Opportunistic bacteria confer the ability to ferment prebiotic starch in the adult cystic fibrosis gut

Chronic disruption of the intestinal microbiota in adult cystic fibrosis (CF) patients is associated with local and systemic inflammation, and has been linked to the risk of serious comorbidities. Supplementation with high amylose maize starch (HAMS) might provide clinical benefit by promoting commensal bacteria and the biosynthesis of immunomodulatory metabolites. However, whether the disrupted CF gut microbiota has the capacity to utilise these substrates is not known. We combined metagenomic sequencing, in vitro fermentation, amplicon sequencing, and metabolomics to define the characteristics of the faecal microbiota in adult CF patients and assess HAMS fermentation capacity. Compared to healthy controls, the faecal metagenome of adult CF patients had reduced bacterial diversity and prevalence of commensal fermentative clades. In vitro fermentation models seeded with CF faecal slurries exhibited reduced acetate levels compared to healthy control reactions, but comparable levels of butyrate and propionate. While the commensal genus Faecalibacterium was strongly associated with short chain fatty acid (SCFA) production by healthy microbiota, it was displaced in this role by Clostridium sensu stricto 1 in the microbiota of CF patients. A subset of CF reactions exhibited enterococcal overgrowth, resulting in lactate accumulation and reduced SCFA biosynthesis. The addition of healthy microbiota to CF faecal slurries failed to displace predominant CF taxa, or substantially influence metabolite biosynthesis. Despite significant microbiota disruption, the adult CF gut microbiota retains the capacity to exploit HAMS. Our findings highlight the potential for taxa associated with the altered CF gut microbiotato mediate prebiotic effects in microbial systems subject to ongoing perturbation, irrespective of the depletion of common commensal clades

Thermal comfort investigation of an outdoor air-conditioned area in a hot and arid environment

Thermal comfort in hot and arid outdoor environments is an industrial challenging field. An outdoor air-conditioned area was designed and built to host sport and social events during summers 2014 and 2015 in Qatar. This article presents a thermal comfort analysis of the outdoor air-conditioned area using computational fluid dynamics, on-site spectators surveys, and on-spot climatic measurements. The study utilized computational fluid dynamics to develop a thermal comfort model of the outdoor air-conditioned area to predict the thermal comfort of the occupants. Five different thermal comfort indices; mean comfort vote, cooling power index, wet-bulb globe temperature index, Humidex, discomfort index, were utilized to assess the thermal comfort of spectators within the conditioned space. The indices utilized different on site measurements of meteorological data and on-site interviews. In comparison to the mean comfort vote of the sampled survey, all thermal comfort indices underestimated the actual thermal comfort percentage except the wet-bulb globe temperature index that overestimated the comfort percentage. The computational fluid dynamics results reasonably predicted most of the thermal comfort indices values. The computational fluid dynamics results overestimated the comfort percentage of mean comfort vote, wet-bulb globe temperature index, and discomfort index, while the thermal comfort percentage was underestimated as indicated by the cooling power index, and Humidex

Conservative management of mallet injuries:A national survey of current practice in the UK

Introduction Mallet injuries are common, and usually treated conservatively. Various systematic reviews have found a lack of evidence regarding best management and it is unclear whether this uncertainty is reflected in current UK practice. Methods An online survey was developed to determine current practice for the conservative treatment of mallet injury amongst specialist hand clinicians in the UK, including physiotherapists, occupational therapists and surgeons. Clinician’s views of study outcome selection were also explored to improve future trials. Results 336 professionals completed the survey. Inconsistency in overall practice was observed in splint type choice, time to discharge to GP, and the assessment of adherence. Greater consistency was observed for recommended duration of continuous immobilisation. Bony injuries were most commonly splinted for six weeks (n=228, 78%) and soft tissue injuries for either eight weeks (n=172, 56%) or six weeks (n=119, 39%). Postimmobilisation splinting was frequently recommended, but duration varied between two and 10 weeks. The outcome rated as most important by all clinicians was patient satisfaction. Discussion There is overall variation in the current UK conservative management of mallet injuries, and the development of a standardised, evidence based protocol is required. Clinicians’ opinions may be used to develop a core set of outcome measures, which will improve standardisation and comparability of future trials.</p

Jockeying for position: the construction of masculine identities

In this paper we examine the construction of masculine identities within a real-life social situation. Using data from an extensive series of interviews with small groups of sixth-form (17-18-year-old) students attending a UK-based, single-sex independent school, the analysis looks at the action orientation of different constructions of identity. More specifically, it focuses upon how the identity talk of one particular group of students were oriented towards managing their subordinate status within the school. In a number of instances the identity of the `new man' was adopted as a strategy of resistance. However, it was found that the more common strategy involved buying back into values embodied within a more traditional definition of masculinity

Impact of long-term erythromycin therapy on the oropharyngeal microbiome and resistance gene reservoir in non-cystic fibrosis bronchiectasis

Published 18 April 2018Long-term macrolide therapy reduces rates of pulmonary exacerbation in bronchiectasis. However, little is known about the potential for macrolide therapy to alter the composition and function of the oropharyngeal commensal microbiota or to increase the carriage of transmissible antimicrobial resistance. We assessed the effect of long-term erythromycin on oropharyngeal microbiota composition and the carriage of transmissible macrolide resistance genes in 84 adults with bronchiectasis, enrolled in the Bronchiectasis and Low-dose Erythromycin Study (BLESS) 48-week placebo-controlled trial of twice-daily erythromycin ethylsuccinate (400 mg). Oropharyngeal microbiota composition and macrolide resistance gene carriage were determined by 16S rRNA gene amplicon sequencing and quantitative PCR, respectively. Long-term erythromycin treatment was associated with a significant increase in the relative abundance of oropharyngeal Haemophilus parainfluenzae (P = 0.041) and with significant decreases in the relative abundances of Streptococcus pseudopneumoniae (P = 0.024) and Actinomyces odontolyticus (P = 0.027). Validation of the sequencing results by quantitative PCR confirmed a significant decrease in the abundance of Actinomyces spp. (P = 0.046). Erythromycin treatment did not result in a significant increase in the number of subjects who carried erm(A), erm(B), erm(C), erm(F), mef(A/E), and msrA macrolide resistance genes. However, the abundance of erm(B) and mef(A/E) gene copies within carriers who had received erythromycin increased significantly (P < 0.05). Our findings indicate that changes in oropharyngeal microbiota composition resulting from long-term erythromycin treatment are modest and are limited to a discrete group of taxa. Associated increases in levels of transmissible antibiotic resistance genes within the oropharyngeal microbiota highlight the potential for this microbial system to act as a reservoir for resistance.IMPORTANCE Recent demonstrations that long-term macrolide therapy can prevent exacerbations in chronic airways diseases have led to a dramatic increase in their use. However, little is known about the wider, potentially adverse impacts of these treatments. Substantial disruption of the upper airway commensal microbiota might reduce its contribution to host defense and local immune regulation, while increases in macrolide resistance carriage would represent a serious public health concern. Using samples from a randomized controlled trial, we show that low-dose erythromycin given over 48 weeks influences the composition of the oropharyngeal commensal microbiota. We report that macrolide therapy is associated with significant changes in the relative abundances of members of the Actinomyces genus and with significant increases in the carriage of transmissible macrolide resistance. Determining the clinical significance of these changes, relative to treatment benefit, now represents a research priority.Jocelyn M. Choo, Guy C. J. Abell, Rachel Thomson, Lucy Morgan, Grant Waterer, David L. Gordon, Steven L. Taylor, Lex E. X. Leong, Steve L. Wesselingh, Lucy D. Burr, Geraint B. Roger

Energy and Climate Implications for Agricultural Nutrient Use Efficiency

Energy and climate change are beginning to dominate the global political agenda and will drive policy formation that will shape the future of agriculture. Energy issues threaten national security and economic stability, as well as access to low-cost nutrient inputs for agriculture. Climate change has the potential to cause serious disruption to agricultural productivity. Paradoxically, nutrient use in agriculture to increase crop yields has the potential to negatively impact climate. This chapter will discuss recent and future energy and climate trends, the relationships between agricultural nutrient use efficiency and biofuels, and how global land limitations will shape agriculture in the future. Comparative gross energy yield and nitrogen use efficiency for ethanol production from crop residue, switchgrass, grain sorghum, sweet sorghum, and corn grain is presented, showing small differences in nitrogen use efficiency, but large differences in gross energy yields. In addition to considering the need to increase crop productivity to meet the demands of a growing population and bioenergy, agricultural nutrient use efficiency must be reconsidered with respect to the important energy and climate challenges shaping agriculture today

Evidence for the strangeness-changing weak decay Ξb−→Λb0π−\Xi_b^-\to\Lambda_b^0\pi^-

Using a $pp$ collision data sample corresponding to an integrated luminosity of 3.0~fb$^{-1}$, collected by the LHCb detector, we present the first search for the strangeness-changing weak decay $\Xi_b^-\to\Lambda_b^0\pi^-$. No $b$ hadron decay of this type has been seen before. A signal for this decay, corresponding to a significance of 3.2 standard deviations, is reported. The relative rate is measured to be ${{f_{\Xi_b^-}}\over{f_{\Lambda_b^0}}}{\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-) = (5.7\pm1.8^{+0.8}_{-0.9})\times10^{-4}$, where $f_{\Xi_b^-}$ and $f_{\Lambda_b^0}$ are the $b\to\Xi_b^-$ and $b\to\Lambda_b^0$ fragmentation fractions, and ${\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-)$ is the branching fraction. Assuming $f_{\Xi_b^-}/f_{\Lambda_b^0}$ is bounded between 0.1 and 0.3, the branching fraction ${\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-)$ would lie in the range from $(0.57\pm0.21)\%$ to $(0.19\pm0.07)\%$.Comment: 7 pages, 2 figures, All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-047.htm

Measurements of long-range near-side angular correlations in sNN=5\sqrt{s_{\text{NN}}}=5TeV proton-lead collisions in the forward region

Two-particle angular correlations are studied in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of $\sqrt{s_{\text{NN}}}=5$TeV, collected with the LHCb detector at the LHC. The analysis is based on data recorded in two beam configurations, in which either the direction of the proton or that of the lead ion is analysed. The correlations are measured in the laboratory system as a function of relative pseudorapidity, $\Delta\eta$, and relative azimuthal angle, $\Delta\phi$, for events in different classes of event activity and for different bins of particle transverse momentum. In high-activity events a long-range correlation on the near side, $\Delta\phi \approx 0$, is observed in the pseudorapidity range $2.0<\eta<4.9$. This measurement of long-range correlations on the near side in proton-lead collisions extends previous observations into the forward region up to $\eta=4.9$. The correlation increases with growing event activity and is found to be more pronounced in the direction of the lead beam. However, the correlation in the direction of the lead and proton beams are found to be compatible when comparing events with similar absolute activity in the direction analysed.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-040.htm

BB flavour tagging using charm decays at the LHCb experiment

An algorithm is described for tagging the flavour content at production of neutral $B$ mesons in the LHCb experiment. The algorithm exploits the correlation of the flavour of a $B$ meson with the charge of a reconstructed secondary charm hadron from the decay of the other $b$ hadron produced in the proton-proton collision. Charm hadron candidates are identified in a number of fully or partially reconstructed Cabibbo-favoured decay modes. The algorithm is calibrated on the self-tagged decay modes $B^+ \to J/\psi \, K^+$ and $B^0 \to J/\psi \, K^{*0}$ using $3.0\mathrm{\,fb}^{-1}$ of data collected by the LHCb experiment at $pp$ centre-of-mass energies of $7\mathrm{\,TeV}$ and $8\mathrm{\,TeV}$. Its tagging power on these samples of $B \to J/\psi \, X$ decays is $(0.30 \pm 0.01 \pm 0.01) \%$.Comment: All figures and tables, along with any supplementary material and additional information, are available at http://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-027.htm

Transactive response DNA-binding protein-43 proteinopathy in oligodendrocytes revealed using an induced pluripotent stem cell model

Oligodendrocytes are implicated in amyotrophic lateral sclerosis pathogenesis and display transactive response DNA-binding protein-43 (TDP-43) pathological inclusions. To investigate the cell autonomous consequences of TDP-43 mutations on human oligodendrocytes, we generated oligodendrocytes from patient-derived induced pluripotent stem cell lines harbouring mutations in the TARDBP gene, namely G298S and M337V. Through a combination of immunocytochemistry, electrophysiological assessment via whole-cell patch clamping, and three-dimensional cultures, no differences in oligodendrocyte differentiation, maturation or myelination were identified. Furthermore, expression analysis for monocarboxylate transporter 1 (a lactate transporter) coupled with a glycolytic stress test showed no deficit in lactate export. However, using confocal microscopy, we report TDP-43 mutation-dependent pathological mis-accumulation of TDP-43. Furthermore, using in vitro patch-clamp recordings, we identified functional Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor dysregulation in oligodendrocytes. Together, these findings establish a platform for further interrogation of the role of oligodendrocytes and cellular autonomy in TDP-43 proteinopathy