Is trauma in Switzerland any different? epidemiology and patterns of injury in major trauma - a 5-year review from a Swiss trauma centre.

Switzerland, the country with the highest health expenditure per capita, is lacking data on trauma care and system planning. Recently, 12 trauma centres were designated to be reassessed through a future national trauma registry by 2015. Lausanne University Hospital launched the first Swiss trauma registry in 2008, which contains the largest database on trauma activity nationwide. METHODS: Prospective analysis of data from consecutively admitted shock room patients from 1 January 2008 to 31 December 2012. Shock room admission is based on physiology and mechanism of injury, assessed by prehospital physicians. Management follows a surgeon-led multidisciplinary approach. Injuries are coded by Association for the Advancement of Automotive Medicine (AAAM) certified coders. RESULTS: Over the 5 years, 1,599 trauma patients were admitted, predominantly males with a median age of 41.4 years and median injury severity score (ISS) of 13. Rate of ISS >15 was 42%. Principal mechanisms of injury were road traffic (40.4%) and falls (34.4%), with 91.5% blunt trauma. Principal patterns were brain (64.4%), chest (59.8%) and extremity/pelvic girdle (52.9%) injuries. Severe (abbreviated injury scale [AIS] score ≥ 3) orthopaedic injuries, defined as extremity and spine injuries together, accounted for 67.1%. Overall, 29.1% underwent immediate intervention, mainly by orthopaedics (27.3%), neurosurgeons (26.3 %) and visceral surgeons (13.9%); 43.8% underwent a surgical intervention within the first 24 hours and 59.1% during their hospitalisation. In-hospital mortality for patients with ISS >15 was 26.2%. CONCLUSION: This is the first 5-year report on trauma in Switzerland. Trauma workload was similar to other European countries. Despite high levels of healthcare, mortality exceeds published rates by >50%. Regardless of the importance of a multidisciplinary approach, trauma remains a surgical disease and needs dedicated surgical resources.

Proteomic analysis of membrane rafts of melanoma cells identifies protein patterns characteristic of the tumor progression stage.

The molecular mechanisms controlling the progression of melanoma from a localized tumor to an invasive and metastatic disease are poorly understood. In the attempt to start defining a functional protein profile of melanoma progression, we have analyzed by LC-MS/MS the proteins associated with detergent resistant membranes (DRMs), which are enriched in cholesterol/sphingolipids-containing membrane rafts, of melanoma cell lines derived from tumors at different stages of progression. Since membrane rafts are involved in several biological processes, including signal transduction and protein trafficking, we hypothesized that the association of proteins with rafts can be regulated during melanoma development and affect protein function and disease progression. We have identified a total of 177 proteins in the DRMs of the cell lines examined. Among these, we have found groups of proteins preferentially associated with DRMs of either less malignant radial growth phase/vertical growth phase (VGP) cells, or aggressive VGP and metastatic cells suggesting that melanoma cells with different degrees of malignancy have different DRM profiles. Moreover, some proteins were found in DRMs of only some cell lines despite being expressed at similar levels in all the cell lines examined, suggesting the existence of mechanisms controlling their association with DRMs. We expect that understanding the mechanisms regulating DRM targeting and the activity of the proteins differentially associated with DRMs in relation to cell malignancy will help identify new molecular determinants of melanoma progression.

Seizure detection with automated EEG analysis: a validation study focusing on periodic patterns.

OBJECTIVE: To evaluate an automated seizure detection (ASD) algorithm in EEGs with periodic and other challenging patterns. METHODS: Selected EEGs recorded in patients over 1year old were classified into four groups: A. Periodic lateralized epileptiform discharges (PLEDs) with intermixed electrical seizures. B. PLEDs without seizures. C. Electrical seizures and no PLEDs. D. No PLEDs or seizures. Recordings were analyzed by the Persyst P12 software, and compared to the raw EEG, interpreted by two experienced neurophysiologists; Positive percent agreement (PPA) and false-positive rates/hour (FPR) were calculated. RESULTS: We assessed 98 recordings (Group A=21 patients; B=29, C=17, D=31). Total duration was 82.7h (median: 1h); containing 268 seizures. The software detected 204 (=76.1%) seizures; all ictal events were captured in 29/38 (76.3%) patients; in only in 3 (7.7%) no seizures were detected. Median PPA was 100% (range 0-100; interquartile range 50-100), and the median FPR 0/h (range 0-75.8; interquartile range 0-4.5); however, lower performances were seen in the groups containing periodic discharges. CONCLUSION: This analysis provides data regarding the yield of the ASD in a particularly difficult subset of EEG recordings, showing that periodic discharges may bias the results. SIGNIFICANCE: Ongoing refinements in this technique might enhance its utility and lead to a more extensive application.

Environment and dispersal paths override life strategies and residence time in determining regional patterns of invasion by alien plants.

We describe a novel dissimilarity framework to analyze spatial patterns of species diversity and illustrate it with alien plant invasions in Northern Portugal. We used this framework to test the hypothesis that patterns of alien invasive plant species richness and composition are differently affected by differences in climate, land use and landscape connectivity (i.e. Geographic distance as a proxy and vectorial objects that facilitate dispersal such as roads and rivers) between pairs of localities at the regional scale. We further evaluated possible effects of plant life strategies (Grime's C-S-R) and residence time. Each locality consisted of a 1 km(2) landscape mosaic in which all alien invasive species were recorded by visiting all habitat types. Multi-model inference revealed that dissimilarity in species richness is more influenced by environmental distance (particularly climate), whereas geographic distance (proxies for dispersal limitations) is more important to explain dissimilarity in species composition, with a prevailing role for ecotones and roads. However, only minor differences were found in the responses of the three C-S-R strategies. Some effect of residence time was found, but only for dissimilarity in species richness. Our results also indicated that environmental conditions (e.g. climate conditions) limit the number of alien species invading a given site, but that the presence of dispersal corridors determines the paths of invasion and therefore the pool of species reaching each site. As geographic distances (e.g. ecotones and roads) tend to explain invasion at our regional scale highlights the need to consider the management of alien invasions in the context of integrated landscape planning. Alien species management should include (but not be limited to) the mitigation of dispersal pathways along linear infrastructures. Our results therefore highlight potentially useful applications of the novel multimodel framework to the anticipation and management of plant invasions. (C) 2013 Elsevier GmbH. All rights reserved.

Splenium of corpus callosum: patterns of interhemispheric interaction in children and adults.

The splenium of the corpus callosum connects the posterior cortices with fibers varying in size from thin late-myelinating axons in the anterior part, predominantly connecting parietal and temporal areas, to thick early-myelinating fibers in the posterior part, linking primary and secondary visual areas. In the adult human brain, the function of the splenium in a given area is defined by the specialization of the area and implemented via excitation and/or suppression of the contralateral homotopic and heterotopic areas at the same or different level of visual hierarchy. These mechanisms are facilitated by interhemispheric synchronization of oscillatory activity, also supported by the splenium. In postnatal ontogenesis, structural MRI reveals a protracted formation of the splenium during the first two decades of human life. In doing so, the slow myelination of the splenium correlates with the formation of interhemispheric excitatory influences in the extrastriate areas and the EEG synchronization, while the gradual increase of inhibitory effects in the striate cortex is linked to the local inhibitory circuitry. Reshaping interactions between interhemispherically distributed networks under various perceptual contexts allows sparsification of responses to superfluous information from the visual environment, leading to a reduction of metabolic and structural redundancy in a child's brain.

The hourglass and the early conservation models--co-existing patterns of developmental constraints in vertebrates.

Developmental constraints have been postulated to limit the space of feasible phenotypes and thus shape animal evolution. These constraints have been suggested to be the strongest during either early or mid-embryogenesis, which corresponds to the early conservation model or the hourglass model, respectively. Conflicting results have been reported, but in recent studies of animal transcriptomes the hourglass model has been favored. Studies usually report descriptive statistics calculated for all genes over all developmental time points. This introduces dependencies between the sets of compared genes and may lead to biased results. Here we overcome this problem using an alternative modular analysis. We used the Iterative Signature Algorithm to identify distinct modules of genes co-expressed specifically in consecutive stages of zebrafish development. We then performed a detailed comparison of several gene properties between modules, allowing for a less biased and more powerful analysis. Notably, our analysis corroborated the hourglass pattern at the regulatory level, with sequences of regulatory regions being most conserved for genes expressed in mid-development but not at the level of gene sequence, age, or expression, in contrast to some previous studies. The early conservation model was supported with gene duplication and birth that were the most rare for genes expressed in early development. Finally, for all gene properties, we observed the least conservation for genes expressed in late development or adult, consistent with both models. Overall, with the modular approach, we showed that different levels of molecular evolution follow different patterns of developmental constraints. Thus both models are valid, but with respect to different genomic features.

Analysis of gene expression patterns in animals

During my PhD, my aim was to provide new tools to increase our capacity to analyse gene expression patterns, and to study on a large-scale basis the evolution of gene expression in animals. Gene expression patterns (when and where a gene is expressed) are a key feature in understanding gene function, notably in development. It appears clear now that the evolution of developmental processes and of phenotypes is shaped both by evolution at the coding sequence level, and at the gene expression level.Studying gene expression evolution in animals, with complex expression patterns over tissues and developmental time, is still challenging. No tools are available to routinely compare expression patterns between different species, with precision, and on a large-scale basis. Studies on gene expression evolution are therefore performed only on small genes datasets, or using imprecise descriptions of expression patterns.The aim of my PhD was thus to develop and use novel bioinformatics resources, to study the evolution of gene expression. To this end, I developed the database Bgee (Base for Gene Expression Evolution). The approach of Bgee is to transform heterogeneous expression data (ESTs, microarrays, and in-situ hybridizations) into present/absent calls, and to annotate them to standard representations of anatomy and development of different species (anatomical ontologies). An extensive mapping between anatomies of species is then developed based on hypothesis of homology. These precise annotations to anatomies, and this extensive mapping between species, are the major assets of Bgee, and have required the involvement of many co-workers over the years. My main personal contribution is the development and the management of both the Bgee database and the web-application.Bgee is now on its ninth release, and includes an important gene expression dataset for 5 species (human, mouse, drosophila, zebrafish, Xenopus), with the most data from mouse, human and zebrafish. Using these three species, I have conducted an analysis of gene expression evolution after duplication in vertebrates.Gene duplication is thought to be a major source of novelty in evolution, and to participate to speciation. It has been suggested that the evolution of gene expression patterns might participate in the retention of duplicate genes. I performed a large-scale comparison of expression patterns of hundreds of duplicated genes to their singleton ortholog in an outgroup, including both small and large-scale duplicates, in three vertebrate species (human, mouse and zebrafish), and using highly accurate descriptions of expression patterns. My results showed unexpectedly high rates of de novo acquisition of expression domains after duplication (neofunctionalization), at least as high or higher than rates of partitioning of expression domains (subfunctionalization). I found differences in the evolution of expression of small- and large-scale duplicates, with small-scale duplicates more prone to neofunctionalization. Duplicates with neofunctionalization seemed to evolve under more relaxed selective pressure on the coding sequence. Finally, even with abundant and precise expression data, the majority fate I recovered was neither neo- nor subfunctionalization of expression domains, suggesting a major role for other mechanisms in duplicate gene retention.

Unraveling dynamics of human physical activity patterns in chronic pain conditions.

Chronic pain is a complex disabling experience that negatively affects the cognitive, affective and physical functions as well as behavior. Although the interaction between chronic pain and physical functioning is a well-accepted paradigm in clinical research, the understanding of how pain affects individuals' daily life behavior remains a challenging task. Here we develop a methodological framework allowing to objectively document disruptive pain related interferences on real-life physical activity. The results reveal that meaningful information is contained in the temporal dynamics of activity patterns and an analytical model based on the theory of bivariate point processes can be used to describe physical activity behavior. The model parameters capture the dynamic interdependence between periods and events and determine a 'signature' of activity pattern. The study is likely to contribute to the clinical understanding of complex pain/disease-related behaviors and establish a unified mathematical framework to quantify the complex dynamics of various human activities.

Up-regulation of macrophage migration inhibitory factor gene and protein expression in glial tumor cells during hypoxic and hypoglycemic stress indicates a critical role for angiogenesis in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most malignant variant of human glial tumors. A prominent feature of this tumor is the occurrence of necrosis and vascular proliferation. The regulation of glial neovascularization is still poorly understood and the characterization of factors involved in this process is of major clinical interest. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine released by leukocytes and by a variety of cells outside of the immune system. Recent work has shown that MIF may function to regulate cellular differentiation and proliferation in normal and tumor-derived cell lines, and may also contribute to the neovascularization of tumors. Our immunohistological analysis of MIF distribution in GBM tissues revealed the strong MIF protein accumulation in close association with necrotic areas and in tumor cells surrounding blood vessels. In addition, MIF expression was frequently associated with the presence of the tumor-suppressor gene p53. To substantiate the concept that MIF might be involved in the regulation of angiogenesis in GBM, we analyzed the MIF gene and protein expression under hypoxic and hypoglycemic stress conditions in vitro. Northern blot analysis showed a clear increase of MIF mRNA after hypoxia and hypoglycemia. We could also demonstrate that the increase of MIF transcripts on hypoxic stress can be explained by a profound transcriptional activation of the MIF gene. In parallel to the increase of MIF transcripts, we observed a significant rise in extracellular MIF protein on angiogenic stimulation. The data of our preliminary study suggest that the up-regulation of MIF expression during hypoxic and hypoglycemic stress might play a critical role for the neovascularization of glial tumors.

Inhibition of angiogenesis by non-steroidal anti-inflammatory drugs: from the bench to the bedside and back.

The formation of new blood vessels, a process globally referred to as angiogenesis, occurs in a number of pathological conditions, such as cancer and chronic inflammation. Recent findings indicate that cyclooxygenase-2 (COX-2), the inducible form of the cyclooxygenase (COX) isoenzymes, acts as a potent inducer of angiogenesis. Non-steroidal anti-inflammatory drugs (NSAIDs) are classical inhibitors of COX enzymes, which are widely prescribed for the treatment of inflammation, pain and fever. Selective COX-2 inhibitors (COXIBs) have been subsequently developed with the purpose to improve the safety profile of this class of therapeutics. More recently, substantial preclinical evidence demonstrated that NSAIDS and COXIBs have anti-angiogenic properties. This newly recognized activity opens the possibility of using these drugs for the treatment of angiogenesis-dependent diseases. In this article we review the most recent advances in understanding the mechanisms by which NSAIDs and COXIBs suppress angiogenesis, and we discuss their potential clinical use as anti-angiogenic drugs.

Patterns of cannabis use and prospective associations with health issues among young males.

BACKGROUND AND AIMS: To test prospective associations between cannabis disorder symptoms/frequency of cannabis use and health issues and to investigate stability versus transience in cannabis use trajectories. DESIGN: Two waves of data collection from the longitudinal Cohort Study on Substance Use Risk Factors (C-SURF). SETTING: A representative sample of young Swiss men in their early 20s from the general population. PARTICIPANTS: A total of 5084 young men (mean age 19.98 ± 1.19 years at time 1). MEASUREMENTS: Cannabis use (life-time use, frequency of use, cannabis disorder symptoms) and self-reported measures of health issues (depression, mental/physical health, health consequences) were assessed. Significant changes in cannabis use were tested using t-test/Wilcoxon's rank test for paired data. Cross-lagged panel models provided evidence regarding longitudinal associations between cannabis use and health issues. FINDINGS: Most of the participants (84.5%) remained in the same use category and cannabis use kept to similar levels at times 1 and 2 (P = 0.114 and P = 0.755; average of 15 ± 2.8 months between times 1 and 2). Cross-lagged panel models showed that cannabis disorder symptoms predicted later health issues (e.g. depression, β = 0.087, P < 0.001; health consequences, β = 0.045, P < 0.05). The reverse paths from health issues to cannabis disorder symptoms and the cross-lagged panel model between frequency of cannabis use and health issues were non-significant. CONCLUSIONS: Patterns of cannabis use showed substantial continuity among young Swiss men in their early 20s. The number of symptoms of cannabis use disorder, rather than the frequency of cannabis use, is a clinically important measure of cannabis use among young Swiss men.

Non-verbal behavioural patterns in trilogue play transitions and family alliances

This case study focuses on non-verbal behaviour in father-mother-infant triads. Analyses were done on transitional moments during which the partners exchanged an active role for a participant-observer role, or vice versa. Transitions are known to be crucial moments for revealing familial transactional mechanisms. Our sample was comprised of six non-clinical families, characterized by different types of functional or problematic alliances (which is the degree of coordination between the partners). Our methodology included micro-analysis of body and gaze formations, facial expressions, and so on. Data were analysed using the research package 'THEME' for the detection of hidden patterns. Different types of non-verbal patterns were found, which may be prototypes corresponding to the different types of alliance. The patterns of the families with high alliances had a more elaborate construction and were more efficient for the concluding of transitions than the patterns of families with low alliances, which were either elementary or laborious. (PsycINFO Database Record (c) 2006 APA, all rights reserved) (journal abstract)

Patterns of gravity induced aggregate migration during casting of fluid concretes

In this paper, aggregate migration patterns during fluid concrete castings are studied through experiments, dimensionless approach and numerical modeling. The experimental results obtained on two beams show that gravity induced migration is primarily affecting the coarsest aggregates resulting in a decrease of coarse aggregates volume fraction with the horizontal distance from the pouring point and in a puzzling vertical multi-layer structure. The origin of this multi layer structure is discussed and analyzed with the help of numerical simulations of free surface flow. Our results suggest that it finds its origin in the non Newtonian nature of fresh concrete and that increasing casting rate shall decrease the magnitude of gravity induced particle migration. (C) 2012 Elsevier Ltd. All rights reserved.