the cooperatively breeding from the independently breeding species. Our results suggest that isotocin is related to sociality in cichlids and may provide a mechanistic substrate for the evolution of sociality

Estimating Small Area Income Deprivation: An Iterative Proportional Fitting Approach

Small area estimation and in particular the estimation of small area income deprivation has potential value in the development of new or alternative components of multiple deprivation indices. These new approaches enable the development of income distribution threshold based as opposed to benefit count based measures of income deprivation and so enable the alignment of regional and national measures such as the Households Below Average Income with small area measures. This paper briefly reviews a number of approaches to small area estimation before describing in some detail an iterative proportional fitting based spatial microsimulation approach. This approach is then applied to the estimation of small area HBAI rates at the small area level in Wales in 2003-5. The paper discusses the results of this approach, contrasts them with contemporary ‘official’ income deprivation measures for the same areas and describes a range of ways to assess the robustness of the results

The patient reporting and action for a safe environment (PRASE) intervention: a feasibility study

Background: There is growing interest in the role of patients in improving patient safety. One such role is providing feedback on the safety of their care. Here we describe the development and feasibility testing of an intervention that collects patient feedback on patient safety, brings together staff to consider this feedback and to plan improvement strategies. We address two research questions: i) to explore the feasibility of the process of systematically collecting feedback from patients about the safety of care as part of the PRASE intervention; and, ii) to explore the feasibility and acceptability of the PRASE intervention for staff, and to understand more about how staff use the patient feedback for service improvement. Method: We conducted a feasibility study using a wait-list controlled design across six wards within an acute teaching hospital. Intervention wards were asked to participate in two cycles of the PRASE (Patient Reporting & Action for a Safe Environment) intervention across a six-month period. Participants were patients on participating wards. To explore the acceptability of the intervention for staff, observations of action planning meetings, interviews with a lead person for the intervention on each ward and recorded researcher reflections were analysed thematically and synthesised. Results: Recruitment of patients using computer tablets at their bedside was straightforward, with the majority of patients willing and able to provide feedback. Randomisation of the intervention was acceptable to staff, with no evidence of differential response rates between intervention and control groups. In general, ward staff were positive about the use of patient feedback for service improvement and were able to use the feedback as a basis for action planning, although engagement with the process was variable. Gathering a multidisciplinary team together for action planning was found to be challenging, and implementing action plans was sometimes hindered by the need to co-ordinate action across multiple services. Discussion: The PRASE intervention was found to be acceptable to staff and patients. However, before proceeding to a full cluster randomised controlled trial, the intervention requires adaptation to account for the difficulties in implementing action plans within three months, the need for a facilitator to support the action planning meetings, and the provision of training and senior management support for participating ward teams. Conclusions: The PRASE intervention represents a promising method for the systematic collection of patient feedback about the safety of hospital care

Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis

Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al

Elevated Incidence of Dental Caries in a Mouse Model of Cystic Fibrosis

Saliva bicarbonate constitutes the main buffering system which neutralizes the pH fall generated by the plaque bacteria during sugar metabolism. We found that the saliva pH is severely decreased in a mouse model of cystic fibrosis disease (CF). Given the close relationship between pH and caries development, we hypothesized that caries incidence might be elevated in the mouse CF model.). are enhanced at low pH values, we speculate that the decrease in the bicarbonate content and pH buffering of the saliva is at least partially responsible for the increased severity of lesions observed in the CF mouse