Antibiotic resistance genes in the gut microbiota of mothers and linked neonates with or without sepsis from low- and middle-income countries.

Early development of the microbiome has been shown to affect general health and physical development of the infant and, although some studies have been undertaken in high-income countries, there are few studies from low- and middle-income countries. As part of the BARNARDS study, we examined the rectal microbiota of 2,931 neonates (term used up to 60 d) with clinical signs of sepsis and of 15,217 mothers screening for blaCTX-M-15, blaNDM, blaKPC and blaOXA-48-like genes, which were detected in 56.1%, 18.5%, 0% and 4.1% of neonates' rectal swabs and 47.1%, 4.6%, 0% and 1.6% of mothers' rectal swabs, respectively. Carbapenemase-positive bacteria were identified by MALDI-TOF MS and showed a high diversity of bacterial species (57 distinct species/genera) which exhibited resistance to most of the antibiotics tested. Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae/E. cloacae complex, the most commonly found isolates, were subjected to whole-genome sequencing analysis and revealed close relationships between isolates from different samples, suggesting transmission of bacteria between neonates, and between neonates and mothers. Associations between the carriage of antimicrobial resistance genes (ARGs) and healthcare/environmental factors were identified, and the presence of ARGs was a predictor of neonatal sepsis and adverse birth outcomes.

Erratum: "A microfluidic chip based model for the study of full thickness human intestinal tissue using dual flow" [Biomicrofluidics 10, 064101 (2016)].

[This corrects the article DOI: 10.1063/1.4964813.].

A multicentred study to validate a consensus bleeding assessment tool developed by the biomedical excellence for safer transfusion collaborative for use in patients with haematological malignancy.

BACKGROUND: There continues to be uncertainty about the optimal approach to documenting bleeding data in platelet transfusion trials, with a desire to apply a common assessment tool across all trials. With this in mind, a consensus bleeding assessment tool (BAT) has been developed by the Biomedical Excellence for Safer Transfusion (BEST) collaborative, based on review of data collection forms used in published randomized trials and following content validation with a range of healthcare professionals at seven haematology centres through BEST members. This study aimed to evaluate reliability and reproducibility of the consensus BAT. METHODS: Replicated clinical assessments of bleeding were undertaken by participants with haematological malignancies recruited at four haematology centres in an international, multicentred, observational study. Concordance of repeat assessments was calculated for agreement in site and grade of bleeding observed. RESULTS: Forty patients consented to participate, and 13 trained bleeding assessors collected these data. Bleeding assessments were carried out on 113 separate days. Of all 225 bleeding assessments, 204 were compared for grade concordance, and 160 were compared for site concordance. There was very good grade concordance (83%, 95% confidence interval 74-93%) and good bleeding site concordance (69%, 95% confidence interval 57-79%) in observations of bleeding. Discordance was primarily in relation to assessing skin bleeding. CONCLUSIONS: Alongside a structured training programme, levels of concordance for a consensus BAT were high. Researchers using assessment tools for bleeding need to balance comprehensive data collection against potential loss of accuracy for some types of bleeding, such as skin findings.

Approaches to education provision for mobile pastoralists.

Experiences of mobile pastoralists often attest to a wide range of contradictions about the presumed advantages of formal education. While effort to 'reach' pastoralists has intensified under the global Education for All movement, there remain considerable difficulties in finding ways to make formal education relate to pastoralist livelihoods and complement endogenous knowledge. This paper examines how these dynamics play out across models of formal and non-formal education service provision, and identifies innovations that offer promising ways forward: Alternative Basic Education, Open and Distance Learning, and Pastoralist Field Schools.

Les expériences rapportées par les pasteurs nomades témoignent souvent de contradictions diverses concernant les avantages présumés de l'éducation formelle. Les efforts visant à proposer une offre adaptée aux pasteurs se sont intensifiés dans le cadre du mouvement de l'Éducation pour tous mais se heurtent à la difficulté d'élaborer des solutions d'éducation formelle en lien avec les moyens de subsistance du pastoralisme et complétant les savoirs endogènes. L'auteur examine l'évolution de ces dynamiques dans différents modèles d'offres d'éducation formelle et non formelle et identifie trois champs d'innovation qui lui paraissent prometteurs pour l'avenir : l'Enseignement élémentaire alternatif, l'apprentissage ouvert et à distance et les écoles pastorales de terrain.

La experiencia de los grupos pastorales nómadas suele evidenciar muy diversas contradicciones que ponen en tela de juicio las presuntas ventajas de la educación formal. Como parte del movimiento mundial en pro de la Educación para Todos se han redoblado esfuerzos para «llegar¼ a los grupos de pastores, pero aun así subsisten considerables dificultades a la hora de encontrar fórmulas para impartirles una enseñanza que guarde relación con sus medios de sustento y venga a completar los conocimientos endógenos. La autora examina el modo en que esta dinámica se articula con los modelos de prestación de servicios educativos formales y no formales y describe innovaciones que abren vías prometedoras: la educación básica alternativa, el aprendizaje abierto y a distancia o las escuelas de campo pastorales.

A microfluidic chip based model for the study of full thickness human intestinal tissue using dual flow.

The study of inflammatory bowel disease, including Ulcerative Colitis and Crohn's Disease, has relied largely upon the use of animal or cell culture models; neither of which can represent all aspects of the human pathophysiology. Presented herein is a dual flow microfluidic device which holds full thickness human intestinal tissue in a known orientation. The luminal and serosal sides are independently perfused ex vivo with nutrients with simultaneous waste removal for up to 72 h. The microfluidic device maintains the viability and integrity of the tissue as demonstrated through Haematoxylin & Eosin staining, immunohistochemistry and release of lactate dehydrogenase. In addition, the inflammatory state remains in the tissue after perfusion on the device as determined by measuring calprotectin levels. It is anticipated that this human model will be extremely useful for studying the biology and testing novel interventions in diseased tissue.

Costs and quality of life associated with acute upper gastrointestinal bleeding in the UK: cohort analysis of patients in a cluster randomised trial.

OBJECTIVES: Data on costs associated with acute upper gastrointestinal bleeding (AUGIB) are scarce. We provide estimates of UK healthcare costs, indirect costs and health-related quality of life (HRQoL) for patients presenting to hospital with AUGIB. SETTING: Six UK university hospitals with >20 AUGIB admissions per month, >400 adult beds, 24 h endoscopy, and on-site access to intensive care and surgery. PARTICIPANTS: 936 patients aged ≥18 years, admitted with AUGIB, and enrolled between August 2012 and March 2013 in the TRIGGER trial of AUGIB comparing restrictive versus liberal red blood cell (RBC) transfusion thresholds. PRIMARY AND SECONDARY OUTCOME MEASURES: Healthcare resource use during hospitalisation and postdischarge up to 28  days, unpaid informal care, time away from paid employment and HRQoL using the EuroQol EQ-5D at 28  days were measured prospectively. National unit costs were used to value resource use. Initial in-hospital treatment costs were upscaled to a UK level. RESULTS: Mean initial in-hospital costs were £2458 (SE=£216) per patient. Inpatient bed days, endoscopy and RBC transfusions were key cost drivers. Postdischarge healthcare costs were £391 (£44) per patient. One-third of patients received unpaid informal care and the quarter in paid employment required time away from work. Mean HRQoL for survivors was 0.74. Annual initial inhospital treatment cost for all AUGIB cases in the UK was estimated to be £155.5 million, with exploratory analyses of the incremental costs of treating hospitalised patients developing AUGIB generating figures of between £143 million and £168 million. CONCLUSIONS: AUGIB is a large burden for UK hospitals with inpatient stay, endoscopy and RBC transfusions as the main cost drivers. It is anticipated that this work will enable quantification of the impact of cost reduction strategies in AUGIB and will inform economic analyses of novel or existing interventions for AUGIB. TRIAL REGISTRATION NUMBER: ISRCTN85757829 and NCT02105532.

Activity levels after pulmonary rehabilitation - what really happens?

OBJECTIVES: To assess the changes in physical activity in subjects with chronic obstructive pulmonary disease over 6months after pulmonary rehabilitation. DESIGN: Prospective, observational study. Activity was measured over 2-day periods at the end of rehabilitation, and repeated every 6weeks for 6months using the ActivPAL uni-axial accelerometer. These results were compared with the shuttle walking test (SWT) and the St. George's Respiratory Disease Questionnaire (SGRDQ). SETTING: UK community hospital. PARTICIPANTS: Adults completing a community rehabilitation programme. MAIN OUTCOME MEASURE: Time spent standing and mobilising ('uptime'). RESULTS: Of 34 subjects recruited, 28 completed the 6-month study period (mean age 69years, mean forced expiratory volume in 1second 1.3l). Participants wore the monitor for 13.8 to 14.2hours/day. At baseline (post-rehabilitation), participants spent 1.7 [standard deviation (SD) 1.3]hours/day walking and 3.5 (SD 2.6)hours/day standing. Taking the group as a whole, mean uptime decreased marginally by 13.6minutes after 24weeks compared with baseline, with significant individual variability. In all but one subject who showed decreased activity, this was apparent after 6weeks. There were no significant changes in the mean SWT or SGRDQ. Significant associations between total uptime and the SWT were found, but coefficients were weak. It was not possible to predict individual responses from baseline data. CONCLUSION: The accelerometer provides useful supplementary data in patients completing rehabilitation programmes, and the results reveal wide variation. The weak associations between activity data and the SWT suggest that monitors provide additional information. More work is required to determine the factors associated with early deterioration in activity in order to design appropriate interventions.

Factors influencing tissue nitrate concentration in field-grown wild rocket (Diplotaxis tenuifolia) in southern England.

Wild rocket (Diplotaxis tenuifolia) is a leafy vegetable known for its high tissue nitrate concentration (TNC) which can exceed the limits set in the relevant European legislation designed to protect human health. The aim of this work was to understand the factors influencing TNC and to develop best practice guidelines to growers. Commercial crops of field-grown wild rocket were studied over two seasons. In 2010, ten separate crops were sampled representing a range of soil types and time periods during the summer. Two fields sampled using a 'W'- or 'X'-shaped sampling pattern demonstrated that 10 incremental samples bulked to make 1 kg of fresh material could be used to provide an adequate sample for determination of TNC in the wild rocket crop, as is the case for other leafy vegetables. Of eight commercial crops sampled in 2010 with an average nitrogen (N) fertiliser application of 104 kg N ha(-1), two exceeded the limit of 6000 mg NO3(-) kg(-1) set in the legislation. In 2011, six N response experiments were carried out, and only two sites showed a significant yield response to N fertiliser. The reason for the lack of response at the other sites was principally due to high levels of soil mineral N prior to drilling, meaning the crops' requirement for N was satisfied without additional fertiliser N. In the experimental situation at an N fertiliser application rate of 120 kg N ha(-1), 50% of crops would have exceeded the 6000 mg NO3(-) kg(-1) limit. In both seasons, low radiation levels in the 5 days prior to harvest were shown to increase TNC, although the relationship was also influenced by N supply. Strategies for optimising N nutrition of field-grown wild rocket are discussed.

The APOL1 genotype of African American kidney transplant recipients does not impact 5-year allograft survival.

Apolipoprotein L-1 (APOL1) gene variants are associated with end-stage renal disease in African Americans (AAs). Here we investigate the impact of recipient APOL1 gene distributions on kidney allograft outcomes. We conducted a retrospective analysis of 119 AA kidney transplant recipients, and found that 58 (48.7%) carried two APOL1 kidney disease risk variants. Contrary to the association seen in native kidney disease, there is no difference in allograft survival at 5-year posttransplant for recipients with high-risk APOL1 genotypes. Thus, we were able to conclude that APOL1 genotypes do not increase risk of allograft loss after kidney transplantations, and carrying 2 APOL1 risk alleles should not be an impediment to transplantation.

Epistaxis in patients taking oral anticoagulant and antiplatelet medication: prospective cohort study.

OBJECTIVES: Epistaxis can be caused or exacerbated by anticoagulant and antiplatelet therapy. This prospective study assessed the prevalence of epistaxis in patients taking anticoagulant and antiplatelet medication, and monitored differences in patients' clinical courses. METHOD: Prospective data were collected for consecutive patients referred with epistaxis from the emergency department over a seven-month period. Emergency department records were used to investigate prevalence and referral rates. RESULTS: Over the study period, 290 patients presented to the emergency department with epistaxis; this represented 0.9 per cent of all emergency attendances. Of these patients, 119 (39 per cent) were referred on to the ENT department, 62 per cent of whom were currently taking anticoagulant or antiplatelet medication. Patients taking anticoagulant and antiplatelet medication were a significantly older group (relative risk 1.50 (1.08-2.28), p = 0.01) requiring longer in-patient stays (relative risk 2.50 (1.01-4.97), p = 0.01) and more aggressive local haemostasis measures. Most patients taking warfarin had an international normalised ratio outside the appropriate range for their disease. Hypertension was not a factor in these patients' clinical course. CONCLUSION: Increasingly, emergency and ENT departments are being presented with epistaxis in patients taking anticoagulant or antiplatelet medication. A better understanding of such medication and its effects may enable more effective management of these patients.

A role for Rab10 in von Willebrand factor release discovered by an AP-1 interactor screen in C. elegans.

BACKGROUND: Endothelial von Willebrand factor (VWF) mediates platelet adhesion and acts as a protective chaperone to clotting factor VIII. Rapid release of highly multimerized VWF is particularly effective in promoting hemostasis. To produce this protein, an elaborate biogenesis is required, culminating at the trans-Golgi network (TGN) in storage within secretory granules called Weibel-Palade bodies (WPB). Failure to correctly form these organelles can lead to uncontrolled secretion of low-molecular-weight multimers of VWF. The TGN-associated adaptor AP-1 and its interactors clathrin, aftiphilin and γ-synergin are essential to initial WPB formation at the Golgi apparatus, and thus to VWF storage and secretion. OBJECTIVES: To identify new proteins implicated in VWF storage and/or secretion. METHODS: A genomewide RNA interference (RNAi) screen was performed in the Nematode C. elegans to identify new AP-1 genetic interactors. RESULTS: The small GTPase Rab10 was found to genetically interact with a partial loss of function of AP-1 in C. elegans. We investigated Rab10 in human primary umbilical vein endothelial cells (HUVECs). We report that Rab10 is enriched at the Golgi apparatus, where WPB are formed, and that in cells where Rab10 expression has been suppressed by siRNA, VWF secretion is altered: the amount of rapidly released VWF was significantly reduced. We also found that Rab8A has a similar function. CONCLUSION: Rab10 and Rab8A are new cytoplasmic factors implicated in WPB biogenesis that play a role in generating granules that can rapidly respond to secretagogue.

Overview of on-board measurements during solar storm periods.

Radiation exposure of aircraft crew caused by cosmic radiation is regulated in Europe by the European Community Council Directive 96/29/EURATOM and implemented into law in almost every country of the European Union. While the galactic cosmic radiation (GCR) leads on average to an exposure of about 3 mSv per year, solar cosmic radiation can lead to 1 mSv per one subsonic flight during solar storm periods. Compared to GCR, solar cosmic radiation shows a much softer proton spectrum but with a larger contribution of several orders of magnitude. This is the reason for the large radiation exposure in high northern and southern geographic latitudes during solar particle events. Here an overview of active radiation in-flight measurements undertaken during solar storms is given. In particular, tissue-equivalent proportional counter on-board measurements are shown and the radiation quality during solar storm periods with that for GCR is compared.

Comparison of codes assessing galactic cosmic radiation exposure of aircraft crew.

The assessment of the exposure to cosmic radiation onboard aircraft is one of the preoccupations of bodies responsible for radiation protection. Cosmic particle flux is significantly higher onboard aircraft than at ground level and its intensity depends on the solar activity. The dose is usually estimated using codes validated by the experimental data. In this paper, a comparison of various codes is presented, some of them are used routinely, to assess the dose received by the aircraft crew caused by the galactic cosmic radiation. Results are provided for periods close to solar maximum and minimum and for selected flights covering major commercial routes in the world. The overall agreement between the codes, particularly for those routinely used for aircraft crew dosimetry, was better than +/-20 % from the median in all but two cases. The agreement within the codes is considered to be fully satisfactory for radiation protection purposes.

Rehabilitation of older patients: day hospital compared with rehabilitation at home. A randomised controlled trial.

OBJECTIVES: To test the hypotheses that older people and their informal carers are not disadvantaged by home-based rehabilitation (HBR) relative to day hospital rehabilitation (DHR) and that HBR is less costly. DESIGN: Two-arm randomised controlled trial. SETTING: Four trusts in England providing both HBR and DHR. PARTICIPANTS: Clinical staff reviewed consecutive referrals to identify subjects who were potentially suitable for randomisation according to the defined inclusion criteria. INTERVENTIONS: Patients were randomised to receive either HBR or DHR. MAIN OUTCOME MEASURES: The primary outcome measure was the Nottingham Extended Activities of Daily Living (NEADL) scale. Secondary outcome measures included the EuroQol 5 dimensions (EQ-5D), Hospital Anxiety and Depression Scale (HADS), Therapy Outcome Measures (TOMs), hospital admissions and the General Health Questionnaire (GHQ-30) for carers. RESULTS: Overall, 89 subjects were randomised and 42 received rehabilitation in each arm of the trial. At the primary end point of 6 months there were 32 and 33 patients in the HBR and DHR arms respectively. Estimated mean scores on the NEADL scale at 6 months, after adjustment for baseline, were not significantly in favour of either HBR or DHR [DHR 30.78 (SD 15.01), HBR 32.11 (SD 16.89), p = 0.37; mean difference -2.139 (95% CI -6.870 to 2.592)]. Analysis of the non-inferiority of HBR over DHR using a 'non-inferiority' limit (10%) applied to the confidence interval estimates for the different outcome measures at 6 months' follow-up demonstrated non-inferiority for the NEADL scale, EQ-5D and HADS anxiety scale and some advantage for HBR on the HADS depression scale, of borderline statistical significance. Similar results were seen at 3 and 12 months' follow-up, with a statistically significant difference in the mean EQ-5D(index) score in favour of DHR at 3 months (p = 0.047). At the end of rehabilitation, a greater proportion of the DHR group showed a positive direction of change from their initial assessment with respect to therapist-rated clinical outcomes; however, a lower proportion of HBR patients showed a negative direction of change and, overall, median scores on the TOMs scales did not differ between the two groups. Fewer patients in the HBR group were admitted to hospital on any occasion over the 12-month observation period [18 (43%) versus 22 (52%)]; however, this difference was not statistically significant. The psychological well-being of patients' carers, measured at 3, 6 and 12 months, was unaffected by whether rehabilitation took place at day hospital or at home. As the primary outcome measure and EQ-5D(index) scores at 6 months showed no significant differences between the two arms of the trial, a cost-minimisation analysis was undertaken. Neither the public costs nor the total costs at the 6-month follow-up point (an average of 213 days' total follow-up) or the 12-month follow-up point (an average of 395 days' total follow-up) were significantly different between the groups. CONCLUSIONS: Compared with DHR, providing rehabilitation in patients' own homes confers no particular disadvantage for patients and carers. The cost of providing HBR does not appear to be significantly different from that of providing DHR. Rehabilitation providers and purchasers need to consider the place of care in the light of local needs, to provide the benefits of both kinds of services. Caution is required when interpreting the results of the RCT because a large proportion of potentially eligible subjects were not recruited to the trial, the required sample size was not achieved and there was a relatively large loss to follow-up. TRIAL REGISTRATION: Current Controlled Trials ISRCTN71801032.

Validation of modelling the radiation exposure due to solar particle events at aircraft altitudes.

Dose assessment procedures for cosmic radiation exposure of aircraft crew have been introduced in most European countries in accordance with the corresponding European directive and national regulations. However, the radiation exposure due to solar particle events is still a matter of scientific research. Here we describe the European research project CONRAD, WP6, Subgroup-B, about the current status of available solar storm measurements and existing models for dose estimation at flight altitudes during solar particle events leading to ground level enhancement (GLE). Three models for the numerical dose estimation during GLEs are discussed. Some of the models agree with limited experimental data reasonably well. Analysis of GLEs during geomagnetically disturbed conditions is still complex and time consuming. Currently available solar particle event models can disagree with each other by an order of magnitude. Further research and verification by on-board measurements is still needed.

A new HLA-A*02 null allele, HLA-A*9213N.

A novel HLA-A*02 null allele, differing from HLA-A*02010101 at codon 60 (TGG tryptophan-->TAG stop), is described.

Comparison of the histology and immunohistochemistry of vaccination-site and non-vaccination-site sarcomas from cats in New Zealand.

AIMS: To compare the histology and immunohistochemistry of vaccination-site sarcomas (VSSs) with non-vaccination-site sarcomas (NVSSs) in cats in New Zealand. To determine whether VSSs in cats in New Zealand have similar histological and immunohistochemical features to those previously described in feline vaccine-associated sarcomas (VASs) in North American studies. METHODS: A retrospective survey of skin biopsies submitted between 2004 and 2006 was performed to identify cutaneous sarcomas from both vaccination and non-vaccination sites in cats. Vaccination sites included the interscapular, shoulder, or dorsal or lateral cervical and thoracic regions. All sarcomas were examined histologically, and smooth muscle actin and desmin were assessed immunohistochemically. Features previously described in VASs were assessed and compared. RESULTS: Sarcomas from 34 cats were identified, 10 of which occurred at vaccination sites. Compared with NVSSs, VSSs were more likely to be located in the hypodermis and have greater cellular pleomorphism, higher mitotic rates, more frequent peripheral lymphocytic aggregates and multinucleated giant cells. VSSs were also more likely than NVSSs to show partial myofibroblastic differentiation, demonstrable using immunohistochemistry. The histological and immunohistochemical features of VSSs in cats in New Zealand are consistent with those previously described in VASs in cats in North America. CONCLUSIONS: The results of this study suggest that VASs occur in cats in New Zealand. CLINICAL RELEVANCE: The occurrence of VASs in cats in New Zealand would provide further support for restriction of the vaccination of cats to the minimum necessary to protect health, and adoption of the New Zealand Veterinary Association guidelines on vaccination.

Identification of a variant HLA-A*3401 allele, A*340102, in an educational DNA typing sample.

A*340102 was first identified in an ASEATTA Educational DNA typing sample, which typed as A*3401, 3401variant. The variant differs from A*3401 by a single silent substitution in exon 2 at nucleotide 309, codon 79 (GGG-->GGT).

Further phenotypic delineation of subtelomeric (terminal) 4q deletion with emphasis on intracranial and reproductive anatomy.

OBJECTIVE: To describe selected morphological and developmental features associated with subtelomeric deletion at chromosome 4q. MATERIALS AND METHODS: A 21-year old female was brought for gynecologic evaluation of menorrhagia. High-resolution metaphase karyotype and subtelomere fluorescent in-situ hybridization (FISH) analysis were used for genotype determination. Pelvic anatomy was characterized via CT and laparoscopy; MR and CT were used for intracranial imaging. RESULTS: A de novo deletion [46,XX del(4)(q32)] was identified cytogenetically and confirmed as a terminal loss via subtelomere FISH. Hand/foot malformation characteristic of deletion at this segment was present. Pelvic CT and laparoscopy revealed normal uterine anatomy. Fallopian tubes appeared grossly unremarkable, and a right ovarian cyst was excised without difficulty. Bilateral broad ligament fibroadipose nodularities were noted adjacent to the uterus between round ligament and fallopian tube. Neurological exam revealed no focal defects, although brain MR identified an abnormal signal intensity at the inferior margin of the globus pallidus, consistent with old lacunar infarct and gliosis. Developmental delay was supported by an observed level of general intellectual function estimated at age seven. CONCLUSION: Terminal deletion of the long arm of chromosome 4 is a rare genetic event associated with a distinctive phenotype dependent on the size of the deletion. Chromosomal losses that span the 4q32 band include mental retardation and mild craniofacial anomalies. Here, further characterization of this disorder is offered including precise quantification of the DNA loss, information on brain morphology and pelvic anatomy. Additional studies will be required to characterize the full developmental and physiologic implications of this unusual genetic disorder.