Mass casualty incidents with multiple burn victims: rationale for a Swiss burn plan.

INTRODUCTION: Mass casualty incidents involving victims with severe burns pose difficult and unique problems for both rescue teams and hospitals. This paper presents an analysis of the published reports with the aim of proposing a rational model for burn rescue and hospital referral for Switzerland. METHODS: Literature review including systematic searches of PubMed/Medline, reference textbooks and journals as well as landmark articles. RESULTS: Since hospitals have limited surge capacities in the event of burn disasters, a special approach to both prehospital and hospital management of these victims is required. Specialized rescue and care can be adequately met and at all levels of needs by deploying mobile burn teams to the scene. These burn teams can bring needed skills and enhance the efficiency of the classical disaster response teams. Burn teams assist with both primary and secondary triage, contribute to initial patient management and offer advice to non-specialized designated hospitals that provide acute care for burn patients with Total Burn Surface Area (TBSA) <20-30%. The main components required for successful deployments of mobile burn teams include socio-economic feasibility, streamlined logistical implementation as well as partnership coordination with other agencies including subsidiary military resources. CONCLUSIONS: Disaster preparedness plans involving burn specialists dispatched from a referral burn center can upgrade and significantly improve prehospital rescue outcome, initial resuscitation care and help prevent an overload to hospital surge capacities in case of multiple burn victims. This is the rationale behind the ongoing development and implementation of the Swiss burn plan.

Determination of Vasopressin and Desmopressin in urine by means of liquid chromatography coupled to quadrupole time-of-flight mass spectrometry for doping control purposes.

The anti-diuretic neurohypophysial hormone Vasopressin (Vp) and its synthetic analogue Desmopressin (Dp, 1-desamino-vasopressin) have received considerable attention from doping control authorities due to their impact on physiological blood parameters. Accordingly, the illicit use of Desmopressin in elite sport is sanctioned by the World Anti-Doping Agency (WADA) and the drug is classified as masking agent. Vp and Dp are small (8-9 amino acids) peptides administered orally as well as intranasally. Within the present study a method to determine Dp and Vp in urinary doping control samples by means of liquid chromatography coupled to quadrupole high resolution time-of-flight mass spectrometry was developed. After addition of Lys-Vasopressin as internal standard and efficient sample clean up with a mixed mode solid phase extraction (weak cation exchange), the samples were directly injected into the LC-MS system. The method was validated considering the parameters specificity, linearity, recovery (80-100%), accuracy, robustness, limit of detection/quantification (20/50 pg mL(-1)), precision (inter/intra-day<10%), ion suppression and stability. The analysis of administration study urine samples collected after a single intranasal or oral application of Dp yielded in detection windows for the unchanged target analyte for up to 20 h at concentrations between 50 and 600 pg mL(-1). Endogenous Vp was detected in concentrations of approximately 20-200 pg mL(-1) in spontaneous urine samples obtained from healthy volunteers. The general requirements of the developed method provide the characteristics for an easy transfer to other anti-doping laboratories and support closing another potential gap for cheating athletes.

Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.

We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10)), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10(-5)). An interaction test confirmed that these estimates differed from each other (P = 4.95 × 10(-13)). This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations.

Global mass wasting during the Middle Ordovician: Meteoritic trigger or plate-tectonic environment ?

Mass wasting at continental margins on a global scale during the Middle Ordovician has recently been related to high meteorite influx. Although a high meteorite influx during the Ordovician should not be neglected, we challenge the idea that mass wasting was mainly produced by meteorite impacts over a period of almost 10 Ma. Having strong arguments against the impact-related hypothesis, we propose an alternative explanation, which is based on a re-evaluation of the mass wasting sites, considering their plate-tectonic distribution and the global sea level curve. A striking and important feature is the distribution of most of the mass wasting sites along continental margins characterised by periods of magmatism, terrane accretion and continental or back-arc rifting, respectively, related to subduction of oceanic lithosphere. Such processes are commonly connected with seismic activity causing earthquakes, which can cause downslope movement of sediment and rock. Considering all that, it seems more likely that most of this mass wasting was triggered by earthquakes related to plate-tectonic processes, which caused destabilisation of continental margins resulting in megabreccias and debris flows. Moreover, the period of mass wasting coincides with sea level drops during global sea level lowstand. In some cases, sea level drops can release pore-water overpressure reducing sediment strength and hence promoting instability of sediment at continental margins. Reduced pore-water overpressure can also destabilise gas hydrate-bearing sediment, causing slope failure, and thus resulting in submarine mass wasting. Overall, the global mass wasting during the Middle Ordovician does not need meteoritic trigger. (C) 2010 International Association for Gondwana Research. Published by Elsevier B.V. All rights reserved.

Marijuana use, diet, body mass index, and cardiovascular risk factors (from the CARDIA study).

Marijuana use has been associated with increased appetite, high caloric diet, acute increase in blood pressure, and decreases in high-density lipoprotein cholesterol and triglycerides. Marijuana is the most commonly used illicit drug in the United States, but its long-term effects on body mass index (BMI) and cardiovascular risk factors are unknown. Using 15 years of longitudinal data from 3,617 black and white young adults participating in the Coronary Artery Risk Development in Young Adults (CARDIA) study, we assessed whether marijuana use was associated with caloric intake, BMI, and cardiovascular risk factors. Of the 3,617 participants, 1,365 (38%) reported ever using marijuana. Marijuana use was associated with male gender, tobacco smoking, and other illicit drug use. More extensive marijuana use was associated with a higher caloric intake (2,746 kcal/day in never users to 3,365 kcal/day in those who used marijuana for > or = 1,800 days over 15 years) and alcohol intake (3.6 to 10.8 drinks/week), systolic blood pressure (112.7 to 116.5 mm Hg), and triglyceride levels (84 to 100 mg/dl or 0.95 to 1.13 mmol/L, all p values for trend < 0.001), but not with higher BMI and lipid and glucose levels. In multivariate analysis, the associations between marijuana use and systolic blood pressure and triglycerides disappeared, having been mainly confounded by greater alcohol use in marijuana users. In conclusion, although marijuana use was not independently associated with cardiovascular risk factors, it was associated with other unhealthy behaviors, such as high caloric diet, tobacco smoking, and other illicit drug use, which all have long-term detrimental effects on health.

Occipitoaxial spinal interarticular stabilization with vertebral artery preservation for atlantal lateral mass failure.

The treatment of craniocervical instability caused by diverse conditions remains challenging. Different techniques have been described to stabilize the craniocervical junction. The authors present 2 cases in which tumoral destruction of the C-1 lateral mass caused craniocervical instability. A one-stage occipitoaxial spinal interarticular stabilization (OASIS) technique with titanium cages and posterior occipitocervical instrumentation was used to reconstruct the C-1 lateral mass and stabilize the craniocervical junction. The ipsilateral vertebral artery was preserved. The OASIS technique offers single-stage tumor resection, C-1 lateral mass reconstruction, and stabilization with a loadsharing construct. It could be an option in the treatment of select cases of C-1 lateral mass failure.

The relation of body mass index and abdominal adiposity with dyslipidemia in 27 general populations of the WHO MONICA Project.

The association between adiposity measures and dyslipidemia has seldom been assessed in a multipopulational setting. 27 populations from Europe, Australia, New Zealand and Canada (WHO MONICA project) using health surveys conducted between 1990 and 1997 in adults aged 35-64 years (n = 40,480). Dyslipidemia was defined as the total/HDL cholesterol ratio >6 (men) and >5 (women). Overall prevalence of dyslipidemia was 25% in men and 23% in women. Logistic regression showed that dyslipidemia was strongly associated with body mass index (BMI) in men and with waist circumference (WC) in women, after adjusting for region, age and smoking. Among normal-weight men and women (BMI<25 kg/m(2)), an increase in the odds for being dyslipidemic was observed between lowest and highest WC quartiles (OR = 3.6, p < 0.001). Among obese men (BMI ≥ 30), the corresponding increase was smaller (OR = 1.2, p = 0.036). A similar weakening was observed among women. Classification tree analysis was performed to assign subjects into classes of risk for dyslipidemia. BMI thresholds (25.4 and 29.2 kg/m(2)) in men and WC thresholds (81.7 and 92.6 cm) in women came out at first stages. High WC (>84.8 cm) in normal-weight men, menopause in women and regular smoking further defined subgroups at increased risk. standard categories of BMI and WC, or their combinations, do not lead to optimal risk stratification for dyslipidemia in middle-age adults. Sex-specific adaptations are necessary, in particular by taking into account abdominal obesity in normal-weight men, post-menopausal age in women and regular smoking in both sexes.

Effect of Pcbs (Aroclor 1254) on spermatogenesis In Testis Of Mouse

Polychlorinated biphenyls (PCBs) are a group of halogenated aromatic hydrocarbons, synthetic chemicals which do not occur naturally in the environment. PCBs are considered potential endocrine disruptors. They are estrogen-like and anti-androgenic chemicals in the environment contain potentially hazardous effects on male reproductive axis resulting in infertility and other hormonal dependent reproductive functions. These toxic substance cause alteration of the endocrine systems, mimic natural hormones and inhibit the action of hormones. The aim of this study is to examine the effect of Polychlorinated biphenyls (PCBs) on testicular development of male reproductive system in mice. The male mice were randomly assigned to five groups with each group comprising twenty-one members. In those mice were administered 0 μg/kg (control group) and 0.5, 5, 50, 500 μg/kg Aroclor 1254 (treated group) by gavages three time per week. Treatment was carried out for 50 days after which the mouse was sacrificed and the body weight, testicular weight; epedidymis weight, sperm mortality, sperm count and sperm abnormality were taken. However, there was no significant difference in testicular/body weight and epididymis/body weight ratio in treated group compared with the control group. According to the analysis of sperm quality, Aroclor 1254 treated group demonstrated significant increased in sperm mortality in 500 μg/kg; decreased the sperm count in 0.5 μg/kg, 5 μg/kg, 50 μg/kg and 500 μg/kg; and significantly elevate the sperm abnormality in 50 μg/kg and 500 μg/kg compared to the control in a dose-dependent manner. The sex hormone levels in the testes were detected by radio-immunoassay (RIA) method. The levels of testosterone and 17β-estradiol did not reveal significant alteration (p< 0.05) in PCBs treated groups compared to the control in a dose-dependent manner. The testis were obtained and subjected to routine histopathology following exposure to PCBs in supplement diet. The diameter of the seminiferous tubule and the number of Sertoli cells in the treated group increased significantly (p< 0.05) in comparison to the control group. For the spermatogenic cell, the number of germ cell in high concentration decreased significantly (p< 0.05). However, spermatogonia cells in PCB treated group showed non-significant difference (p< 0.05) compared to the control. vii Western blot analysis was used to determine the level of protein between the control and treated group. The level of Proliferating cell nuclear antigen (PCNA) was determined and the results have shown no significant alteration between the treated groups and the control. the level of sex hormone receptor (ER α/β); Androgen receptor (AR) were identified in the testes to detect the proliferative effect induced by PCBs. Statistical analyses of AR, ER α and ER β did not reveal significant difference between the control and the treated groups. In the present study, we continue to investigate adverse effect of Aroclor 1254 and their mechanism on spermatogenesis. The result of Sperm quality and histopathology showed that Aroclor 1254 at low concentration induce inhibitory effect on testicular function of male mouse.

Premissas historicas do surgimento e desenvolvimento dos mass-media nos paises lusofonos

A nossa investigacao esta dedicada a paises que falam essencialmente a lingua portuguesa, nao sera de admirar que a maioria dos livros por nos usados sejam de autores e ediccao portuguesa. No decorrer deste trabalho recorremos a livros e trabalhos academicos de autores como: Carvalho, Arons de: A Censura À Imprensa Na Época Marcelista; Minerva,Coimbra, 1999; Evora, Silvino Lopes: As fontes jornalísticas na televisão caboverdiana, ediccoes FCC, Universidade do Minho,2004; Fontcuberta: Mar de, A Notícia – Pistas para compreender o mundo; Editorial Notícias “Tradução de Fernando Cascais”,Lisboa, 1999; Mata, Maria José: A Autocrítica no Jornalismo – O ombudsman na imprensa nacional e estrangeira; Minerva Editora,Coimbra, 2002; Pigeat, Henri: Médias et Déontologie – Règles du jeu ou jeu sans règles; Presses Universitaires Francaises, Paris, 1997; Sodré, Nelson Werneck. História da imprensa no Brasil. 2ª ed., Rio de Janeiro: Graal, 1977; Sousa, Jorge Pedro: As Notícias e os seus Efeitos; Minerva Editora,Coimbra, 2000; Veiga Manuel: Cabo Verde insularidade e Literatura, editions Karthala, Paris, 1998; Bem como, um conjunto de leis e projectos de lei ligados a comunicacao social, e algumas entrevistas. Estrutura do trabalho: Esta tese e constituida de: introducao, tres capitulos, conclusao, bibliografia e alguns anexos num total de . Na introducao explica-se a escolha do tema, a sua actualidade, o objecto de investigacao e claro a sua inovacao. No primeiro capitulo estudamos o context do aparecimento dos media nos paises lusofonos nos exemplos de Cabo Verde, Brasil, e Portugal. No Segundo cappitulo, analizamos as leis, os processos de controlo e financiamento dos mass-media e a regulacao dos conteudos dos programas de radio e televisao. No terceiro capitulo, a situacao actual dos meios de comunicacao social e do Jornalismo na CPLP, nele esta tambem exposta a parte practica do trabalho ou seja a analize da relacao do publico com os media e o nivel de confianca do publico na informacao por eles veiculada.

Simultaneous determination of plasma levels of fluvoxamine and of the enantiomers of fluoxetine and norfluoxetine by gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric method is presented which allows the simultaneous determination of the plasma concentrations of fluvoxamine and of the enantiomers of fluoxetine and norfluoxetine after derivatization with the chiral reagent, (S)-(-)-N-trifluoroacetylprolyl chloride. No interference was observed from endogenous compounds following the extraction of plasma samples from six different human subjects. The standard curves were linear over a working range of 10 to 750 ng/ml for racemic fluoxetine and norfluoxetine and of 50 to 500 ng/ml for fluvoxamine. Recoveries ranged from 50 to 66% for the three compounds. Intra- and inter-day coefficients of variation ranged from 4 to 10% for fluvoxamine and from 4 to 13% for fluoxetine and norfluoxetine. The limits of quantitation of the method were found to be 2 ng/ml for fluvoxamine and 1 ng/ml for the (R)- and (S)-enantiomers of fluoxetine and norfluoxetine, hence allowing its use for single dose pharmacokinetics. Finally, by using a steeper gradient of temperature, much shorter analysis times are obtained if one is interested in the concentrations of fluvoxamine alone.

GENETIC AND BIOCHEMICAL ANALYSIS OF THE TESTIS-SPECIFIC ZINC FINGER PROTEIN CTCFL/BORIS

Abstract en FrançaisCTCFL a d'abord été identifié comme un paralogue de la protéine ubiquitaire CTCF en raison de sa forte homologie entre leurs onze « zinc fingers », un domaine de liaison à l'ADN. Parmi ses nombreux rôles, la liaison des zinc fingers de CTCF à la région de contrôle de l'empreinte (ICR) maternelle non-méthylée Igf2/H19, contrôle l'expression empreinte (monoallélique) de H19 et IGF2 dans les cellules somatiques. La méthylation de l'ICR Igf2/H19 paternelle est nécessaire à l'expression empreinte de ces deux gènes. Bien que le mécanisme par lequel l'ICR est méthylé soit mal compris, il est connu que l'établissement de la méthylation se produit pendant le développement des cellules germinales mâles et que les ADN méthyltransférases de novo DNMT3A et DNMT3L sont essentiels. Par conséquent, CTCFL fournit un bon candidat pour un rôle dans la méthylation de l'ICR paternelle Igf2/H19 en raison de son expression restreinte à certains types de cellules où la méthylation de l'ICR a lieu (spermatogonies et spermatocytes) ainsi qu'en raison sa capacité à lier les ICR lgf2/HÎ9 dans ces cellules. Les premiers travaux expérimentaux de cette thèse portent sur le rôle possible des mutations de CTCFL chez les patients atteints du syndrome de Silver-Russell (SRS), où une diminution de la méthylation de l'ICR IGF2/H19 a été observée chez 60% d'entre eux. Admettant que CTCFL pourrait être muté chez ces patients, j'ai examiné les mutations possibles de CTCFL chez 35 d'entre eux par séquençage de l'ADN et analyse du nombre de copies d'exons. N'ayant trouvé aucune mutation chez ces patients, cela suggère que les mutations de CTCFL ne sont pas associées au SRS. Les travaux expérimentaux suivants ont porté sur les modifications post-traductionnelles de CTCFL par la protéine SU MO « small ubiquitin-like modifier » (SUMO). La modification de protéines par SU MO change les interactions avec d'autres molécules (ADN ou protéines). Comme CTCFL régule sans doute l'expression d'un certain nombre de gènes dans le cancer et que plusieurs facteurs de transcription sont régulés par SUMO, j'ai mené des expériences pour déterminer si CTCFL est sumoylé. En effet, j'ai observé que CTCFL est sumoylated in vitro et in vivo et j'ai déterminé les deux résidus d'attachement de SUMO aux lysines 181 et 645. Utilisant les mutants de CTCFL K181R et K645R ne pouvant pas être sumoylated, j'ai évalué les conséquences fonctionnelles de la modification par SUMO. Je n'ai trouvé aucun changement significatif dans la localisation subcellulaire, la demi-vie ou la liaison à l'ADN, mais ai constaté que la sumoylation module à la fois {'activation CTCFL-dépendante et la répression de l'expression génique. Il s'agit de la première modification post-traductionnelle décrite pour CTCFL et les conséquences possibles de cette modification sont discutées pour le cancer et les testicules normaux. Avec cette thèse, j'espère avoir ajouté des résultats importants à l'étude de CTCFL et donné quelques idées pour de futures recherches.AbstractJeremiah Bernier-Latmani, Institute of Pathology, University of Lausanne, CHUVCTCFL was first identified as a paralog of the ubiquitous protein CTCF because of high homology between their respective eleven zinc fingers, a DNA binding domain. Among its many roles, CTCF zinc finger-mediated binding to the unmethylated maternal Igf2/H19 imprinting control region (ICR), controls the imprinted (monoallelic) expression of Igf2 and H19 in somatic cells. Methylation of the paternal Igf2/H19 ICR is necessary for the imprinted expression of the two genes. Although the mechanism by which the ICR is methylated is incompletely understood, it is known that establishment of methylation occurs during male germ cell development and the de novo DNA methyltransferases DNMT3A and DNMT3L are essential. Therefore, CTCFL provided a good candidate to play a role in methylation of the paternal Igf2/H19 ICR because of its restricted expression to cell types where ICR methylation takes place (spermatogonia and spermatocytes) and its ability to bind the Igf2/H19 ICR in these cells. The first experimental work of this thesis investigated the possible role of CTCFL mutations in Silver-Russell syndrome (SRS) patients, where it has been observed that 60% of the patients have reduced methylation of the IGF2/HÎ9 ICR. Reasoning that CTCFL could be mutated in these patients, I screened 35 patients for mutations in CTCFL by DNA sequencing and exon copy number analysis, I did not find any mutations in these patients suggesting that mutations of CTCFL are not associated with SRS. The next experimental work of my thesis focused on posttranslational modification of CTCFL by small ubiquitin-like modifier (SUMO) protein. SUMO modification of proteins changes the interactions with other molecules (DNA or protein). As CTCFL arguably regulates the expression of a number of genes in cancer and many transcription factors are regulated by SUMO, I conducted experiments to assess whether CTCFL is sumoylated. I found that CTCFL is sumoylated in vitro and in vivo and determined the two residues of SUMO attachment to be lysines 181 and 645. Using K181R, K645R mutated CTCFL- which cannot be detected to be sumoylated-1 assessed the functional consequences of SUMO modification. I found no significant changes in subcellular localization, half-life or DNA binding, but found that sumoylation modulates both CTCFL-dependent activation and repression of gene expression. This is the first posttranslational modification described for CTCFL and possible consequences of this modification are discussed in both cancer and normal testis. With this thesis, I hope I have added important findings to the study of CTCFL and provide some ideas for future research.

Determination of oseltamivir and oseltamivir carboxylate in human plasma by liquid chromatography-tandem mass spectrometry

Introduction: Oseltamivir phosphate (OP), the prodrug of oseltamivir carboxylate (OC; active metabolite), is marketed since 10 years for the treatment of seasonal influenza flu. It has recently received renewed attention because of the threat of avian flu H5N1 in 2006-7 and the 2009-10 A/H1N1 pandemic. However, relatively few studies have been published on OP and OC clinical pharmacokinetics. The disposition of OC and the dosage adaptation of OP in specific populations, such as young children or patients undergoing extrarenal epuration, have also received poor attention. An analytical method was thus developed to assess OP and OC plasma concentrations in patients receiving OP and presenting with comorbidities or requiring intensive care. Methods: A high performance liquid chromatography coupled to tandem mass spectrometry method (HPLC-MS/MS) requiring 100-µL aliquot of plasma for quantification within 6 min of OP and OC was developed. A combination of protein precipitation with acetonitrile, followed by dilution of supernant in suitable buffered solvent was used as an extraction procedure. After reverse phase chromatographic separation, quantification was performed by electro-spray ionization-triple quadrupole mass spectrometry. Deuterated isotopic compounds of OP and OC were used as internal standards. Results: The method is sensitive (lower limit of quantification: 5 ng/mL for OP and OC), accurate (intra-/inter-assay bias for OP and OC: 8.5%/5.5% and 3.7/0.7%, respectively) and precise (intra-/inter-assay CV%: 5.2%/6.5% and 6.3%/9.2%, respectively) over the clinically relevant concentration range (upper limits of quantification 5000 ng/mL). Of importance, OP, as in other previous reports, was found not to be stable ex vivo in plasma on standard anticoagulants (i.e. EDTA, heparin or citrate). This poor stability of OP has been prevented by collecting blood samples on commercial fluoride/oxalate tubes. Conclusions: This new simple, rapid and robust HPLC-MS/MS assay for quantification of OP and OC plasma concentrations offers an efficient tool for concentration monitoring of OC. Its exposure can probably be controlled with sufficient accuracy by thorough dosage adjustment according to patient characteristics (e.g. renal clearance). The usefulness of systematic therapeutic drug monitoring in patients appears therefore questionable. However, pharmacokinetic studies are still needed to extend knowledge to particular subgroups of patients or dosage regimens.

The association between body mass index and patients' experiences with inpatient care.

OBJECTIVE: To explore the association between patients' body mass index (BMI) and their experiences with inpatient care. DESIGN: Cross-sectional. Mail survey. SETTING: University Hospital of Geneva. PARTICIPANTS: Questionnaires were mailed to 2385 eligible adult patients, 6 weeks after discharge (response rate = 69%). MAIN OUTCOME MEASURES: Patients' experiences with care were measured using the Picker inpatient survey questionnaire. BMI was calculated using self-reported height and weight. Main dependent variables were the global Picker patient experience (PPE-15) score and nine dimension-specific problem scores, scored from 0 (no reported problems) to 1 (all items coded as problems). We used linear regressions, adjusting for age, gender, education, subjective health, smoking and hospitalization, to assess the association between patients' BMI and their experiences with inpatient care. RESULTS: Of the patients, 4.8% were underweight, 50.8% had normal weight, 30.3% were overweight and 14.1% were obese. Adjusted analysis shows that compared with normal weight, obesity was significantly associated with fewer problematic items in the surgery-related information domain, and being underweight or overweight was associated with more problematic items in the involvement of family/friends domain. The global PPE-15 score was significantly higher (more problems) for underweight patients. CONCLUSIONS: Underweight patients, but not obese patients, reported more problems during hospitalization.