Pregnancy outcome following maternal exposure to statins: a multicentre prospective study.

OBJECTIVE: This contribution addresses the risk associated with exposure to statins during pregnancy. DESIGN: Multicentre observational prospective controlled study. SETTING: European Network of Teratology Information Services. POPULATION: Pregnant women who contacted one of 11 participating centres, seeking advice about exposure to statins during pregnancy, or to agents known to be nonteratogenic. METHODS: Pregnancies exposed during first trimester to statins were followed up prospectively, and their outcomes were compared with a matched control group. MAIN OUTCOME MEASURES: Rates of major birth defects, live births, miscarriages, elective terminations, preterm deliveries and gestational age and birthweight at delivery. RESULTS: We collected observations from 249 exposed pregnancies and 249 controls. The difference in the rate of major birth defects between the statin-exposed and the control groups was small and statistically nonsignificant (4.1% versus 2.7% odds ratio [OR] 1.5; 95% confidence interval [95% CI] 0.5-4.5, P = 0.43). In an adjusted Cox model, the difference between miscarriage rates was also small and not significant (hazard ratio 1.36, 95% CI 0.63-2.93, P = 0.43). Premature birth was more frequent in exposed pregnancies (16.1% versus 8.5%; OR 2.1, 95% CI 1.1-3.8, P = 0.019). Nonetheless, median gestational age at birth (39 weeks, interquartile range [IQR] 37-40 versus 39 weeks, IQR 38-40, P = 0.27) and birth weight (3280 g, IQR 2835-3590 versus 3250 g, IQR 2880-3630, P = 0.95) did not differ between exposed and non-exposed pregnancies. CONCLUSIONS: This study did not detect a teratogenic effect of statins. Its statistical power remains insufficient to challenge current recommendations of treatment discontinuation during pregnancy.

Primary cutaneous posttransplant lymphoproliferative disorders in solid organ transplant recipients: a multicenter European case series.

Primary cutaneous posttransplant lymphoproliferative disorders (PTLD) are rare. This retrospective, multicenter study of 35 cases aimed to better describe this entity. Cases were (re)-classified according to the WHO-EORTC or the WHO 2008 classifications of lymphomas. Median interval between first transplantation and diagnosis was 85 months. Fifty-seven percent of patients had a kidney transplant. Twenty-four cases (68.6%) were classified as primary cutaneous T cell lymphoma (CTCL) and 11 (31.4%) as primary cutaneous B cell PTLD. Mycosis fungoides (MF) was the most common (50%) CTCL subtype. Ten (90.9%) cutaneous B cell PTLD cases were classified as EBV-associated B cell lymphoproliferations (including one plasmablastic lymphoma and one lymphomatoid granulomatosis) and one as diffuse large B cell lymphoma, other, that was EBV-negative. Sixteen (45.7%) patients died after a median follow-up of 19.5 months (11 [68.8%] with CTCL [6 of whom had CD30(+) lymphoproliferative disorders (LPD)] and 5 [31.2%] with cutaneous B cell PTLD. Median survival times for all patients, CTCL and cutaneous B cell PTLD subgroups were 93, 93, and 112 months, respectively. Survival rates for MF were higher than those for CD30(+) LPD. The spectrum of primary CTCL in organ transplant recipients (OTR) is similar to that in the general population. The prognosis of posttransplant primary cutaneous CD30(+) LPD is worse than posttransplant MF and than its counterpart in the immunocompetent population. EBV-associated cutaneous B cell LPD predominates in OTR.

Calceology : an introduction to North Western European archaeological leather footwear (Neolithic period to c. AD 1600)

Calceology is the study of recovered archaeological leather footwear and is comprised of conservation, documentation and identification of leather shoe components and shoe styles. Recovered leather shoes are complex artefacts that present technical, stylistic and personal information about the culture and people that used them. The current method in calceological research for typology and chronology is by comparison with parallel examples, though its use poses problems by an absence of basic definitions and the lack of a taxonomic hierarchy. The research findings of the primary cutting patterns, used for making all leather footwear, are integrated with the named style method and the Goubitz notation, resulting in a combined methodology as a basis for typological organisation for recovered footwear and a chronology for named shoe styles. The history of calceological research is examined in chapter two and is accompanied by a review of methodological problems as seen in the literature. Through the examination of various documentation and research techniques used during the history of calceological studies, the reasons why a standard typology and methodology failed to develop are investigated. The variety and continual invention of a new research method for each publication of a recovered leather assemblage hindered the development of a single standard methodology. Chapter three covers the initial research with the database through which the primary cutting patterns were identified and the named styles were defined. The chronological span of each named style was established through iterative cross-site sedation and named style comparisons. The technical interpretation of the primary cutting patterns' consistent use is due to constraints imposed by the leather and the forms needed to cover the foot. Basic parts of the shoe patterns and the foot are defined, plus terms provided for identifying the key points for pattern making. Chapter four presents the seventeen primary cutting patterns and their sub-types, these are divided into three main groups: six integral soled patterns, four hybrid soled patterns and seven separately soled patterns. Descriptions of the letter codes, pattern layout, construction principle, closing seam placement and list of sub-types are included in the descriptions of each primary cutting pattern. The named shoe styles and their relative chronology are presented in chapter five. Nomenclature for the named styles is based on the find location of the first published example plus the primary cutting pattern code letter. The named styles are presented in chronological order from Prehistory through to the late 16th century. Short descriptions of the named styles are given and illustrated with examples of recovered archaeological leather footwear, reconstructions of archaeological shoes and iconographical sources. Chapter six presents documentation of recovered archaeological leather using the Goubitz notation, an inventory and description of style elements and fastening methods used for defining named shoe styles, technical information about sole/upper constructions and the consequences created by the use of lasts and sewing forms for style identification and fastening placement in relation to the instep point. The chapter concludes with further technical information about the implications for researchers about shoemaking, pattern making and reconstructive archaeology. The conclusion restates the original research question of why a group of primary cutting patterns appear to have been used consistently throughout the European archaeological record. The quantitative and qualitative results from the database show the use of these patterns but it is the properties of the leather that imposes the use of the primary cutting patterns. The combined methodology of primary pattern identification, named style and artefact registration provides a framework for calceological research.

How political parties, rather than member-states, are building the European Union

Political party formation and coalition building in the European Parliament is being a driving force for making governance of the highly pluralistic European Union relatively effective and consensual. In spite of successive enlargements and the very high number of electoral partiesobtaining representation in the European Union institutions, the number of effective European Political Groups in the European Parliament has decreased from the first direct election in 1979 to the fifth in 1999. The formal analysis of national party¹s voting power in different Europeanparty configurations can explain the incentives for national parties to join large European Political Groups instead of forming smaller nationalistic groupings. Empirical evidence shows increasing cohesion of European Political Groups and an increasing role of the European Parliament in EU inter-institutional decision making. As a consequence of this evolution, intergovernmentalism is being replaced with federalizing relations. The analysis can support positive expectations regarding the governability of the European Union after further enlargements provided that new member states have party systems fitting the European PoliticalGroups.

Survey on batch-to-batch variation in spray paints: a collaborative study

This study represents the most extensive analysis of batch-to-batch variations in spray paint samples to date. The survey was performed as a collaborative project of the ENFSI (European Network of Forensic Science Institutes) Paint and Glass Working Group (EPG) and involved 11 laboratories. Several studies have already shown that paint samples of similar color but from different manufacturers can usually be differentiated using an appropriate analytical sequence. The discrimination of paints from the same manufacturer and color (batch-to-batch variations) is of great interest and these data are seldom found in the literature. This survey concerns the analysis of batches from different color groups (white, papaya (special shade of orange), red and black) with a wide range of analytical techniques and leads to the following conclusions. Colored batch samples are more likely to be differentiated since their pigment composition is more complex (pigment mixtures, added pigments) and therefore subject to variations. These variations may occur during the paint production but may also occur when checking the paint shade in quality control processes. For these samples, techniques aimed at color/pigment(s) characterization (optical microscopy, microspectrophotometry (MSP), Raman spectroscopy) provide better discrimination than techniques aimed at the organic (binder) or inorganic composition (fourier transform infrared spectroscopy (FTIR) or elemental analysis (SEM - scanning electron microscopy and XRF - X-ray fluorescence)). White samples contain mainly titanium dioxide as a pigment and the main differentiation is based on the binder composition (Csingle bondH stretches) detected either by FTIR or Raman. The inorganic composition (elemental analysis) also provides some discrimination. Black samples contain mainly carbon black as a pigment and are problematic with most of the spectroscopic techniques. In this case, pyrolysis-GC/MS represents the best technique to detect differences. Globally, Py-GC/MS may show a high potential of discrimination on all samples but the results are highly dependent on the specific instrumental conditions used. Finally, the discrimination of samples when data was interpreted visually as compared to statistically using principal component analysis (PCA) yielded very similar results. PCA increases sensitivity and could perform better on specific samples, but one first has to ensure that all non-informative variation (baseline deviation) is eliminated by applying correct pre-treatments. Statistical treatments can be used on a large data set and, when combined with an expert's opinion, will provide more objective criteria for decision making.

Transmitted drug resistant HIV-1 and association with virologic and CD4 cell count response to combination antiretroviral therapy in the EuroSIDA Study.

OBJECTIVES: To investigate prevalence of transmitted drug-resistant human immunodeficiency virus (TDR) and factors associated with TDR and to compare virological and CD4 count response to combination antiretroviral therapy. METHODS: In this study, 525 mostly chronically infected EuroSIDA patients were included who had genotypic resistance tests performed on plasma samples collected while antiretroviral therapy naive. TDR was defined as at least one resistance mutation from a list proposed for genotypic TDR surveillance. Multivariable logistic regression was used to analyze factors associated with detection of TDR, with virological (viral load<500 copies/mL) and CD4 count response (>or=50% increase) to combination antiretroviral therapy at months 6-12. RESULTS: The overall prevalence of TDR was 11.4%, which was stable over 1996-2004. There were no significant differences in virological suppression (those resistant to at least one drug prescribed versus susceptible), adjusted odds ratio: 0.68 (95% confidence interval: 0.27 to 1.71; P=0.408) or CD4 count response, adjusted odds ratio: 1.65 (95% confidence interval: 0.73 to 3.73; P=0.231). CONCLUSIONS: Prevalence of TDR in antiretroviral-naive patients was found to be in line with other European studies. No significant differences were found in virological and CD4 count response after initiation of first-line combination antiretroviral therapy between resistant and susceptible patients, possibly due to the small number of patients with resistance and consequently low power.

Economic integration and corruption: The corrupt soul of the European Union

We study the link between corruption and economic integration. We show that if an economic union establishes a common regulation for public procurement, the country more prone to corruption benefits more from integration. However, if the propensities to corruption are too distinct, the less corrupt country will not be willing to join the union. This difference in corruption propensities can be offset by a difference in efficiency. We also show that corruption is lower if integration occurs. A panel data analysis for the European Union confirms that more corrupt countries are more favorable towards integration but less acceptable as potential new members.

Epidemiologic study of low back pain in 1398 Swiss conscripts between 1985 and 1992.

The two objectives of this study, based on a sample of 1398 Swiss army conscripts born in 1966 who participated in a first study in 1985, were to measure the prevalence of low back pain (LBP) at age 26 years and its incidence between 19 and 26 years and to analyze the relationship between LBP and occupational, nonoccupational, or physical risk factors. The lifetime prevalence of LBP at age 26 was 69.1% and the incidence of LBP between 19 and 26, 44.7%. A history of LBP or a pathological physical examination result at age 19 did not predict the prevalence or the incidence at age 26. Standing, twisting, vibration, and heavy work were significantly associated with chronic LBP and/or the 1-year prevalence of LBP at age 26 (P < 0.05). The evolution of sport and leisure-time activities from age 19 to 26 did not differ between people with or without LBP. The ergonomic organization of the workplace should represent a major element of future strategies to prevent LBP.

Cape Verde - Diagnostic Trade Inttegration study Update - 2013

This Report is an update of the Cape Verde Diagnostic Trade Integration Study, titled Cape Verde’s Insertion into the Global Economy, produced and validated by the Government of Cape Verde in December 2008. Like the previous 2008 study, this Cape Verde Diagnostic Trade Integration Study Update provides a critical examination of the major institutional and production constraints that hinder Cape Verde’s ability to capitalize fully on the growth and welfare gains from its integration into the world economy. As a policy report, this study offers a set of priority policies and measures that can be implemented by both the public and private sectors to mitigate and surmount these supply side and institutional constraints. These recommendations are summarized in an Action Matrix. The Report is fruit of the generous support of the multi-donor program the Enhanced Integrated Framework (EIF). In every crisis there is an opportunity. Four years after the validation of the country’s first Diagnostic Trade Integration Study in 2008, Cape Verde finds itself in a drastically altered external environment. Cape Verde faces a worsened external environment than four years ago, when it was also traversing years of crisis as global food and energy prices escalated. Just as the country was validating its first trade study in late 2008, and celebrating its graduation from the list of Least Developed Countries, the onset of the deepest global recession in recent memory triggered an even worse external situation as the country’s principal source of markets, investments, remittances and aid, the Eurozone, unraveled economically and politically. As the Eurozone crisis spread, it was Cape Verde’s misfortune that the crisis contaminated precisely its biggest Eurozone partners and donors, such as Portugal, Spain and Italy. For such a highly dependent and exposed economy like that of Cape Verde, the deteriorating external sector has had a substantial negative impact on its macroeconomic performance. At the time of the validation workshop and graduation in 2008, no one could have foreseen or predicted the severity of the global crisis that followed. Despite traversing these years of adversity and external shocks, and suffering palpable setbacks, Cape Verde’s economy had proven surprisingly resilient, especially its principal sector, tourism. To its great credit, the country’s economic fundamentals are solid, and have been carefully and prudently managed over the years. For this reason alone, the country has thus far weathered the global and Eurozone crisis. Yet the near and medium term future remains uncertain. The country’s margin for maneuver has narrowed, its options far more limited, and hard choices lie ahead. Thus, there is no better time than now to analyze Cape Verde’s position in the global economy, and to examine the many challenges and opportunities it faces. The first diagnostic trade study outlined an ambitious agenda and set of policy strategies to enhance Cape Verde’s participation in the global economy. Written prior to the global crisis, the study did not, and could not, anticipate the scope and depth of the subsequent global and Eurozone crises. A few short months before the validation of the first DTIS Cape Verde joined the World Trade Organization (WTO). It has spent these four years adjusting to this status and implementing its commitments. At the same time, the country seeks greater economic integration with the European Union. Since 2008 the government has been investing heavily in the country’s economic infrastructure, focusing especially on fostering transformation in key sectors like agriculture, fisheries, tourism and creative industries. For these and many other reasons, it is both timely and urgent to review the road traveled since 2008. It is an opportune moment to reassess the country’s options, to rethink strategies, and to chart a new way forward that it is practical, implementable, and that builds on the country’s competitive advantages and current successes.

Genomewide association study using a high-density single nucleotide polymorphism array and case-control design identifies a novel essential hypertension susceptibility locus in the promoter region of endothelial NO synthase.

Essential hypertension is a multifactorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a 2-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions. The discovery phase consisted of 1865 cases and 1750 controls genotyped with 1M Illumina array. Best hits were followed up in a validation panel of 1385 cases and 1246 controls that were genotyped with a custom array of 14 055 markers. We identified a new hypertension susceptibility locus (rs3918226) in the promoter region of the endothelial NO synthase gene (odds ratio: 1.54 [95% CI: 1.37-1.73]; combined P=2.58 · 10(-13)). A meta-analysis, using other in silico/de novo genotyping data for a total of 21 714 subjects, resulted in an overall odds ratio of 1.34 (95% CI: 1.25-1.44; P=1.032 · 10(-14)). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI: 0.16-3.66) for systolic and 1.40 (95% CI: 0.25-2.55) for diastolic blood pressure. We identified in silico a potential binding site for ETS transcription factors directly next to rs3918226, suggesting a potential modulation of endothelial NO synthase expression. Biological evidence links endothelial NO synthase with hypertension, because it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus.

Tectonics of the Simplon massif and Lepontine gneiss dome: deformation structures due to collision between the underthrusting European plate and the Adriatic indenter

this study presents a review of published geological data, combined with original observations on the tectonics of the simplon massif and the Lepontine gneiss dome in the Western Alps. New observations concern the geometry of the Oligocene Vanzone back fold, formed under amphibolite facies conditions, and of its root between Domodossola and Locarno, which is cut at an acute angle by the Miocene, epi- to anchizonal, dextral centovalli strike-slip fault. the structures of the simplon massif result from collision over 50 Ma between two plate boundaries with a different geometry: the underthrusted European plate and the Adriatic indenter. Detailed mapping and analysis of a complex structural interference pattern, combined with observations on the metamorphic grade of the superimposed structures and radiometric data, allow a kinematic model to be developed for this zone of oblique continental collision. the following main Alpine tectonic phases and structures may be distinguished: 1. NW-directed nappe emplacement, starting in the Early Eocene (similar to 50 Ma); 2. W, SW and S- verging transverse folds; 3. transpressional movements on the dextral simplon ductile shear zone since similar to 32 Ma; 4. formation of the Bergell - Vanzone backfolds and of the southern steep belt during the Oligocene, emplacement of the mantle derived 31 - 29 Ma Bergell and Biella granodiorites and porphyritic andesites as well as intrusions of 29-25 Ma crustal aplites and pegmatites; 5. formation of the dextral discrete Rhone-Simplon line and the centovalli line during the Miocene, accompanied by the pull-apart development of the Lepontine gneiss dome - Dent blanche (Valpelline) depression. It is suggested that movements of shortening in fan shaped NW, W and sW directions accompanied the more regular NW- to WNW-directed displacement of the Adriatic indenter during continental collision.

Granulomatosis-associated common variable immunodeficiency disorder: a case-control study versus sarcoidosis.

The aim of the present study was to investigate to what extent interstitial lung disease (ILD) in common variable immunodeficiency disorder (CVID)-associated granulomatous disease (GD) is similar to pulmonary sarcoidosis 20 patients with CVID/GD were included in a retrospective study conducted by the Groupe Sarcoïdose Francophone. Medical records were centralised. Patients were compared with 60 controls with sarcoidosis. Clinical examination showed more frequent crackles in patients than controls (45% versus 1.7%, respectively; p<0.001). On thoracic computed tomography scans, nodules (often multiple and with smooth margins), air bronchograms and halo signs were more frequent in patients than controls (80% versus 42%, respectively; p=0.004) as well as bronchiectasis (65% versus 23%, respectively; p<0.001). The micronodule distribution was perilymphatic in 100% of controls and in 42% of patients (p<0.001). Bronchoalveolar lavage analysis showed lower T-cell CD4/CD8 ratios in patients than in controls (mean±sd 1.6±1.1 versus 5.3±4, respectively; p<0.01). On pathological analysis, nodules and consolidations corresponded to granulomatous lesions with or without lymphocytic disorders in most cases. Mortality was higher in patients than controls (30% versus 0%, respectively) and resulted from common variable immunodeficiency complications. ILD in CVID/GD presents a specific clinical picture and evolution that are markedly different from those of sarcoidosis.

Superficial soft tissue sarcomas (S-STS): a study of 367 patients from the French Sarcoma Group (FSG) database.

AIM: The specific natural history of superficial soft tissue sarcomas (S-STS) has been rarely considered. We describe the clinical characteristics of a large series of S-STS (N=367) from the French Sarcoma Group (GSF-GETO) database and analyse the prognostic factors affecting outcome. METHODS: We performed univariate and multivariate analyses for overall survival (OS), metastasis-free survival (MFS) and local recurrence-free survival (LRFS). RESULTS: The median age was 59 years. Fifty-eight percent patients were female. Tumour locations were as follows: extremities, 55%; trunk wall, 35.4%; head and neck, 8% and unknown, 1.6%. Median tumour size was 3.0 cm. The most frequent tumour types were unclassified sarcoma (24.3%) and leiomyosarcoma (22.3%). Thirty-three percent of cases were grade 3. Median follow-up was 6.18 years. The 5-year OS, MFS and LRFS rates were 80.9%, 80.7% and 74.7%, respectively. Multivariate analysis retained histological type and wide resection for predicting LRFS and histological type and grade as prognostic factors of MFS. The factors influencing OS were age, histological type, grade and wide resection. STS with early invasion into but not through the underlying fascia had a significantly poorer MFS than with strict S-STS. CONCLUSION: S-STS represent a separate category characterised by a better outcome. Adequate surgery, i.e. wide resection, is essential in the management of S-STS.