mPUMA: a computational approach to microbiota analysis by de novo assembly of operational taxonomic units based on protein-coding barcode sequences.

BACKGROUND: Formation of operational taxonomic units (OTU) is a common approach to data aggregation in microbial ecology studies based on amplification and sequencing of individual gene targets. The de novo assembly of OTU sequences has been recently demonstrated as an alternative to widely used clustering methods, providing robust information from experimental data alone, without any reliance on an external reference database. RESULTS: Here we introduce mPUMA (microbial Profiling Using Metagenomic Assembly, http://mpuma.sourceforge.net), a software package for identification and analysis of protein-coding barcode sequence data. It was developed originally for Cpn60 universal target sequences (also known as GroEL or Hsp60). Using an unattended process that is independent of external reference sequences, mPUMA forms OTUs by DNA sequence assembly and is capable of tracking OTU abundance. mPUMA processes microbial profiles both in terms of the direct DNA sequence as well as in the translated amino acid sequence for protein coding barcodes. By forming OTUs and calculating abundance through an assembly approach, mPUMA is capable of generating inputs for several popular microbiota analysis tools. Using SFF data from sequencing of a synthetic community of Cpn60 sequences derived from the human vaginal microbiome, we demonstrate that mPUMA can faithfully reconstruct all expected OTU sequences and produce compositional profiles consistent with actual community structure. CONCLUSIONS: mPUMA enables analysis of microbial communities while empowering the discovery of novel organisms through OTU assembly

Feasibility of the STarT back screening tool in chiropractic clinics: a cross-sectional study of patients with low back pain

The STarT back screening tool (SBT) allocates low back pain (LBP) patients into three risk groups and is intended to assist clinicians in their decisions about choice of treatment. The tool consists of domains from larger questionnaires that previously have been shown to be predictive of non-recovery from LBP. This study was performed to describe the distribution of depression, fear avoidance and catastrophising in relation to the SBT risk groups. A total of 475 primary care patients were included from 19 chiropractic clinics. They completed the SBT, the Major Depression Inventory (MDI), the Fear Avoidance Beliefs Questionnaire (FABQ), and the Coping Strategies Questionnaire. Associations between the continuous scores of the psychological questionnaires and the SBT were tested by means of linear regression, and the diagnostic performance of the SBT in relation to the other questionnaires was described in terms of sensitivity, specificity and likelihood ratios

Increasing condom use in heterosexual men: development of a theory-based interactive digital intervention

Increasing condom use to prevent sexually transmitted infections is a key public health goal. Interventions are more likely to be effective if they are theory- and evidence-based. The Behaviour Change Wheel (BCW) provides a framework for intervention development. To provide an example of how the BCW was used to develop an intervention to increase condom use in heterosexual men (the MenSS website), the steps of the BCW intervention development process were followed, incorporating evidence from the research literature and views of experts and the target population. Capability (e.g. knowledge) and motivation (e.g. beliefs about pleasure) were identified as important targets of the intervention. We devised ways to address each intervention target, including selecting interactive features and behaviour change techniques. The BCW provides a useful framework for integrating sources of evidence to inform intervention content and deciding which influences on behaviour to target

Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition

BACKGROUND:Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.METHODS:We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare.RESULTS:All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events.CONCLUSIONS:Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations

Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index

Cigarette smoking is associated with lower body mass index (BMI), and a commonly cited reason for unwillingness to quit smoking is a concern about weight gain. Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region (chromosome 15q25) is robustly associated with smoking quantity in smokers, but its association with BMI is unknown. We hypothesized that genotype would accurately reflect smoking exposure and that, if smoking were causally related to weight, it would be associated with BMI in smokers, but not in never smokers

GPAQ-R: development and psychometric properties of a version of the general practice assessment questionnaire for use for revalidation by general practitioners in the UK.

BACKGROUND: The General Practice Assessment Questionnaire (GPAQ) has been widely used to assess patient experience in general practice in the UK since 2004. In 2013, new regulations were introduced by the General Medical Council (GMC) requiring UK doctors to undertake periodic revalidation, which includes assessment of patient experience for individual doctors. We describe the development of a new version of GPAQ - GPAQ-R which addresses the GMC's requirements for revalidation as well as additional NHS requirements for surveys that GPs may need to carry out in their own practices. METHODS: Questionnaires were given out by doctors or practice staff after routine consultations in line with the guidance given by the General Medical Council for surveys to be used for revalidation. Data analysis and practice reports were provided independently. RESULTS: Data were analysed for questionnaires from 7258 patients relating to 164 GPs in 29 general practices. Levels of missing data were generally low (typically 4.5-6%). The number of returned questionnaires required to achieve reliability of 0.7 were around 35 for individual doctor communication items and 29 for a composite score based on doctor communication items. This suggests that the responses to GPAQ-R had similar reliability to the GMC's own questionnaire and we recommend 30 completed GPAQ-R questionnaires are sufficient for revalidation purposes. However, where an initial screen raises concern, the survey might be repeated with 50 completed questionnaires in order to increase reliability. CONCLUSIONS: GPAQ-R is a development of a well-established patient experience questionnaire used in general practice in the UK since 2004. This new version can be recommended for use in order to meet the UK General Medical Council's requirements for surveys to be used in revalidation of doctors. It also meets the needs of GPs to ask about patient experience relating to aspects of practice care that are not specific to individual general practitioners (e.g. receptionists, telephone access) which meet other survey requirements of the National Health Service in England. Use of GPAQ-R has the potential to reduce the number of surveys that GPs need to carry out in their practices to meet the various regulatory requirements which they face

CR1 Knops blood group alleles are not associated with severe malaria in the Gambia

The Knops blood group antigen erythrocyte polymorphisms have been associated with reduced falciparum malaria-based in vitro rosette formation (putative malaria virulence factor). Having previously identified single-nucleotide polymorphisms (SNPs) in the human complement receptor 1 (CR1/CD35) gene underlying the Knops antithetical antigens Sl1/Sl2 and McC(a)/McC(b), we have now performed genotype comparisons to test associations between these two molecular variants and severe malaria in West African children living in the Gambia. While SNPs associated with Sl:2 and McC(b+) were equally distributed among malaria-infected children with severe malaria and control children not infected with malaria parasites, high allele frequencies for Sl 2 (0.800, 1,365/1,706) and McC(b) (0.385, 658/1706) were observed. Further, when compared to the Sl 1/McC(a) allele observed in all populations, the African Sl 2/McC(b) allele appears to have evolved as a result of positive selection (modified Nei-Gojobori test Ka-Ks/s.e.=1.77, P-value &lt;0.05). Given the role of CR1 in host defense, our findings suggest that Sl 2 and McC(b) have arisen to confer a selective advantage against infectious disease that, in view of these case-control study data, was not solely Plasmodium falciparum malaria. Factors underlying the lack of association between Sl 2 and McC(b) with severe malaria may involve variation in CR1 expression levels

Initial results of multilevel principal components analysis of facial shape

Traditionally, active shape models (ASMs) do not make a distinction between groups in the subject population and they rely on methods such as (single-level) principal components analysis (PCA). Multilevel principal components analysis (PCA) allows one to model between-group effects and within-group effects explicitly. Three dimensional (3D) laser scans were taken from 240 subjects (38 Croatian female, 35 Croatian male, 40 English female, 40 English male, 23 Welsh female, 27 Welsh male, 23 Finnish female, and 24 Finnish male) and 21 landmark points were created subsequently for each scan. After Procrustes transformation, eigenvalues from mPCA and from single-level PCA based on these points were examined. mPCA indicated that the first two eigenvalues of largest magnitude related to within-groups components, but that the next largest eigenvalue related to between-groups components. Eigenvalues from single-level PCA always had a larger magnitude than either within-group or between-group eigenvectors at equivalent eigenvalue number. An examination of the first mode of variation indicated possible mixing of between-group and within-group effects in single-level PCA. Component scores for mPCA indicated clustering with country and gender for the between-groups components (as ex-pected), but not for the within-group terms (also as expected). Clustering of component scores for single-level PCA was harder to resolve. In conclusion, mPCA is viable method of forming shape models that offers distinct advantages over single-level PCA when groups occur naturally in the subject population

The incidence of scarring on the dorsum of the hand

When undertaking image comparison of the hand between accused and perpetrator, it is not unusual for scars to be identified on the back of the hand. To investigate the occurrence of scarring in a discreet sample, a database of 238 individuals was examined, and the dorsum of the right and left hands was gridded for each individual. The position, size and type of scar were recorded within each grid. It was found that, in general, males exhibited a higher incidence of scarring than females. However, males were more likely to show scarring on their left hand whereas females were more likely to exhibit scarring on their right hand. Contrary to the literature, scarring was not most prevalent along the borders of the hand but occurred more frequently in association with the index and middle finger corridor regions. Surgical scars were rare as were large scars whereas linear scars smaller than 6 mm were the most frequently identified. Close to half of the sample did not exhibit scarring on one hand. The importance of understanding the pattern of scarring on the back of the hand is discussed in the light of forensic image comparison analysis

Stretchable liquid-crystal blue-phase gels

Liquid crystalline polymers are materials of considerable scientific interest and technological value to society [1-3]. An important subset of such materials exhibit rubber-like elasticity; these can combine the remarkable optical properties of liquid crystals with the favourable mechanical properties of rubber and, further, exhibit behaviour not seen in either type of material independently [2]. Many of their properties depend crucially on the particular mesophase employed. Stretchable liquid crystalline polymers have previously been demonstrated in the nematic, chiral nematic, and smectic mesophases [2,4]. Here were report the fabrication of a stretchable gel of blue phase I, which forms a self-assembled, three-dimensional photonic crystal that may have its optical properties manipulated by an applied strain and, further, remains electro-optically switchable under a moderate applied voltage. We find that, unlike its undistorted counterpart, a mechanically deformed blue phase exhibits a Pockels electro-optic effect, which sets out new theoretical challenges and new possibilities for low-voltage electro-optic devices.Comment: 15 pages, 6 figures, additional data and discussion included. Supplementary videos available from F. Castles on reques