The Trypanosoma brucei AIR9-like protein is cytoskeleton-associated and is required for nucleus positioning and accurate cleavage furrow placement

AIR9 is a cytoskeleton-associated protein in Arabidopsis thaliana with roles in cytokinesis and cross wall maturation, and reported homologues in land plants and excavate protists, including trypanosomatids. We show that the Trypanosoma brucei AIR9-like protein, TbAIR9, is also cytoskeleton-associated and colocalises with the subpellicular microtubules. We find it to be expressed in all life cycle stages and show that it is essential for normal proliferation of trypanosomes in vitro. Depletion of TbAIR9 from procyclic trypanosomes resulted in increased cell length due to increased microtubule extension at the cell posterior. Additionally, the nucleus was re-positioned to a location posterior to the kinetoplast, leading to defects in cytokinesis and the generation of aberrant progeny. In contrast, in bloodstream trypanosomes, depletion of TbAIR9 had little effect on nucleus positioning, but resulted in aberrant cleavage furrow placement and the generation of non-equivalent daughter cells following cytokinesis. Our data provide insight into the control of nucleus positioning in this important pathogen and emphasise differences in the cytoskeleton and cell cycle control between two life cycle stages of the T. brucei parasite

Adaptive response of neonatal sepsis-derived Group B Streptococcus to bilirubin

This work was funded by the Neonatal Unit Endowment Fund, Aberdeen Maternity Hospital. RH is funded by a career researcher fellowship from NHS Research Scotland. SG was funded by the MRC Flagship PhD programme. We are grateful for the support of Dr Phil Cash and Aberdeen Proteomics, at University of Aberdeen, in completing this project. Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-018-24811-3.Peer reviewedPublisher PD

Individual, social and environmental factors influencing dietary behaviour in shift workers with type 2 diabetes working in UK healthcare: A cross-sectional survey

BACKGROUND: The present study aimed to understand the individual, social and environmental factors influencing dietary behaviour in shift workers with type 2 diabetes (T2D) working in UK healthcare settings. METHODS: A cross-sectional study was conducted using data collected from an anonymous online survey. Participant agreement was measured using five-point Likert scale (strongly disagree to strongly agree) against 38 belief statements informed by the Theoretical Domains Framework (TDF) of behaviour change. RESULTS: From the complete responses (n = 119), 65% worked shifts without nights, 27% worked mixed shift rota including nights and 8% worked only night shifts. The statements ranked with the highest agreements were in the TDF domains: Environment Context/Resources (ECR) - mainly identified as a barrier to healthy eating, Behaviour Regulation (BR) and intention (IN) - identified as enablers to healthy eating. For the belief statement 'the available options for purchasing food are too expensive' (ECR), 80% of night workers and 75% non-night workers agreed/strongly agreed. Taking their own food to work to prevent making unhealthy food choices (BR) had agreement/strong agreement in 73% of non-night and 70% night workers; 74% non-night workers and 80% of night workers agreed/strongly agreed with the statement 'I would like to eat healthily at work' (IN). Mixed shift workers agreed that following dietary advice was easier when working a non-night compared to a night shift (p = 0.002). CONCLUSIONS: Access and affordability of food were identified as important determinants of dietary behaviour during shifts. The findings support interventions targeting the food environment for shift workers with T2D

Variation in referral and access to new psychological therapy services by age: an empirical quantitative study.

Background: Older people with common mental health problems (CMHPs) are known to have reduced rates of referral to psychological therapy. Aim: We aimed to assess referral rates to the Improving Access to Psychological Therapies (IAPT) service, contact with a therapist and clinical outcome by age. Design and Setting: Empirical research using patient episodes of care from South West IAPT. Method: By analysing 82,513 episodes of care (2010-2011), referral rates and clinical improvement were compared to both total population and estimated prevalence in each age group using IAPT data. Probable recovery of those completing treatment were calculated for each group. Results: Estimated prevalence of CMHPs peaks in 45–49 year olds (20.59% of population). The proportions of patients identified with CMHPs being referred peaks at 20-24 years (22.95%) and reduces with increase in age thereafter to 6.00% for 70-74 year olds. Once referred, the proportion of those attending first treatment increases with age between 18 years (57.64%) and 64 years (76.97%). In addition, the percentage of those having a clinical improvement gradually increases from the age 20 years (12.94%) to 69 years (20.74%). Conclusion: Younger adults are more readily referred to IAPT services. However, as a proportion of those referred, probabilities of attending once, attending more than once, and clinical improvement, increase with age. It is uncertain whether optimum levels of referral have been reached for young adults. It is important to establish whether changes to service configuration, treatment options, and GP behaviour can increase referrals for middle-aged and older adults

Visions: Chaos in Naango

Trailer: https://www.youtube.com/watch?v=kxjqjJNMSFQ Website: http://www.visionsthegame.com Development Blog: http://visionsthegame.tumblr.com Facebook: https://www.facebook.com/visionsthegame/?fref=ts Twitter: https://twitter.com/visionsthegame Email: [email protected]

The unequal burden of human-wildlife conflict

The costs of human-wildlife conflict are measurably more impactful in areas of the developing world where the loss of cattle can mean the entire livelihood of a family being erased.Human-wildlife conflict is one of the most pressing sustainable development challenges globally. This is particularly the case where ecologically and economically important wildlife impact the livelihoods of humans. Large carnivores are one such group and their co-occurrence with low-income rural communities often results in real or perceived livestock losses that place increased costs on already impoverished households. Here we show the disparities associated with the vulnerability to conflict arising from large carnivores on cattle (Bos taurus) globally. Across the distribution of 18 large carnivores, we find that the economic vulnerability to predation losses (as measured by impacts to annual per capita income) is between two and eight times higher for households in transitioning and developing economies when compared to developed ones. This potential burden is exacerbated further in developing economies because cattle keepers in these areas produce on average 31% less cattle meat per animal than in developed economies. In the lowest-income areas, our estimates suggest that the loss of a single cow or bull equates to nearly a year and a half of lost calories consumed by a child. Finally, our results show that 82% of carnivore range falls outside protected areas, and five threatened carnivores have over one third of their range located in the most economically sensitive conflict areas. This unequal burden of human-carnivore conflict sheds light on the importance of grappling with multiple and conflicting sustainable development goals: protecting life on land and eliminating poverty and hunger

Mortality and its risk factors in Malawian children admitted to hospital with clinical pneumonia, 2001–12: a retrospective observational study

Background Few studies have reported long-term data on mortality rates for children admitted to hospital with pneumonia in Africa. We examined trends in case fatality rates for all-cause clinical pneumonia and its risk factors in Malawian children between 2001 and 2012. Methods Individual patient data for children (<5 years) with clinical pneumonia who were admitted to hospitals participating in Malawi’s Child Lung Health Programme between 2001 and 2012 were recorded prospectively on a standardised medical form. We analysed trends in pneumonia mortality and children’s clinical characteristics, and we estimated the association of risk factors with case fatality for children younger than 2 months, 2–11 months of age, and 12–59 months of age using separate multivariable mixed eff ects logistic regression models. Findings Between November, 2012, and May, 2013, we retrospectively collected all available hard copies of yellow forms from 40 of 41 participating hospitals. We examined 113 154 pneumonia cases, 104 932 (92∧7%) of whom had mortality data and 6903 of whom died, and calculated an overall case fatality rate of 6·6% (95% CI 6·4–6·7). The case fatality rate signifi cantly decreased between 2001 (15·2% [13·4–17·1]) and 2012 (4·5% [4·1–4·9]; ptrend<0·0001). Univariable analyses indicated that the decrease in case fatality rate was consistent across most subgroups. In multivariable analyses, the risk factors signifi cantly associated with increased odds of mortality were female sex, young age, very severe pneumonia, clinically suspected Pneumocystis jirovecii infection, moderate or severe underweight, severe acute malnutrition, disease duration of more than 21 days, and referral from a health centre. Increasing year between 2001 and 2012 and increasing age (in months) were associated with reduced odds of mortality. Fast breathing was associated with reduced odds of mortality in children 2–11 months of age. However, case fatality rate in 2012 remained high for children with very severe pneumonia (11·8%), severe undernutrition (15·4%), severe acute malnutrition (34·8%), and symptom duration of more than 21 days (9·0%). Interpretation Pneumonia mortality and its risk factors have steadily improved in the past decade in Malawi; however, mortality remains high in specifi c subgroups. Improvements in hospital care may have reduced case fatality rates though a lack of suffi cient data on quality of care indicators and the potential of socioeconomic and other improvements outside the hospital precludes adequate assessment of why case-fatality rates fell. Results from this study emphasise the importance of eff ective national systems for data collection. Further work combining this with data on trends in the incidence of pneumonia in the community are needed to estimate trends in the overall risk of mortality from pneumonia in children in Malawi

Mortality and its risk factors in Malawian children admitted to hospital with clinical pneumonia, 2001-12: a retrospective observational study.

BACKGROUND: Few studies have reported long-term data on mortality rates for children admitted to hospital with pneumonia in Africa. We examined trends in case fatality rates for all-cause clinical pneumonia and its risk factors in Malawian children between 2001 and 2012. METHODS: Individual patient data for children (<5 years) with clinical pneumonia who were admitted to hospitals participating in Malawi's Child Lung Health Programme between 2001 and 2012 were recorded prospectively on a standardised medical form. We analysed trends in pneumonia mortality and children's clinical characteristics, and we estimated the association of risk factors with case fatality for children younger than 2 months, 2-11 months of age, and 12-59 months of age using separate multivariable mixed effects logistic regression models. FINDINGS: Between November, 2012, and May, 2013, we retrospectively collected all available hard copies of yellow forms from 40 of 41 participating hospitals. We examined 113 154 pneumonia cases, 104 932 (92·7%) of whom had mortality data and 6903 of whom died, and calculated an overall case fatality rate of 6·6% (95% CI 6·4-6·7). The case fatality rate significantly decreased between 2001 (15·2% [13·4-17·1]) and 2012 (4·5% [4·1-4·9]; ptrend<0·0001). Univariable analyses indicated that the decrease in case fatality rate was consistent across most subgroups. In multivariable analyses, the risk factors significantly associated with increased odds of mortality were female sex, young age, very severe pneumonia, clinically suspected Pneumocystis jirovecii infection, moderate or severe underweight, severe acute malnutrition, disease duration of more than 21 days, and referral from a health centre. Increasing year between 2001 and 2012 and increasing age (in months) were associated with reduced odds of mortality. Fast breathing was associated with reduced odds of mortality in children 2-11 months of age. However, case fatality rate in 2012 remained high for children with very severe pneumonia (11·8%), severe undernutrition (15·4%), severe acute malnutrition (34·8%), and symptom duration of more than 21 days (9·0%). INTERPRETATION: Pneumonia mortality and its risk factors have steadily improved in the past decade in Malawi; however, mortality remains high in specific subgroups. Improvements in hospital care may have reduced case fatality rates though a lack of sufficient data on quality of care indicators and the potential of socioeconomic and other improvements outside the hospital precludes adequate assessment of why case-fatality rates fell. Results from this study emphasise the importance of effective national systems for data collection. Further work combining this with data on trends in the incidence of pneumonia in the community are needed to estimate trends in the overall risk of mortality from pneumonia in children in Malawi. FUNDING: Bill & Melinda Gates Foundation

Metabolomics Distinction of Cigarette Smokers from Non-Smokers Using Non-Stationary Benchtop Nuclear Magnetic Resonance (NMR) Analysis of Human Saliva

Implementations of high-field nuclear magnetic resonance (NMR) facilities into metabolomics studies are unfortunately restricted by their large dimensions, high costings, and specialist technical staff requirements. Therefore, here the application and practical advantages offered by low-field (60 MHz), compact NMR spectrometers for probing the metabolic profiles of human saliva was explored, as was their value in salivary metabolomics studies. Saliva samples were collected from cigarette smoking (n = 11) and non-smoking (n = 31) human participants. 1H NMR spectra were acquired on both low-field (60 MHz) and medium-field (400 MHz) spectrometers. Metabolomics analyses were employed to evaluate the consistencies of salivary metabolite levels determined, and their abilities to distinguish between smokers and non-smokers. Low-field 1H NMR analysis detected up to 15, albeit permitted the reliable quantification of 5, potentially key diagnostic biomolecules simultaneously (LLOQ values 250–400 μmol/L), although these were limited to those with the most prominent resonances. Such low-field profiles were also found to be suitable for salivary metabolomics investigations, which confirmed the successful discrimination between smoking and non-smoking participant sample donors. Differences observed between these groups were largely ascribable to upregulated salivary levels of methanol, and its metabolite formate, in the smoking group, but higher smoking-mediated concentrations of acetate, propionate and glycine may arise from a diminished salivary flow-rate in these participants. In conclusion, determination of salivary biomolecules using low-field, benchtop 1H NMR analysis techniques were found to be valuable for bioanalytical and metabolomics investigations. Future perspectives for the applications of this non-stationary NMR technique, for example for the on-site ‘point-of-care’ testing of saliva samples for diagnostic oral disease screening purposes at dental surgeries and community pharmacies, are considered

QOL-26. Exploring the experience of young people receiving remotely delivered Acceptance and Commitment Therapy following treatment for a brain tumour

Despite high survival rates of children and young people diagnosed with a brain tumour, survival is often associated with poor psychological, physical, and social outcomes. Acceptance and Commitment Therapy (ACT) is an evidence-based psychological intervention shown to improve psychological and physical outcomes in adults and children with chronic disease, including cancer. The ACT Now study investigates the feasibility of ACT delivered remotely with young people who have experienced a brain tumour. This study aims to describe participant experience whilst better understanding the impact of therapy and capturing the barriers and facilitators to engagement. Participants of the ACT Now study were invited to take part in a semi-structured interview with questions covering experience of study initiation, receipt of ACT, remote delivery and overall impact of ACT. Ten participants who had previously undergone treatment for a brain tumour have been interviewed to date. Interviews were transcribed verbatim and coded into broad themes. We found that pre-therapy mood and altruism served as motivation for interviewees’ involvement in the study. Interviewees reported hoping to learn coping techniques to navigate fluctuating moods and the pressures of young adult life. Despite the technology used for remote delivery occasionally malfunctioning, interviewees reported increased ability to access therapy via this method. However, an overall preference for face-to-face therapy delivery was reported with interviewees describing that they felt communication might have been easier in person. The therapeutic relationship and the therapists’ flexible schedules were seen as facilitators to session attendance. Barriers to attendance were scarcely reported but included scheduling conflicts due to work or school. ACT was highly regarded amongst interviewees and provided an opportunity for them to learn about themselves and how they can live in accordance with their personal values. Interviewees benefitted from ACT psychologically, physically, and socially and reported an overall positive experience of study involvement