Inter-informant agreement and prevalence estimates for mood syndromes: Direct interview vs. family history method.

BACKGROUND: The use of the family history method is recommended in family studies as a type of proxy interview of non-participating relatives. However, using different sources of information can result in bias as direct interviews may provide a higher likelihood of assigning diagnoses than family history reports. The aims of the present study were to: 1) compare diagnoses for threshold and subthreshold mood syndromes from interviews to those relying on information from relatives; 2) test the appropriateness of lowering the diagnostic threshold and combining multiple reports from the family history method to obtain comparable prevalence estimates to the interviews; 3) identify factors that influence the likelihood of agreement and reporting of disorders by informants. METHODS: Within a family study, 1621 informant-index subject pairs were identified. DSM-5 diagnoses from direct interviews of index subjects were compared to those derived from family history information provided by their first-degree relatives. RESULTS: 1) Inter-informant agreement was acceptable for Mania, but low for all other mood syndromes. 2) Except for Mania and subthreshold depression, the family history method provided significantly lower prevalence estimates. The gap improved for all other syndromes after lowering the threshold of the family history method. 3) Individuals who had a history of depression themselves were more likely to report depression in their relatives. LIMITATIONS: Low proportion of affected individuals for manic syndromes and lack of independence of data. CONCLUSIONS: The higher likelihood of reporting disorders by affected informants entails the risk of overestimation of the size of familial aggregation of depression.

The association between need for touch and desire for unique products and consumer (inter)dependent problem-solving

Some people cannot buy products without first touching them, believing that doing so will create more assurance and information and reduce uncertainty. The international consumer marketing literature suggests an instrument to measure consumers' necessity for pohysical contact, called Need for Touch (NFT). This paper analyzes whether the Need for Touch structure is empirically consistent. Based on a literature review, we suggest six hypotheses in order to assess the nomological, convergent, and discriminant validity of the phenomenon. Departing from these, data supported four assumptions in the predicted direction. Need for Touch was associated with Need for Input and with Need for Cognition. Need for Touch was not associated with traditional marketing channels. The results also showed the dual characterization of Need for Touch as a bi-dimensional construct. The moderator effect indicated that when the consumer has a higher (vs. lower) Need for Touch autotelic score, the experiential motivation for shopping played a more (vs. less) important role in impulsive motivation. Our Study 3 supports the NFT structure and shows new associations with the need for unique products and dependent decisions.

Sales restriction, quality selection and the mode of competition

A regulator imposing “sales restrictions” on firms competing in oligopolistic markets may enhance quality provision by the firms. Moreover, for most restrictions levels, the impact on quality selection is invariant to the mode of competition

Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis C.

BACKGROUND/AIMS: While several risk factors for the histological progression of chronic hepatitis C have been identified, the contribution of HCV genotypes to liver fibrosis evolution remains controversial. The aim of this study was to assess independent predictors for fibrosis progression. METHODS: We identified 1189 patients from the Swiss Hepatitis C Cohort database with at least one biopsy prior to antiviral treatment and assessable date of infection. Stage-constant fibrosis progression rate was assessed using the ratio of fibrosis Metavir score to duration of infection. Stage-specific fibrosis progression rates were obtained using a Markov model. Risk factors were assessed by univariate and multivariate regression models. RESULTS: Independent risk factors for accelerated stage-constant fibrosis progression (>0.083 fibrosis units/year) included male sex (OR=1.60, [95% CI 1.21-2.12], P<0.001), age at infection (OR=1.08, [1.06-1.09], P<0.001), histological activity (OR=2.03, [1.54-2.68], P<0.001) and genotype 3 (OR=1.89, [1.37-2.61], P<0.001). Slower progression rates were observed in patients infected by blood transfusion (P=0.02) and invasive procedures or needle stick (P=0.03), compared to those infected by intravenous drug use. Maximum likelihood estimates (95% CI) of stage-specific progression rates (fibrosis units/year) for genotype 3 versus the other genotypes were: F0-->F1: 0.126 (0.106-0.145) versus 0.091 (0.083-0.100), F1-->F2: 0.099 (0.080-0.117) versus 0.065 (0.058-0.073), F2-->F3: 0.077 (0.058-0.096) versus 0.068 (0.057-0.080) and F3-->F4: 0.171 (0.106-0.236) versus 0.112 (0.083-0.142, overall P<0.001). CONCLUSIONS: This study shows a significant association of genotype 3 with accelerated fibrosis using both stage-constant and stage-specific estimates of fibrosis progression rates. This observation may have important consequences for the management of patients infected with this genotype.

Swiss Interdisciplinary Management Programme for Heart Failure (SWIM-HF): a randomised controlled trial study of an outpatient inter-professional management programme for heart failure patients in Switzerland.

PRINCIPLES: International guidelines for heart failure (HF) care recommend the implementation of inter-professional disease management programmes. To date, no such programme has been tested in Switzerland. The aim of this randomised controlled trial (RCT) was to test the effect on hospitalisation, mortality and quality of life of an adult ambulatory disease management programme for patients with HF in Switzerland.METHODS: Consecutive patients admitted to internal medicine in a Swiss university hospital were screened for decompensated HF. A total of 42 eligible patients were randomised to an intervention (n = 22) or usual care group (n = 20). Medical treatment was optimised and lifestyle recommendations were given to all patients. Intervention patients additionally received a home visit by a HF-nurse, followed by 17 telephone calls of decreasing frequency over 12 months, focusing on self-care. Calls from the HF nurse to primary care physicians communicated health concerns and identified goals of care. Data were collected at baseline, 3, 6, 9 and 12 months. Mixed regression analysis (quality of life) was used. Outcome assessment was conducted by researchers blinded to group assignment.RESULTS: After 12 months, 22 (52%) patients had an all-cause re-admission or died. Only 3 patients were hospitalised with HF decompensation. No significant effect of the intervention was found on HF related to quality of life.CONCLUSIONS: An inter-professional disease management programme is possible in the Swiss healthcare setting but effects on outcomes need to be confirmed in larger studies.

Phylogenetic approach reveals that virus genotype largely determines HIV set-point viral load.

HIV virulence, i.e. the time of progression to AIDS, varies greatly among patients. As for other rapidly evolving pathogens of humans, it is difficult to know if this variance is controlled by the genotype of the host or that of the virus because the transmission chain is usually unknown. We apply the phylogenetic comparative approach (PCA) to estimate the heritability of a trait from one infection to the next, which indicates the control of the virus genotype over this trait. The idea is to use viral RNA sequences obtained from patients infected by HIV-1 subtype B to build a phylogeny, which approximately reflects the transmission chain. Heritability is measured statistically as the propensity for patients close in the phylogeny to exhibit similar infection trait values. The approach reveals that up to half of the variance in set-point viral load, a trait associated with virulence, can be heritable. Our estimate is significant and robust to noise in the phylogeny. We also check for the consistency of our approach by showing that a trait related to drug resistance is almost entirely heritable. Finally, we show the importance of taking into account the transmission chain when estimating correlations between infection traits. The fact that HIV virulence is, at least partially, heritable from one infection to the next has clinical and epidemiological implications. The difference between earlier studies and ours comes from the quality of our dataset and from the power of the PCA, which can be applied to large datasets and accounts for within-host evolution. The PCA opens new perspectives for approaches linking clinical data and evolutionary biology because it can be extended to study other traits or other infectious diseases.

Transferts inter-hospitaliers de patients entre cantons suisses

ECTIFS: Analyser les mouvements de patients entre cantons et selon les pathologies principales. Présentation du contexte, des enjeux et de l'interprétation des données. MÉTHODOLOGIE: Analyse, faite à partir de la base de données de la Statistique Hospitalière Suisse, de tous les transferts survenus entre 1998 et 2008 selon les variables suivantes : le sexe, l'âge, le canton d'hospitalisation, le canton de domicile du sujet et la pathologie. RÉSULTATS: Les transferts inter-cantonaux représentaient entre 2.7% (Genève) et 81.6% (Appenzell Rhodes intérieur) de la totalité des transferts entre hôpitaux. La majorité des transferts concerne les pathologies suivantes : cardiovasculaire (20.1%), ostéo-articulaire (9.3%), troubles mentaux (6.5%), oncologique (4.6%) et troubles respiratoires (2.6%). Les facteurs influençant la santé (28.7%) et les causes externes (12%) n'ont pas été inclus dans l'analyse. Le flux des transferts est orienté selon les tendances suivantes : attraction des cantons possédant un hôpital universitaire, l'accessibilité géographique (distances/obstacles), diversité des mouvements selon les pathologies et l'influence linguistique. L'attractivité des cantons est associée au nombre d'hôpitaux (r=0.82, p<0.001) ou de lits (r=0.85, p<0.001) qu'ils possèdent ainsi qu'à leur densité de lits (r=0.51, p<0.01), mais pas à leur densité hospitalière (r=0.08, p<0.7). CONCLUSION: Les cantons universitaires jouent leur rôle de pôle de compétences. Ce phénomène confirme que les transferts se font selon une logique de rationalisation des moyens techniques. Les mouvements de patients sont plus importants dans les cantons alémaniques. On constate une tendance moins forte parmi les cantons latins à " exporter " des patients. Les accords inter-cantonaux de transferts jouent un rôle dans le flux des patients en Suisse. [Auteur]

Local Competition, Inbreeding, and the Evolution of Sex-Biased Dispersal.

Using game theory, we developed a kin-selection model to investigate the consequences of local competition and inbreeding depression on the evolution of natal dispersal. Mating systems have the potential to favor strong sex biases in dispersal because sex differences in potential reproductive success affect the balance between local resource competition and local mate competition. No bias is expected when local competition equally affects males and females, as happens in monogamous systems and also in polygynous or promiscuous ones as long as female fitness is limited by extrinsic factors (breeding resources). In contrast, a male-biased dispersal is predicted when local mate competition exceeds local resource competition, as happens under polygyny/promiscuity when female fitness is limited by intrinsic factors (maximal rate of processing resources rather than resources themselves). This bias is reinforced by among-sex interactions: female philopatry enhances breeding opportunities for related males, while male dispersal decreases the chances that related females will inbreed. These results meet empirical patterns in mammals: polygynous/promiscuous species usually display a male-biased dispersal, while both sexes disperse in monogamous species. A parallel is drawn with sex-ratio theory, which also predicts biases toward the sex that suffers less from local competition. Optimal sex ratios and optimal sex-specific dispersal show mutual dependence, which argues for the development of coevolution models.

Acquired antibody responses against Plasmodium vivax infection vary with host genotype for duffy antigen receptor for chemokines (DARC).

BACKGROUND: Polymorphism of the Duffy Antigen Receptor for Chemokines (DARC) is associated with susceptibility to and the severity of Plasmodium vivax malaria in humans. P. vivax uses DARC to invade erythrocytes. Individuals lacking DARC are 'resistant' to P. vivax erythrocytic infection. However, susceptibility to P. vivax in DARC+ individuals is reported to vary between specific DARC genotypes. We hypothesized that the natural acquisition of antibodies to P. vivax blood stages may vary with the host genotype and the level of DARC expression. Furthermore, high parasitemia has been reported to effect the acquisition of immunity against pre-erythrocytic parasites. We investigated the correlation between host DARC genotypes and the frequency and magnitude of antibodies against P. vivax erythrocytic stage antigens. METHODOLOGY/FINDINGS: We assessed the frequencies and magnitudes of antibody responses against P. vivax and P. falciparum sporozoite and erythrocytic antigens in Colombian donors from malaria-endemic regions. The frequency and level of naturally-acquired antibodies against the P. vivax erythrocytic antigens merozoite surface protein 1 (PvMSP1) and Duffy binding protein (PvDBP) varied with the host DARC genotypes. Donors with one negative allele (FY*B/FY*Bnull and FY*A/FY*Bnull) were more likely to have anti-PvMSP1 and anti-PvDBP antibodies than those with two positive alleles (FY*B/FY*B and FY*A/FY*B). The lower IgG3 and IgG1 components of the total IgG response may account for the decreased responses to P. vivax erythrocytic antigens with FY*A/FY*B and FY*B/FY*B genotypes. No such association was detected with P. falciparum erythrocytic antigens, which does not use DARC for erythrocyte invasion. CONCLUSION/SIGNIFICANCE: Individuals with higher DARC expression, which is associated with higher susceptibility to P. vivax infection, exhibited low frequencies and magnitudes of P. vivax blood-stage specific antibody responses. This may indicate that one of the primary mechanisms by which P. vivax evades host immunity is through DARC indirectly down-regulating humoral responses against erythrocytic invasion and development.

Cell disposition of raltegravir and newer antiretrovirals in HIV-infected patients: high inter-individual variability in raltegravir cellular penetration.

Objectives The site of pharmacological activity of raltegravir is intracellular. Our aim was to determine the extent of raltegravir cellular penetration and whether raltegravir total plasma concentration (C(tot)) predicts cellular concentration (C(cell)). Methods Open-label, prospective, pharmacokinetic study on HIV-infected patients on a stable raltegravir-containing regimen. Plasma and peripheral blood mononuclear cells were simultaneously collected during a 12 h dosing interval after drug intake. C(tot) and C(cell) of raltegravir, darunavir, etravirine, maraviroc and ritonavir were measured by liquid chromatography coupled to tandem mass spectrometry after protein precipitation. Longitudinal mixed effects analysis was applied to the C(cell)/C(tot) ratio. Results Ten HIV-infected patients were included. The geometric mean (GM) raltegravir total plasma maximum concentration (C(max)), minimum concentration (C(min)) and area under the time-concentration curve from 0-12 h (AUC(0-12)) were 1068 ng/mL, 51.1 ng/mL and 4171 ng·h/mL, respectively. GM raltegravir cellular C(max), C(min) and AUC(0-12) were 27.5 ng/mL, 2.9 ng/mL and 165 ng·h/mL, respectively. Raltegravir C(cell) corresponded to 5.3% of C(tot) measured simultaneously. Both concentrations fluctuate in parallel, with C(cell)/C(tot) ratios remaining fairly constant for each patient without a significant time-related trend over the dosing interval. The AUC(cell)/AUC(tot) GM ratios for raltegravir, darunavir and etravirine were 0.039, 0.14 and 1.55, respectively. Conclusions Raltegravir C(cell) correlated with C(tot) (r = 0.86). Raltegravir penetration into cells is low overall (∼5% of plasma levels), with distinct raltegravir cellular penetration varying by as much as 15-fold between patients. The importance of this finding in the context of development of resistance to integrase inhibitors needs to be further investigated.

Relationship of imatinib-free plasma levels and target genotype with efficacy and tolerability

Imatinib has revolutionised the treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours (GIST). Using a nonlinear mixed effects population model, individual estimates of pharmacokinetic parameters were derived and used to estimate imatinib exposure (area under the curve, AUC) in 58 patients. Plasma-free concentration was deduced from a model incorporating plasma levels of alpha(1)-acid glycoprotein. Associations between AUC (or clearance) and response or incidence of side effects were explored by logistic regression analysis. Influence of KIT genotype was also assessed in GIST patients. Both total (in GIST) and free drug exposure (in CML and GIST) correlated with the occurrence and number of side effects (e.g. odds ratio 2.7+/-0.6 for a two-fold free AUC increase in GIST; P<0.001). Higher free AUC also predicted a higher probability of therapeutic response in GIST (odds ratio 2.6+/-1.1; P=0.026) when taking into account tumour KIT genotype (strongest association in patients harbouring exon 9 mutation or wild-type KIT, known to decrease tumour sensitivity towards imatinib). In CML, no straightforward concentration-response relationships were obtained. Our findings represent additional arguments to further evaluate the usefulness of individualizing imatinib prescription based on a therapeutic drug monitoring programme, possibly associated with target genotype profiling of patients.

Telecommunications Competition Survey for Retail Local Voice Services in Iowa, January 26, 2004

Survey of retail local voice services for Iowa Utilities Board

Toronto Waterfront Internacional Competition

Concurs internacional restringit per invitació per a la Toronto Waterfront international competition

Anisotropic dispersion, space competition, and the slowdown of the Neolithic transition

The front speed of the Neolithic (farmer) spread in Europe decreased as it reached Northern latitudes, where the Mesolithic (huntergatherer) population density was higher. Here, we describe a reaction diffusion model with (i) an anisotropic dispersion kernel depending on the Mesolithicpopulation density gradient and (ii) a modified population growth equation. Both effects are related to the space available for the Neolithic population. The model is able to explain the slowdown of the Neolithic front as observed from archaeological data