The battle of the SNPs

This month’s Genome Watch highlights new perspectives on polygenic adaptation and its consequences for fitness in microbial populations

The UK quality and outcomes framework pay-for-performance scheme and spirometry: rewarding quality or just quantity? A cross-sectional study in Rotherham, UK

Background: Accurate spirometry is important in the management of COPD. The UK Quality and Outcomes Framework pay-for-performance scheme for general practitioners includes spirometry related indicators within its COPD domain. It is not known whether high achievement against QOF spirometry indicators is associated with spirometry to BTS standards. Methods: Data were obtained from the records of 3,217 patients randomly sampled from 5,649 patients with COPD in 38 general practices in Rotherham, UK. Severity of airflow obstruction was categorised by FEV1 (% predicted) according to NICE guidelines. This was compared with clinician recorded COPD severity. The proportion of patients whose spirometry met BTS standards was calculated in each practice using a random sub-sample of 761 patients. The Spearman rank correlation between practice level QOF spirometry achievement and performance against BTS spirometry standards was calculated. Results: Spirometry as assessed by clinical records was to BTS standards in 31% of cases (range at practice level 0% to 74%). The categorisation of airflow obstruction according to the most recent spirometry results did not agree well with the clinical categorisation of COPD recorded in the notes (Cohen's kappa = 0.34, 0.30 - 0.38). 12% of patients on COPD registers had FEV1 (% predicted) results recorded that did not support the diagnosis of COPD. There was no association between quality, as measured by adherence to BTS spirometry standards, and either QOF COPD9 achievement (Spearman's rho = -0.11), or QOF COPD10 achievement (rho = 0.01). Conclusion: The UK Quality and Outcomes Framework currently assesses the quantity, but not the quality of spirometry

Temporal trends in mode, site and stage of presentation with the introduction of colorectal cancer screening: a decade of experience from the West of Scotland

background:  Population colorectal cancer screening programmes have been introduced to reduce cancer-specific mortality through the detection of early-stage disease. The present study aimed to examine the impact of screening introduction in the West of Scotland. methods:  Data on all patients with a diagnosis of colorectal cancer between January 2003 and December 2012 were extracted from a prospectively maintained regional audit database. Changes in mode, site and stage of presentation before, during and after screening introduction were examined. results:  In a population of 2.4 million, over a 10-year period, 14 487 incident cases of colorectal cancer were noted. Of these, 7827 (54%) were males and 7727 (53%) were socioeconomically deprived. In the postscreening era, 18% were diagnosed via the screening programme. There was a reduction in both emergency presentation (20% prescreening vs 13% postscreening, P0.001) and the proportion of rectal cancers (34% prescreening vs 31% pos-screening, P0.001) over the timeframe. Within non-metastatic disease, an increase in the proportion of stage I tumours at diagnosis was noted (17% prescreening vs 28% postscreening, P0.001). conclusions:  Within non-metastatic disease, a shift towards earlier stage at diagnosis has accompanied the introduction of a national screening programme. Such a change should lead to improved outcomes in patients with colorectal cancer

Rectal cancer in old age –is it appropriately managed? Evidence from population-based analysis of routine data across the English national health service

Background: There is significant debate as to where to draw the line between undertreating older rectal cancer patients and minimising treatment risks. This study sought to examine the use of radical rectal cancer treatments and associated outcomes in relation to age across the English NHS. Methods: Patient, tumour and treatment characteristics for all patients diagnosed with a first primary rectal cancer in England between 1st April 2009 and 31st December 2014 were obtained from the CORECT-R data repository. Descriptive analyses and adjusted logistic regression models were undertaken to examine any association between age and the use of major resection and post-surgical outcomes. Funnel plots were used to show variation in adjusted rates of major resection. Results: The proportion of patients who underwent a major surgical resection fell from 66.5% to 31.7%, amongst those aged <70 and aged ≥80 respectively. After adjustment, 30-day post-operative mortality, failure to rescue and prolonged length of stay were significantly higher among the oldest group when compared to the youngest. Patient reported outcomes were not significantly worse amongst older patients. Significant variation was observed in adjusted surgical resection rates in the oldest patients between NHS Trusts. The probability of death due to cancer was comparable across all age groups. Conclusions: Older patients who are selected for surgery have good outcomes, often comparable to their younger counterparts. Significant variation in the treatment of older patients could not be explained by differences in measured characteristics and required further investigation

Multilevel latent class casemix modelling: a novel approach to accommodate patient casemix

<p>Abstract</p> <p>Background</p> <p>Using routinely collected patient data we explore the utility of multilevel latent class (MLLC) models to adjust for patient casemix and rank Trust performance. We contrast this with ranks derived from Trust standardised mortality ratios (SMRs).</p> <p>Methods</p> <p>Patients with colorectal cancer diagnosed between 1998 and 2004 and resident in Northern and Yorkshire regions were identified from the cancer registry database (n = 24,640). Patient age, sex, stage-at-diagnosis (Dukes), and Trust of diagnosis/treatment were extracted. Socioeconomic background was derived using the Townsend Index. Outcome was survival at 3 years after diagnosis. MLLC-modelled and SMR-generated Trust ranks were compared.</p> <p>Results</p> <p>Patients were assigned to two classes of similar size: one with reasonable prognosis (63.0% died within 3 years), and one with better prognosis (39.3% died within 3 years). In patient class one, all patients diagnosed at stage B or C died within 3 years; in patient class two, all patients diagnosed at stage A, B or C survived. Trusts were assigned two classes with 51.3% and 53.2% of patients respectively dying within 3 years. Differences in the ranked Trust performance between the MLLC model and SMRs were all within estimated 95% CIs.</p> <p>Conclusions</p> <p>A novel approach to casemix adjustment is illustrated, ranking Trust performance whilst facilitating the evaluation of factors associated with the patient journey (e.g. treatments) and factors associated with the processes of healthcare delivery (e.g. delays). Further research can demonstrate the value of modelling patient pathways and evaluating healthcare processes across provider institutions.</p

Exploring forest structural complexity by multi-scale segmentation of VHR imagery

Forests are complex ecological systems, characterised by multiple-scale structural and dynamical patterns which are not inferable from a system description that spans only a narrow window of resolution; this makes their investigation a difficult task using standard field sampling protocols. We segment a QuickBird image covering a beech forest in an initial stage of old-growthness – showing, accordingly, a good degree of structural complexity – into three segmentation levels. We apply field-based diversity indices of tree size, spacing, species assemblage to quantify structural heterogeneity amongst forest regions delineated by segmentation. The aim of the study is to evaluate, on a statistical basis, the relationships between spectrally delineated image segments and observed spatial heterogeneity in forest structure, including gaps in the outer canopy. Results show that: some 45% of the segments generated at the coarser segmentation scale (level 1) are surrounded by structurally different neighbours; level 2 segments distinguish spatial heterogeneity in forest structure in about 63% of level 1 segments; level 3 image segments detect better canopy gaps, rather than differences in the spatial pattern of the investigated structural indices. Results support also the idea of a mixture of macro and micro structural heterogeneity within the beech forest: large size populations of trees homogeneous for the examined structural indices at the coarser segmentation level, when analysed at a finer scale, are internally heterogeneous; and vice versa. Findings from this study demonstrate that multiresolution segmentation is able to delineate scale-dependent patterns of forest structural heterogeneity, even in an initial stage of old-growth structural differentiation. This tool has therefore a potential to improve the sampling design of field surveys aimed at characterizing forest structural complexity across multiple spatio-temporal scales.L'articolo è disponibile sul sito dell'editore www.sciencedirect.co

Media(ted) discourses and climate change : a focus on political subjectivity and (dis)engagement

Research has shown that the media are the main source of information and the main factor shaping people’s awareness and concern in relation to climate change and therefore have an important role in setting the public agenda. As a key forum for the production, reproduction and transformation of the meaning of public issues, the media influence understandings of risks, responsibilities, as well as of the functioning of democratic politics. This article argues that the media also matter to citizens’ perception of their (potential) political agency or their political subjectivity. Media representations construct particular ‘subject positions’ for individuals and cultivate dispositions to action or inaction. The article discusses the importance of citizens’ political engagement with climate change and points out some aspects of media(ted) discourses that may constrain the perceived possibilities of participation in the politics of climate change. While engagement with climate change has multiple dimensions and a number of barriers have been identified through empirical studies, this article offers a critique of the role of the media in political engagement with the problem and suggests avenues for future research.The author is grateful to the Portuguese Funda A, o para a CiIncia e a Tecnologia for funding the project 'The Politics of Climate Change: Discourses and Representations' (POCI/COM56973/2004), to Jan Zienkowski for relevant comments on this paper, and to the reviewers who provided detailed feedback

Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity

Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations