Long diagnostic delay in Crohn's disease is associated with complicated disease course and increased operation rate

Background: We have recently shown that the median diagnostic delay to establish Crohn's disease (CD) diagnosis (i.e. the period from first symptom onset to diagnosis) in the Swiss IBD Cohort (SIBDC) was 9 months. Seventy five percent of all CD patients were diagnosed within 24 months. The clinical impact of a long diagnostic delay on the natural history of CD is unknown. Aim: To compare the frequency and type of CD-related complications in the patient groups with long diagnostic delay (>24 months) vs. the ones diagnosed within 24 months. Methods: Retrospective analysis of data from the SIBDCS, comprising a large sample of CD patients followed in hospitals and private practices across Switzerland. The proportions of the following outcomes were compared between groups of patients diagnosed 1, 2-5, 6-10, 11-15, and ≥ 16 years ago and stratified according to the length of diagnostic delay: bowel stenoses, internal fistulas, perianal fistulas, CD-related surgical interventions, and extraintestinal manifestations. Results: Two hundred CD patients (121 female, mean age 44.9 ± 15.0 years, 38% smokers, 71% ever treated with immunomodulators and 35% with anti-TNF) with long diagnostic delay were compared to 697 CD patients (358 female, mean age 39.1 ± 14.9 years, 33% smokers, 74% ever treated with immunomodulators and 33% with anti-TNF) diagnosed within 24 months. No differences in the outcomes were observed between the two patient groups within year one after CD diagnosis. Among those diagnosed 2-5 years ago, CD patients with long diagnostic delay (n = 45) presented more frequently with internal fistulas (11.1% vs. 3.1%, p = 0.03) and bowel stenoses (28.9% vs. 15.7%, p = 0.05), and they more frequently underwent CD-related operations (15.6% vs. 5.0%, p = 0.02) compared to the patients diagnosed within 24 months (n = 159). Among those diagnosed 6-10 years ago, CD patients with long diagnostic delay (n = 48) presented more frequently with extraintestinal manifestations (60.4% vs. 34.6%, p = 0.001) than those diagnosed within 24 months (n = 182). For the patients diagnosed 11-15 years ago, no differences in outcomes were found between the long diagnostic delay group (n = 106) and the one diagnosed within 24 months (n = 32). Among those diagnosed ≥ 16 years ago, the group with long diagnostic delay (n = 71) more frequently underwent CD-related operations (63.4% vs. 46.5%, p = 0.01) compared to the group diagnosed with CD within 24 months (n = 241). Conclusions: A long diagnostic delay in CD patients is associated with a more complicated disease course and higher number of CD-related operations in the years following the diagnosis. Our results indicate that efforts should be undertaken to shorten the diagnostic delay in CD patients in order to reduce the risk for progression towards a complicated disease phenotype.

Scaled and adjusted restricted tests in multi-sample analysis of moment structures

We extend to score, Wald and difference test statistics the scaled and adjusted corrections to goodness-of-fit test statistics developed in Satorra and Bentler (1988a,b). The theory is framed in the general context of multisample analysis of moment structures, under general conditions on the distribution of observable variables. Computational issues, as well as the relation of the scaled and corrected statistics to the asymptotic robust ones, is discussed. A Monte Carlo study illustrates thecomparative performance in finite samples of corrected score test statistics.

Bringing game theory to hypothesis testing: Establishing finite sample bounds on inference

Small sample properties are of fundamental interest when only limited data is avail-able. Exact inference is limited by constraints imposed by speci.c nonrandomizedtests and of course also by lack of more data. These e¤ects can be separated as we propose to evaluate a test by comparing its type II error to the minimal type II error among all tests for the given sample. Game theory is used to establish this minimal type II error, the associated randomized test is characterized as part of a Nash equilibrium of a .ctitious game against nature.We use this method to investigate sequential tests for the di¤erence between twomeans when outcomes are constrained to belong to a given bounded set. Tests ofinequality and of noninferiority are included. We .nd that inference in terms oftype II error based on a balanced sample cannot be improved by sequential sampling or even by observing counter factual evidence providing there is a reasonable gap between the hypotheses.

My older sibling was drunk - younger siblings' drunkenness in relation to parental monitoring and the parent-adolescent relationship.

This study explored the links between having older siblings who get drunk, satisfaction with the parent-adolescent relationship, parental monitoring, and adolescents' risky drinking. Regression models were conducted based on a national representative sample of 3725 8th to 10th graders in Switzerland (mean age 15.0, SD = .93) who indicated having older siblings. Results showed that both parental factors and older siblings' drinking behaviour shape younger siblings' frequency of risky drinking. Parental monitoring showed a linear dose-response relationship, and siblings' influence had an additive effect. There was a non-linear interaction effect between parent-adolescent relationship and older sibling's drunkenness. The findings suggest that, apart from avoiding an increasingly unsatisfactory relationship with their children, parental monitoring appears to be important in preventing risky drinking by their younger children, even if the older sibling drinks in such a way. However, a satisfying relationship with parents does not seem to be sufficient to counterbalance older siblings' influence.

Some hypothesis tests for the covariance matrix when the dimension is large compared to the sample size

This paper analyzes whether standard covariance matrix tests work whendimensionality is large, and in particular larger than sample size. Inthe latter case, the singularity of the sample covariance matrix makeslikelihood ratio tests degenerate, but other tests based on quadraticforms of sample covariance matrix eigenvalues remain well-defined. Westudy the consistency property and limiting distribution of these testsas dimensionality and sample size go to infinity together, with theirratio converging to a finite non-zero limit. We find that the existingtest for sphericity is robust against high dimensionality, but not thetest for equality of the covariance matrix to a given matrix. For thelatter test, we develop a new correction to the existing test statisticthat makes it robust against high dimensionality.

Robust response transformations based on optimal prediction

Nonlinear regression problems can often be reduced to linearity by transforming the response variable (e.g., using the Box-Cox family of transformations). The classic estimates of the parameter defining the transformation as well as of the regression coefficients are based on the maximum likelihood criterion, assuming homoscedastic normal errors for the transformed response. These estimates are nonrobust in the presence of outliers and can be inconsistent when the errors are nonnormal or heteroscedastic. This article proposes new robust estimates that are consistent and asymptotically normal for any unimodal and homoscedastic error distribution. For this purpose, a robust version of conditional expectation is introduced for which the prediction mean squared error is replaced with an M scale. This concept is then used to develop a nonparametric criterion to estimate the transformation parameter as well as the regression coefficients. A finite sample estimate of this criterion based on a robust version of smearing is also proposed. Monte Carlo experiments show that the new estimates compare favorably with respect to the available competitors.

The disturbing 'rise' of global income inequality

We use aggregate GDP data and within-country income shares for theperiod 1970-1998 to assign a level of income to each person in theworld. We then estimate the gaussian kernel density function for theworldwide distribution of income. We compute world poverty rates byintegrating the density function below the poverty lines. The $1/daypoverty rate has fallen from 20% to 5% over the last twenty five years.The $2/day rate has fallen from 44% to 18%. There are between 300 and500 million less poor people in 1998 than there were in the 70s.We estimate global income inequality using seven different popularindexes: the Gini coefficient, the variance of log-income, two ofAtkinson s indexes, the Mean Logarithmic Deviation, the Theil indexand the coefficient of variation. All indexes show a reduction in globalincome inequality between 1980 and 1998. We also find that most globaldisparities can be accounted for by across-country, not within-country,inequalities. Within-country disparities have increased slightly duringthe sample period, but not nearly enough to offset the substantialreduction in across-country disparities. The across-country reductionsin inequality are driven mainly, but not fully, by the large growth rateof the incomes of the 1.2 billion Chinese citizens. Unless Africa startsgrowing in the near future, we project that income inequalities willstart rising again. If Africa does not start growing, then China, India,the OECD and the rest of middle-income and rich countries diverge awayfrom it, and global inequality will rise. Thus, the aggregate GDP growthof the African continent should be the priority of anyone concerned withincreasing global income inequality.

Using composite estimators to improve both domain and total area estimation

In this article we propose using small area estimators to improve the estimatesof both the small and large area parameters. When the objective is to estimateparameters at both levels accurately, optimality is achieved by a mixed sampledesign of fixed and proportional allocations. In the mixed sample design, oncea sample size has been determined, one fraction of it is distributedproportionally among the different small areas while the rest is evenlydistributed among them. We use Monte Carlo simulations to assess theperformance of the direct estimator and two composite covariant-freesmall area estimators, for different sample sizes and different sampledistributions. Performance is measured in terms of Mean Squared Errors(MSE) of both small and large area parameters. It is found that the adoptionof small area composite estimators open the possibility of 1) reducingsample size when precision is given, or 2) improving precision for a givensample size.

O efeito do sorriso na percepção psicológica da pessoa

O objectivo do estudo foi o de verificar o efeito do sorriso na percepção psicológica da pessoa em jovens, adultos, idosos e jovens negros. Pretendia-se verificar se o sorriso contribui para os traços diferenciais entre os grupos humanos em estudo e se o mesmo era descritor de género. O estudo envolveu um delineamento transversal analítico ou estudo não-experimental, também classificado por estudo pós-facto, estudo de observação passiva ou estudo correlacional e de observação, de comparação entre grupos, mediante o juízo ou julgamento psicológico da face neutra e do tipo de sorriso contrastados, de matriz factorial 4 x 2 x 2 (face neutra, sorriso fechado, sorriso superior, sorriso largo; género dos estímulos; género dos respondentes) e a sua finalidade foi descrever a percepção psicológica do sorriso em função das variáveis género do estímulo, género do respondente e grupo étnico, na Escala de Percepção do Sorriso (EPS), em formato diferenciador semântico, com 19 itens bipolares opostos, tendo a avaliação sido feita numa escala ordinal de 1 a 7 pontos, nas dimensões Avaliação (12 itens) e Movimento Expressivo (7 itens) resultante dos estudos preliminares sobre a atractividade facial (estudo preliminar 1) e a escolha de dípolos de adjectivos preditores para percepção psicológica da face neutra (estudo preliminar 2). Nos estudos principais 1, 2 e 3 foram utilizados 24 estímulos fotográficos apresentando o tipo de sorriso (fechado, superior e largo) e a face neutra (12 do estímulo mulher e 12 do estímulo homem) referentes aos três grupos etários (18-25 anos, 40-50 anos e 60-70 anos) e a Escala de Percepção do Sorriso (EPS) foi aplicada a uma amostra não probabilística ou intencional do tipo homogénea de 480 participantes portugueses de ambos os géneros (240 mulheres e 240 homens) distribuídos por grupos etários de jovens (80 mulheres e 80 homens, média: 22.2 anos), adultos (80 mulheres e 80 homens, média: 43.1 anos) e idosos (80 mulheres e 80 homens, média: 65.0 anos) No estudo principal 4, foram utilizados 8 estímulos fotográficos apresentando o tipo de sorriso (fechado, superior e largo) e a face neutra (4 do estímulo mulher e 4 do estímulo homem) de universitários de Cabo Verde, a estudar em Portugal, e a Escala de Percepção do Sorriso (EPS) foi aplicada a uma amostra não probabilística ou intencional do tipo homogénea de 160 participantes de ambos os géneros (80 mulheres e 80 homens) e estudantes universitários portugueses (média: 21.8 anos). Os resultados revelam e confirmam o efeito do sorriso na percepção psicológica da pessoa, à semelhança de outros estudos, isto é, sorrir torna a percepção psicológica mais positiva ou negativa e verifica-se que tal sucede em função do género do estímulo e do género do respondente. As diferenças significativas na percepção da face neutra e tipo de sorriso contrastados são justificadas pela pertença de género de quem os percepciona e pela pertença do género de quem é percepcionado. Tal apenas não sucede no factor Avaliação do grupo dos adultos. Os resultados obtidos indicam que, quer no factor Avaliação quer no factor Movimento Expressivo, os tipos de sorriso largo e superior são os que registam médias ponderadas mais elevadas. Pelo contrário, a face neutra e o sorriso fechado registam valores menos elevados na percepção. A análise da percepção da pessoa em função da face neutra e tipo de sorriso contrastados revelou uma correspondência entre a expressão facial, o género do estímulo e o género do respondente. No factor Avaliação, a mulher é percepcionada mais positivamente que o homem, verificando-se o inverso no factor Movimento Expressivo no grupo dos adultos e dos idosos. Verificou-se efeito do sorriso na percepção psicológica dos estímulos de cor negra. No grupo dos jovens que percepcionaram estímulos de cor negra, o homem é considerado mais positivo que a mulher em ambos os factores. O efeito significativo do género revela que a sua percepção é condicionada pelo seu próprio género. Os resultados apontam ainda para a configuração pronunciada de uma hierarquização ascendente da face neutra e tipo de sorriso contrastados em dois conjuntos bem delimitados e distinguindo diferentes formas topográficas de sorrir: a face neutra e o sorriso fechado e o sorriso superior e o sorriso largo.

How wide is the gap? An investigation of gender wage differences using quantile regression

In this paper we examine the determinants of wages and decompose theobserved differences across genders into the "explained by differentcharacteristics" and "explained by different returns components"using a sample of Spanish workers. Apart from the conditionalexpectation of wages, we estimate the conditional quantile functionsfor men and women and find that both the absolute wage gap and thepart attributed to different returns at each of the quantiles, farfrom being well represented by their counterparts at the mean, aregreater as we move up in the wage range.

O efeito do sorriso na percepção psicológica da pessoa

O objectivo do estudo foi o de verificar o efeito do sorriso na percepção psicológica da pessoa em jovens, adultos, idosos e jovens negros. Pretendia-se verificar se o sorriso contribui para os traços diferenciais entre os grupos humanos em estudo e se o mesmo era descritor de género. O estudo envolveu um delineamento transversal analítico ou estudo não-experimental, também classificado por estudo pós-facto, estudo de observação passiva ou estudo correlacional e de observação, de comparação entre grupos, mediante o juízo ou julgamento psicológico da face neutra e do tipo de sorriso contrastados, de matriz factorial 4 x 2 x 2 (face neutra, sorriso fechado, sorriso superior, sorriso largo; género dos estímulos; género dos respondentes) e a sua finalidade foi descrever a percepção psicológica do sorriso em função das variáveis género do estímulo, género do respondente e grupo étnico, na Escala de Percepção do Sorriso (EPS), em formato diferenciador semântico, com 19 itens bipolares opostos, tendo a avaliação sido feita numa escala ordinal de 1 a 7 pontos, nas dimensões Avaliação (12 itens) e Movimento Expressivo (7 itens) resultante dos estudos preliminares sobre a atractividade facial (estudo preliminar 1) e a escolha de dípolos de adjectivos preditores para percepção psicológica da face neutra (estudo preliminar 2). Nos estudos principais 1, 2 e 3 foram utilizados 24 estímulos fotográficos apresentando o tipo de sorriso (fechado, superior e largo) e a face neutra (12 do estímulo mulher e 12 do estímulo homem) referentes aos três grupos etários (18-25 anos, 40-50 anos e 60-70 anos) e a Escala de Percepção do Sorriso (EPS) foi aplicada a uma amostra não probabilística ou intencional do tipo homogénea de 480 participantes portugueses de ambos os géneros (240 mulheres e 240 homens) distribuídos por grupos etários de jovens (80 mulheres e 80 homens, média: 22.2 anos), adultos (80 mulheres e 80 homens, média: 43.1 anos) e idosos (80 mulheres e 80 homens, média: 65.0 anos) No estudo principal 4, foram utilizados 8 estímulos fotográficos apresentando o tipo de sorriso (fechado, superior e largo) e a face neutra (4 do estímulo mulher e 4 do estímulo homem) de universitários de Cabo Verde, a estudar em Portugal, e a Escala de Percepção do Sorriso (EPS) foi aplicada a uma amostra não probabilística ou intencional do tipo homogénea de 160 participantes de ambos os géneros (80 mulheres e 80 homens) e estudantes universitários portugueses (média: 21.8 anos). Os resultados revelam e confirmam o efeito do sorriso na percepção psicológica da pessoa, à semelhança de outros estudos, isto é, sorrir torna a percepção psicológica mais positiva ou negativa e verifica-se que tal sucede em função do género do estímulo e do género do respondente. As diferenças significativas na percepção da face neutra e tipo de sorriso contrastados são justificadas pela pertença de género de quem os percepciona e pela pertença do género de quem é percepcionado. Tal apenas não sucede no factor Avaliação do grupo dos adultos. Os resultados obtidos indicam que, quer no factor Avaliação quer no factor Movimento Expressivo, os tipos de sorriso largo e superior são os que registam médias ponderadas mais elevadas. Pelo contrário, a face neutra e o sorriso fechado registam valores menos elevados na percepção. A análise da percepção da pessoa em função da face neutra e tipo de sorriso contrastados revelou uma correspondência entre a expressão facial, o género do estímulo e o género do respondente. No factor Avaliação, a mulher é percepcionada mais positivamente que o homem, verificando-se o inverso no factor Movimento Expressivo no grupo dos adultos e dos idosos. Verificou-se efeito do sorriso na percepção psicológica dos estímulos de cor negra. No grupo dos jovens que percepcionaram estímulos de cor negra, o homem é considerado mais positivo que a mulher em ambos os factores. O efeito significativo do género revela que a sua percepção é condicionada pelo seu próprio género. Os resultados apontam ainda para a configuração pronunciada de uma hierarquização ascendente da face neutra e tipo de sorriso contrastados em dois conjuntos bem delimitados e distinguindo diferentes formas topográficas de sorrir: a face neutra e o sorriso fechado e o sorriso superior e o sorriso largo.

Frequency and Type of Side Effects of Immunomodulating Medication in the Swiss Inflammatory Bowel Disease Cohort

Background: Medical treatment of inflammatory bowel disease (IBD) is becoming more and more complex, as several classes of immuno-modulating drugs (IMD) are often used simultaneously. Thus, the probability of adverse effects is greatly increased. Most studies reporting on adverse effects focus on single therapy, and studies providing a global survey of side effects for multiple treatments are lacking. Aim: To assess the type and frequency of adverse events in IBD patients treated with single and multiple IMD therapy. Methods: Analysis of data from the Swiss IBD Cohort Study (SIBDCS) that collects data on a large sample of IBD patients from hospitals and private practices across Switzerland. The following IMD categories were analyzed: 5-ASA, azathioprine (Aza), 6-mercaptopurine (6-MP), methotrexate (MTX), anti-TNF (infliximab, adalimumab, certolizumab-pegol), cyclosporine, tacrolimus, and steroids. The following side effects were assessed: hepatitis, pancreatitis, leucopenia, thrombopenia, nephritis, allergic reaction, pneumonitis, infections (including tuberculosis), osteoporosis, abdominal pain/diarrhea (unrelated to IBD activity), cataract, diabetes, exanthema, hirsutism, lupus-like syndrome, myalgias, depression/psychosis, tumor development. Results: A total of 1,961 patients were analyzed (977 [50%] female, mean age 42.1 ± 14.4 years): 1,119 with Crohn's disease (CD), 800 with ulcerative colitis (UC), and 42 with indeterminate colitis (IC). Three-hundred eighteen (16.2%) patients were not treated with any of the above-mentioned medications, while 650 (33.2%), 569 (29%) and 424 (21.6%) patients had one-, two-, and three- or more- IMD therapy, respectively. Of the 1,643 patients treated with IMD, 535 (32.6%) patients reported at least one side effect. We found a significant correlation between the number of drugs used by a patient and the frequency of side effects (17.4% side effects for one drug, 29% for 2 drugs, and 60.6% for three or more drugs, p < 0.001). The frequency of side effects for the different IMD classes were as follows: 5-ASA (n = 980 treated patients) 10.8%, Aza/6-MP (n = 636) 51.9% (pancreatitis in 57 = 9%, hepatitis in 17 = 2.7% of treated patients), MTX (n = 146) 42.5% (hepatitis in 4 = 2.7% of treated patients), anti-TNF (n = 255) 23.1%, cyclosporine (n = 49) 10.2%, tacrolimus (n = 5) 20%, steroids (systemic or topical, n = 1,150) 9.6%. Conclusion: IBD treatment is associated with a significant number of side effects. A direct correlation between the number of IMD used simultaneously and the frequency of side effects was observed. The results of this study indicate that treating physicians should be vigilant for the occurrence of side effects in IBD patients under single and/or multiple drug therapy.

Nonlinear models and small sample performance of the generalized method of moments

In this paper I explore the issue of nonlinearity (both in the datageneration process and in the functional form that establishes therelationship between the parameters and the data) regarding the poorperformance of the Generalized Method of Moments (GMM) in small samples.To this purpose I build a sequence of models starting with a simple linearmodel and enlarging it progressively until I approximate a standard (nonlinear)neoclassical growth model. I then use simulation techniques to find the smallsample distribution of the GMM estimators in each of the models.

An inequality for uniform deviations of sample averages from their means

We derive a new inequality for uniform deviations of averages from their means. The inequality is a common generalization of previous results of Vapnik and Chervonenkis (1974) and Pollard (1986). Usingthe new inequality we obtain tight bounds for empirical loss minimization learning.