Subclinical hypothyroidism and the risk of coronary heart disease and mortality.

CONTEXT: Data regarding the association between subclinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospective cohort studies. This might reflect differences in participants' age, sex, thyroid-stimulating hormone (TSH) levels, or preexisting cardiovascular disease. OBJECTIVE: To assess the risks of coronary heart disease (CHD) and total mortality for adults with subclinical hypothyroidism. DATA SOURCES AND STUDY SELECTION: The databases of MEDLINE and EMBASE (1950 to May 31, 2010) were searched without language restrictions for prospective cohort studies with baseline thyroid function and subsequent CHD events, CHD mortality, and total mortality. The reference lists of retrieved articles also were searched. DATA EXTRACTION: Individual data on 55,287 participants with 542,494 person-years of follow-up between 1972 and 2007 were supplied from 11 prospective cohorts in the United States, Europe, Australia, Brazil, and Japan. The risk of CHD events was examined in 25,977 participants from 7 cohorts with available data. Euthyroidism was defined as a TSH level of 0.50 to 4.49 mIU/L. Subclinical hypothyroidism was defined as a TSH level of 4.5 to 19.9 mIU/L with normal thyroxine concentrations. RESULTS: Among 55,287 adults, 3450 had subclinical hypothyroidism (6.2%) and 51,837 had euthyroidism. During follow-up, 9664 participants died (2168 of CHD), and 4470 participants had CHD events (among 7 studies). The risk of CHD events and CHD mortality increased with higher TSH concentrations. In age- and sex-adjusted analyses, the hazard ratio (HR) for CHD events was 1.00 (95% confidence interval [CI], 0.86-1.18) for a TSH level of 4.5 to 6.9 mIU/L (20.3 vs 20.3/1000 person-years for participants with euthyroidism), 1.17 (95% CI, 0.96-1.43) for a TSH level of 7.0 to 9.9 mIU/L (23.8/1000 person-years), and 1.89 (95% CI, 1.28-2.80) for a TSH level of 10 to 19.9 mIU/L (n = 70 events/235; 38.4/1000 person-years; P <.001 for trend). The corresponding HRs for CHD mortality were 1.09 (95% CI, 0.91-1.30; 5.3 vs 4.9/1000 person-years for participants with euthyroidism), 1.42 (95% CI, 1.03-1.95; 6.9/1000 person-years), and 1.58 (95% CI, 1.10-2.27, n = 28 deaths/333; 7.7/1000 person-years; P = .005 for trend). Total mortality was not increased among participants with subclinical hypothyroidism. Results were similar after further adjustment for traditional cardiovascular risk factors. Risks did not significantly differ by age, sex, or preexisting cardiovascular disease. CONCLUSIONS: Subclinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels, particularly in those with a TSH concentration of 10 mIU/L or greater.

HIV-1 coreceptor usage and CXCR4-specific viral load predict clinical disease progression during combination antiretroviral therapy

Background: Although combination antiretroviral therapy (cART) dramatically reduces rates of AIDS and death, a minority of patients experience clinical disease progression during treatment. <p>Objective: To investigate whether detection of CXCR4(X4)-specific strains or quantification of X4-specific HIV-1 load predict clinical outcome. Methods: From the Swiss HIV Cohort Study, 96 participants who initiated cART yet subsequently progressed to AIDS or death were compared with 84 contemporaneous, treated nonprogressors. A sensitive heteroduplex tracking assay was developed to quantify plasma X4 and CCR5 variants and resolve HIV-1 load into coreceptor-specific components. Measurements were analyzed as cofactors of progression in multivariable Cox models adjusted for concurrent CD4 cell count and total viral load, applying inverse probability weights to adjust for sampling bias. Results: Patients with X4 variants at baseline displayed reduced CD4 cell responses compared with those without X4 strains (40 versus 82 cells/mu l; P= 0.012). The adjusted multivariable hazard ratio (HR) for clinical progression was 4.8 [95% confidence interval (Cl) 2.3-10.0] for those demonstrating X4 strains at baseline. The X4-specific HIV-1 load was a similarly independent predictor, with HR values of 3.7(95%Cl, 1.2-11.3) and 5.9 (95% Cl, 2.2-15.0) for baseline loads of 2.2-4.3 and > 4.3 log(10)copies/ml, respectively, compared with < 2.2 log(10)copies/ml. Conclusions: HIV-1 coreceptor usage and X4-specific viral loads strongly predicted disease progression during cART, independent of and in addition to CD4 cell count or total viral load. Detection and quantification of X4 strains promise to be clinically useful biomarkers to guide patient management and study HIV-1 pathogenesis.

Central corneal thickness, intraocular pressure, and degree of myopia in an adult myopic population aged 20 to 40 years in southeast Spain: determination and relationships.

Objective: To determine the values of, and study the relationships among, central corneal thickness (CCT), intraocular pressure (IOP), and degree of myopia (DM) in an adult myopic population aged 20 to 40 years in Almeria (southeast Spain). To our knowledge this is first study of this kind in this region. Methods: An observational, descriptive, cross-sectional study was done in which a sample of 310 myopic patients (620 eyes) aged 20 to 40 years was selected by gender- and age-stratified sampling, which was proportionally fixed to the size of the population strata for which a 20% prevalence of myopia, 5% epsilon, and a 95% confidence interval were hypothesized. We studied IOP, CCT, and DM and their relationships by calculating the mean, standard deviation, 95% confidence interval for the mean, median, Fisher’s asymmetry coefficient, range (maximum, minimum), and the Brown-Forsythe’s robust test for each variable (IOP, CCT, and DM). Results: In the adult myopic population of Almeria aged 20 to 40 years (mean of 29.8), the mean overall CCT was 550.12 μm. The corneas of men were thicker than those of women (P = 0.014). CCT was stable as no significant differences were seen in the 20- to 40-year-old subjects’ CCT values. The mean overall IOP was 13.60 mmHg. Men had a higher IOP than women (P = 0.002). Subjects over 30 years (13.83) had a higher IOP than those under 30 (13.38) (P = 0.04). The mean overall DM was −4.18 diopters. Men had less myopia than women (P < 0.001). Myopia was stable in the 20- to 40-year-old study population (P = 0.089). A linear relationship was found between CCT and IOP (R2 = 0.152, P ≤ 0.001). CCT influenced the IOP value by 15.2%. However no linear relationship between DM and IOP, or between CCT and DM, was found. Conclusions: CCT was found to be similar to that reported in other studies in different populations. IOP tends to increase after the age of 30 and is not accounted for by alterations in CCT values.

Real-life versus package insert: a post-marketing study on adverse-event rates of the virosomal hepatitis A vaccine Epaxal® in healthy travellers.

There are various methods to collect adverse events (AEs) in clinical trials. The methods how AEs are collected in vaccine trials is of special interest: solicited reporting can lead to over-reporting events that have little or no biological relationship to the vaccine. We assessed the rate of AEs listed in the package insert for the virosomal hepatitis A vaccine Epaxal(®), comparing data collected by solicited or unsolicited self-reporting. In an open, multi-centre post-marketing study, 2675 healthy travellers received single doses of vaccine administered intramuscularly. AEs were recorded based on solicited and unsolicited questioning during a four-day period after vaccination. A total of 2541 questionnaires could be evaluated (95.0% return rate). Solicited self-reporting resulted in significantly higher (p<0.0001) rates of subjects with AEs than unsolicited reporting, both at baseline (18.9% solicited versus 2.1% unsolicited systemic AEs) and following immunization (29.6% versus 19.3% local AEs; 33.8% versus 18.2% systemic AEs). This could indicate that actual reporting rates of AEs with Epaxal(®) may be substantially lower than described in the package insert. The distribution of AEs differed significantly between the applied methods of collecting AEs. The most common AEs listed in the package insert were reported almost exclusively with solicited questioning. The reporting of local AEs was more likely than that of systemic AEs to be influenced by subjects' sex, age and study centre. Women reported higher rates of AEs than men. The results highlight the need for detailing the methods how vaccine tolerability was reported and assessed.

Prevalence and determinants of AK in Euromelanoma screenees

Actinic keratosis (AK) is the most common skin lesion with malignant potential, and one of the main reasons for consulting a dermatologist. Found predominantly on sun-exposed body sites in fairskinned, older and male subjects, AK is among the strongest predictors of skin cancer, and a precursor of SCC. However, estimates of prevalence and study of determinants of AK are relatively scarce and generally based on small, hospital-based series. Clinical suspicion of AK is a reliable predictor of diagnosis. The presence of AK is documented by dermatologists during the Euromelanoma screening examinations so that the Euromelanoma database probably constitutes the largest series of AK cases worldwide. This study aimed at (1) describing the prevalence and risk pattern of AK among Euromelanoma screenees during the 2009-2013 time period, and (2) identifying determinants of AK by means of multivariate analysis. In particular, the contribution of host characteristics, sun exposure and sunrelated behaviour to the risk of AK was explored. Results will be discussed in the light of this large, self-selected, Pan-European series.

Introduction to University and the ICT Sector

The innovative subject “Introduction to ICT” combines a general Introductory Course to the University with elements around the Information and Communication Technologies sector (including the ICT engineer competence profile, market aspects, etc.)This new course has been developed and implemented in three degree programmes offered by the Polytechnic School at Universitat Pompeu Fabra, Barcelona. The course team consists of thirteen teachers,including business professionals, librarians, computer technicians, institutional representatives as well as an educationalist responsible for advising on methodology and study techniques. The subject was designed for a high number of students (260). At the end of the course, we collected quantitative and qualitativeinformation about the students’ satisfaction. The findings show the positive vision that they had about the topics worked during the subject. This paper describes the course, its implementation and evaluation and, of course, the details of the findings that we collected about students' satisfaction.

A two-stage approach for tonic identification in indian art music

In this paper we propose a new approach for tonic identification in Indian art music and present a proposal for acomplete iterative system for the same. Our method splits the task of tonic pitch identification into two stages. In the first stage, which is applicable to both vocal and instrumental music, we perform a multi-pitch analysis of the audio signal to identify the tonic pitch-class. Multi-pitch analysisallows us to take advantage of the drone sound, which constantlyreinforces the tonic. In the second stage we estimate the octave in which the tonic of the singer lies and is thusneeded only for the vocal performances. We analyse the predominant melody sung by the lead performer in order to establish the tonic octave. Both stages are individually evaluated on a sizable music collection and are shown toobtain a good accuracy. We also discuss the types of errors made by the method.Further, we present a proposal for a system that aims to incrementally utilize all the available data, both audio and metadata in order to identify the tonic pitch. It produces a tonic estimate and a confidence value, and is iterative in nature. At each iteration, more data is fed into the systemuntil the confidence value for the identified tonic is above a defined threshold. Rather than obtain high overall accuracy for our complete database, ultimately our goal is to develop a system which obtains very high accuracy on a subset of the database with maximum confidence.

Appropriateness of colonoscopy in Europe (EPAGE II): presentation of methodology, general results, and analysis of complications.

BACKGROUND AND STUDY AIMS: Appropriate use of colonoscopy is a key component of quality management in gastrointestinal endoscopy. In an update of a 1998 publication, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE II) defined appropriateness criteria for various colonoscopy indications. This introductory paper therefore deals with methodology, general appropriateness, and a review of colonoscopy complications. METHODS:The RAND/UCLA Appropriateness Method was used to evaluate the appropriateness of various diagnostic colonoscopy indications, with 14 multidisciplinary experts using a scale from 1 (extremely inappropriate) to 9 (extremely appropriate). Evidence reported in a comprehensive updated literature review was used for these decisions. Consolidation of the ratings into three appropriateness categories (appropriate, uncertain, inappropriate) was based on the median and the heterogeneity of the votes. The experts then met to discuss areas of disagreement in the light of existing evidence, followed by a second rating round, with a subsequent third voting round on necessity criteria, using much more stringent criteria (i. e. colonoscopy is deemed mandatory). RESULTS: Overall, 463 indications were rated, with 55 %, 16 % and 29 % of them being judged appropriate, uncertain and inappropriate, respectively. Perforation and hemorrhage rates, as reported in 39 studies, were in general < 0.1 % and < 0.3 %, respectively CONCLUSIONS: The updated EPAGE II criteria constitute an aid to clinical decision-making but should in no way replace individual judgment. Detailed panel results are freely available on the internet (www.epage.ch) and will thus constitute a reference source of information for clinicians.

A non-interventional phase IV Belgian survey to assess the antiviral effectiveness of pegylated interferon-alpha-2b and ribavirin treatment according to the stage of liver fibrosis in previously untreated patients with genotype 1/4/5/6 chronic hepatitis C (PRACTICE).

BACKGROUND AND STUDY AIMS: This was an observational, non-interventional, multicenter, phase IV study, in patients with genotype 1/4/5/6 chronic hepatitis C (CHC). The primary objectives were to evaluate SVR in patients with no or minimal fibrosis (METAVIR F0-F1) versus well established fibrosis (F2-F4), and to estimate response on Weeks 12, 24 and 48 on treatment in previously untreated patients with genotypes 1/4/5/6 CHC. PATIENTS AND METHODS: 538 patients treated with pegylated interferon alfa 2b 1.5 mcg/kg in combination with ribavirin 800-1200 mg/day were enrolled in 55 sites in Belgium and Luxembourg, 505 being considered for the analysis. 40% of the patients were female and 60% male, the average age was 47.5 years, 10.5% were 65 or older. RESULTS: SVR was observed in 35% of the patients, EVR in 68%, of which pEVR in 33% and cEVR in 35%. SVR was observed in 43% of the low fibrosis group (F0, F1) and 30% of the high fibrosis group (F2, F3, F4) (p = 0.005). SVR rates were 34% for genotype 1, 37% for genotype 4, and 47% for genotype 5 (NS). Multivariate analysis showed that EVR and baseline METAVIR score are independent prognostic factors for SVR. CONCLUSIONS: This trial confirms that fibrosis stage and early viral response are the most important key-factors to predict sustained response, suggesting that the earlier patients are treated, the better the outcome. Non-invasive techniques enable us to closely monitor progression of fibrosis, allowing a better selection of patients for antiviral treatment in the DAA-era.

Money, Fame and the Allocation of Talent: Brain Drain, the Matthew Effect and the Institution of Science

The earning structure in science is known to be flat relative to the one in the private sector, which could cause a brain drain toward the private sector. In this paper, we assume that agents value both money and fame and study the role of the institution of science in the allocation of talent between the science sector and the private sector. Following works on the Sociology of Science, we model the institution of science as a mechanism distributing fame (i.e. peer recognition). We show that since the intrinsic performance is less noisy signal of talent in the science sector than in the private sector, a good institution of science can mitigate the brain drain. We also find that providing extra monetary incentives through the market might undermine the incentives provided by the institution and thereby worsen the brain drain. Finally, we study the optimal balance between monetary and non-monetary incentives in science.

Valuation bubbles and sequential bubbles

Price bubbles in an Arrow-Debreu valuation equilibrium in infinite-timeeconomy are a manifestation of lack of countable additivity of valuationof assets. In contrast, known examples of price bubbles in sequentialequilibrium in infinite time cannot be attributed to the lack of countableadditivity of valuation. In this paper we develop a theory of valuation ofassets in sequential markets (with no uncertainty) and study the nature ofprice bubbles in light of this theory. We consider an operator, calledpayoff pricing functional, that maps a sequence of payoffs to the minimumcost of an asset holding strategy that generates it. We show that thepayoff pricing functional is linear and countably additive on the set ofpositive payoffs if and only if there is no Ponzi scheme, and providedthat there is no restriction on long positions in the assets. In the knownexamples of equilibrium price bubbles in sequential markets valuation islinear and countably additive. The presence of a price bubble indicatesthat the asset's dividends can be purchased in sequential markers at acost lower than the asset's price. We also present examples of equilibriumprice bubbles in which valuation is nonlinear but not countably additive.

Optimal monetary and fiscal policy in a currency union

We lay out a tractable model for fiscal and monetary policy analysis in a currency union, and study its implications for the optimal design of such policies. Monetary policy is conducted by a common central bank, which sets the interest rate for the union as a whole. Fiscal policy is implemented at the countrylevel, through the choice of government spending. The model incorporates country-specific shocks and nominal rigidities. Under our assumptions, the optimal cooperative policy arrangement requires that inflation be stabilized at the union level by the common central bank, while fiscal policy is used by each country for stabilization purposes. By contrast, when the fiscal authorities act in a non-coordinated way, their joint actions lead to a suboptimal outcome, and make the common central bank face a trade-off between inflation and output gap stabilization at the union level.

Money, fame and the allocation of talent: Brain drain and the institution of science

The earning structure in science is known to be flat relative to the one in theprivate sector, which could cause a brain drain toward the private sector. In thispaper, we assume that agents value both money and fame and study the role ofthe institution of science in the allocation of talent between the science sector andthe private sector. Following works on the Sociology of Science, we model theinstitution of science as a mechanism distributing fame (i.e. peer recognition). Weshow that since the intrinsic performance is less noisy signal of talent in the sciencesector than in the private sector, a good institution of science can mitigate thebrain drain. We also find that providing extra monetary incentives through themarket might undermine the incentives provided by the institution and therebyworsen the brain drain. Finally, we study the optimal balance between monetaryand non-monetary incentives in science.

Monetary policy shocks and transmission in Italy: A VAR analysis

This paper provides updated empirical evidence about the real and nominal effects of monetary policy in Italy, by using structural VAR analysis. We discuss different empirical approaches that have been used in order to identify monetary policy exogenous shocks. We argue that the data support the view that the Bank of Italy, at least in the recent past, has been targeting the rate on overnight interbank loans. Therefore, we interpret shocks to the overnight rate as purely exogenous monetary policy shocks and study how different macroeconomic variables react to such shocks.

Pre-analytical and methodological challenges in red blood cell microparticle proteomics.

Microparticles are phospholipid vesicles shed mostly in biological fluids, such as blood or urine, by various types of cells, such as red blood cells (RBCs), platelets, lymphocytes, endothelial cells. These microparticles contain a subset of the proteome of their parent cell, and their ready availability in biological fluid has raised strong interest in their study, as they might be markers of cell damage. However, their small size as well as their particular physico-chemical properties makes them hard to detect, size, count and study by proteome analysis. In this review, we report the pre-analytical and methodological caveats that we have faced in our own research about red blood cell microparticles in the context of transfusion science, as well as examples from the literature on the proteomics of various kinds of microparticles.