Motivation, values, and work design as drivers of participation in the R open source project for statistical computing.

One of the cornerstones of the R system for statistical computing is the multitude of packages contributed by numerous package authors. This amount of packages makes an extremely broad range of statistical techniques and other quantitative methods freely available. Thus far, no empirical study has investigated psychological factors that drive authors to participate in the R project. This article presents a study of R package authors, collecting data on different types of participation (number of packages, participation in mailing lists, participation in conferences), three psychological scales (types of motivation, psychological values, and work design characteristics), and various socio-demographic factors. The data are analyzed using item response models and subsequent generalized linear models, showing that the most important determinants for participation are a hybrid form of motivation and the social characteristics of the work design. Other factors are found to have less impact or influence only specific aspects of participation.

The grand old party - a party of values?

In this article we explore the semantic space spanned by self-reported statements of Republican voters. Our semantic structure analysis uses multidimensional scaling and social network analysis to extract, explore, and visualize word patterns and word associations in response to the stimulus statement "I'm a Republican, because …" which were collected from the official website of the Republican Party. With psychological value theory as our backdrop, we examine the association of specific keywords within and across the statements, compute clusters of statements based on these associations, and explore common word sequences Republican voters use to characterize their political association with the Party.

On maximum likelihood estimation of the concentration parameter of von Mises-Fisher distributions.

Maximum likelihood estimation of the concentration parameter of von Mises-Fisher distributions involves inverting the ratio [Formula: see text] of modified Bessel functions and computational methods are required to invert these functions using approximative or iterative algorithms. In this paper we use Amos-type bounds for [Formula: see text] to deduce sharper bounds for the inverse function, determine the approximation error of these bounds, and use these to propose a new approximation for which the error tends to zero when the inverse of [Formula: see text] is evaluated at values tending to [Formula: see text] (from the left). We show that previously introduced rational bounds for [Formula: see text] which are invertible using quadratic equations cannot be used to improve these bounds.

On standard conjugate families for natural exponential families with bounded natural parameter space.

Diaconis and Ylvisaker (1979) give necessary conditions for conjugate priors for distributions from the natural exponential family to be proper as well as to have the property of linear posterior expectation of the mean parameter of the family. Their conditions for propriety and linear posterior expectation are also sufficient if the natural parameter space is equal to the set of all [Formula: see text]-dimensional real numbers. In this paper their results are extended to characterize when conjugate priors are proper if the natural parameter space is bounded. For the special case where the natural exponential family is through a spherical probability distribution  [Formula: see text], we show that the proper conjugate priors can be characterized by the behavior of the moment generating function of [Formula: see text] at the boundary of the natural parameter space, or the second-order tail behavior of [Formula: see text]. In addition, we show that if these families are non-regular, then linear posterior expectation never holds. The results for this special case are also extended to natural exponential families through elliptical probability distributions.

On conjugate families and Jeffreys priors for von Mises-Fisher distributions.

This paper discusses characteristics of standard conjugate priors and their induced posteriors in Bayesian inference for von Mises-Fisher distributions, using either the canonical natural exponential family or the more commonly employed polar coordinate parameterizations. We analyze when standard conjugate priors as well as posteriors are proper, and investigate the Jeffreys prior for the von Mises-Fisher family. Finally, we characterize the proper distributions in the standard conjugate family of the (matrix-valued) von Mises-Fisher distributions on Stiefel manifolds.

Amos-type bounds for modified Bessel function ratios.

We systematically investigate lower and upper bounds for the modified Bessel function ratio [Formula: see text] by functions of the form [Formula: see text] in case [Formula: see text] is positive for all [Formula: see text], or equivalently, where [Formula: see text] or [Formula: see text] is a negative integer. For [Formula: see text], we give an explicit description of the set of lower bounds and show that it has a greatest element. We also characterize the set of upper bounds and its minimal elements. If [Formula: see text], the minimal elements are tangent to [Formula: see text] in exactly one point [Formula: see text], and have [Formula: see text] as their lower envelope. We also provide a new family of explicitly computable upper bounds. Finally, if [Formula: see text] is a negative integer, we explicitly describe the sets of lower and upper bounds, and give their greatest and least elements, respectively.

Modelling human immunodeficiency virus ribonucleic acid levels with finite mixtures for censored longitudinal data.

The measurement of human immunodeficiency virus ribonucleic acid levels over time leads to censored longitudinal data. Suitable models for dynamic modelling of these levels need to take this data characteristic into account. If groups of patients with different developments of the levels over time are suspected the model class of finite mixtures of mixed effects models with censored data is required. We describe the model specification and derive the estimation with a suitable expectation-maximization algorithm. We propose a convenient implementation using closed form formulae for the expected mean and variance of the truncated multivariate distribution. Only efficient evaluation of the cumulative multivariate normal distribution function is required. Model selection as well as methods for inference are discussed. The application is demonstrated on the clinical trial ACTG 315 data.

Diencephalic serotonin transporter availability predicts both transporter occupancy and treatment response to sertraline in obsessive-compulsive checkers.

BACKGROUND: To our knowledge, no studies have investigated the predictive value of central serotonin transporter (SERT) availability for treatment response to serotonin reuptake inhibitors (SSRIs) in patients with obsessive-compulsive disorder (OCD). This study used brain imaging to examine the relationship between pretreatment SERT availability and transporter occupancy as well as treatment response by sertraline in patients displaying prominent behavioral checking compulsions (OC checkers). METHODS: Single photon emission computed tomography (SPECT) was used to measure thalamic-hypothalamic SERT availability with [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane in 28 nondepressed OC checkers at baseline and after 14 weeks of treatment with sertraline (175 mg daily). SERT availability was correlated with OC severity and treatment response as assessed with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Associations between individual transporter occupancies and clinical parameters were investigated. RESULTS: 1) Correlation analyses between thalamic-hypothalamic SERT availability and OC severity showed significant negative associations at baseline and after treatment with sertraline. 2) Pretreatment SERT availability correlated significantly with both transporter occupancy and treatment response; in addition, a positive association was found between transporter occupancy and treatment response directly. 3) Using multivariate statistical models, the data demonstrated that higher pretreatment SERT availability significantly predicted higher occupancy rates as well as better treatment response 14 weeks later. CONCLUSIONS: Higher pretreatment thalamic-hypothalamic SERT availability may predict both higher occupancy rates and better treatment response to sertraline. The data suggest a strong connection between transporter occupancy and treatment response.

Changes in thalamus-hypothalamus serotonin transporter availability during clomipramine administration in patients with obsessive-compulsive disorder.

To the authors' knowledge there is as of yet no study demonstrating in vivo alterations in human serotonin transporters (SERT) during clomipramine treatment in patients with obsessive-compulsive disorder. The only study in which SERT binding has been investigated in obsessive-compulsive disorder (OCD) patients before and after treatment is a small pilot study by Stengler-Wenzke et al (2006), who treated five OCD patients with citalopram. In the study at hand, we measured transporter availability in the thalamus-hypothalamus with [(123)I] beta-CIT single photon emission computed tomography (SPECT) in 24 patients with DSM-IV OCD. All patients displayed prominent behavioral checking compulsions (OC-checkers). At baseline and upon medication after 12 weeks of treatment with clomipramine (150 mg daily) 24 non-depressed OC-checkers underwent a SPECT measurement of brain SERT availability using [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane. For quantification of brain serotonin transporter availability, a ratio of specific to non-displaceable [(123)I] beta-CIT brain binding was used (BP(ND)=(thalamus and hypothalamus-cerebellum)/cerebellum). The SERT availability was compared between baseline and after treatment and correlated with severity of OC symptomatology and treatment response as assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). After treatment with clomipramine patients showed a 48% reduced brain serotonin transporter availability in the thalamus-hypothalamus, as compared with values at baseline (0.72+/-0.12 vs 1.39+/-0.18, p<0.001). Correlations between brain SERT availability and OC symptomatology (Y-BOCS scores) revealed significantly negative associations both at baseline and after treatment (r=-0.46; p<0.05 and r=-0.53; p<0.01 respectively). These data suggest that the SERT availability values could be considered a biological indicator of disease severity. Moreover, in search of predictors we found that higher pretreatment SERT availability significantly predicted better treatment response 12 weeks later (B=14.145+/-4.514; t=3.133; p=0.005). These results provide further support for an important role of alterations in serotonergic neurons in the pathophysiology of OCD.

Tourette's syndrome is not associated with interleukin-10 receptor 1 variants on chromosome 11q23.3.

Interleukin-10 receptor 1 (IL-10R1) single nucleotide polymorphisms, located on chromosome 11q23 - a strong candidate for linkage with Tourette's syndrome (TS) - have been investigated for association with TS. DNA of 77 patients with a DSM-IV (Diagnostic and Statistical Manual IV) diagnosis of TS and 250 healthy controls was genotyped. IL-10R1 was not associated with TS.

Additional support for linkage of schizophrenia and bipolar disorder to chromosome 3q29.

After publishing a genome scan and follow-up fine mapping, suggesting schizophrenia and bipolar disorder linkage to chromosome 3q29, we now genotyped 11 additional SNPs (single nucleotide polymorphisms), in order to narrow down a potential candidate region. Linkage was performed using the GENEHUNTER program version 2.1r3. A NPL score Z(all) of 3.891 (p=0.000156) was observed with SNP rs225. In short, we found significant linkage scores most telomeric on chromosome 3q29, spanning 3.46 Mbp (7 SNPs).

[123I]-beta-CIT SPECT imaging shows reduced thalamus-hypothalamus serotonin transporter availability in 24 drug-free obsessive-compulsive checkers.

Numerous findings indicate alterations in brain serotonin systems in obsessive-compulsive disorder (OCD). We investigated the in vivo availability of thalamus-hypothalamus serotonin transporters (SERT) in patients with DSM-IV OCD who displayed prominent behavioral checking compulsions (OC-checkers). Four hours after injection of [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([(123)I]-beta-CIT), single photon emission computed tomography (SPECT) scans were performed in 24 medication-free non-depressed OC-checkers and 24 age- and gender-matched healthy controls. For quantification of brain serotonin transporter availability, a ratio of specific to non-displaceable [(123)I]-beta-CIT brain binding was used (V''(3)=(thalamus and hypothalamus-cerebellum)/cerebellum). Drug-free non-depressed OC-checkers showed an 18% reduced brain serotonin transporter availability in the thalamus and hypothalamus, as compared with healthy control subjects (1.38+/-0.19 vs 1.69+/-0.21; p<0.001). There was a strong negative correlation between severity of OC symptomatology (Y-BOCS scores) and SERT availability (r=-0.80; p<0.001). Moreover, we found a significant positive correlation between illness duration and serotonin transporter availability (r=0.43; p<0.05). This first report of significantly reduced [(123)I]-beta-CIT binding in the thalamus-hypothalamus region in OC-checkers suggests reduced brain serotonin transporter availability, which is more pronounced with increased severity of OC symptomatology and short duration of illness. The results provide direct evidence for an involvement of the serotonergic system in the pathophysiology of OCD.

Homozygosity of the interleukin-10 receptor 1 G330R allele is associated with schizophrenia.

Infections of unknown origin and an altered immune response have been hypothesized to play a role in the pathogenesis of schizophrenia. We have previously identified two single nucleotide polymorphisms (SNPs) of the IL-10 receptor 1 (IL-10R1) causing a substitution of glycine 330 to arginine (G330R) and of serine 138 to glycine (S138G). A possible association between these IL-10R1 variants and schizophrenia has been investigated in the present study. DNA of 101 unrelated Austrian patients with a DSM-III-R (Diagnostic and Statistical Manual of Mental Disorders) consensus diagnosis of schizophrenia (n = 70) or schizoaffective disorder (n = 31) and DNA of 121 German schizophrenic patients (DSM-III-R) was analyzed for the presence of S138G and G330R by allele-specific multiplex PCRs. Data from patients were compared with 250 unrelated, psychiatric healthy controls. No difference in allele frequency was detected between patients and controls (G330R: 34.0% vs. 30.0%, P = 0.208; S138G: 19.7% vs. 16.6%, P = 0.235; by Fisher's exact test). However, there was a significant difference in genotype distribution (wt/wt, wt/mut, mut/mut) for G330R between patients (46.8%, 38.3%, 14.9%) and controls (47.6%, 44.8%, 7.6%; Fisher's test P = 0.032). No such difference was seen for S138G. Our results suggest that homozygosity of the IL-10R1 G330R allele is associated with schizophrenia and may contribute to the expression of disease phenotype in susceptible individuals.

A GABRB3 promoter haplotype associated with childhood absence epilepsy impairs transcriptional activity.

Childhood absence epilepsy (CAE) is considered to exhibit a complex non-Mendelian pattern of inheritance. So far, only few CAE susceptibility genes have been identified. In a previous study of our group, an association between the GABA(A) receptor beta3 subunit (GABRB3) gene and CAE was shown. To further investigate this association, we screened 45 CAE patients of the first study for mutations in the 10 exons, the exon-intron boundaries and the regulatory sequences of GABRB3. Although we found no functionally relevant mutation, we did identify 13 single nucleotide polymorphisms (SNPs) in the GABRB3 gene region from the exon 1a promoter to the beginning of intron 3. Using these SNPs we defined four haplotypes for the respective GABRB3 gene region. A transmission disequilibrium test in the same 45 CAE patients and their parents indicated a significant association of this region and CAE (P=0.007075). Reporter gene assays in NT2 cells using exon 1a promoter constructs indicated that the disease-associated haplotype 2 promoter causes a significantly lower transcriptional activity than the haplotype 1 promoter that is over-represented in the controls. In silico analysis suggested that an exchange from T (haplotype 1) to C (haplotype 2) within this promoter impairs binding of the neuron-specific transcriptional activator N-Oct-3. Electrophoretic mobility shift assays demonstrated that the respective polymorphism reduces the nuclear protein binding affinity, thus explaining the results of the reporter gene assays. Reduced expression of the GABRB3 gene could therefore be one potential cause for the development of CAE, pathogenetically relevant in our patient group.

Bioconductor: open software development for computational biology and bioinformatics.

The Bioconductor project is an initiative for the collaborative creation of extensible software for computational biology and bioinformatics. The goals of the project include: fostering collaborative development and widespread use of innovative software, reducing barriers to entry into interdisciplinary scientific research, and promoting the achievement of remote reproducibility of research results. We describe details of our aims and methods, identify current challenges, compare Bioconductor to other open bioinformatics projects, and provide working examples.

A quantitative comparison of functional MRI cluster analysis.

The aim of this work is to compare the efficiency and power of several cluster analysis techniques on fully artificial (mathematical) and synthesized (hybrid) functional magnetic resonance imaging (fMRI) data sets. The clustering algorithms used are hierarchical, crisp (neural gas, self-organizing maps, hard competitive learning, k-means, maximin-distance, CLARA) and fuzzy (c-means, fuzzy competitive learning). To compare these methods we use two performance measures, namely the correlation coefficient and the weighted Jaccard coefficient (wJC). Both performance coefficients (PCs) clearly show that the neural gas and the k-means algorithm perform significantly better than all the other methods using our setup. For the hierarchical methods the ward linkage algorithm performs best under our simulation design. In conclusion, the neural gas method seems to be the best choice for fMRI cluster analysis, given its correct classification of activated pixels (true positives (TPs)) whilst minimizing the misclassification of inactivated pixels (false positives (FPs)), and in the stability of the results achieved.

Guided self-help versus cognitive-behavioral group therapy in the treatment of bulimia nervosa.

OBJECTIVE: The aim of the current study was to evaluate whether guided self-help was effective in the short and long term in the treatment of bulimia nervosa. METHOD: Eighty-one patients with bulimia nervosa were randomly assigned to either a self-help manual with a maximum of 18 short weekly visits (guided self-help) or to 18 weekly 1.5-h sessions of cognitive-behavioral group therapy (CBT). The primary outcome variables were monthly frequencies of self-reported binge eating and vomiting episodes. Secondary outcome variables were eating disorder-related psychopathology (assessed with the Eating Disorders Inventory [EDI]) and depression (assessed by the Beck Depression Inventory [BDI]). Patients were followed up 1 year after the end of treatment. RESULTS: A mixed-effects linear regression analysis indicated that subjects in both treatment conditions showed a significant decrease over time in binge eating and vomiting frequencies, in the scores of the EDI subscales, and in the BDI. Both treatment modalities led to a sustained improvement at follow-up. A separate analysis of the completer sample showed significantly higher remission rates in the self-help condition (74%) compared with the CBT condition (44%) at follow-up. CONCLUSIONS: Guided self-help incorporating the use of a self-help manual offers an approach that can be effective in the short and long-term treatment of bulimia nervosa.

Efficacy of fluvoxamine in preventing relapse in alcohol dependence: a one-year, double-blind, placebo-controlled multicentre study with analysis by typology.

Patients with a diagnosis of alcohol dependence, detoxified and abstinent for 10-30 days, were randomly allocated to placebo or the serotonin reuptake inhibitor, fluvoxamine (up to 300 mg per day), plus counselling and support. In the intention to treat sample of 493, there was a trend for the fluvoxamine group to do worse than the placebo group on the primary outcome criteria: abstinence; and relapse defined as drinking > or =5 units on an occasion and > or =4 such occasions in a week, or > or =12 units on an occasion (1 unit = 9g ethanol). When typology of alcoholism was assigned by scores on the Tridimensional Personality Questionnaire, Types I and II had similar rates of survival without relapse on placebo (PLC I: 19.3%, n = 135; PLC II: 18.2%, n = 110), but on fluvoxamine Type II did worse than Type I (FLU I: 13.7%, n = 131; FLU II: 6.14%, n = 114) (P < 0.01). When typology was assigned on the basis of age of onset of alcohol problems (< or = age 25, or > age 25), early-onset patients in the fluvoxamine group relapsed more frequently than late-onset patients in that group (no longer significant after adjustment for gender), as did those who commenced regular drinking before age 25 (both with and without adjustment for gender). One explanation for our finding could be that impulsivity in early-onset or Type II patients may be accentuated by serotonin enhancement.

Possible linkage of schizophrenia and bipolar affective disorder to chromosome 3q29; a follow-up.

The present linkage study is a follow-up within the chromosome 3q29 region in schizophrenia and bipolar affective disorder families, based on our recently published genome scan, resulting in evidence for linkage of both disorders to this region (marker D3S1265: NPL [non parametric lod] score Z(all)=3.74, P=0.003). Using the same family sample (five pedigrees with schizophrenic index patients and three pedigrees with index bipolar disorder patients N=86; 50 of them were available for genotyping), genotyping of eight additional markers close to D3S1265 was done. Five of those new markers (three centromeric and two telomeric of D3S1265) spanning 4.14 cM (centiMorgan) could be used for statistical analyses ("new markers"). Moreover, marker D3S1265, genotyped within the published genome scan, was used for additional calculations. Linkage analysis was performed using the GENEHUNTER program version 2.1r3. Within newly genotyped markers the highest NPL score Z(all) observed was 1.93296 with the telomeric SNP (single nucleotide polymorphism) rs1835669, corresponding to P=0.032166. Statistical analysis including D3S1265, located in between the newly genotyped markers, resulted in a peak NPL score Z(all)=4.00179 with marker D3S1265, that is P=0.000128. Doing subset analyses of the bipolar disorder and schizophrenia families separately with new markers and D3S1265, linkage signals arose substantially from bipolar disorder families, with contribution from schizophrenia families, too. The results of our follow-up study support our previous linkage finding of schizophrenia and bipolar affective disorder to chromosome 3q29.

Life after death: posttraumatic stress disorder in survivors of cardiac arrest--prevalence, associated factors, and the influence of sedation and analgesia.

OBJECTIVE: Cardiac arrest is possibly one of the most traumatizing conditions for patients, but to date, its influence on psychic morbidity remains unknown. Posttraumatic stress disorder is a unique symptom configuration after an extreme event consisting of intrusion re-experiencing, avoidance and numbness, and hyperarousal symptoms. We studied a) the prevalence of posttraumatic stress disorder (PTSD) in long term survivors of cardiac arrest; b) the role of specific stress factors related to cardiac arrest for the development of PTSD; and c) the influence of sedation and analgesia during or after cardiac arrest on the occurrence of PTSD. DESIGN: Prospective, cohort study. SETTING: University teaching hospital. PATIENTS: Analysis was performed in cardiac arrest survivors who were discharged with favorable neurologic outcome during an 8-yr period (1991-1999). INTERVENTIONS: All patients received the Davidson Trauma Score for the assessment of PTSD and a modified German version of the EuroQol questionnaire for assessment of quality of life. Cardiac arrest circumstances and administration of sedation and analgesia were assessed. MEASUREMENTS AND MAIN RESULTS: Of 1,630 initially resuscitated patients, 270 patients were discharged with good neurologic outcome. A total of 226 patients were contacted, and 143 patients (63% of all eligible patients) completed the study. Mean time from cardiac arrest to follow up was 45 months (range, 24-66). Thirty-nine patients (27%; 95% confidence interval, 21% to 35%) had a Davidson Trauma Score >40 and fulfilled criteria for PTSD. Patients with PTSD had a significantly lower quality of life. The only independent risk factor for the development of PTSD was younger age. There was no difference between patients with or without PTSD regarding the use of sedation and analgesia during or after cardiac arrest. CONCLUSION: The prevalence of PTSD in cardiac arrest survivors is high. Besides younger age, neither clinical factors nor the use of sedation and analgesia were associated with development of PTSD.