A temperate river estuary is a sink for methanotrophs adapted to extremes of pH, temperature and salinity

River Tyne (UK) estuarine sediments harbour a genetically and functionally diverse community of methane-oxidizing bacteria (methanotrophs), the composition and activity of which were directly influenced by imposed environmental conditions (pH, salinity, temperature) that extended far beyond those found in situ. In aerobic sediment slurries methane oxidation rates were monitored together with the diversity of a functional gene marker for methanotrophs (pmoA). Under near in situ conditions (4-30°C, pH 6-8, 1-15gl-1 NaCl), communities were enriched by sequences affiliated with Methylobacter and Methylomonas spp. and specifically a Methylobacter psychrophilus-related species at 4-21°C. More extreme conditions, namely high temperatures ≥40°C, high ≥9 and low ≤5 pH, and high salinities ≥35gl-1 selected for putative thermophiles (Methylocaldum), acidophiles (Methylosoma) and haloalkaliphiles (Methylomicrobium). The presence of these extreme methanotrophs (unlikely to be part of the active community in situ) indicates passive dispersal from surrounding environments into the estuary

Correction Approach for Delta Function Convolution Model Fitting of Fluorescence Decay Data in the Case of a Monoexponential Reference Fluorophore

A correction is proposed to the Delta function convolution method (DFCM) for fitting a multiexponential decay model to time-resolved fluorescence decay data using a monoexponential reference fluorophore. A theoretical analysis of the discretised DFCM multiexponential decay function shows the presence an extra exponential decay term with the same lifetime as the reference fluorophore that we denote as the residual reference component. This extra decay component arises as a result of the discretised convolution of one of the two terms in the modified model function required by the DFCM. The effect of the residual reference component becomes more pronounced when the fluorescence lifetime of the reference is longer than all of the individual components of the specimen under inspection and when the temporal sampling interval is not negligible compared to the quantity (τ(R)(−1) – τ(−1))(−1), where τ(R) and τ are the fluorescence lifetimes of the reference and the specimen respectively. It is shown that the unwanted residual reference component results in systematic errors when fitting simulated data and that these errors are not present when the proposed correction is applied. The correction is also verified using real data obtained from experiment

Assessment of the healthy worker survivor effect in the relationship between psychosocial work-related factors and hypertension.

OBJECTIVES: The healthy worker survivor effect (HWSE) usually leads to underestimation of the effects of harmful occupational exposures. HWSE is characterised by the concomitance of three associations: (1) job status-subsequent exposure, (2) job status-disease and (3) previous exposure-job status. No study has reported the coexistence of these associations in the relationship between psychosocial work-related factors and health. We assessed if HWSE is present when measuring the effects of cumulative exposure to psychosocial work-related factors on the prevalence of hypertension in white-collar workers. METHODS: Data were obtained from two timepoints (1991-1993 at baseline and 1999-2001 at follow-up) of a prospective cohort study. At baseline, the population was composed of 9188 white-collar employees (women: 49.9%) in Quebec City. Job strain as psychosocial work-related factor and blood pressure were measured using validated methods. Job status (retirees vs employees) at follow-up was self-reported. Multiple multilevel robust Poisson regressions were used to estimate prevalence ratios of hypertension and risk ratios of retirement separately by gender. We performed multiple imputations to control selection bias due to missing values. RESULTS: Retirement eliminated the subsequent exposure to job strain de facto and was associated with the reduction in the prevalence of hypertension in younger (-33%) and older (-11%) men and in older women (-39%). Job strain was associated with job status in younger men and in women of any age. CONCLUSION: Data showed the presence of HWSE in younger men and older women given the coexistence of the three structural associations

Multiphoton Multispectral Fluorescence Lifetime Tomography for the Evaluation of Basal Cell Carcinomas

We present the first detailed study using multispectral multiphoton fluorescence lifetime imaging to differentiate basal cell carcinoma cells (BCCs) from normal keratinocytes. Images were acquired from 19 freshly excised BCCs and 27 samples of normal skin (in & ex vivo). Features from fluorescence lifetime images were used to discriminate BCCs with a sensitivity/specificity of 79%/93% respectively. A mosaic of BCC fluorescence lifetime images covering >1 mm2 is also presented, demonstrating the potential for tumour margin delineation. Using 10,462 manually segmented cells from the image data, we quantify the cellular morphology and spectroscopic differences between BCCs and normal skin for the first time. Statistically significant increases were found in the fluorescence lifetimes of cells from BCCs in all spectral channels, ranging from 19.9% (425–515 nm spectral emission) to 39.8% (620–655 nm emission). A discriminant analysis based diagnostic algorithm allowed the fraction of cells classified as malignant to be calculated for each patient. This yielded a receiver operator characteristic area under the curve for the detection of BCC of 0.83. We have used both morphological and spectroscopic parameters to discriminate BCC from normal skin, and provide a comprehensive base for how this technique could be used for BCC assessment in clinical practice

Nature and human nature

1974-75 Champion International Corporation Lectureship.Gerald W. Williams Collectio

Comparison of the outcome of kidney transplantation after pulsatile or continuous ex vivo hypothermic machine perfusion of kidneys donated after cardiac death: analysis of kidney pairs

Background Hypothermic machine perfusion is used to improve renal perfusion and reduce the rate of early and late graft dysfunction. It has been used in our unit since 2001. It has two modes of flow: continuous or pulsatile. The aim of this study is to compare the modes of perfusion in terms of perfusion-related parameters, graft survival and estimated glomerular filtration rate. Methods All donation after cardiac death kidneys between 2002 and 2014 were reviewed. Sixty-four pairs of kidneys were identified of which one kidney underwent pulsatile and the other continuous perfusion. Machine parameters including resistance and perfusion flow index levels at 0, 1, 2, 3, 4 hours were recorded and glutathione S-transferase measured in perfusate. Delayed graft function frequency, estimated glomerular filtration rate from the 1st week of transplantation until 5th year and graft survival rates were determined. Results Machine parameters were similar at all time points. Delayed graft function frequency, estimated glomerular filtration rates and graft survival were equivalent irrespective of perfusion mode. Conclusion Pulsatile perfusion may be regarded as more physiological. However, we could not identify differences in short or long term outcomes following transplantation of kidneys from the same donor that had been perfused under pulsatile or continuous conditions

Fungal model systems and the elucidation of pathogenicity determinants

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.Peer reviewedPublisher PD

Motor Neuron Disease Register for England, Wales and Northern Ireland-an analysis of incidence in England.

Amyotrophic lateral sclerosis (ALS) has a reported incidence of 1-2/100,000 person-years. It is estimated that there are 5000 people with ALS in the UK at any one time; however, the true figure and geographical distribution, are unknown. In this study, we describe the establishment of a population register for England, Wales, and Northern Ireland and report-estimated incidence. Methods: People with a diagnosis of ALS given by a consultant neurologist and whose postcode of residence is within England, Wales, or Northern Ireland were eligible. The catchment area was based on six data contributors that had been participating since 2016. All centres included in this analysis were in England, and therefore Wales and Northern Ireland are not included in this report. Crude age- and sex-specific incidence rates were estimated using population census records for the relevant postcodes from Office of National Statistics census data. These rates were standardized to the UK population structure using direct standardization. Results: There were 232 people in the database with a date of diagnosis between 2017 and 2018, when missing data were imputed there were an estimated 287-301 people. The denominator population of the catchment area is 7,251,845 according to 2011 UK census data. Age- and sex-adjusted incidence for complete cases was 1.61/100,000 person-years (95% confidence interval 1.58, 1.63), and for imputed datasets was 2.072/100,000 person-years (95% CI 2.072, 2.073). Discussion: We found incidence in this previously unreported area of the UK to be similar to other published estimates. As the MND Register for England, Wales, and Northern Ireland grows we will update incidence estimates and report on further analyses

Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis.

OBJECTIVE: To test blood and CSF neurofilament light chain (NfL) levels in relation to disease progression and survival in amyotrophic lateral sclerosis (ALS). METHODS: Using an electrochemiluminescence immunoassay, NfL levels were measured in samples from 2 cohorts of patients with sporadic ALS and healthy controls, recruited in London (ALS/control, plasma: n = 103/42) and Oxford (ALS/control, serum: n = 64/36; paired CSF: n = 38/20). NfL levels in patients were measured at regular intervals for up to 3 years. Change in ALS Functional Rating Scale-Revised score was used to assess disease progression. Survival was evaluated using Cox regression and Kaplan-Meier analysis. RESULTS: CSF, serum, and plasma NfL discriminated patients with ALS from healthy controls with high sensitivity (97%, 89%, 90%, respectively) and specificity (95%, 75%, 71%, respectively). CSF NfL was highly correlated with serum levels (r = 0.78, p < 0.0001). Blood NfL levels were approximately 4 times as high in patients with ALS compared with controls in both cohorts, and maintained a relatively constant expression during follow-up. Blood NfL levels at recruitment were strong, independent predictors of survival. The highest tertile of blood NfL at baseline had a mortality hazard ratio of 3.91 (95% confidence interval 1.98-7.94, p < 0.001). CONCLUSION: Blood-derived NfL level is an easily accessible biomarker with prognostic value in ALS. The individually relatively stable levels longitudinally offer potential for NfL as a pharmacodynamic biomarker in future therapeutic trials. CLASSIFICATION OF EVIDENCE: This report provides Class III evidence that the NfL electrochemiluminescence immunoassay accurately distinguishes patients with sporadic ALS from healthy controls