Genomic Analysis of Salmonella enterica Serovar Typhimurium DT160 Associated with a 14-Year Outbreak, New Zealand, 1998–2012

During 1998–2012, an extended outbreak of Salmonella enterica serovar Typhimurium definitive type 160 (DT160) affected >3,000 humans and killed wild birds in New Zealand. However, the relationship between DT160 within these 2 host groups and the origin of the outbreak are unknown. Whole-genome sequencing was used to compare 109 Salmonella Typhimurium DT160 isolates from sources throughout New Zealand. We provide evidence that DT160 was introduced into New Zealand around 1997 and rapidly propagated throughout the country, becoming more genetically diverse over time. The genetic heterogeneity was evenly distributed across multiple predicted functional protein groups, and we found no evidence of host group differentiation between isolates collected from human, poultry, bovid, and wild bird sources, indicating ongoing transmission between these host groups. Our findings demonstrate how a comparative genomic approach can be used to gain insight into outbreaks, disease transmission, and the evolution of a multihost pathogen after a probable point-source introduction

HIV-1 Inhibits Phagocytosis and Inflammatory Cytokine Responses of Human Monocyte-Derived Macrophages to P. falciparum Infected Erythrocytes

HIV-1 infection increases the risk and severity of malaria by poorly defined mechanisms. We investigated the effect of HIV-1Ba-L infection of monocyte-derived macrophages (MDM) on phagocytosis of opsonised P. falciparum infected erythrocytes (IE) and subsequent proinflammatory cytokine secretion. Compared to mock-infected MDM, HIV-1 infection significantly inhibited phagocytosis of IE (median (IQR) (10 (0–28) versus (34 (27–108); IE internalised/100 MDM; p = 0.001) and decreased secretion of IL-6 (1,116 (352–3,387) versus 1,552 (889–6,331); pg/mL; p = 0.0078) and IL-1β (16 (7–21) versus 33 (27–65); pg/mL; p = 0.0078). Thus inadequate phagocytosis and cytokine production may contribute to impaired control of malaria in HIV-1 infected individuals

Caregiver education in Parkinson’s disease: formative evaluation of a standardized program in seven European countries

The formative evaluation of a standardized psychosocial education program for patients with Parkinson's disease (PD) and their caregivers. The results of the participation of the caregivers are presented next to the data of the patients. Caregivers (n = 137) and patients with PD (n = 151) participated in the 8-week program in separate groups. Measurements were performed on psychosocial problems (BELA-P/A-k), health state (EQ-5D VAS), quality of life (PDQ-39) and depression (SDS) 1 week before and 1 week after the program. Participants rated their mood on a visual analogue scale before and after each session, and they filled in an evaluation questionnaire after the last session. Scores on the BELA-P/A-k improved significantly on the 'bothered by scale' as well as the 'need for help scale'. No improvements were found on EQ-5D VAS, PDQ-39 and SDS. Mood ratings improved significantly after each session. Most participants evaluated the program as positive. Feedback led to improvements in the program, which are incorporated in a final manual. The program was feasible to run in the different countries. This exploratory study led to improvements in the program and recommendations for further research. A study on the effectiveness of the program is the next step.Pathophysiology of paroxysmal and chronic degenerative progressive disorder of the central and periferal nervous syste

Mapping medical careers: Questionnaire assessment of career preferences in medical school applicants and final-year students

BACKGROUND: The medical specialities chosen by doctors for their careers play an important part in the workforce planning of health-care services. However, there is little theoretical understanding of how different medical specialities are perceived or how choices are made, despite there being much work in general on this topic in occupational psychology, which is influenced by Holland's RIASEC (Realistic-Investigative-Artistic-Social-Enterprising-Conventional) typology of careers, and Gottfredson's model of circumscription and compromise. In this study, we use three large-scale cohorts of medical students to produce maps of medical careers. METHODS: Information on between 24 and 28 specialities was collected in three UK cohorts of medical students (1981, 1986 and 1991 entry), in applicants (1981 and 1986 cohorts, N = 1135 and 2032) or entrants (1991 cohort, N = 2973) and in final-year students (N = 330, 376, and 1437). Mapping used Individual Differences Scaling (INDSCAL) on sub-groups broken down by age and sex. The method was validated in a population sample using a full range of careers, and demonstrating that the RIASEC structure could be extracted. RESULTS: Medical specialities in each cohort, at application and in the final-year, were well represented by a two-dimensional space. The representations showed a close similarity to Holland's RIASEC typology, with the main orthogonal dimensions appearing similar to Prediger's derived orthogonal dimensions of 'Things-People' and 'Data-Ideas'. CONCLUSIONS: There are close parallels between Holland's general typology of careers, and the structure we have found in medical careers. Medical specialities typical of Holland's six RIASEC categories are Surgery (Realistic), Hospital Medicine (Investigative), Psychiatry (Artistic), Public Health (Social), Administrative Medicine (Enterprising), and Laboratory Medicine (Conventional). The homology between medical careers and RIASEC may mean that the map can be used as the basis for understanding career choice, and for providing career counselling

Antibodies to a Full-Length VAR2CSA Immunogen Are Broadly Strain-Transcendent but Do Not Cross-Inhibit Different Placental-Type Parasite Isolates

The high molecular weight, multidomain VAR2CSA protein mediating adhesion of Plasmodium falciparum-infected erythrocytes in the placenta is the leading candidate for a pregnancy malaria vaccine. However, it has been difficult so far to generate strong and consistent adhesion blocking antibody responses against most single-domain VAR2CSA immunogens. Recent advances in expression of the full-length recombinant protein showed it binds with much greater specificity and affinity to chondroitin sulphate A (CSA) than individual VAR2CSA domains. This raises the possibility that a specific CSA binding pocket(s) is formed in the full length antigen and could be an important target for vaccine development. In this study, we compared the immunogenicity of a full-length VAR2CSA recombinant protein containing all six Duffy binding-like (DBL) domains to that of a three-domain construct (DBL4-6) in mice and rabbits. Animals immunized with either immunogen acquired antibodies reacting with several VAR2CSA individual domains by ELISA, but antibody responses against the highly conserved DBL4 domain were weaker in animals immunized with full-length DBL1-6 recombinant protein compared to DBL4-6 recombinant protein. Both immunogens induced cross-reactive antibodies to several heterologous CSA-binding parasite lines expressing different VAR2CSA orthologues. However, antibodies that inhibited adhesion of parasites to CSA were only elicited in rabbits immunized with full-length immunogen and inhibition was restricted to the homologous CSA-binding parasite. These findings demonstrate that partial and full-length VAR2CSA immunogens induce cross-reactive antibodies, but inhibitory antibody responses to full-length immunogen were highly allele-specific and variable between animal species

Social and occupational factors associated with psychological distress and disorder among disaster responders: a systematic review

BACKGROUND: When disasters occur, there are many different occupational groups involved in rescue, recovery and support efforts. This study aimed to conduct a systematic literature review to identify social and occupational factors affecting the psychological impact of disasters on responders. METHODS: Four electronic literature databases (MEDLINE®, Embase, PsycINFO® and Web of Science) were searched and hand searches of reference lists were carried out. Papers were screened against specific inclusion criteria (e.g. published in peer-reviewed journal in English; included a quantitative measure of wellbeing; participants were disaster responders). Data was extracted from relevant papers and thematic analysis was used to develop a list of key factors affecting the wellbeing of disaster responders. RESULTS: Eighteen thousand five papers were found and 111 included in the review. The psychological impact of disasters on responders appeared associated with pre-disaster factors (occupational factors; specialised training and preparedness; life events and health), during-disaster factors (exposure; duration on site and arrival time; emotional involvement; peri-traumatic distress/dissociation; role-related stressors; perceptions of safety, threat and risk; harm to self or close others; social support; professional support) and post-disaster factors (professional support; impact on life; life events; media; coping strategies). CONCLUSIONS: There are steps that can be taken at all stages of a disaster (before, during and after) which may minimise risks to responders and enhance resilience. Preparedness (for the demands of the role and the potential psychological impact) and support (particularly from the organisation) are essential. The findings of this review could potentially be used to develop training workshops for professionals involved in disaster response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40359-016-0120-9) contains supplementary material, which is available to authorized users

The kinetics of antibody binding to Plasmodium falciparum VAR2CSA PfEMP1 antigen and modelling of PfEMP1 antigen packing on the membrane knobs

<p>Abstract</p> <p>Background</p> <p>Infected humans make protective antibody responses to the PfEMP1 adhesion antigens exported by <it>Plasmodium falciparum </it>parasites to the erythrocyte membrane, but little is known about the kinetics of this antibody-receptor binding reaction or how the topology of PfEMP1 on the parasitized erythrocyte membrane influences antibody association with, and dissociation from, its antigenic target.</p> <p>Methods</p> <p>A Quartz Crystal Microbalance biosensor was used to measure the association and dissociation kinetics of VAR2CSA PfEMP1 binding to human monoclonal antibodies. Immuno-fluorescence microscopy was used to visualize antibody-mediated adhesion between the surfaces of live infected erythrocytes and atomic force microscopy was used to obtain higher resolution images of the membrane knobs on the infected erythrocyte to estimate knob surface areas and model VAR2CSA packing density on the knob.</p> <p>Results</p> <p>Kinetic analysis indicates that antibody dissociation from the VAR2CSA PfEMP1 antigen is extremely slow when there is a high avidity interaction. High avidity binding to PfEMP1 antigens on the surface of <it>P. falciparum</it>-infected erythrocytes in turn requires bivalent cross-linking of epitopes positioned within the distance that can be bridged by antibody. Calculations of the surface area of the knobs and the possible densities of PfEMP1 packing on the knobs indicate that high-avidity cross-linking antibody reactions are constrained by the architecture of the knobs and the large size of PfEMP1 molecules.</p> <p>Conclusions</p> <p>High avidity is required to achieve the strongest binding to VAR2CSA PfEMP1, but the structures that display PfEMP1 also tend to inhibit cross-linking between PfEMP1 antigens, by holding many binding epitopes at distances beyond the 15-18 nm sweep radius of an antibody. The large size of PfEMP1 will also constrain intra-knob cross-linking interactions. This analysis indicates that effective vaccines targeting the parasite's vulnerable adhesion receptors should primarily induce strongly adhering, high avidity antibodies whose association rate constant is less important than their dissociation rate constant.</p

Citizen science breathes new life into participatory agricultural research : A review

Participatory research can improve the efficiency, effectiveness, and scope of research processes, and foster social inclusion, empowerment and sustainability. Yet despite four decades of agricultural research institutions exploring and developing methods for participatory research, it has never become mainstream in the agricultural technology development cycle. Citizen science promises an innovative approach to participation in research, using the unique facilities of new digital technologies, but its potential in agricultural research participation has not been systematically probed. To this end, we conducted a critical literature review. We found that citizen science opens up four opportunities for creatively reshaping research: i) new possibilities for interdisciplinary collaboration, ii) rethinking configurations of socio-computational systems, iii) research on democratization of science more broadly, and iv) new accountabilities. Citizen science also brings a fresh perspective on the barriers to institutionalizing participation in the agricultural sciences. Specifically, we show how citizen science can reconfigure cost-motivation-accountability combinations using digital tools, open up a larger conceptual space of experimentation, and stimulate new collaborations. With appropriate and persistent institutional support and investment, citizen science can therefore have a lasting impact on how agricultural science engages with farming communities and wider society, and more fully realize the promises of participation

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies