Interpreting 16S metagenomic data without clustering to achieve sub-OTU resolution

The standard approach to analyzing 16S tag sequence data, which relies on clustering reads by sequence similarity into Operational Taxonomic Units (OTUs), underexploits the accuracy of modern sequencing technology. We present a clustering-free approach to multi-sample Illumina datasets that can identify independent bacterial subpopulations regardless of the similarity of their 16S tag sequences. Using published data from a longitudinal time-series study of human tongue microbiota, we are able to resolve within standard 97% similarity OTUs up to 20 distinct subpopulations, all ecologically distinct but with 16S tags differing by as little as 1 nucleotide (99.2% similarity). A comparative analysis of oral communities of two cohabiting individuals reveals that most such subpopulations are shared between the two communities at 100% sequence identity, and that dynamical similarity between subpopulations in one host is strongly predictive of dynamical similarity between the same subpopulations in the other host. Our method can also be applied to samples collected in cross-sectional studies and can be used with the 454 sequencing platform. We discuss how the sub-OTU resolution of our approach can provide new insight into factors shaping community assembly.Comment: Updated to match the published version. 12 pages, 5 figures + supplement. Significantly revised for clarity, references added, results not change

Do children with neurological disabilities use more inpatient resources: an observational study.

BACKGROUND: Advances in healthcare have improved the survival of children with neurological disabilities (ND). Studies in the US have shown that children with ND use a substantial proportion of resources in children's hospitals, however, little research has been conducted in the UK. We aimed to test the hypothesis that children with neurological disabilities use more inpatient resources than children without neurological disabilities, and to quantify any significant differences in resource use. METHODS: A retrospective observational study was conducted, looking at the number of hospital admissions, total inpatient days and the reason for admissions for paediatric inpatients from January 1st to March 31st 2015. Inpatients were assigned into one of three groups: children without ND, children with one ND, and children with more than one ND. RESULTS: The sample population included 942 inpatients (mean age 6y 6mo). Children with at least one ND accounted for 15.3% of the inpatients, 17.7% of total hospital inpatient admission episodes, and 27.8% of the total inpatients days. Neurological disability had a statistically significant effect on total hospital admissions (p < 0.001). Neurological disability also had a statistically significant effect on total inpatient days (p < 0.001). Neurological disability increased the length of inpatient stay across medicine, specialties, and surgery. CONCLUSIONS: Children with ND had more frequent hospital admission episode and longer inpatient stays. We identified a smaller group within this population, with arguably more complex neurological disabilities, children with more than one ND. This group had the highest number of admissions and longest inpatient stays. More frequent hospital admissions and longer inpatient stays may place children with ND at greater risk of the adverse effects of hospitalisations. We recommend further investigations looking at each the effects of the different categories of ND on inpatient resource use, and repeat of this study at a national level and over a longer period of time

Recording problems and diagnoses in clinical care: developing guidance for healthcare professionals and system designers

BACKGROUND: Accurate recording of problems and diagnoses in health records is key to safe and effective patient care, yet it is often done poorly. Electronic health record systems vary in their functionality and ease of use, and are not optimally designed for easy recording and sharing of clinical information. There is a lack of professional consensus and guidance on how problems and diagnoses should be recorded. METHODS: The Professional Record Standards Body commissioned work led by the Royal College of Physicians Health Informatics Unit to carry out a literature review, draft guidance, carry out an online consultation and round table discussion, and produce a report including recommendations for systems. A patient workshop was held to explore patient preferences for mechanisms for sharing diagnosis information between primary and secondary care. RESULTS: Consensus was reached among medical specialties on key elements of diagnosis recording, and draft guidance was produced ready for piloting in a variety of care settings. Patients were keen for better ways for diagnosis information to be shared. DISCUSSION: Improving the recording of diagnoses and problems will require a major effort of which the new guidance is only a part. The guidance needs to be embedded in training, and clinical systems need to have improved, standardised functionality. Front-line clinicians, specialist societies, clinical informaticians and patients need to be engaged in developing information models for diagnoses to support care and research, accessible via user-friendly interfaces

Thermographic imaging in sports and exercise medicine: A Delphi study and consensus statement on the measurement of human skin temperature

This is an accepted manuscript of an article published by Elsevier in Journal of Thermal Biology on 18/07/2017, available online: https://doi.org/10.1016/j.jtherbio.2017.07.006 The accepted version of the publication may differ from the final published version.© 2017 Elsevier Ltd The importance of using infrared thermography (IRT) to assess skin temperature (tsk) is increasing in clinical settings. Recently, its use has been increasing in sports and exercise medicine; however, no consensus guideline exists to address the methods for collecting data in such situations. The aim of this study was to develop a checklist for the collection of tsk using IRT in sports and exercise medicine. We carried out a Delphi study to set a checklist based on consensus agreement from leading experts in the field. Panelists (n  =  24) representing the areas of sport science (n = 8; 33%), physiology (n = 7; 29%), physiotherapy (n = 3; 13%) and medicine (n = 6; 25%), from 13 different countries completed the Delphi process. An initial list of 16 points was proposed which was rated and commented on by panelists in three rounds of anonymous surveys following a standard Delphi procedure. The panel reached consensus on 15 items which encompassed the participants’ demographic information, camera/room or environment setup and recording/analysis of tsk using IRT. The results of the Delphi produced the checklist entitled “Thermographic Imaging in Sports and Exercise Medicine (TISEM)” which is a proposal to standardize the collection and analysis of tsk data using IRT. It is intended that the TISEM can also be applied to evaluate bias in thermographic studies and to guide practitioners in the use of this technique.Published versio

Effect of antenatal multiple micronutrient supplementation on anthropometry and blood pressure in mid-childhood in Nepal: follow-up of a double-blind randomised controlled trial

Background: In a randomized controlled trial in southern Nepal, we found that children born to mothers who had taken multiple micronutrient supplements during pregnancy had mean birthweight 77 g greater than a control group allocated to iron and folic acid supplements. They were a mean 204 g heavier at 2·5 years of age and their systolic blood pressure was a mean 2·5 mmHg lower. We followed the same children up in mid-childhood, hypothesizing that these differences would be sustained. Methods: We identified children from the original trial and measured anthropometry, body composition using bioelectrical impedance (with population-specific isotope calibration), blood pressure, and renal dimensions by ultrasound. We documented socieconomic status, household food security, and air pollution.Results: We assessed 841 children (422 control, 419 intervention) at mean age 8·5 years. Unadjusted differences (intervention minus control) were 0·05 z-scores (95% CI -0·09, 0·19) in weight-for-age, 0·02 z-scores (-0·10, 0·15) in height-for-age, and 0·04 z-scores (-0·09, 0·18) in body-mass-index-for-age. There was no difference in blood pressure. Adjusted differences were similar for all outcomes. Discussion: Differences in phenotype between children born to mothers who received antenatal multiple micronutrient or iron and folate supplements were not apparent at 8·5 years. Our findings did not extend to physiological differences or potential longer-term effects

Cross-sectional study of asthma and rhinitis symptoms in the context of exposure to air pollution in Nepal

Asthma is common in children worldwide, although its prevalence varies substantially by location. The prevalence of wheeze over a 12-month period ranged from 2.1% to 32.2% in the older age group (13–14 years) and 4.1% to 32.1% in the younger age group (6–7 years) [1]. There is a positive association between current symptoms of asthma in younger and older children with gross national income [2], and it is generally slightly less common in girls than boys in the younger group [1–3]. Exposure to air pollution is associated with asthma exacerbations. Odds ratios for wheeze in the past year and the use of solely an open fire for cooking were 2.17 (95% CI 1.64–2.87) for children aged 6–7 years and 1.35 (95% CI 1.11–1.64) for children aged 13–14 years [4]. Nepalese children are exposed to high levels of indoor air pollution from the burning of biomass fuels [5]. This study aimed to estimate their prevalence of asthma, and to investigate the association of air pollution and risk of wheeze and rhinitis symptoms using personal exposure estimates of air pollution

Epigenetics as a mechanism driving polygenic clinical drug resistance

Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance

Effects of antenatal multiple micronutrient supplementation on lung function in mid-childhood: follow-up of a double-blind randomised controlled trial in Nepal

A randomised trial of prenatal multiple micronutrient supplementation in Nepalese women increased birthweight and weight at 2 years of age in offspring, compared to those born to mothers who only received iron and folic acid supplements. Further follow-up of this cohort provided an opportunity to investigate the effect of antenatal multiple micronutrients on subsequent lung function by measuring spirometry at 7-9 years of age in C: hildren born during the trial. 841 children (80% of the cohort) were seen at mean±sd 8.5±0.4 years. Technically successful spirometry results were obtained in 793 (94.3%) children, 50% of whom had been randomised to micronutrient supplementation. Background characteristics, including anthropometry, were similar in the two allocation groups. Lung function was also similar, mean (95% CI) difference in z-scores (supplementation minus control) was -0.08 (-0.19-0.04), -0.05 (-0.17-0.06) and -0.04 (-0.15-0.07) for forced expiratory volume in 1 s (FEV1), forced vital capacity and FEV1/FVC, respectively. Compared with healthy white children, FEV1 and FVC in the "healthy" Nepalese children were ∼1 (∼13%) z-score lower, with no difference in FEV1/FVC. We conclude that, compared with routine iron and folic acid, multiple micronutrient supplementation during pregnancy has no effect on spirometric lung function in Nepalese children at 8.5 years of age

Very Low Tidal Volume Ventilation with Associated Hypercapnia - Effects on Lung Injury in a Model for Acute Respiratory Distress Syndrome

BACKGROUND: Ventilation using low tidal volumes with permission of hypercapnia is recommended to protect the lung in acute respiratory distress syndrome. However, the most lung protective tidal volume in association with hypercapnia is unknown. The aim of this study was to assess the effects of different tidal volumes with associated hypercapnia on lung injury and gas exchange in a model for acute respiratory distress syndrome. METHODOLOGY/PRINCIPAL FINDINGS: In this randomized controlled experiment sixty-four surfactant-depleted rabbits were exposed to 6 hours of mechanical ventilation with the following targets: Group 1: tidal volume = 8-10 ml/kg/PaCO(2) = 40 mm Hg; Group 2: tidal volume = 4-5 ml/kg/PaCO(2) = 80 mm Hg; Group 3: tidal volume = 3-4 ml/kg/PaCO(2) = 120 mm Hg; Group 4: tidal volume = 2-3 ml/kg/PaCO(2) = 160 mm Hg. Decreased wet-dry weight ratios of the lungs, lower histological lung injury scores and higher PaO(2) were found in all low tidal volume/hypercapnia groups (group 2, 3, 4) as compared to the group with conventional tidal volume/normocapnia (group 1). The reduction of the tidal volume below 4-5 ml/kg did not enhance lung protection. However, oxygenation and lung protection were maintained at extremely low tidal volumes in association with very severe hypercapnia and no adverse hemodynamic effects were observed with this strategy. CONCLUSION: Ventilation with low tidal volumes and associated hypercapnia was lung protective. A tidal volume below 4-5 ml/kg/PaCO(2) 80 mm Hg with concomitant more severe hypercapnic acidosis did not increase lung protection in this surfactant deficiency model. However, even at extremely low tidal volumes in association with severe hypercapnia lung protection and oxygenation were maintained