Mixed Candida albicans strain populations in colonized and infected mucosal tissues

Multilocus sequence typing of six Candida albicans colonies from primary isolation plates revealed instances of colony-to-colony microvariation and carriage of two strain types in single oropharyngeal and vaginal samples. Higher rates of colony variation in commensal samples suggest selection of types from mixed populations either in the shift to pathogenicity or the response to antifungal treatment

Distribution, organization and expression of genes concerned with anaerobic lactate utilization in human intestinal bacteria

Lactate accumulation in the human gut is linked to a range of deleterious health impacts. However, lactate is consumed and converted to the beneficial short-chain fatty acids butyrate and propionate by indigenous lactate-utilizing bacteria. To better understand the underlying genetic basis for lactate utilization, transcriptomic analyses were performed for two prominent lactate-utilizing species from the human gut, Anaerobutyricum soehngenii and Coprococcus catus , during growth on lactate, hexose sugar or hexose plus lactate. In A. soehngenii L2-7 six genes of the lactate utilization (lct) cluster, including NAD-independent d-lactate dehydrogenase (d-iLDH), were co-ordinately upregulated during growth on equimolar d- and l-lactate (dl-lactate). Upregulated genes included an acyl-CoA dehydrogenase related to butyryl-CoA dehydrogenase, which may play a role in transferring reducing equivalents between reduction of crotonyl-CoA and oxidation of lactate. Genes upregulated in C. catus GD/7 included a six-gene cluster (lap) encoding propionyl CoA-transferase, a putative lactoyl-CoA epimerase, lactoyl-CoA dehydratase and lactate permease, and two unlinked acyl-CoA dehydrogenase genes that are candidates for acryloyl-CoA reductase. A d-iLDH homologue in C. catus is encoded by a separate, partial lct, gene cluster, but not upregulated on lactate. While C. catus converts three mols of dl-lactate via the acrylate pathway to two mols propionate and one mol acetate, some of the acetate can be re-used with additional lactate to produce butyrate. A key regulatory difference is that while glucose partially repressed lct cluster expression in A. soehngenii , there was no repression of lactate-utilization genes by fructose in the non-glucose utilizer C. catus . This suggests that these species could occupy different ecological niches for lactate utilization in the gut, which may be important factors to consider when developing lactate-utilizing bacteria as novel candidate probiotics

The Rate and Molecular Spectrum of Spontaneous Mutations in Arabidopsis thaliana

To take complete advantage of information on within-species polymorphism and divergence from close relatives, one needs to know the rate and the molecular spectrum of spontaneous mutations. To this end, we have searched for de novo spontaneous mutations in the complete nuclear genomes of five Arabidopsis thaliana mutation accumulation lines that had been maintained by single-seed descent for 30 generations. We identified and validated 99 base substitutions and 17 small and large insertions and deletions. Our results imply a spontaneous mutation rate of 7 × 10−9 base substitutions per site per generation, the majority of which are G:C→A:T transitions. We explain this very biased spectrum of base substitution mutations as a result of two main processes: deamination of methylated cytosines and ultraviolet light–induced mutagenesis

Formate cross-feeding and cooperative metabolic interactions revealed by transcriptomics in co-cultures of acetogenic and amylolytic human colonic bacteria

© 2018 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.Peer reviewedPublisher PD

Multi-wavelength study of a new Galactic SNR G332.5-5.6

We present compelling evidence for confirmation of a Galactic supernova remnant (SNR) candidate, G332.5-5.6, based initially on identification of new, filamentary, optical emission line nebulosity seen in the arcsecond resolution images from the AAO/UKST HAlpha survey. The extant radio observations and X-ray data which we have independently re-reduced, together with new optical spectroscopy of the large-scale fragmented nebulosity, confirms the identification. Optical spectra, taken across five different, widely separated nebula regions of the remnant as seen on the HAlpha images, show average ratios of [NII]/HAlpha =2.42, [SII]/HAlpha = 2.10, and [SII] 6717/6731 = 1.23, as well as strong [OI] 6300, 6364A and [OII] 3727A emission. These ratios are firmly within those typical of SNRs. Here, we also present the radio-continuum detection of the SNR at 20/13cm from observations with the Australia Telescope Compact Array (ATCA). Radio emission is also seen at 4850 MHz, in the PMN survey (Griffith and Wright 1993) and at 843 MHz from the SUMSS survey (Bock, Large and Sadler 1999). We estimate an angular diameter of ~30 arcmin and obtain an average radio spectral index of alpha = -0.6 +- 0.1 which indicates the non-thermal nature of G332.5-5.6. Fresh analysis of existing ROSAT X-ray data in the vicinity also confirms the existence of the SNR. The distance to G332.5-5.6 has been independently estimated by Reynoso and Green (2007) as 3.4 kpc based on measurements of the HI lambda21 cm line seen in absorption against the continuum emission. Our cruder estimates via assumptions on the height of the dust layer (3.1 kpc) and using the Sigma-D relation (4 kpc) are in good agreement.Comment: 14 pages, 18 figures. Accepted for publishing in the MNRA

Repetitive arm functional tasks after stroke (RAFTAS): a pilot randomised controlled trial

Background Repetitive functional task practise (RFTP) is a promising treatment to improve upper limb recovery following stroke. We report the findings of a study to determine the feasibility of a multi-centre randomised controlled trial to evaluate this intervention. Methods A pilot randomised controlled trial was conducted. Patients with new reduced upper limb function were recruited within 14 days of acute stroke from three stroke units in North East England. Participants were randomised to receive a four week upper limb RFTP therapy programme consisting of goal setting, independent activity practise, and twice weekly therapy reviews in addition to usual post stroke rehabilitation, or usual post stroke rehabilitation. The recruitment rate; adherence to the RFTP therapy programme; usual post stroke rehabilitation received; attrition rate; data quality; success of outcome assessor blinding; adverse events; and the views of study participants and therapists about the intervention were recorded. Results Fifty five eligible patients were identified, 4-6% of patients screened at each site. Twenty four patients participated in the pilot study. Two of the three study sites met the recruitment target of 1-2 participants per month. The median number of face to face therapy sessions received was 6 [IQR 3-8]. The median number of daily repetitions of activities recorded was 80 [IQR 39-80]. Data about usual post stroke rehabilitation were available for 18/24 (75%). Outcome data were available for 22/24 (92%) at one month and 20/24 (83%) at three months. Outcome assessors were unblinded to participant group allocation for 11/22 (50%) at one month and 6/20 (30%) at three months. Four adverse events were considered serious as they resulted in hospitalisation. None were related to study treatment. Feedback from patients and local NHS therapists about the RFTP programme was mainly positive. Conclusions A multi-centre randomised controlled trial to evaluate an upper limb RFTP therapy programme provided early after stroke is feasible and acceptable to patients and therapists, but there are issues which needed to be addressed when designing a Phase III study. A Phase III study will need to monitor and report not only recruitment and attrition but also adherence to the intervention, usual post stroke rehabilitation received, and outcome assessor blinding

Canadian Hydrogen Intensity Mapping Experiment (CHIME) Pathfinder

A pathfinder version of CHIME (the Canadian Hydrogen Intensity Mapping Experiment) is currently being commissioned at the Dominion Radio Astrophysical Observatory (DRAO) in Penticton, BC. The instrument is a hybrid cylindrical interferometer designed to measure the large scale neutral hydrogen power spectrum across the redshift range 0.8 to 2.5. The power spectrum will be used to measure the baryon acoustic oscillation (BAO) scale across this poorly probed redshift range where dark energy becomes a significant contributor to the evolution of the Universe. The instrument revives the cylinder design in radio astronomy with a wide field survey as a primary goal. Modern low-noise amplifiers and digital processing remove the necessity for the analog beamforming that characterized previous designs. The Pathfinder consists of two cylinders 37\,m long by 20\,m wide oriented north-south for a total collecting area of 1,500 square meters. The cylinders are stationary with no moving parts, and form a transit instrument with an instantaneous field of view of $\sim$100\,degrees by 1-2\,degrees. Each CHIME Pathfinder cylinder has a feedline with 64 dual polarization feeds placed every $\sim$30\,cm which Nyquist sample the north-south sky over much of the frequency band. The signals from each dual-polarization feed are independently amplified, filtered to 400-800\,MHz, and directly sampled at 800\,MSps using 8 bits. The correlator is an FX design, where the Fourier transform channelization is performed in FPGAs, which are interfaced to a set of GPUs that compute the correlation matrix. The CHIME Pathfinder is a 1/10th scale prototype version of CHIME and is designed to detect the BAO feature and constrain the distance-redshift relation.Comment: 20 pages, 12 figures. submitted to Proc. SPIE, Astronomical Telescopes + Instrumentation (2014

A smartphone-based test for the assessment of attention deficits in delirium: A case-control diagnostic test accuracy study in older hospitalised patients.

BACKGROUND: Delirium is a common and serious acute neuropsychiatric syndrome which is often missed in routine clinical care. Inattention is the core cognitive feature. Diagnostic test accuracy (including cut-points) of a smartphone Delirium App (DelApp) for assessing attention deficits was assessed in older hospital inpatients. METHODS: This was a case-control study of hospitalised patients aged ≥65 years with delirium (with or without pre-existing cognitive impairment), who were compared to patients with dementia without delirium, and patients without cognitive impairment. Reference standard delirium assessment, which included a neuropsychological test battery, was based on Diagnostic and Statistical Manual of Mental Disorders-5 criteria. A separate blinded assessor administered the DelApp arousal assessment (score 0-4) and attention task (0-6) yielding an overall score of 0 to 10 (lower scores indicate poorer performance). Analyses included receiver operating characteristic curves and sensitivity and specificity. Optimal cut-points for delirium detection were determined using Youden's index. RESULTS: A total of 187 patients were recruited, mean age 83.8 (range 67-98) years, 152 (81%) women; n = 61 with delirium; n = 61 with dementia without delirium; and n = 65 without cognitive impairment. Patients with delirium performed poorly on the DelApp (median score = 4/10; inter-quartile range 3.0, 5.5) compared to patients with dementia (9.0; 5.5, 10.0) and those without cognitive impairment (10.0; 10.0, 10.0). Area under the curve for detecting delirium was 0.89 (95% Confidence Interval 0.84, 0.94). At an optimal cut-point of ≤8, sensitivity was 91.7% (84.7%, 98.7%) and specificity 74.2% (66.5%, 81.9%) for discriminating delirium from the other groups. Specificity was 68.3% (56.6%, 80.1%) for discriminating delirium from dementia (cut-point ≤6). CONCLUSION: Patients with delirium (with or without pre-existing cognitive impairment) perform poorly on the DelApp compared to patients with dementia and those without cognitive impairment. A cut-point of ≤8/10 is suggested as having optimal sensitivity and specificity. The DelApp is a promising tool for assessment of attention deficits associated with delirium in older hospitalised adults, many of whom have prior cognitive impairment, and should be further validated in representative patient cohorts

A feasibility randomised controlled trial of a motivational interviewing-based intervention for weight loss maintenance in adults

Background Obesity has significant health and NHS cost implications. Relatively small reductions in weight have clinically important benefits, but long-term weight loss maintenance (WLM) is challenging. Behaviour change interventions have been identified as key for WLM. Motivation is crucial to supporting behaviour change, and motivational interviewing (MI) has been identified as a successful approach to changing health behaviours. The study was designed as an adequately powered, pragmatic randomised controlled trial (RCT); however, owing to recruitment issues, the study became a feasibility trial. Objectives To assess recruitment, retention, feasibility, acceptability, compliance and delivery of a 12-month intervention to support WLM. Secondary objectives were to assess the impact of the intervention on body mass index (BMI) and other secondary outcomes. Design Three-arm individually randomised controlled trial comprising an intensive arm, a less intensive arm and a control arm. Setting Community setting in South Wales and the East Midlands. Participants Individuals aged 18�70 years with a current or previous BMI of ??30 kg/m2 who could provide evidence of at least 5% weight loss during the previous 12 months. Intervention Participants received individually tailored MI, which included planning and self-monitoring. The intensive arm received six face-to-face sessions followed by nine telephone sessions. The less intensive arm received two face-to-face sessions followed by two telephone sessions. The control arm received a leaflet advising them on healthy lifestyle. Main outcome measures Feasibility outcomes included numbers recruited, retention and adherence. The primary effectiveness outcome was BMI at 12 months post randomisation. Secondary outcomes included waist circumference, waist-to-hip ratio, physical activity, proportion maintaining weight loss, diet, quality of life, health service resource usage, binge eating and well-being. A process evaluation assessed intervention delivery, adherence, and participants� and practitioners� views. Economic analysis aimed to assess cost-effectiveness in terms of quality-adjusted life-years (QALYs). Results A total of 170 participants were randomised. Retention was good (84%) and adherence was excellent (intensive, 83%; less intensive, 91%). The between-group difference in mean BMI indicated the intensive arm had BMIs 1.0?kg/m2 lower than the controls [95% confidence interval (CI) �2.2 kg/m2 to 0.2?kg/m2]. Similarly, a potential difference was found in weight (average difference of 2.8?kg, 95% CI �6.1 kg to 0.5?kg). The intensive arm had odds of maintaining on average 43% [odds ratio(OR) 1.4, 95% CI 0.6 to 3.5] higher than controls. None of these findings were statistically significant. Further analyses controlling for level of adherence indicated that average BMI was 1.2?kg/m2 lower in the intensive arm than the control arm (95% CI �2.5?kg/m2 to 0.0?kg/m2). The intensive intervention led to a statistically significant difference in weight (mean �3.7?kg, 95% CI �7.1?kg to �0.3?kg). The other secondary outcomes showed limited evidence of differences between groups. The intervention was delivered as planned, and both practitioners and participants were positive about the intervention and its impact. Although not powered to assess cost-effectiveness, results of this feasibility study suggest that neither intervention as currently delivered is likely to be cost-effective in routine practice. Conclusion This is the first trial of an intervention for WLM in the UK, the intervention is feasible and acceptable, and retention and adherence were high. The main effectiveness outcome showed a promising mean difference in the intensive arm. Owing to the small sample size, we are limited in the conclusions we can draw. However, findings suggest that the intensive intervention may facilitate long-term weight maintenance and, therefore, further testing in an effectiveness trial may be indicated. Research examining WLM is in its infancy, further research is needed to develop our understanding of WLM and to expand theory to inform the development of interventions to be tested in rigorously designed RCTs with cost-effectiveness assessed