Vaniprevir with pegylated interferon alpha-2a and ribavirin in treatment-naïve patients with chronic hepatitis C: a randomized phase II study.

Vaniprevir (MK-7009) is a macrocyclic hepatitis C virus (HCV) nonstructural protein 3/4A protease inhibitor. The aim of the present phase II study was to examine virologic response rates with vaniprevir in combination with pegylated interferon alpha-2a (Peg-IFN-α-2a) plus ribavirin (RBV). In this double-blind, placebo-controlled, dose-ranging study, treatment-naïve patients with HCV genotype 1 infection (n = 94) were randomized to receive open-label Peg-IFN-α-2a (180 μg/week) and RBV (1,000-1,200 mg/day) in combination with blinded placebo or vaniprevir (300 mg twice-daily [BID], 600 mg BID, 600 mg once-daily [QD], or 800 mg QD) for 28 days, then open-label Peg-IFN-α-2a and RBV for an additional 44 weeks. The primary efficacy endpoint was rapid viral response (RVR), defined as undetectable plasma HCV RNA at week 4. Across all doses, vaniprevir was associated with a rapid two-phase decline in viral load, with HCV RNA levels approximately 3 log(10) IU/mL lower in vaniprevir-treated patients, compared to placebo recipients. Rates of RVR were significantly higher in each of the vaniprevir dose groups, compared to the control regimen (68.8%-83.3% versus 5.6%; P < 0.001 for all comparisons). There were numerically higher, but not statistically significant, early and sustained virologic response rates with vaniprevir, as compared to placebo. Resistance profile was predictable, with variants at R155 and D168 detected in a small number of patients. No relationship between interleukin-28B genotype and treatment outcomes was demonstrated in this study. The incidence of adverse events was generally comparable between vaniprevir and placebo recipients; however, vomiting appeared to be more common at higher vaniprevir doses. CONCLUSION: Vaniprevir is a potent HCV protease inhibitor with a predictable resistance profile and favorable safety profile that is suitable for QD or BID administration.

Correlation of wear in vivo and six laboratory wear methods.

OBJECTIVE: We examined the correlation between clinical wear rates of restorative materials and enamel (TRAC Research Foundation, Provo, USA) and the results of six laboratory test methods (ACTA, Alabama (generalized, localized), Ivoclar (vertical, volumetric), Munich, OHSU (abrasion, attrition), Zurich). METHODS: Individual clinical wear data were available from clinical trials that were conducted by TRAC Research Foundation (formerly CRA) together with general practitioners. For each of the n=28 materials (21 composite resins for intra-coronal restorations [20 direct and 1 indirect], 5 resin materials for crowns, 1 amalgam, enamel) a minimum of 30 restorations had been placed in posterior teeth, mainly molars. The recall intervals were up to 5 years with the majority of materials (n=27) being monitored, however, only for up to 2 years. For the laboratory data, the databases MEDLINE and IADR abstracts were searched for wear data on materials which were also clinically tested by TRAC Research Foundation. Only those data for which the same test parameters (e.g. number of cycles, loading force, type of antagonist) had been published were included in the study. A different quantity of data was available for each laboratory method: Ivoclar (n=22), Zurich (n=20), Alabama (n=17), OHSU and ACTA (n=12), Munich (n=7). The clinical results were summed up in an index and a linear mixed model was fitted to the log wear measurements including the following factors: material, time (0.5, 1, 2 and 3 years), tooth (premolar/molar) and gender (male/female) as fixed effects, and patient as random effect. Relative ranks were created for each material and method; the same was performed with the clinical results. RESULTS: The mean age of the subjects was 40 (±12) years. The materials had been mostly applied in molars (81%) and 95% of the intracoronal restorations were Class II restorations. The mean number of individual wear data per material was 25 (range 14-42). The mean coefficient of variation of clinical wear data was 53%. The only significant correlation was reached by OHSU (abrasion) with a Spearman r of 0.86 (p=0.001). Zurich, ACTA, Alabama generalized wear and Ivoclar (volume) had correlation coefficients between 0.3 and 0.4. For Zurich, Alabama generalized wear and Munich, the correlation coefficient improved if only composites for direct use were taken into consideration. The combination of different laboratory methods did not significantly improve the correlation. SIGNIFICANCE: The clinical wear of composite resins is mainly dependent on differences between patients and less on the differences between materials. Laboratory methods to test conventional resins for wear are therefore less important, especially since most of them do not reflect the clinical wear.

Role of retroviral restriction factors in the interferon-α-mediated suppression of HIV-1 in vivo.

The antiviral potency of the cytokine IFN-α has been long appreciated but remains poorly understood. A number of studies have suggested that induction of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 (APOBEC3) and bone marrow stromal cell antigen 2 (BST-2/tetherin/CD317) retroviral restriction factors underlies the IFN-α-mediated suppression of HIV-1 replication in vitro. We sought to characterize the as-yet-undefined relationship between IFN-α treatment, retroviral restriction factors, and HIV-1 in vivo. APOBEC3G, APOBEC3F, and BST-2 expression levels were measured in HIV/hepatitis C virus (HCV)-coinfected, antiretroviral therapy-naïve individuals before, during, and after pegylated IFN-α/ribavirin (IFN-α/riba) combination therapy. IFN-α/riba therapy decreased HIV-1 viral load by -0.921 (±0.858) log(10) copies/mL in HIV/HCV-coinfected patients. APOBEC3G/3F and BST-2 mRNA expression was significantly elevated during IFN-α/riba treatment in patient-derived CD4+ T cells (P < 0.04 and P < 0.008, paired Wilcoxon), and extent of BST-2 induction was correlated with reduction in HIV-1 viral load during treatment (P < 0.05, Pearson's r). APOBEC3 induction during treatment was correlated with degree of viral hypermutation (P < 0.03, Spearman's ρ), and evolution of the HIV-1 accessory protein viral protein U (Vpu) during IFN-α/riba treatment was suggestive of increased BST-2-mediated selection pressure. These data suggest that host restriction factors play a critical role in the antiretroviral capacity of IFN-α in vivo, and warrant investigation into therapeutic strategies that specifically enhance the expression of these intrinsic immune factors in HIV-1-infected individuals.

Female adolescents' views on a youth-friendly clinic.

OBJECTIVE: To assess satisfaction among female patients of a youth friendly clinic and to determine with which factors this was associated. METHODS: A cross-sectional survey was conducted in an adolescent clinic in Lausanne, Switzerland, between March and May 2008. All female patients who had made at least one previous visit were eligible. Three hundred and eleven patients aged 12-22 years were included. We performed bivariate analysis to compare satisfied and non-satisfied patients and constructed a log-linear model. RESULTS: Ninety-four percent of patients were satisfied. Satisfied female adolescents were significantly more likely to feel that their complaints were heard, that the caregiver understood their problems, to have no change of physician, to have received the correct treatment/help and to follow the caregiver's advice. The log-linear model highlighted four factors directly linked with patient satisfaction: outcome of care, continuity of care, adherence to treatment and the feeling of being understood. CONCLUSIONS: The main point for female adolescent patient satisfaction lies in a long term, trustworthy relationship with their caregiver. Confidentiality and accessibility were secondary for our patients.

Flying High and Laying Low in the Public and Private Sectors: A Comparison of Pay Differentials for Full-Time Male Employees in Britain

Using new linked employee-employer data for Britain in 2004, this paper shows that, on average, full-time male public sector employees earn 11.7 log wage points more than their private sector counterparts. Decomposition analysis reveals that the majority of this pay premium is associated with public sector employees having individual characteristics associated with higher pay and to their working in higher paid occupations. Further focussing analysis on the highly skilled and unskilled occupations in both sectors, reveals evidence of workplace segregation positively impacting on earnings in the private sector for the highly skilled, and in the public sector for the unskilled. Substantial earnings gaps between the highly skilled and unskilled are found, and the unexplained components in these gaps are very similar regardless of sector.

Growth and Survival Determinants of Chinese Private Firms: Fieldwork evidence and econometric estimates

This paper reports on one of the first empirical attempts to investigate small firm growth and survival, and their determinants, in the Peoples’ Republic of China. The work is based on field work evidence gathered from a sample of 83 Chinese private firms (mainly SMEs) collected initially by face-to-face interviews, and subsequently by follow-up telephone interviews a year later. We extend the models of Gibrat (1931) and Jovanovic (1982), which traditionally focus on size and age alone (e.g. Brock and Evans, 1986), to a ‘comprehensive’ growth model with two types of additional explanatory variables: firm-specific (e.g. business planning); and environmental (e.g. choice of location). We estimate two econometric models: a ‘basic’ age-size-growth model; and a ‘comprehensive’ growth model, using Heckman’s two-step regression procedure. Estimation is by log-linear regression on cross-section data, with corrections for sample selection bias and heteroskedasticity. Our results refute a pure Gibrat model (but support a more general variant) and support the learning model, as regards the consequences of size and age for growth; and our extension to a comprehensive model highlights the importance of location choice and customer orientation for the growth of Chinese private firms. In the latter model, growth is explained by variables like planning, R&D orientation, market competition, elasticity of demand etc. as well as by control variables. Our work on small firm growth achieves two things. First, it upholds the validity of ‘basic’ size-age-growth models, and successfully applies them to the Chinese economy. Second, it extends the compass of such models to a ‘comprehensive’ growth model incorporating firm-specific and environmental variables.

Long-term fluctuation of relative afferent pupillary defect in subjects with normal visual function.

PURPOSE: To determine whether the relative afferent pupillary defect (RAPD) remains constant over time in normal subjects. METHODS: Seventeen normal subjects were tested with infrared pupillography and automated perimetry in four sessions over 3 years. The changes in RAPD and visual field asymmetry between testing sessions were compared. RESULTS: The range of RAPD was 0.0 to 0.3 log unit, and the difference in the mean deviation between the eyes on automated static perimetry was 0 to 3 dB. Eight subjects repeatedly had an RAPD in the same eye. There was no correlation between the RAPD and the visual field asymmetry at the same visit. Changes in the magnitude of the RAPD between any two sessions were typically small (median, 0.08 log unit; 25th percentile, 0.04 log unit; 75th percentile, 0.15 log unit). CONCLUSIONS: Some normal subjects may show a persistent but small RAPD in the absence of detectable pathologic disease. Therefore, an isolated RAPD in the range of 0.3 log unit that is not associated with any other significant historical or clinical finding should probably be considered benign.

Growth Rate Estimation in the presence of Unit Roots

This study addresses the issue of the presence of a unit root on the growth rate estimation by the least-squares approach. We argue that when the log of a variable contains a unit root, i.e., it is not stationary then the growth rate estimate from the log-linear trend model is not a valid representation of the actual growth of the series. In fact, under such a situation, we show that the growth of the series is the cumulative impact of a stochastic process. As such the growth estimate from such a model is just a spurious representation of the actual growth of the series, which we refer to as a “pseudo growth rate”. Hence such an estimate should be interpreted with caution. On the other hand, we highlight that the statistical representation of a series as containing a unit root is not easy to separate from an alternative description which represents the series as fundamentally deterministic (no unit root) but containing a structural break. In search of a way around this, our study presents a survey of both the theoretical and empirical literature on unit root tests that takes into account possible structural breaks. We show that when a series is trendstationary with breaks, it is possible to use the log-linear trend model to obtain well defined estimates of growth rates for sub-periods which are valid representations of the actual growth of the series. Finally, to highlight the above issues, we carry out an empirical application whereby we estimate meaningful growth rates of real wages per worker for 51 industries from the organised manufacturing sector in India for the period 1973-2003, which are not only unbiased but also asymptotically efficient. We use these growth rate estimates to highlight the evolving inter-industry wage structure in India.

Regional productivity variation and the impact of public capital stock: an analysis with spatial interaction, with reference to Spain

In this paper we examine whether variations in the level of public capital across Spain‟s Provinces affected productivity levels over the period 1996-2005. The analysis is motivated by contemporary urban economics theory, involving a production function for the competitive sector of the economy („industry‟) which includes the level of composite services derived from „service‟ firms under monopolistic competition. The outcome is potentially increasing returns to scale resulting from pecuniary externalities deriving from internal increasing returns in the monopolistic competition sector. We extend the production function by also making (log) labour efficiency a function of (log) total public capital stock and (log) human capital stock, leading to a simple and empirically tractable reduced form linking productivity level to density of employment, human capital and public capital stock. The model is further extended to include technological externalities or spillovers across provinces. Using panel data methodology, we find significant elasticities for total capital stock and for human capital stock, and a significant impact for employment density. The finding that the effect of public capital is significantly different from zero, indicating that it has a direct effect even after controlling for employment density, is contrary to some of the earlier research findings which leave the question of the impact of public capital unresolved.

Sexual dysfunction among young men : prevalence and associated factors

Les dysfonctions sexuelles représentent une préoccupation importante et parfois mésestimée dans la population masculine générale. L'éjaculation précoce et les dysfonctions érectiles faisant partie des dysfonctions sexuelles les plus fréquentes, nous avons choisi, dans le présent article, de nous concentrer sur ces deux aspects. Selon plusieurs études, la prévalence d'éjaculation précoce se situe entre 17 et 30%. Les associations décrites avec l'éjaculation précoce concernent le stress, la dépression et un jeune âge (<25 ans). La prévalence de dysfonction érectile, quant à elle, oscille entre 2 et plus de 80% dépendant principalement de l'âge. Beaucoup d'autres facteurs associés ont été décrits dans la littérature, tels que le diabète, les pathologies cardiovasculaires ou neurologiques, les médicaments, l'obésité ou l'inactivité physique. Tous ces facteurs étant plus fréquents au sein de populations vieillissantes, nous disposons de peu d'études concernant la dysfonction érectile chez de jeunes hommes. Notre étude propose donc d'évaluer la prévalence d'éjaculation précoce et de dysfonction érectile chez une population de jeunes hommes et d'étudier les associations possibles avec les consommations de substances, l'index de masse corporelle (IMC), l'activité physique ou la santé mentale. Chaque homme suisse entre 18 et 25 ans est appelé à participer à 2 journées de recrutement militaire. De septembre 2010 à mai 2011, les jeunes hommes recrutés à Lausanne et à Zürich (N= 9761) ont été invités à participer à l'étude C-SURF (Cohort Study on Substance Use Risk Factors). 5276 d'entre eux acceptèrent de répondre au questionnaire complet, et 73% (N=3886) le firent de manière effective. Le but de notre recherche étant d'étudier les dysfonctions sexuelles, nous nous sommes concentrés sur les participants sexuellement actifs (N=2507) et les avons divisés en 2 groupes, selon qu'ils présentaient ou non la dysfonction étudiée. Pour chaque dysfonction (éjaculation précoce et dysfonction érectile), nous avons utilisé une analyse bivariée afin de comparer les deux groupes (avec ou sans trouble) quant à d'éventuels facteurs associés. A cause de la nature transversale de l'étude, nous ne pouvions pas postuler de lien de cause à effet entre ces facteurs et les dysfonctions sexuelles, raison pour laquelle nous avons choisi d'utiliser des modèles log-linéaires pour mettre en exergue les associations significatives. Nos résultats montrent une prévalence d'éjaculation précoce de 11.4% avec comme associations principales la consommation de tabac et de drogues illégales (autres que le cannabis). La prévalence des dysfonctions érectiles est quant à elle proche du 30% et s'associe principalement avec l'usage de médicaments, ainsi qu'avec la santé physique et la santé mentale. Un jeune homme suisse sur trois souffre ainsi d'au moins une dysfonction sexuelle. Beaucoup de facteurs compromettants pour la santé y sont possiblement associés, raison pour laquelle les professionnels de la santé devraient saisir chaque occasion pour parler de sexualité avec leurs jeunes patients de sexe masculin.

Growth and Survival Determinants of Chinese Private Firms: Fieldwork evidence and econometric estimates

This paper reports on one of the first empirical attempts to investigate small firm growth and survival, and their determinants, in the Peoples’ Republic of China. The work is based on field work evidence gathered from a sample of 83 Chinese private firms (mainly SMEs) collected initially by face-to-face interviews, and subsequently by follow-up telephone interviews a year later. We extend the models of Gibrat (1931) and Jovanovic (1982), which traditionally focus on size and age alone (e.g. Brock and Evans, 1986), to a ‘comprehensive’ growth model with two types of additional explanatory variables: firm-specific (e.g. business planning); and environmental (e.g. choice of location). We estimate two econometric models: a ‘basic’ age-size-growth model; and a ‘comprehensive’ growth model, using Heckman’s two-step regression procedure. Estimation is by log-linear regression on cross-section data, with corrections for sample selection bias and heteroskedasticity. Our results refute a pure Gibrat model (but support a more general variant) and support the learning model, as regards the consequences of size and age for growth; and our extension to a comprehensive model highlights the importance of location choice and customer orientation for the growth of Chinese private firms. In the latter model, growth is explained by variables like planning, R&D orientation, market competition, elasticity of demand etc. as well as by control variables. Our work on small firm growth achieves two things. First, it upholds the validity of ‘basic’ size-age-growth models, and successfully applies them to the Chinese economy. Second, it extends the compass of such models to a ‘comprehensive’ growth model incorporating firm-specific and environmental variables.

Estudio de la patogenia de clostridium perfringens tipo b y d en pequeños rumiantes

Proyecto de investigación realizado a partir de una estancia en la University of California, Davis, Estados Unidos, entre octubre y desembre del 2007. Clostridium perfringens (C. perfringens) tipo C causa enteritis necrotizante en humanos y enterotoxemias en animales domésticos. Esta bacteria produce beta toxina (CPB), alfa toxina (CPA) y perfringolisina (PFO) durante la fase logarítimca de crecimiento. En nuestro estudio se evaluó la relación entre CPB y la virulencia del aislamiento CN3685 de Cl. perfringens tipo C en un modelo caprino con inoculación intraduodenal. De manera similar a la infección natural por C. perfringens tipo C, el cultivo vegetativo del tipo salvaje de CN3685 provocó dolor abdominal, diarrea hemorrágica, enteritis necrotizante, colitis, edema pulmonar, hidropericardio y muerte en 2 cabritos, a las 24 horas postinoculación. Por otro lado, mediante tecnología Targe Tron® se prepararon mutantes isogénicos carentes de toxina CPB, los cuales fueron inoculados siguiendo el modelo anteriormente descrito. Los resultados mostraron que estos mutantes carecían de todo tipo de virulencia, ya que no se observaron signos clínicos durante las primeras 24 h postinoculación ni tampoco lesiones macroscópicas ni histopatológicas. Posteriormente se desarrolló un modelo experimental similar a los anteriores, en los que se había repuesto la capacidad de producción de CPB en los mutantes. Los dos animales inoculados con estos mutantes complementarios presentaron signos clínicos y lesiones similares a las observadas en el caso del tipo salvaje. Estos resultados muestran que la toxina CPB es necesaria y suficiente para inducir la enfermedad causada por CN3685. Esto a su vez, demuestra la importancia de este tipo de toxina en la patogénesis de C. perfringems tìpo C.

UK House Prices: Convergence Clubs and Spillovers

This paper uses the log t test to analyse the convergence of house prices across UK regions and the presence of spillovers e ects. We nd that UK house prices can be grouped into four clusters. Moreover we document the dynamics of the house price spillovers across regions.

The convenient calculation of some test statistics in models of discrete choice

The paper considers the use of artificial regression in calculating different types of score test when the log

A new look at the Heston characteristic function

A new expression for the characteristic function of log-spot in Heston model is presented. This expression more clearly exhibits its properties as an analytic characteristic function and allows us to compute the exact domain of the moment generating function. This result is then applied to the volatility smile at extreme strikes and to the control of the moments of spot. We also give a factorization of the moment generating function as product of Bessel type factors, and an approximating sequence to the law of log-spot is deduced.