Pulmonary embolism severity index and troponin testing for the selection of low-risk patients with acute symptomatic pulmonary embolism.

Summary Background: The combination of the Pulmonary Embolism Severity Index (PESI) and troponin testing could help physicians identify appropriate patients with acute pulmonary embolism (PE) for early hospital discharge. Methods: This prospective cohort study included a total of 567 patients from a single center registry with objectively confirmed acute symptomatic PE. On the basis of the PESI, each patient was classified into 1 of 5 classes (I to V). At the time of hospital admission, patients had troponin I (cTnI) levels measured. The endpoint of the study was all-cause mortality within 30 days after diagnosis. We calculated the mortality rates in 4 patient groups: group 1: PESI class I-II plus cTnI <0.1 ng mL(-1); group 2: PESI classes III-V plus cTnI <0.1 ng mL(-1); group 3: PESI classes I-II plus cTnI >/= 0.1 ng mL(-1); and group 4: PESI classes III-V plus cTnI >/= 0.1 ng mL(-1). Results: The study cohort had a 30-day mortality of 10% (95% confidence interval [CI], 7.6 to 12.5%). Mortality rates in the 4 groups were 1.3%, 14.2%, 0% and 15.4%, respectively. Compared to non-elevated cTnl, the low-risk PESI had a higher negative predictive value (NPV) (98.9% vs 90.8%) and negative likelihood ratio (NLR) (0.1 vs 0.9) for predicting mortality. The addition of non-elevated cTnI to low-risk PESI did not improve the NPV or the NLR compared to either test alone. Conclusions: Compared to cTnl testing, PESI classification more accurately identified patients with PE who are at low risk of all-cause death within 30-days of presentation.

Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia.

Candidaemia is the fourth most common cause of bloodstream infection, with a high mortality rate of up to 40%. Identification of host genetic factors that confer susceptibility to candidaemia may aid in designing adjunctive immunotherapeutic strategies. Here we hypothesize that variation in immune genes may predispose to candidaemia. We analyse 118,989 single-nucleotide polymorphisms (SNPs) across 186 loci known to be associated with immune-mediated diseases in the largest candidaemia cohort to date of 217 patients of European ancestry and a group of 11,920 controls. We validate the significant associations by comparison with a disease-matched control group. We observe significant association between candidaemia and SNPs in the CD58 (P = 1.97 × 10(-11); odds ratio (OR) = 4.68), LCE4A-C1orf68 (P = 1.98 × 10(-10); OR = 4.25) and TAGAP (P = 1.84 × 10(-8); OR = 2.96) loci. Individuals carrying two or more risk alleles have an increased risk for candidaemia of 19.4-fold compared with individuals carrying no risk allele. We identify three novel genetic risk factors for candidaemia, which we subsequently validate for their role in antifungal host defence.

Discharge properties of single neurons in the dorsal nucleus of the lateral lemniscus of the rat.

The aim of the present study was to characterize the discharge properties of single neurons in the dorsal nucleus of the lateral lemniscus (DNLL) of the rat. In the absence of acoustic stimulation, two types of spontaneous discharge patterns were observed: units tended to fire in a bursting or in a nonbursting mode. The distribution of units in the DNLL based on spontaneous firing rate followed a rostrocaudal gradient: units with high spontaneous rates were most commonly located in the rostral part of the DNLL, whereas in the caudal part units had lower spontaneous discharge rates. The most common response pattern of DNLL units to 200 ms binaural noise bursts contained a prominent onset response followed by a lower but steady-state response and an inhibitory response in the early-off period. Thresholds of response to noise bursts were on average higher for DNLL units than for units recorded in the inferior colliculus under the same experimental conditions. The DNLL units were arranged according to a mediolateral sensitivity gradient with the lowest threshold units in the most lateral part of the nucleus. In the rat, as in other mammals, the most common DNLL binaural input type was an excitatory response to contralateral ear stimulation and inhibitory response to ipsilateral ear stimulation (EI type). Pure tone bursts were in general a more effective stimulus compared to noise bursts. Best frequency (BF) was established for 97 DNLL units and plotted according to their spatial location. The DNLL exhibits a loose tonotopic organization, where there is a concentric pattern with high BF units located in the most dorsal and ventral parts of the DNLL and lower BF units in the middle part of the nucleus.

Puce a ADN: pourquoi et pour qui [Array CGH: why and to whom]

Structural genomic abnormalities play a key role in the pathogenesis of human disorders and represent one of the first causes of mental impairment, complex syndromes and tumors. In order to detect these chromosomal abnormalities, many methodologies have been developed with limits. The new ARRAY based Comparative Genomic Hybridization (ARRAY CGH) is a revolutionary approach which allows to characterize very small genetic abnormalities undetectable by the standard approaches and in the absence of any associated clinical information. The aim of this article is to describe why the application of a new array CGH methodology is necessary in the etiological search for genetic diseases, what the limits of the standard approaches are and to whom arrayCGH analyses can be applied in a pediatric environment. Examples of our practice will be presented.

Quality of Web-based information on obsessive compulsive disorder.

BACKGROUND: The Internet is increasingly used as a source of information for mental health issues. The burden of obsessive compulsive disorder (OCD) may lead persons with diagnosed or undiagnosed OCD, and their relatives, to search for good quality information on the Web. This study aimed to evaluate the quality of Web-based information on English-language sites dealing with OCD and to compare the quality of websites found through a general and a medically specialized search engine. METHODS: Keywords related to OCD were entered into Google and OmniMedicalSearch. Websites were assessed on the basis of accountability, interactivity, readability, and content quality. The "Health on the Net" (HON) quality label and the Brief DISCERN scale score were used as possible content quality indicators. Of the 235 links identified, 53 websites were analyzed. RESULTS: The content quality of the OCD websites examined was relatively good. The use of a specialized search engine did not offer an advantage in finding websites with better content quality. A score ≥16 on the Brief DISCERN scale is associated with better content quality. CONCLUSION: This study shows the acceptability of the content quality of OCD websites. There is no advantage in searching for information with a specialized search engine rather than a general one. Practical implications: The Internet offers a number of high quality OCD websites. It remains critical, however, to have a provider-patient talk about the information found on the Web.

Quality of Web-based information on obsessive compulsive disorder.

BACKGROUND: The Internet is increasingly used as a source of information for mental health issues. The burden of obsessive compulsive disorder (OCD) may lead persons with diagnosed or undiagnosed OCD, and their relatives, to search for good quality information on the Web. This study aimed to evaluate the quality of Web-based information on English-language sites dealing with OCD and to compare the quality of websites found through a general and a medically specialized search engine. METHODS: Keywords related to OCD were entered into Google and OmniMedicalSearch. Websites were assessed on the basis of accountability, interactivity, readability, and content quality. The "Health on the Net" (HON) quality label and the Brief DISCERN scale score were used as possible content quality indicators. Of the 235 links identified, 53 websites were analyzed. RESULTS: The content quality of the OCD websites examined was relatively good. The use of a specialized search engine did not offer an advantage in finding websites with better content quality. A score ≥16 on the Brief DISCERN scale is associated with better content quality. CONCLUSION: This study shows the acceptability of the content quality of OCD websites. There is no advantage in searching for information with a specialized search engine rather than a general one. Practical implications: The Internet offers a number of high quality OCD websites. It remains critical, however, to have a provider-patient talk about the information found on the Web.

Use of mobile devices to answer online surveys: implications for research.

BACKGROUND: There is a growing use of mobile devices to access the Internet. We examined whether participants who used a mobile device to access a brief online survey were quicker to respond to the survey but also, less likely to complete it than participants using a traditional web browser. FINDINGS: Using data from a recently completed online intervention trial, we found that participants using mobile devices were quicker to access the survey but less likely to complete it compared to participants using a traditional web browser. More concerning, mobile device users were also less likely to respond to a request to complete a six week follow-up survey compared to those using traditional web browsers. CONCLUSIONS: With roughly a third of participants using mobile devices to answer an online survey in this study, the impact of mobile device usage on survey completion rates is a concern. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01521078.

Opportunistic testing for urogenital infection with Chlamydia trachomatis in south-western Switzerland, 2012 : a feasibility study

The feasibility of opportunistic screening of urogenital infections with Chlamydia trachomatis was assessed in a cross-sectional study in 2012, in two cantons of south-western Switzerland: Vaud and Valais. Sexually active persons younger than 30 years, not tested for C. trachomatis in the last three months, were invited for free C. trachomatis testing by PCR in urine or self-applied vaginal swabs. Of 2,461 consenting participants, 1,899 (77%) were women and all but six (0.3%) submitted a sample. Forty-seven per cent of female and 25% of male participants were younger than 20 years. Overall, 134 (5.5%) of 2,455 tested participants had a positive result and were followed up. Seven per cent of all candidates for screening were not invited, 10% of invited candidates were not eligible, 15% of the eligible candidates declined participation, 5% of tested participants testing positive were not treated, 29% of those treated were not retested after six months and 9% of those retested were positive for C. trachomatis. Opportunistic C. trachomatis testing proved technically feasible and acceptable, at least if free of charge. Men and peripheral rural regions were more difficult to reach. Efforts to increase testing and decrease dropout at all stages of the screening procedure are necessary.

Reply to Budowle, Ge, Chakraborty and Gill-King: use of prior odds for missing persons identifications

Prior probabilities represent a core element of the Bayesian probabilistic approach to relatedness testing. This letter opinions on the commentary 'Use of prior odds for missing persons identifications' by Budowle et al. (2011), published recently in this journal. Contrary to Budowle et al. (2011), we argue that the concept of prior probabilities (i) is not endowed with the notion of objectivity, (ii) is not a case for computation and (iii) does not require new guidelines edited by the forensic DNA community - as long as probability is properly considered as an expression of personal belief. Please see related article: http://www.investigativegenetics.com/content/3/1/3

On metapopulation resistance to drift and extinction.

The spatial configuration of metapopulations (numbers, sizes, and localization of patches) affects their ability to resist demographic extinction and genetic drift, but sometimes with opposite effects. Small and isolated patches, for instance, contribute marginally to demography but may play a large role in genetics by maintaining a sizeable amount of genetic variance among demes. In source-sink systems, similarly, connectivity may be beneficial in terms of effective size, but detrimental in terms of survival, by lowering the reproductive value of source populations. How to reconcile these opposite effects? Here we propose an analytical framework that integrates fixation time (ability to resist genetic drift) and extinction time (ability to resist demographic extinction) into a single index of resistance, measuring the ability of a metapopulation to maintain its demo-genetic integrity. We then illustrate with numerical examples how conflicting demands may be resolved.

Clients of sex workers in Switzerland: it makes sense to counsel and propose rapid test for HIV on the street, a preliminary report.

BACKGROUND: Clients of street sex workers may be at higher risk for HIV infection than the general population. Furthermore, there is a lack of knowledge regarding HIV testing of clients of sex workers in developed countries. METHOD: This pilot study assessed the feasibility and acceptance of rapid HIV testing by the clients of street-based sex workers in Lausanne, Switzerland. For 5 evenings, clients in cars were stopped by trained field staff for face-to-face interviews focusing on sex-related HIV risk behaviors and HIV testing history. The clients were then offered a free anonymous rapid HIV test in a bus parked nearby. Rapid HIV testing and counselling were performed by experienced nurse practitioners. Clients with reactive tests were offered confirmatory testing, medical evaluation, and care in our HIV clinic. RESULT: We intercepted 144 men, 112 (77.8%) agreed to be interviewed. Among them, 50 (46.6%) had never been tested for HIV. A total of 31 (27.7%) rapid HIV tests were performed, 16 (51.6%) in clients who had not previously been tested. None were reactive. Initially, 19 (16.9%) additional clients agreed to HIV testing but later declined due to the 40-minute queue for testing. CONCLUSION: This pilot study showed that rapid HIV testing in the red light district of Lausanne was feasible, and that the clients of sex workers accepted testing at an unexpectedly high rate. This setting seems particularly appropriate for targeted HIV screening, since more than 40% of the clients had not previously been tested for HIV even though they engaged in sex-related HIV risk behaviour.

Nestmate recognition and the genetic relatedness of nests in the ant Formica pratensis

Genetic relatedness of the mound-building ant Formica pratensis was determined by means of microsatellite DNA polymorphism, and its impact on nestmate recognition was tested in a population in Southern Sweden (Oeland). Recognition between nests was measured by testing aggression levels between single pairs of workers. The genetic distances of nests (Nei's genetic distance) and the spatial distance of nests were correlated and both showed a strong relation to the aggression behavior. Multiple regression analysis revealed a stronger impact of genetic relatedness rather than spatial distances on aggression behavior. Neighbouring nests were more closely related than distant nests, which may reflect budding as a possible spreading mechanism. The genetic distance data showed that nestmate recognition was strongly genetically influenced in F. pratensis.

Further characterisation of the 91500 zircon crystal

This paper reports the results from a second characterisation of the 91500 zircon, including data from electron probe microanalysis, laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS), secondary ion mass spectrometry (SIMS) and laser fluorination analyses. The focus of this initiative was to establish the suitability of this large single zircon crystal for calibrating in situ analyses of the rare earth elements and oxygen isotopes, as well as to provide working values for key geochemical systems. In addition to extensive testing of the chemical and structural homogeneity of this sample, the occurrence of banding in 91500 in both backscattered electron and cathodoluminescence images is described in detail. Blind intercomparison data reported by both LA-ICP-MS and SIMS laboratories indicate that only small systematic differences exist between the data sets provided by these two techniques. Furthermore, the use of NIST SRM 610 glass as the calibrant for SIMS analyses was found to introduce little or no systematic error into the results for zircon. Based on both laser fluorination and SIMS data, zircon 91500 seems to be very well suited for calibrating in situ oxygen isotopic analyses.

Putative adverse outcome pathways relevant to neurotoxicity.

The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways.

Effects of age, birth cohort and period of death on Swiss cancer mortality, 1951-1984.

Swiss death certification data over the period 1951-1984 for total cancer mortality and 30 major cancer sites in the population aged 25 to 74 years were analysed using a log-linear Poisson model with arbitrary constraints on the parameters to isolate the effects of birth cohort, calendar period of death and age. The overall pattern of total cancer mortality in males was stable for period values and showed some moderate decreases in cohort values restricted to the generations born after 1930. Cancer mortality trends were more favourable in females, with steady, though moderate, declines in both cohort and period values. According to the estimates from the model, the worst affected generation for male lung cancer was that born around 1910, and a flattening of trends or some moderate decline was observed for more recent cohorts, although this decline was considerably more limited than in other European countries. There were decreases in cohort and period values for stomach, intestine and oesophageal cancer in both sexes and (cervix) uteri in females. Increases were observed in both cohort and period trends for pancreas and liver in males and for several other neoplasms, including prostate, brain, leukaemias and lymphomas, restricted, however, for the latter sites, to the earlier cohorts and hence partly attributable to improved diagnosis and certification in the elderly. Although age values for lung cancer in females were around 10-times lower than in males, upward trends in female lung cancer cohort values were observed in subsequent cohorts and for period values from the late 1960's onwards. Therefore, future trends in female lung cancer mortality should continue to be monitored. The application of these age/period/cohort models thus provides a summary guide for the reading and interpretation of cancer mortality trends, although it cannot replace careful inspection of single age-specific rates.