Total-body digital X-ray in trauma. An experience report on the first operational full body scanner in Europe and its possible role in ATLS

When patients enter our emergency room with suspected multiple injuries, Statscan provides a full body anterior and lateral image for initial diagnosis, and then zooms in on specific smaller areas for a more detailed evaluation. In order to examine the possible role of Statscan in the management of multiply injured patients we implemented a modified ATLS((R)) algorithm, where X-ray of C-spine, chest and pelvis have been replaced by single-total a.p./lat. body radiograph. Between 15 October 2006 and 1 February 2007 143 trauma patients (mean ISS 15+/-14 (3-75)) were included. We compared the time in resuscitation room to 650 patients (mean ISS 14+/-14 (3-75)) which were treated between 1 January 2002 and 1 January 2004 according to conventional ATLS protocol. The total-body scanning time was 3.5 min (3-6 min) compared to 25.7 (8-48 min) for conventional X-rays, The total ER time was unchanged 28.7 min (13-58 min) compared to 29.1 min (15-65 min) using conventional plain radiography. In 116/143 patients additional CT scans were necessary. In 98/116 full body trauma CT scans were performed. In 18/116 patients selective CT scans were ordered based on Statscan findings. In 43/143 additional conventional X-rays had to be performed, mainly due to inadequate a.p. views of fractured bones. All radiographs were transmitted over the hospital network (Picture Archiving and Communication System, PACS) for immediate simultaneous viewing at different places. The rapid availability of images for interpretation because of their digital nature and the reduced need for repeat exposures because of faulty radiography are also felt to be strengths.

Differential expression of stx2 variants in Shiga toxin-producing Escherichia coli belonging to seropathotypes A and C

Only a subset of Shiga toxin (Stx)-producing Escherichia coli (STEC) are human pathogens, but the characteristics that account for differences in pathogenicity are not well understood. In this study, we investigated the distribution of the stx variants coding for Stx2 and its variants in highly virulent STEC of seropathotype A and low-pathogenic STEC of seropathotype C. We analysed and compared transcription of the corresponding genes, production of Shiga toxins, and stx-phage release in basal as well as in induced conditions. We found that the stx(2) variant was mainly associated with strains of seropathotype A, whereas most of the strains of seropathotype C possessed the stx(2-vhb) variant, which was frequently associated with stx(2), stx(2-vha) or stx(2c). Levels of stx(2) and stx(2)-related mRNA were higher in strains belonging to seropathotype A and in those strains of seropathotype C that express the stx(2) variant than in the remaining strains of seropathotype C. The stx(2-vhb) genes were the least expressed, in basal as well as in induced conditions, and in many cases did not seem to be carried by an inducible prophage. A clear correlation was observed between stx mRNA levels and stx-phage DNA in the culture supernatants, suggesting that most stx(2)-related genes are expressed only when they are carried by a phage. In conclusion, some relationship between stx(2)-related gene expression in vitro and the seropathotype of the STEC strains was observed. A higher expression of the stx(2) gene and a higher release of its product, in basal as well as in induced conditions, was observed in pathogenic strains of seropathotype A. A subset of strains of seropathotype C shows the same characteristics and could be a high risk to human health.

Connective tissue growth factor, steatosis and fibrosis in patients with chronic hepatitis C

BACKGROUND/AIM: Both steatosis and insulin resistance have been linked to accelerated fibrosis in chronic hepatitis C. Connective tissue growth factor (CTGF) plays a major role in extracellular matrix production in fibrotic disorders including cirrhosis, and its expression is stimulated in vitro by insulin and glucose. We hypothesized that CTGF may link steatosis, insulin resistance and fibrosis. METHODS: We included 153 chronic hepatitis C patients enrolled in the Swiss Hepatitis C Cohort Study and for whom a liver biopsy and plasma samples were available. CTGF expression was assessed quantitatively by immunohistochemistry. In 94 patients (57 with genotypes non-3), plasma levels of glucose, insulin and leptin were also measured. CTGF synthesis was investigated by immunoblotting on LX-2 stellate cells. RESULTS: Connective tissue growth factor expression was higher in patients with steatosis (P=0.039) and in patients with fibrosis (P=0.008) than those without these features. CTGF levels were neither associated with insulinaemia or with glycaemia, nor with inflammation. By multiple regression analysis, CTGF levels were independently associated with steatosis, a past history of alcohol abuse, plasma leptin and HCV RNA levels; when only patients with genotypes non-3 were considered, CTGF levels were independently associated with a past history of alcohol abuse, plasma leptin levels and steatosis. Leptin stimulated CTGF synthesis in LX-2 cells. CONCLUSIONS: In patients with chronic hepatitis C and steatosis, CTGF may promote fibrosis independently of inflammation. CTGF may link steatosis and fibrosis via increased leptin levels.

[Strengthening the reporting of observational studies in epidemiology (STROBE): explanation and elaboration]

Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalisability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and editors developed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations to improve the quality of reporting of observational studies. The STROBE Statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results and discussion sections of articles. Eighteen items are common to cohort studies, case-control studies and cross-sectional studies and four are specific to each of the three study designs. The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors and readers. This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the STROBE Statement. The meaning and rationale for each checklist item are presented. For each item, one or several published examples and, where possible, references to relevant empirical studies and methodological literature are provided. Examples of useful flow diagrams are also included. The STROBE Statement, this document, and the associated Web site (http://www.strobe-statement.org/) should be helpful resources to improve reporting of observational research.

RNA interference-mediated c-MYC inhibition prevents cell growth and decreases sensitivity to radio- and chemotherapy in childhood medulloblastoma cells

BACKGROUND: With current treatment strategies, nearly half of all medulloblastoma (MB) patients die from progressive tumors. Accordingly, the identification of novel therapeutic strategies remains a major goal. Deregulation of c-MYC is evident in numerous human cancers. In MB, over-expression of c-MYC has been shown to cause anaplasia and correlate with unfavorable prognosis. METHODS: To study the role of c-MYC in MB biology, we down-regulated c-MYC expression by using small interfering RNA (siRNA) and investigated changes in cellular proliferation, cell cycle analysis, apoptosis, telomere maintenance, and response to ionizing radiation (IR) and chemotherapeutics in a representative panel of human MB cell lines expressing different levels of c-MYC (DAOY wild-type, DAOY transfected with the empty vector, DAOY transfected with c-MYC, D341, and D425). RESULTS: siRNA-mediated c-MYC down-regulation resulted in an inhibition of cellular proliferation and clonogenic growth, inhibition of G1-S phase cell cycle progression, and a decrease in human telomerase reverse transcriptase (hTERT) expression and telomerase activity. On the other hand, down-regulation of c-MYC reduced apoptosis and decreased the sensitivity of human MB cells to IR, cisplatin, and etoposide. This effect was more pronounced in DAOY cells expressing high levels of c-MYC when compared with DAOY wild-type or DAOY cells transfected with the empty vector. CONCLUSION: In human MB cells, in addition to its roles in growth and proliferation, c-MYC is also a potent inducer of apoptosis. Therefore, targeting c-MYC might be of therapeutic benefit when used sequentially with chemo- and radiotherapy rather than concomitantly.

Cystatin C is independently associated with total and cardiovascular mortality in individuals undergoing coronary angiography. The Ludwigshafen Risk and Cardiovascular Health (LURIC) study.

AIMS Cystatin C is a well established marker of kidney function. There is evidence that cystatin C concentrations are also associated with mortality. The present analysis prospectively evaluated the associations of cystatin C with all-cause and cardiovascular (CV) mortality in a well-characterized cohort of persons undergoing angiography, but without overt renal insufficiency. METHODS Cystatin C was available in 2998 persons (mean age: 62.7 ± 10.5 years; 30.3% women). Of those 2346 suffered from coronary artery disease (CAD) and 652 (controls) did not. Creatinine (mean ± SD: 83.1 ± 47.8 vs. 74.1 ± 24.7 μmol/L, p = 0.036) but not Cystatin C (mean ± SD: 1.02 ± 0.44 vs. 0.92 ± 0.26 mg/L, p = 0.065) was significantly higher in patients with CAD. After a median follow-up of 9.9 years, in total 898 (30%) deaths occurred, 554 (18.5%) due to CV disease and 326 (10.9%) due to non-CV causes. Multivariable-adjusted Cox analysis (adjusting for eGFR and established cardiovascular risk factors, lipid lowering therapy, angiographic coronary artery disease, and C-reactive protein) revealed that patients in the highest cystatin C quartile were at an increased risk for all-cause (hazard ratio (HR) 1.93, 95% CI 1.50-2.48) and CV mortality (HR 2.05 95% CI 1.48-2.84) compared to those in the lowest quartile. The addition of cystatin C to a model consisting of established cardiovascular risk factors increased the area under the receiver-operating characteristic curve for CV and all-cause mortality, but the difference was statistically not significant. However, reclassification analysis revealed significant improvement by addition of cystatin C for CV and all-cause mortality (p < 0.001), respectively. CONCLUSION The concentration of cystatin C is strongly associated with long-term all-cause and cardiovascular mortality in patients referred to coronary angiography, irrespective of creatinine-based renal function.

Corrective experiences in psychotherapy: Definitions, processes, consequences, and research directions

After 5 years of conceptualizing, investigating, and writing about corrective experiences (CEs), we (the authors of this chapter) met to talk about what we learned. In this chapter, we summarize our joint understanding of (a) the definition of CEs; (b) the contexts in which CEs occur; (c) client, therapist, and external factors that facilitate CEs; (d) the consequences of CEs; and (e) ideas for future theoretical, clinical, empirical, and training directions. As will become evident, the authors of this chapter, who represent a range of theoretical orientations, reached consensus on some CE-related topics but encountered controversy and lively debate about other topics. (PsycINFO Database Record (c) 2013 APA, all rights reserved)

The significant effect of endometriosis on physical, mental and social wellbeing: results from an international cross-sectional survey.

STUDY QUESTION To what extent do the management of endometriosis and the symptoms that remain after treatment affect the quality of life in women with the disease? SUMMARY ANSWER Many women with endometriosis had impaired quality of life and continued to suffer from endometriosis-associated symptoms even though their endometriosis has been managed in tertiary care centres. WHAT IS KNOWN ALREADY The existing literature indicates that quality of life and work productivity is reduced in women with endometriosis. However, most studies have small sample sizes, are treatment related or examine newly diagnosed patients only. STUDY DESIGN, SIZE, DURATION A cross-sectional questionnaire-based survey among 931 women with endometriosis treated in 12 tertiary care centres in 10 countries. PARTICIPANTS/MATERIALS, SETTING, METHODS Women diagnosed with endometriosis who had at least one contact related to endometriosis-associated symptoms during 2008 with a participating centre were enrolled into the study. The study investigated the effect of endometriosis on education, work and social wellbeing, endometriosis-associated symptoms and health-related quality of life, by using questions obtained from the World Endometriosis Research Foundation (WERF) GSWH instrument (designed and validated for the WERF Global Study on Women's Health) and the Short Form 36 version 2 (SF-36v2). MAIN RESULTS AND THE ROLE OF CHANCE Of 3216 women invited to participate in the study, 1450 (45%) provided informed consent and out of these, 931 (931/3216 = 29%) returned the questionnaires. Endometriosis had affected work in 51% of the women and affected relationships in 50% of the women at some time during their life. Dysmenorrhoea was reported by 59%, dyspareunia by 56% and chronic pelvic pain by 60% of women. Quality of life was decreased in all eight dimensions of the SF-36v2 compared with norm-based scores from a general US population (all P < 0.01). Multivariate regression analysis showed that number of co-morbidities, chronic pain and dyspareunia had an independent negative effect on both the physical and mental component of the SF-36v2. LIMITATIONS, REASONS FOR CAUTION The fact that women were enrolled in tertiary care centres could lead to a possible over-representation of women with moderate-to-severe endometriosis, because the participating centres typically treat more complex and referred cases of endometriosis. The response rate was relatively low. Since there was no Institute Review Board approval to do a non-responder investigation on basic characteristics, some uncertainty remains regarding the representativeness of the investigated population. WIDER IMPLICATIONS OF THE FINDINGS This international multicentre survey represents a large group of women with endometriosis, in all phases of the disease, which increases the generalizability of the data. Women still suffer from frequent symptoms, despite tertiary care management, in particular chronic pain and dyspareunia. As a result their quality of life is significantly decreased. A patient-centred approach with extensive collaboration across disciplines, such as pain specialists, psychologists, sexologists and social workers, may be a valuable strategy to improve the long-term care of women with endometriosis. STUDY FUNDING/COMPETING INTEREST(S) The WERF EndoCost study is funded by the World Endometriosis Research Foundation (WERF) through grants received from Bayer Schering Pharma AG, Takeda Italia Farmaceutici SpA, Pfizer Ltd and the European Society of Human Reproduction and Embryology. The sponsors did not have a role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript. L.H. is the chief executive and T.D. was a board member of WERF at the time of funding. T.D. holds the Merck-Serono Chair in Reproductive Medicine and Surgery, and the Ferring Chair in Reproductive Medicine at the Katholieke Universiteit Leuven in Belgium and has served as consultant/research collaborator for Merck-Serono, Schering-Plough, Astellas and Arresto.

Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): Explanation and elaboration

Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalisability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and editors developed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations to improve the quality of reporting of observational studies. The STROBE Statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results and discussion sections of articles. Eighteen items are common to cohort studies, case-control studies and cross-sectional studies and four are specific to each of the three study designs. The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors and readers. This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the STROBE Statement. The meaning and rationale for each checklist item are presented. For each item, one or several published examples and, where possible, references to relevant empirical studies and methodological literature are provided. Examples of useful flow diagrams are also included. The STROBE Statement, this document, and the associated Web site (http://www.strobe-statement.org/) should be helpful resources to improve reporting of observational research.

Choosing and using diversity indices: insights for ecological applications from the German Biodiversity Exploratories

Biodiversity, a multidimensional property of natural systems, is difficult to quantify partly because of the multitude of indices proposed for this purpose. Indices aim to describe general properties of communities that allow us to compare different regions, taxa, and trophic levels. Therefore, they are of fundamental importance for environmental monitoring and conservation, although there is no consensus about which indices are more appropriate and informative. We tested several common diversity indices in a range of simple to complex statistical analyses in order to determine whether some were better suited for certain analyses than others. We used data collected around the focal plant Plantago lanceolata on 60 temperate grassland plots embedded in an agricultural landscape to explore relationships between the common diversity indices of species richness (S), Shannon's diversity (H'), Simpson's diversity (D-1), Simpson's dominance (D-2), Simpson's evenness (E), and Berger-Parker dominance (BP). We calculated each of these indices for herbaceous plants, arbuscular mycorrhizal fungi, aboveground arthropods, belowground insect larvae, and P.lanceolata molecular and chemical diversity. Including these trait-based measures of diversity allowed us to test whether or not they behaved similarly to the better studied species diversity. We used path analysis to determine whether compound indices detected more relationships between diversities of different organisms and traits than more basic indices. In the path models, more paths were significant when using H', even though all models except that with E were equally reliable. This demonstrates that while common diversity indices may appear interchangeable in simple analyses, when considering complex interactions, the choice of index can profoundly alter the interpretation of results. Data mining in order to identify the index producing the most significant results should be avoided, but simultaneously considering analyses using multiple indices can provide greater insight into the interactions in a system.

Detection system for Escherichia coli-specific virulence genes: absence of virulence determinants in B and C strains

We describe a rational approach to simultaneously test Escherichia coli strains for the presence of known virulence genes in a reverse dot blot procedure. Specific segments of virulence genes of E. coli designed to have similar hybridization parameters were subcloned on plasmids and subsequently amplified by PCR as unlabeled probes in amounts sufficient to be bound to nylon membranes. Various pathogenic isolates and laboratory strains of E. coli were probed for the presence of virulence genes by labeling the genomic DNA of these strains with digoxigenin and then hybridizing them to the prepared nylon membranes. These hybridization results demonstrated that besides the E. coli K-12 safety strain derivatives, E. coli B and C strains are also devoid of genes encoding any of the investigated virulence factors. In contrast, pathogenic E. coli control strains, used to evaluate the method, showed typical hybridization patterns. The described probes and their easy application on a single filter were shown to provide a useful tool for the safety assessment of E. coli strains to be used as hosts in biotechnological processes. This approach might also be used for the identification and characterization of clinically significant E. coli isolates from human and animal species.

Contrasting interannual and multidecadal NAO variability

Decadal and longer timescale variability in the winter North Atlantic Oscillation (NAO) has considerable impact on regional climate, yet it remains unclear what fraction of this variability is potentially predictable. This study takes a new approach to this question by demonstrating clear physical differences between NAO variability on interannual-decadal (<30 year) and multidecadal (>30 year) timescales. It is shown that on the shorter timescale the NAO is dominated by variations in the latitude of the North Atlantic jet and storm track, whereas on the longer timescale it represents changes in their strength instead. NAO variability on the two timescales is associated with different dynamical behaviour in terms of eddy-mean flow interaction, Rossby wave breaking and blocking. The two timescales also exhibit different regional impacts on temperature and precipitation and different relationships to sea surface temperatures. These results are derived from linear regression analysis of the Twentieth Century and NCEP-NCAR reanalyses and of a high-resolution HiGEM General Circulation Model control simulation, with additional analysis of a long sea level pressure reconstruction. Evidence is presented for an influence of the ocean circulation on the longer timescale variability of the NAO, which is particularly clear in the model data. As well as providing new evidence of potential predictability, these findings are shown to have implications for the reconstruction and interpretation of long climate records.

All-Cause Mortality and Liver-Related Outcomes Following Successful Antiviral Treatment for Chronic Hepatitis C

BACKGROUND: Antiviral therapy for the hepatitis C virus (HCV) reduces all-cause and liver-related morbidity and mortality. Few studies are available from populations with multiple medical and psychiatric comorbidities where the impact of successful antiviral therapy might be limited. AIM: The purpose of this study was to determine the effect of sustained virologic response (SVR) on all-cause and liver-related mortality in a cohort of HCV patients treated in an integrated hepatitis/mental health clinic. METHODS: This was a retrospective review of all patients who initiated antiviral treatment for chronic HCV between January 1, 1997 and December 31, 2009. Cox regression analysis was used to determine factors involved in all-cause mortality, liver-related events and hepatocellular carcinoma. RESULTS: A total of 536 patients were included in the analysis. Median follow-up was 7.5 years. Liver and non-liver-related mortality occurred in 2.7 and 5.0 % of patients with SVR and in 17.8 and 6.4 % of patients without SVR. In a multivariate analysis, SVR was the only factor associated with reduced all-cause mortality (HR 0.47; 95 % CI 0.26-0.85; p = 0.012) and reduced liver-related events (HR 0.23; 95 % CI 0.08-0.66, p = 0.007). Having stage 4 liver fibrosis increased all-cause mortality (HR 2.50; 95 % CI 1.23-5.08; p = 0.011). Thrombocytopenia at baseline (HR 2.66; 95 % CI 1.22-5.79; p = 0.014) and stage 4 liver fibrosis (HR 4.87; 95 % CI 1.62-14.53; p = 0.005) increased liver-related events. CONCLUSIONS: Despite significant medical and psychiatric comorbidities, SVR markedly reduced liver-related outcomes without a significant change in non-liver-related mortality after a median follow-up of 7.5 years.

New LA-ICP-MS cryocell and calibration technique for sub-millimeter analysis of ice cores

Ice cores provide a robust reconstruction of past climate. However, development of timescales by annual-layer counting, essential to detailed climate reconstruction and interpretation, on ice cores collected at low-accumulation sites or in regions of compressed ice, is problematic due to closely spaced layers. Ice-core analysis by laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS) provides sub-millimeter-scale sampling resolution (on the order of 100μm in this study) and the low detection limits (ng L–1) necessary to measure the chemical constituents preserved in ice cores. We present a newly developed cryocell that can hold a 1m long section of ice core, and an alternative strategy for calibration. Using ice-core samples from central Greenland, we demonstrate the repeatability of multiple ablation passes, highlight the improved sampling resolution, verify the calibration technique and identify annual layers in the chemical profile in a deep section of an ice core where annual layers have not previously been identified using chemistry. In addition, using sections of cores from the Swiss/Italian Alps we illustrate the relationship between Ca, Na and Fe and particle concentration and conductivity, and validate the LA-ICP-MS Ca profile through a direct comparison with continuous flow analysis results.

Melting of metasomatized peridotite at 4–6 GPa and up to 1200 °C: an experimental approach

The phase assemblages and compositions in a K-bearing lherzolite + H2O system are determined between 4 and 6 GPa and 850–1200 °C, and the melting reactions occurring at subarc depth in subduction zones are constrained. Experiments were performed on a rocking multi-anvil apparatus. The experiments had around 16 wt% water content, and hydrous melt or aqueous fluid was segregated and trapped in a diamond aggregate layer. The compositions of the aqueous fluid and hydrous melt phases were measured using the cryogenic LA-ICP-MS technique. The residual lherzolite consists of olivine, orthopyroxene, clinopyroxene, and garnet, while diamond (C) is assumed to be inert. Hydrous and alkali-rich minerals were absent from the run products due to preferred dissolution of K2O (and Na2O) to the aqueous fluid/hydrous melt phases. The role of phlogopite in melting relations is, thus, controlled by the water content in the system: at the water content of around 16 wt% used here, phlogopite is unstable and thus does not participate in melting reactions. The water-saturated solidus, i.e., the first appearance of hydrous melt in the K–lherzolite composition, is located between 900 and 1000 °C at 4 GPa and between 1000 and 1100 °C at 5 and 6 GPa. Compositional jumps between hydrous melt and aqueous fluid at the solidus include a significant increase in the total dissolved solids load. All melts/fluids are peralkaline and calcium-rich. The melting reactions at the solidus are peritectic, as olivine, clinopyroxene, garnet, and H2O are consumed to generate hydrous melt plus orthopyroxene. Our fluid/melt compositional data demonstrate that the water-saturated hybrid peridotite solidus lies above 1000 °C at depths greater than 150 km and that the second critical endpoint is not reached at 6 GPa for a K2O–Na2O–CaO–FeO–MgO–Al2O3–SiO2–H2O–Cr2O3(–TiO2) peridotite composition.