Trauma-induced coagulopathy in severely injured patients: knowledge lost in translation?

Many guidelines exist on how to treat patients with multiple injuries correctly in an accident and emergency setting. The aim of the present work was to find out how well patients are treated focusing on trauma induced coagulopathy (TIC), and what anaesthetists involved in trauma care think about their own experiences with TIC.

Lost in translation: the impact of publication language on citation frequency in the scientific dental literature

Citation metrics are commonly used as a proxy for scientific merit and relevance. Papers published in English, however, may exhibit a higher citation frequency than research articles published in other languages, though this issue has not yet been investigated from a Swiss perspective where English is not the native language.

A multifactorial analysis of explicitation in translation

The search for translation universals has been an important topic in translation studies over the past decades. In this paper, we focus on the notion of explicitation through a multifaceted study of causal connectives, integrating four different variables: the role of the source and the target languages, the influence of specific connectives and the role of the discourse relation they convey. Our results indicate that while source and target languages do not globally influence explicitation, specific connectives have a significant impact on this phenomenon. We also show that in English and French, the most frequently used connectives for explicitation share a similar semantic profile. Finally, we demonstrate that explicitation also varies across different discourse relations, even when they are conveyed by a single connective.

Population transcriptomics of life-history variation in the genus Salmo

In this study, we demonstrate the power of applying complementary DNA (cDNA) microarray technology to identifying candidate loci that exhibit subtle differences in expression levels associated with a complex trait in natural populations of a nonmodel organism. Using a highly replicated experimental design involving 180 cDNA microarray experiments, we measured gene-expression levels from 1098 transcript probes in 90 individuals originating from six brown trout (Salmo trutta) and one Atlantic salmon (Salmo salar) population, which follow either a migratory or a sedentary life history. We identified several candidate genes associated with preparatory adaptations to different life histories in salmonids, including genes encoding for transaldolase 1, constitutive heat-shock protein HSC70-1 and endozepine. Some of these genes clustered into functional groups, providing insight into the physiological pathways potentially involved in the expression of life-history related phenotypic differences. Such differences included the down-regulation of genes involved in the respiratory system of future migratory individuals. In addition, we used linear discriminant analysis to identify a set of 12 genes that correctly classified immature individuals as migratory or sedentary with high accuracy. Using the expression levels of these 12 genes, 17 out of 18 individuals used for cross-validation were correctly assigned to their respective life-history phenotype. Finally, we found various candidate genes associated with physiological changes that are likely to be involved in preadaptations to seawater in anadromous populations of the genus Salmo, one of which was identified to encode for nucleophosmin 1. Our findings thus provide new molecular insights into salmonid life-history variation, opening new perspectives in the study of this complex trait.

Pollinator responses to variation in floral display and flower size in dioecious Sagittaria latifolia (Alismataceae)

In animal-pollinated plants with unisexual flowers, sexual dimorphism in floral traits may be the consequence of pollinator-mediated selection. Experimental investigations of the effects of variation in flower size and floral display on pollinator visitation can provide insights into the evolution of floral dimorphism in dioecious plants. Here, we investigated pollinator responses to experimental arrays of dioecious Sagittaria latifolia in which we manipulated floral display and flower size. We also examined whether there were changes in pollinator visitation with increasing dimorphism in flower size. In S. latifolia, males have larger flowers and smaller floral displays than females. Visitation by pollinators, mainly flies and bees, was more frequent for male than for female inflorescences and increased with increasing flower size, regardless of sex. The number of insect visits per flower decreased with increasing floral display in males but remained constant in females. Greater sexual dimorphism in flower size increased visits to male inflorescences but had no influence on the number of visits to female inflorescences. These results suggest that larger flower sizes would be advantageous to both females and males, and no evidence was found that females suffer from increased flower-size dimorphism. Small daily floral displays may benefit males by allowing extended flowering periods and greater opportunities for effective pollen dispersal.

Variation in hepatic regulation of metabolism during the dry period and in early lactation in dairy cows

The purpose of this study was to investigate variations in hepatic regulation of metabolism during the dry period, after parturition, and in early lactation in dairy cows. For this evaluation, cows were divided into 2 groups based on the plasma concentration of beta-hydroxybutyric acid (BHBA) in wk 4 postpartum (PP; group HB, BHBA >0.75 mmol/L; group LB, BHBA <0.75 mmol/L, respectively). Liver biopsies were obtained from 28 cows at drying off (mean 59 +/- 8 d antepartum), on d 1, and in wk 4 and 14 PP. Blood samples were collected every 2 wk during this entire period. Liver samples were analyzed for mRNA abundance of genes related to carbohydrate metabolism (pyruvate carboxylase, PC; phosphoenolpyruvate carboxykinase, PEPCK; citrate synthase, CS), fatty acid biosynthesis (ATP citrate lyase, ACLY) and oxidation (acyl-CoA synthetase long-chain, ACSL; carnitine palmitoyltransferase 1A, CPT 1A; carnitine palmitoyltransferase 2, CPT 2; acyl-coenzyme A dehydrogenase very long chain, ACADVL), cholesterol biosynthesis (3-hydroxy-3-methylglutaryl-coenzyme A synthase 1, HMGCS1), ketogenesis (3-hydroxy-3-methylglutaryl-coenzyme A synthase 2, HMGCS2), and of genes encoding the transcription factors peroxisome proliferator-activated receptor alpha (PPARalpha), peroxisome proliferator-activated receptor gamma (PPARgamma), and sterol regulatory element binding factor 1 (SREBF1). Blood plasma was assayed for concentrations of glucose, BHBA, nonesterified fatty acids, cholesterol, triglycerides, insulin, insulin-like growth factor-I, and thyroid hormones. In both groups, plasma parameters followed a pattern usually observed in dairy cows. However, changes were moderate and the energy balance in cows turned positive in wk 7 PP for both groups. Additionally, the energy balance and milk yield were similar for both groups after parturition onwards. Significant group effects were found at drying off, when plasma concentrations of triglycerides were higher in LB than in HB, and in wk 4 PP, when plasma concentrations of glucose and IGF-I were lower in HB than in LB. Similarly, moderate changes in mRNA expression of hepatic genes between the different time points were observed, although HB cows showed more adaptive performance than LB cows based on changes in mRNA expression of PEPCKc, PEPCKm, CS, CPT 1A, CPT 2, and PPARalpha. Part of the variation measured in this study was explained by parity. Significant Spearman rank correlation coefficients between the variables were not similar at each time point and were not similar between the groups at each time point, suggesting that metabolic regulation differs between cows. In conclusion, metabolic regulation in dairy cows is a dynamic system, and differs obviously between cows at different metabolic stages related to parturition.

Exploring the periodicity of cardiovascular events in Switzerland: Variation in deaths and hospitalizations across seasons, day of the week and hour of the day

Purpose The purpose of this study is to explore the periodical patterns of events and deaths related to cardiovascular disease (CVD), acute myocardial infarction (AMI) and stroke in Swiss adults (≥18years). Methods Mortality data for period 1969–2007 (N=869,863 CVD events) and hospitalization data for period 1997–2008 (N=959,990 CVD events) were used. The annual, weekly and circadian distribution of CVD-related deaths and events were assessed. Multivariate analysis was conducted using multinomial logistic regression adjusting for age, gender and calendar year and considering deaths from respiratory diseases, accidents or other causes as competitive events. Results CVD deaths and hospitalizations occurred less frequently in the summer months. Similar patterns were found for AMI and stroke. No significant weekly variation for CVD deaths was found. Stratification by age and gender showed subjects aged <65years to present a higher probability of dying on Mondays and Saturday, only for men. This finding was confirmed after multivariate adjustment. Finally, a circadian variation in CVD mortality was observed, with a first peak in the morning (8–12am) and a smaller second peak in the late afternoon (2–6pm). This pattern persisted after multivariate adjustment and was more pronounced for AMI than for stroke. Conclusion There is a periodicity of hospitalizations and deaths related to CVD, AMI and stroke in Switzerland. This pattern changes slightly according to the age and sex of the subjects. Although the underlying mechanisms are not fully identified, preventive measures should take into account these aspects to develop better strategies of prevention and management of CVD.

Analysis of Phenotypic Variation in Childhood Wheezing Disorders

Recurrent wheezing or asthma is a common problem in children that has increased considerably in prevalence in the past few decades. The causes and underlying mechanisms are poorly understood and it is thought that a numb er of distinct diseases causing similar symptoms are involved. Due to the lack of a biologically founded classification system, children are classified according to their observed disease related features (symptoms, signs, measurements) into phenotypes. The objectives of this PhD project were a) to develop tools for analysing phenotypic variation of a disease, and b) to examine phenotypic variability of wheezing among children by applying these tools to existing epidemiological data. A combination of graphical methods (multivariate co rrespondence analysis) and statistical models (latent variables models) was used. In a first phase, a model for discrete variability (latent class model) was applied to data on symptoms and measurements from an epidemiological study to identify distinct phenotypes of wheezing. In a second phase, the modelling framework was expanded to include continuous variability (e.g. along a severity gradient) and combinations of discrete and continuo us variability (factor models and factor mixture models). The third phase focused on validating the methods using simulation studies. The main body of this thesis consists of 5 articles (3 published, 1 submitted and 1 to be submitted) including applications, methodological contributions and a review. The main findings and contributions were: 1) The application of a latent class model to epidemiological data (symptoms and physiological measurements) yielded plausible pheno types of wheezing with distinguishing characteristics that have previously been used as phenotype defining characteristics. 2) A method was proposed for including responses to conditional questions (e.g. questions on severity or triggers of wheezing are asked only to children with wheeze) in multivariate modelling.ii 3) A panel of clinicians was set up to agree on a plausible model for wheezing diseases. The model can be used to generate datasets for testing the modelling approach. 4) A critical review of methods for defining and validating phenotypes of wheeze in children was conducted. 5) The simulation studies showed that a parsimonious parameterisation of the models is required to identify the true underlying structure of the data. The developed approach can deal with some challenges of real-life cohort data such as variables of mixed mode (continuous and categorical), missing data and conditional questions. If carefully applied, the approach can be used to identify whether the underlying phenotypic variation is discrete (classes), continuous (factors) or a combination of these. These methods could help improve precision of research into causes and mechanisms and contribute to the development of a new classification of wheezing disorders in children and other diseases which are difficult to classify.

Quantum dot cytotoxicity in vitro: An investigation into the cytotoxic effects of a series of different surface chemistries and their core/shell materials

Abstract The aim of this study was to assess the effects of a series of different surface coated quantum dots (QDs) (organic, carboxylated [COOH] and amino [NH(2)] polytethylene glycol [PEG]) on J774.A1 macrophage cell viability and to further determine which part of the QDs cause such toxicity. Cytotoxic examination (MTT assay and LDH release) showed organic QDs to induce significant cytotoxicity up to 48 h, even at a low particle concentration (20 nM), whilst both COOH and NH(2) (PEG) QDs caused reduced cell viability and cell membrane permeability after 24 and 48 h exposure at 80 nM. Subsequent analysis of the elements that constitute the QD core, core/shell and (organic QD) surface coating showed that the surface coating drives QD toxicity. Elemental analysis (ICP-AES) after 48 h, however, also observed a release of Cd from organic QDs. In conclusion, both the specific surface coating and core material can have a significant impact on QD toxicity.

Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study

Hepatitis C virus (HCV) induces chronic infection in 50% to 80% of infected persons; approximately 50% of these do not respond to therapy. We performed a genome-wide association study to screen for host genetic determinants of HCV persistence and response to therapy.

Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta-analysis

Unexplained differences between classes of antihypertensive drugs in their effectiveness in preventing stroke might be due to class effects on intraindividual variability in blood pressure. We did a systematic review to assess any such effects in randomised controlled trials.

Insights on the role of diabetes and geographic variation in patients with critical limb ischaemia

Patients with critical limb ischaemia (CLI) unsuitable for revascularisation have a high rate of amputation and mortality (30% and 25% at 1 year, respectively). Localised gene therapy using plasmid DNA encoding acidic fibroblast growth factor (NV1FGF, riferminogene pecaplasmid) has showed an increased amputation-free survival in a phase II trial. This article provides the rationale, design and baseline characteristics of CLI patients enrolled in the pivotal phase III trial (EFC6145/TAMARIS).