Clostridium difficile in England: can we stop washing our hands? – Authors' reply

In their letter, Esther van Kleef and colleagues describe a mathematical model showing that hospital infection control interventions can preferentially reduce hospital-adapted strains over community-adapted strains within and outside hospitals, questioning our conclusion that restrictions in fluoroquinolone use were responsible for most of the decline in Clostridium difficile infection.1 “All models are wrong, but some are useful” (George E P Box). The key is not whether a model can reproduce findings from an empirical study, but whether the assumptions underpinning it are sufficiently plausible. Unfortunately, several features are implausible in van Kleef and colleagues' model, which seems more appropriate for meticillin-resistant Staphylococcus aureus (MRSA)

Prospective, randomized evaluation of a personal digital assistant-based research tool in the emergency department

Background Personal digital assistants (PDA) offer putative advantages over paper for collecting research data. However, there are no data prospectively comparing PDA and paper in the emergency department. The aim of this study was to prospectively compare the performance of PDA and paper enrollment instruments with respect to time required and errors generated. Methods We randomized consecutive patients enrolled in an ongoing prospective study to having their data recorded either on a PDA or a paper data collection instrument. For each method, we recorded the total time required for enrollment, and the time required for manual transcription (paper) onto a computer database. We compared data error rates by examining missing data, nonsensical data, and errors made during the transcription of paper forms. Statistical comparisons were performed by Kruskal-Wallis and Poisson regression analyses for time and errors, respectively. Results We enrolled 68 patients (37 PDA, 31 paper). Two of 31 paper forms were not available for analysis. Total data gathering times, inclusive of transcription, were significantly less for PDA (6:13 min per patient) compared to paper (9:12 min per patient; p < 0.001). There were a total of 0.9 missing and nonsense errors per paper form compared to 0.2 errors per PDA form (p < 0.001). An additional 0.7 errors per paper form were generated during transcription. In total, there were 1.6 errors per paper form and 0.2 errors per PDA form (p < 0.001). Conclusion Using a PDA-based data collection instrument for clinical research reduces the time required for data gathering and significantly improves data integrity

Clostridium difficile trehalose metabolism variants are common and not associated with adverse patient outcomes when variably present in the same lineage

Background: Clostridium difficile ribotype-027, ribotype-078, and ribotype-017 are virulent and epidemic lineages. Trehalose metabolism variants in these ribotypes, combined with increased human trehalose consumption, have been hypothesised to have contributed to their emergence and virulence. Methods: 5232 previously whole-genome sequenced C. difficile isolates were analysed. Clinical isolates were used to investigate the impact of trehalose metabolism variants on mortality. Import data were used to estimate changes in dietary trehalose. Ribotype-027 virulence was investigated in a clinically reflective gut model. Findings: Trehalose metabolism variants found in ribotype-027 and ribotype-017 were widely distributed throughout C. difficile clade-2 and clade-4 in 24/29 (83%)and 10/11 (91%)of sequence types (STs), respectively. The four-gene trehalose metabolism cluster described in ribotype-078 was common in genomes from all five clinically-important C. difficile clades (40/167 [24%]STs). The four-gene cluster was variably present in 208 ribotype-015 infections (98 [47%]); 27/208 (13%)of these patients died within 30-days of diagnosis. Adjusting for age, sex, and infecting ST, there was no association between 30-day all-cause mortality and the four-gene cluster (OR 0.36 [95%CI 0.09–1.34, p = 0.13]). Synthetic trehalose imports in the USA, UK, Germany and the EU were < 1 g/capita/year during 2000–2006, and < 9 g/capita/year 2007–2012, compared with dietary trehalose from natural sources of ~100 g/capita/year. Trehalose supplementation did not increase ribotype-027 virulence in a clinically-validated gut model. Interpretation: Trehalose metabolism variants are common in C. difficile. Increases in total dietary trehalose during the early-mid 2000s C. difficile epidemic were likely relatively minimal. Alternative explanations are required to explain why ribotype-027, ribotype-078 and ribotype-017 have been successful

Contrasting responses of mean and extreme snowfall to climate change

Snowfall is an important element of the climate system, and one that is expected to change in a warming climate. Both mean snowfall and the intensity distribution of snowfall are important, with heavy snowfall events having particularly large economic and human impacts. Simulations with climate models indicate that annual mean snowfall declines with warming in most regions but increases in regions with very low surface temperatures. The response of heavy snowfall events to a changing climate, however, is unclear. Here I show that in simulations with climate models under a scenario of high emissions of greenhouse gases, by the late twenty-first century there are smaller fractional changes in the intensities of daily snowfall extremes than in mean snowfall over many Northern Hemisphere land regions. For example, for monthly climatological temperatures just below freezing and surface elevations below 1,000 metres, the 99.99th percentile of daily snowfall decreases by 8% in the multimodel median, compared to a 65% reduction in mean snowfall. Both mean and extreme snowfall must decrease for a sufficiently large warming, but the climatological temperature above which snowfall extremes decrease with warming in the simulations is as high as −9 °C, compared to −14 °C for mean snowfall. These results are supported by a physically based theory that is consistent with the observed rain–snow transition. According to the theory, snowfall extremes occur near an optimal temperature that is insensitive to climate warming, and this results in smaller fractional changes for higher percentiles of daily snowfall. The simulated changes in snowfall that I find would influence surface snow and its hazards; these changes also suggest that it may be difficult to detect a regional climate-change signal in snowfall extremes.National Science Foundation (U.S.) (Grant AGS-1148594)United States. National Aeronautics and Space Administration (ROSES Grant 09-IDS09-0049

Female Genitalia Concealment Promotes Intimate Male Courtship in a Water Strider

Violent coercive mating initiation is typical for animals with sexual conflict over mating. In these species, the coevolutionary arms-race between female defenses against coercive mating and male counter-adaptations for increased mating success leads to coevolutionary chases of male and female traits that influence the mating. It has been controversial whether one of the sexes can evolve traits that allow them to “win” this arms race. Here, we use morphological analysis (traditional and scanning electron micrographs), laboratory experiments and comparative methods to show how females of a species characterized by typical coercive mating initiation appear to “win” a particular stage of the sexual conflict by evolving morphology to hide their genitalia from direct, forceful access by males. In an apparent response to the female morphological adaptation, males of this species added to their typically violent coercive mounting of the female new post-mounting, pre-copulatory courtship signals produced by tapping the water's surface with the mid-legs. These courtship signals are intimate in the sense that they are aimed at the female, on whom the male is already mounted. Females respond to the signals by exposing their hidden genitalia for copulatory intromission. Our results indicate that the apparent victory of coevolutionary arms race by one sex in terms of morphology may trigger evolution of a behavioral phenotype in the opposite sex

Difficulties in assessing cytomegalovirus-associated gastric perforation in an HIV-infected patient

BACKGROUND: Active Cytomegalovirus (CMV) infection is a common complication in advanced symptomatic Human Immunodeficiency Virus (HIV) infection. CMV-induced intestinal perforations are hard to diagnose and may be observed throughout the gastrointestinal tract. Isolated stomach perforation is exceptional. CASE PRESENTATION: A 47-year-old man was admitted to our intensive care unit with multiorgan failure. Gastrointestinal endoscopic examination showed erythematous gastritis but normal duodenum and colon. CMV blood culture was positive. Histologic examination of a gastric biopsy showed inflammatory infiltrate and immunostaining typical intranuclear CMV inclusion bodies. Concomitant abdominal CT scan disclosed large peripancreatic hypodensities without pneumoperitoneum. The patient died despite supportive therapies and ganciclovir infusion. Postmortem examination showed a 4-cm gastric perforation adhering to the transverse colon and liver, with a thick necrotic inflammatory coating around the pancreas. The whole GI tract, except the stomach, was normal. As other causes, especially Helicobacter pylori infection could be ruled out, a causal relationship between CMV and gastric disease was assumed. CONCLUSION: CMV may be responsible for gastric perforations, with difficulties in assessing the diagnosis. Early diagnosis based on cautious endoscopy and histopathologic examination is needed to make a favorable outcome possible

Sensible heat has significantly affected the global hydrological cycle over the historical period

Globally, latent heating associated with a change in precipitation is balanced by changes to atmospheric radiative cooling and sensible heat fluxes. Both components can be altered by climate forcing mechanisms and through climate feedbacks, but the impacts of climate forcing and feedbacks on sensible heat fluxes have received much less attention. Here we show, using a range of climate modelling results, that changes in sensible heat are the dominant contributor to the present global-mean precipitation change since preindustrial time, because the radiative impact of forcings and feedbacks approximately compensate. The model results show a dissimilar influence on sensible heat and precipitation from various drivers of climate change. Due to its strong atmospheric absorption, black carbon is found to influence the sensible heat very differently compared to other aerosols and greenhouse gases. Our results indicate that this is likely caused by differences in the impact on the lower tropospheric stability

Whole genome sequencing and de novo assembly identifies Sydney-like variant noroviruses and recombinants during the winter 2012/2013 outbreak in England

Background: Norovirus is the commonest cause of epidemic gastroenteritis among people of all ages. Outbreaks frequently occur in hospitals and the community, costing the UK an estimated £110 m per annum. An evolutionary explanation for periodic increases in norovirus cases, despite some host-specific post immunity is currently limited to the identification of obvious recombinants. Our understanding could be significantly enhanced by full length genome sequences for large numbers of intensively sampled viruses, which would also assist control and vaccine design. Our objective is to develop rapid, high-throughput, end-to-end methods yielding complete norovirus genome sequences. We apply these methods to recent English outbreaks, placing them in the wider context of the international norovirus epidemic of winter 2012. Method. Norovirus sequences were generated from 28 unique clinical samples by Illumina RNA sequencing (RNA-Seq) of total faecal RNA. A range of de novo sequence assemblers were attempted. The best assembler was identified by validation against three replicate samples and two norovirus qPCR negative samples, together with an additional 20 sequences determined by PCR and fractional capillary sequencing. Phylogenetic methods were used to reconstruct evolutionary relationships from the whole genome sequences. Results: Full length norovirus genomes were generated from 23/28 samples. 5/28 partial norovirus genomes were associated with low viral copy numbers. The de novo assembled sequences differed from sequences determined by capillary sequencing by <0.003%. Intra-host nucleotide sequence diversity was rare, but detectable by mapping short sequence reads onto its de novo assembled consensus. Genomes similar to the Sydney 2012 strain caused 78% (18/23) of cases, consistent with its previously documented association with the winter 2012 global outbreak. Interestingly, phylogenetic analysis and recombination detection analysis of the consensus sequences identified two related viruses as recombinants, containing sequences in prior circulation to Sydney 2012 in open reading frame (ORF) 2. Conclusion: Our approach facilitates the rapid determination of complete norovirus genomes. This method provides high resolution of full norovirus genomes which, when coupled with detailed epidemiology, may improve the understanding of evolution and control of this important healthcare-associated pathogen

Polymorphic variants of genes involved in homocysteine metabolism in celiac disease

Celiac disease (CD) is a polygenic chronic enteropathy conferring an increased risk for various nutrient deficiency states. Hyperhomocysteinemia is a frequent finding in CD and may be related to the development of venous thrombosis, cardiovascular disease, and stroke in untreated CD patients. Recently, a possible excess in the frequency of the MTHFR c.677C>T (rs1801133) gene variant in CD patients was reported. The purpose of this study was to determine if there exist differences in the distribution of polymorphic variants of genes involved in homocysteine/methyl group metabolism between CD patients and the general population. A set of 10 gene polymorphisms (MTHFR rs1801133, MTR rs1805087, MTHFD1 rs2236225, MTRR rs1801394, CBS 844ins68, BHMT1 rs7356530 and rs3733890, BHMT2 rs526264 and rs625879, and TCN2 rs1801198) was tested in 134 patients with CD and 160 matched healthy controls. The frequency of the MTR rs1805087 GG genotype in CD patients was lower than in controls (0.01 and 0.06, respectively), although statistical significance was not achieved (P = 0.06). For the other analyzed polymorphisms, there was no evidence of difference in both allelic and genotypic distribution between cases and controls. The exhaustive Multifactor Dimensionality Reduction analysis revealed no combination of interactive polymorphisms predicting the incidence of CD. In contrast to the well-documented clinical observations of increased risks of vascular disease in patients with longstanding untreated CD, in our group of patients no significant association with CD was found for all tested polymorphic variants of genes involved in homocysteine metabolism. These findings should be replicated in studies with a larger sample size

Multi-level modeling of social factors and preterm delivery in Santiago de Chile

<p>Abstract</p> <p>Background</p> <p>Birth before the 37th week of gestation (preterm birth) is an important cause of infant and neonatal mortality, but has been little studied outside of wealthy nations. Chile is an urbanized Latin American nation classified as "middle-income" based on its annual income per capita of about $6000.</p> <p>Methods</p> <p>We studied the relations between maternal social status and neighborhood social status on risk of preterm delivery in this setting using multilevel regression analyses of vital statistics data linked to geocoded decennial census data. The analytic data set included 56,970 births from 2004 in the metropolitan region of Santiago, which constitutes about 70% of all births in the study area and about 25% of all births in Chile that year. Dimensionality of census data was reduced using principal components analysis, with regression scoring to create a single index of community socioeconomic advantage. This was modeled along with years of maternal education in order to predict preterm birth and preterm low birthweight.</p> <p>Results</p> <p>Births in Santiago displayed an advantaged pattern of preterm risk, with only 6.4% of births delivering before 37 weeks. Associations were observed between risk of outcomes and individual and neighborhood factors, but the magnitudes of these associations were much more modest than reported in North America.</p> <p>Conclusion</p> <p>While several potential explanations for this relatively flat social gradient might be considered, one possibility is that Chile's egalitarian approach to universal prenatal care may have reduced social inequalities in these reproductive outcomes.</p