Isolating endogenous visuo-spatial attentional effects using the novel visual-evoked spread spectrum analysis (VESPA) technique

In natural visual environments, we use attention to select between relevant and irrelevant stimuli that are presented simultaneously. Our attention to objects in our visual field is largely controlled endogenously, but is also affected exogenously through the influence of novel stimuli and events. The study of endogenous and exogenous attention as separate mechanisms has been possible in behavioral and functional imaging studies, where multiple stimuli can be presented continuously and simultaneously. It has also been possible in electroencephalogram studies using the steady-state visual-evoked potential (SSVEP); however, it has not been possible in conventional event-related potential (ERP) studies, which are hampered by the need to present suddenly onsetting stimuli in isolation. This is unfortunate as the ERP technique allows for the analysis of human physiology with much greater temporal resolution than functional magnetic resonance imaging or the SSVEP. While ERP studies of endogenous attention have been widely reported, these experiments have a serious limitation in that the suddenly onsetting stimuli, used to elicit the ERP, inevitably have an exogenous, attention-grabbing effect. Recently we have shown that it is possible to derive separate event-related responses to concurrent, continuously presented stimuli using the VESPA (visual-evoked spread spectrum analysis) technique. In this study we employed an experimental paradigm based on this method, in which two pairs of diagonally opposite, non-contiguous disc-segment stimuli were presented, one pair to be ignored and the other to be attended. VESPA responses derived for each pair showed a strong modulation at 90–100 ms (during the visual P1 component), demonstrating the utility of the method for isolating endogenous visuospatial attention effects

Differences between naive and memory T cell phenotype in Malawian and UK adolescents: a role for Cytomegalovirus?

Background: Differences in degree of environmental exposure to antigens in early life have been hypothesized to lead to differences in immune status in individuals from different populations, which may have implications for immune responses in later years.Methods: Venous blood from HIV-negative adolescents and blood from the umbilical cords of babies, born to HIV-negative women, post-delivery was collected and analysed using flow cytometry. T cell phenotype was determined from peripheral blood lymphocytes and cytomegalovirus (CMV) seropositivity was assessed by ELISA in adolescents.Results: HIV-negative Malawian adolescents were shown to have a lower percentage of naive T cells (CD45RO-CD62L(hi)CD11a(lo)), a higher proportion of memory T cells and a higher percentage of CD28(-) memory (CD28(-)CD45RO(+)) T cells compared to age-matched UK adolescents. Malawian adolescents also had a lower percentage of central memory (CD45RA(-)CCR7(+)) T cells and a higher percentage of stable memory (CD45RA(+)CCR7(-)) T cells than UK adolescents. All of the adolescents tested in Malawi were seropositive for CMV (59/59), compared to 21/58 (36%) of UK adolescents. CMV seropositivity in the UK was associated with a reduced percentage of naive T cells and an increased percentage of CD28- memory T cells in the periphery. No differences in the proportions of naive and memory T cell populations were observed in cord blood samples from the two sites.Conclusion: It is likely that these differences between Malawian and UK adolescents reflect a greater natural exposure to various infections, including CMV, in the African environment and may imply differences in the ability of these populations to induce and maintain immunological memory to vaccines and natural infections

Author Correction: Dynamic regulation of canonical TGFβ signalling by endothelial transcription factor ERG protects from liver fibrogenesis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance.

INTRODUCTION: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. METHODS: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). RESULTS: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). CONCLUSIONS: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations

Childbirth-related posttraumatic stress disorder: definition, risk factors, pathophysiology, diagnosis, prevention, and treatment

Psychological birth trauma and childbirth-related posttraumatic stress disorder represent a substantial burden of disease with 6.6 million mothers and 1.7 million fathers or co-parents affected by childbirth-related posttraumatic stress disorder worldwide each year. There is mounting evidence to indicate that parents who develop childbirth-related posttraumatic stress disorder do so as a direct consequence of a traumatic childbirth experience. High-risk groups, such as those who experience preterm birth, stillbirth, or preeclampsia, have higher prevalence rates. The main risks include antenatal factors (eg, depression in pregnancy, fear of childbirth, poor health or complications in pregnancy, history of trauma or sexual abuse, or mental health problems), perinatal factors (eg, negative subjective birth experience, operative birth, obstetrical complications, and severe maternal morbidity, as well as maternal near misses, lack of support, dissociation), and postpartum factors (eg, depression, postpartum physical complications, and poor coping and stress). The link between birth events and childbirth-related posttraumatic stress disorder provides a valuable opportunity to prevent traumatic childbirths and childbirth-related posttraumatic stress disorder from occurring in the first place. Childbirth-related posttraumatic stress disorder is an extremely distressing mental disorder and has a substantial negative impact on those who give birth, fathers or co-parents, and, potentially, the whole family. Still, a traumatic childbirth experience and childbirth-related posttraumatic stress disorder remain largely unrecognized in maternity services and are not routinely screened for during pregnancy and the postpartum period. In fact, there are gaps in the evidence on how, when, and who to screen. Similarly, there is a lack of evidence on how best to treat those affected. Primary prevention efforts (eg, screening for antenatal risk factors, use of trauma-informed care) are aimed at preventing a traumatic childbirth experience and childbirth-related posttraumatic stress disorder in the first place by eliminating or reducing risk factors for childbirth-related posttraumatic stress disorder. Secondary prevention approaches (eg, trauma-focused psychological therapies, early psychological interventions) aim to identify those who have had a traumatic childbirth experience and to intervene to prevent the development of childbirth-related posttraumatic stress disorder. Tertiary prevention (eg, trauma-focused cognitive behavioural therapy and eye movement desensitization and reprocessing) seeks to ensure that people with childbirth-related posttraumatic stress disorder are identified and treated to recovery so that childbirth-related posttraumatic stress disorder does not become chronic. Adequate prevention, screening, and intervention could alleviate a considerable amount of suffering in affected families. In light of the available research on the impact of childbirth-related posttraumatic stress disorder on families, it is important to develop and evaluate assessment, prevention, and treatment interventions that target the birthing person, the couple dyad, the parent-infant dyad, and the family as a whole. Further research should focus on the inclusion of couples in different constellations and, more generally, on the inclusion of more diverse populations in diverse settings. The paucity of national and international policy guidance on the prevention, care, and treatment of psychological birth trauma and the lack of formal psychological birth trauma services and training, highlight the need to engage with service managers and policy makers

Social disorganization and history of child sexual abuse against girls in sub-Saharan Africa : a multilevel analysis

Background: Child sexual abuse (CSA) is a considerable public health problem. Less focus has been paid to the role of community level factors associated with CSA. The aim of this study was to examine the association between neighbourhood-level measures of social disorganization and CSA. Methods: We applied multiple multilevel logistic regression analysis on Demographic and Health Survey data for 6,351 adolescents from six countries in sub-Saharan Africa between 2006 and 2008. Results: The percentage of adolescents that had experienced CSA ranged from 1.04% to 5.84%. There was a significant variation in the odds of reporting CSA across the communities, suggesting 18% of the variation in CSA could be attributed to community level factors. Respondents currently employed were more likely to have reported CSA than those who were unemployed (odds ratio [OR] = 2.05, 95% confidence interval [CI] 1.48 to 2.83). Respondents from communities with a high family disruption rate were 57% more likely to have reported CSA (OR=1.57, 95% CI 1.14 to 2.16). Conclusion: We found that exposure to CSA was associated with high community level of family disruption, thus suggesting that neighbourhoods may indeed have significant important effects on exposure to CSA. Further studies are needed to explore pathways that connect the individual and neighbourhood levels, that is, means through which deleterious neighbourhood effects are transmitted to individuals

Management, regulation and environmental impacts of nitrogen fertilization in northwestern Europe under the Nitrates Directive; a benchmark study

Implementation of the Nitrates Directive (NiD) and its environmental impacts were compared for member states in the northwest of the European Union (Ireland, United Kingdom, Denmark, the Netherlands, Belgium, Northern France and Germany). The main sources of data were national reports for the third reporting period for the NiD (2004–2007) and results of the MITERRA-EUROPE model. Implementation of the NiD in the considered member states is fairly comparable regarding restrictions for where and when to apply fertilizer and manure, but very different regarding application limits for N fertilization. Issues of concern and improvement of the implementation of the NiD are accounting for the fertilizer value of nitrogen in manure, and relating application limits for total nitrogen (N) to potential crop yield and N removal. The most significant environmental effect of the implementation of the NiD since 1995 is a major contribution to the decrease of the soil N balance (N surplus), particularly in Belgium, Denmark, Ireland, the Netherlands and the United Kingdom. This decrease is accompanied by a modest decrease of nitrate concentrations since 2000 in fresh surface waters in most countries. This decrease is less prominent for groundwater in view of delayed response of nitrate in deep aquifers. In spite of improved fertilization practices, the southeast of the Netherlands, the Flemish Region and Brittany remain to be regions of major concern in view of a combination of a high nitrogen surplus, high leaching fractions to groundwater and tenacious exceedance of the water quality standards. On average the gross N balance in 2008 for the seven member states in EUROSTAT and in national reports was about 20 kg N ha<sup>−1</sup> yr<sup>−1</sup> lower than by MITERRA. The major cause is higher estimates of N removal in national reports which can amount to more than 50 kg N ha<sup>−1</sup> yr<sup>−1</sup>. Differences between procedures in member states to assess nitrogen balances and water quality and a lack of cross-boundary policy evaluations are handicaps when benchmarking the effectiveness of the NiD. This provides a challenge for the European Commission and its member states, as the NiD remains an important piece of legislation for protecting drinking water quality in regions with many private or small public production facilities and controlling aquatic eutrophication from agricultural sources

Being a quantitative interviewer: qualitatively exploring interviewers' experiences in a longitudinal cohort study

<p>Abstract</p> <p>Background</p> <p>Many studies of health outcomes rely on data collected by interviewers administering highly-structured (quantitative) questionnaires to participants. Little appears to be known about the experiences of such interviewers. This paper explores interviewer experiences of working on a longitudinal study in New Zealand (the Prospective Outcomes of injury Study - POIS). Interviewers administer highly-structured questionnaires to participants, usually by telephone, and enter data into a secure computer program. The research team had expectations of interviewers including: consistent questionnaire administration, timeliness, proportions of potential participants recruited and an empathetic communication style. This paper presents results of a focus group to qualitatively explore with the team of interviewers their experiences, problems encountered, strategies, support systems used and training.</p> <p>Methods</p> <p>A focus group with interviewers involved in the POIS interviews was held; it was audio-recorded and transcribed. The analytical method was thematic, with output intended to be descriptive and interpretive.</p> <p>Results</p> <p>Nine interviewers participated in the focus group (average time in interviewer role was 31 months). Key themes were: 1) the positive aspects of the quantitative interviewer role (i.e. relationships and resilience, insights gained, and participants' feedback), 2) difficulties interviewers encountered and solutions identified (i.e. stories lost or incomplete, forgotten appointments, telling the stories, acknowledging distress, stories reflected and debriefing and support), and 3) meeting POIS researcher expectations (i.e. performance standards, time-keeping, dealing exclusively with the participant and maintaining privacy).</p> <p>Conclusions</p> <p>Interviewers demonstrated great skill in the way they negotiated research team expectations whilst managing the relationships with participants. Interviewers found it helpful to have a research protocol in place in the event of sensitive situations - this appeared to alleviate the pressure on interviewers to carry the burden of responsibility. Interviewers are employed to scientifically gather quantitative data, yet their effectiveness relies largely on their humanity. We propose that the personal connection generated between the interviewers and participants was important, and enabled successful follow-up rates for the study. The enjoyment of these relationships was crucial to interviewers and helped balance the negative aspects of their role. Our results suggest that experienced quantitative interviewers endeavour, as do many qualitative researchers, to carefully and respectfully negotiate the requirements of the interview within a relationship they form with participants: being sensitive to the needs of participants and respectful of their wishes - and establishing an ethical relationship.</p

Total immersion : Designing for affective symbiosis in a virtual reality game with haptics, biosensors, and emotive agents

Peer reviewe

Analysis of host responses to Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa.

BACKGROUND: Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. METHODS: We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. RESULTS: There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST(-) and TST(+) contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST(+) contacts (LTBI) compared to TB and TST(-) contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. CONCLUSIONS: Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may be useful for vaccine efficacy trials