Chemotaxis When Bacteria Remember: Drift versus Diffusion

{\sl Escherichia coli} ({\sl E. coli}) bacteria govern their trajectories by switching between running and tumbling modes as a function of the nutrient concentration they experienced in the past. At short time one observes a drift of the bacterial population, while at long time one observes accumulation in high-nutrient regions. Recent work has viewed chemotaxis as a compromise between drift toward favorable regions and accumulation in favorable regions. A number of earlier studies assume that a bacterium resets its memory at tumbles -- a fact not borne out by experiment -- and make use of approximate coarse-grained descriptions. Here, we revisit the problem of chemotaxis without resorting to any memory resets. We find that when bacteria respond to the environment in a non-adaptive manner, chemotaxis is generally dominated by diffusion, whereas when bacteria respond in an adaptive manner, chemotaxis is dominated by a bias in the motion. In the adaptive case, favorable drift occurs together with favorable accumulation. We derive our results from detailed simulations and a variety of analytical arguments. In particular, we introduce a new coarse-grained description of chemotaxis as biased diffusion, and we discuss the way it departs from older coarse-grained descriptions.Comment: Revised version, journal reference adde

Display of probability densities for data from a continuous distribution

Based on cumulative distribution functions, Fourier series expansion and Kolmogorov tests, we present a simple method to display probability densities for data drawn from a continuous distribution. It is often more efficient than using histograms.Comment: 5 pages, 4 figures, presented at Computer Simulation Studies XXIV, Athens, GA, 201

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.ope

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Development of evidence-based clinical practice guidelines (CPGs): comparing approaches

<p>Abstract</p> <p>Background</p> <p>While the potential of clinical practice guidelines (CPGs) to support implementation of evidence has been demonstrated, it is not currently being achieved. CPGs are both poorly developed and ineffectively implemented. To improve clinical practice and health outcomes, both well-developed CPGs and effective methods of CPG implementation are needed. We sought to establish whether there is agreement on the fundamental characteristics of an evidence-based CPG development process and to explore whether the level of guidance provided in CPG development handbooks is sufficient for people using these handbooks to be able to apply it.</p> <p>Methods</p> <p>CPG development handbooks were identified through a broad search of published and grey literature. Documents published in English produced by national or international organisations purporting to support development of evidence-based CPGs were included. A list of 14 key elements of a CPG development process was developed. Two authors read each handbook. For each handbook a judgement was made as to how it addressed each element; assigned as: 'mentioned and clear guidance provided', 'mentioned but limited practical detail provided ', or 'not mentioned'.</p> <p>Results</p> <p>Six CPG development handbooks were included. These were produced by the Council of Europe, the National Health and Medical Research Council of Australia, the National Institute for Health and Clinical Excellence in the UK, the New Zealand Guidelines Group, the Scottish Intercollegiate Guideline Network, and the World Health Organization (WHO).</p> <p>There was strong concordance between the handbooks on the key elements of an evidence-based CPG development process. All six of the handbooks require and provide guidance on establishment of a multidisciplinary guideline development group, involvement of consumers, identification of clinical questions or problems, systematic searches for and appraisal of research evidence, a process for drafting recommendations, consultation with others beyond the guideline development group, and ongoing review and updating of the CPG.</p> <p>Conclusion</p> <p>The key elements of an evidence-based CPG development process are addressed with strong concordance by existing CPG development handbooks. Further research is required to determine why these key elements are often not addressed by CPG developers.</p

Warfarin therapy and incidence of cerebrovascular complications in left-sided native valve endocarditis

International audienceAnticoagulant therapy has been anticipated to increase the risk of cerebrovascular complications (CVC) in native valve endocarditis (NVE). This study investigates the relationship between ongoing oral anticoagulant therapy and the incidence of symptomatic CVC in left-sided NVE. In a prospective cohort study, the CVC incidence was compared between NVE patients with and without ongoing warfarin. Among 587 NVE episodes, 48 (8%) occurred in patients on warfarin. A symptomatic CVC was seen in 144 (25%) patients, with only three on warfarin. CVC were significantly less frequent in patients on warfarin (6% vs. 26%, odds ratio [OR] 0.20, 95% confidence interval [CI] 0.06-0.6,  = 0.006). No increase in haemorrhagic lesions was detected in patients on warfarin. aetiology (adjusted OR [aOR] 6.3, 95% CI 3.8-10.4) and vegetation length (aOR 1.04, 96% CI 1.01-1.07) were risk factors for CVC, while warfarin on admission (aOR 0.26, 95% CI 0.07-0.94), history of congestive heart failure (adjusted OR 0.22, 95% CI 0.1-0.52) and previous endocarditis (aOR 0.1, 95% CI 0.01-0.79) correlated with lower CVC frequency

Young pregnant women's views on the acceptability of screening for chlamydia as part of routine antenatal care

<p>Abstract</p> <p>Background</p> <p>In pregnancy, untreated chlamydia infection has been associated with adverse outcomes for both mother and infant. Like most women, pregnant women infected with chlamydia do not report genital symptoms, and are therefore unlikely to be aware of their infection. The aim of this study was to determine the acceptability of screening pregnant women aged 16-25 years for chlamydia as part of routine antenatal care.</p> <p>Methods</p> <p>As part of a larger prospective, cross-sectional study of pregnant women aged 16-25 years attending antenatal services across Melbourne, Australia, 100 women were invited to participate in a face-to-face, semi structured interview on the acceptability of screening for chlamydia during pregnancy. Women infected with chlamydia were oversampled (n = 31).</p> <p>Results</p> <p>Women had low levels of awareness of chlamydia before the test, retained relatively little knowledge after the test and commonly had misconceptions around chlamydia transmission, testing and sequelae. Women indicated a high level of acceptance and support for chlamydia screening, expressing their willingness to undertake whatever care was necessary to ensure the health of their baby. There was a strong preference for urine testing over other methods of specimen collection. Women questioned why testing was not already conducted alongside other antenatal STI screening tests, particularly in view of the risks chlamydia poses to the baby. Women who tested positive for chlamydia had mixed reactions, however, most felt relief and gratitude at having had chlamydia detected and reported high levels of partner support.</p> <p>Conclusions</p> <p>Chlamydia screening as part of routine antenatal care was considered highly acceptable among young pregnant women who recognized the benefits of screening and strongly supported its implementation as part of routine antenatal care. The acceptability of screening is important to the uptake of chlamydia screening in future antenatal screening strategies.</p

Haloarchaea swim slowly for optimal chemotactic efficiency in low nutrient environments

Archaea have evolved to survive in some of the most extreme environments on earth. Life in extreme, nutrient-poor conditions gives the opportunity to probe fundamental energy limitations on movement and response to stimuli, two essential markers of living systems. Here we use three-dimensional holographic microscopy and computer simulations to reveal that halophilic archaea achieve chemotaxis with power requirements one hundred-fold lower than common eubacterial model systems. Their swimming direction is stabilised by their flagella (archaella), enhancing directional persistence in a manner similar to that displayed by eubacteria, albeit with a different motility apparatus. Our experiments and simulations reveal that the cells are capable of slow but deterministic chemotaxis up a chemical gradient, in a biased random walk at the thermodynamic limit

Budesonide and Formoterol Reduce Early Innate Anti-Viral Immune Responses In Vitro

Asthma is a chronic inflammatory airways disease in which respiratory viral infections frequently trigger exacerbations. Current treatment of asthma with combinations of inhaled corticosteroids and long acting beta2 agonists improves asthma control and reduces exacerbations but what impact this might have on innate anti-viral immunity is unclear. We investigated the in vitro effects of asthma drugs on innate anti-viral immunity. Peripheral blood mononuclear cells (PBMC) from healthy and asthmatic donors were cultured for 24 hours with the Toll-like receptor 7 agonist, imiquimod, or rhinovirus 16 (RV16) in the presence of budesonide and/or formoterol. Production of proinflammatory cytokines and expression of anti-viral intracellular signalling molecules were measured by ELISA and RT-PCR respectively. In PBMC from healthy donors, budesonide alone inhibited IP-10 and IL-6 production induced by imiquimod in a concentration-dependent manner and the degree of inhibition was amplified when budesonide and formoterol were used in combination. Formoterol alone had little effect on these parameters, except at high concentrations (10−6 M) when IL-6 production increased. In RV16 stimulated PBMC, the combination of budesonide and formoterol inhibited IFNα and IP-10 production in asthmatic as well as healthy donors. Combination of budesonide and formoterol also inhibited RV16-stimulated expression of the type I IFN induced genes myxovirus protein A and 2′, 5′ oligoadenylate synthetise. Notably, RV16 stimulated lower levels of type Myxovirus A and oligoadenylate synthase in PBMC of asthmatics than control donors. These in vitro studies demonstrate that combinations of drugs commonly used in asthma therapy inhibit both early pro-inflammatory cytokines and key aspects of the type I IFN pathway. These findings suggest that budesonide and formoterol curtail excessive inflammation induced by rhinovirus infections in patients with asthma, but whether this inhibits viral clearance in vivo remains to be determined

Patterns of Multimorbidity in the Aged Population. Results from the KORA-Age Study

Multimorbidity is a common problem in aged populations with a wide range of individual and societal consequences. The objective of the study was to explore patterns of comorbidity and multimorbidity in an elderly population using different analytical approaches. Data were gathered from the population-based KORA-Age project, which included 4,127 persons aged 65–94 years living in the city of Augsburg and its two surrounding counties in Southern Germany. Information on the presence of 13 chronic conditions was collected in a standardized telephone interview and a self-administered questionnaire. Patterns of comorbidity and multimorbidity were analyzed using prevalence figures, logistic regression models and exploratory tetrachoric factor analysis. The prevalence of multimorbidity (≥2 diseases) was 58.6% in the total sample. Hypertension and diabetes (Odds Ratio [OR] 2.95, 99.58% confidence interval [CI] [2.19–3.96]), as well as hypertension and stroke (OR 2.00, 99.58% CI [1.26–3.16]) most often occurred in combination. This association was independent of age, sex and the presence of other conditions. Using factor analysis, we identified four patterns of multimorbidity: the first pattern includes cardiovascular and metabolic diseases, the second includes joint, liver, lung and eye diseases, the third covers mental and neurologic diseases and the fourth pattern includes gastrointestinal diseases and cancer. 44% of the persons were assigned to at least one of the four multimorbidity patterns; 14% could be assigned to both the cardiovascular/metabolic and the joint/liver/lung/eye pattern. Further common pairs were the mental/neurologic pattern combined with the cardiovascular/metabolic pattern (7.2%) or the joint/liver/lung/eye pattern (5.3%), respectively. Our results confirmed the existence of co-occurrence of certain diseases in elderly persons, which is not caused by chance. Some of the identified patterns of multimorbidity and their overlap may indicate common underlying pathological mechanisms