Predicting the evolution of Kaposi sarcoma, in the highly active antiretroviral therapy era.

BACKGROUND: The outcome of Kaposi sarcoma varies. While many patients do well on highly active antiretroviral therapy, others have progressive disease and need chemotherapy. In order to predict which patients are at risk of unfavorable evolution, we established a prognostic score. METHOD: The survival analysis (Kaplan-Meier method; Cox proportional hazards models) of 144 patients with Kaposi sarcoma prospectively included in the Swiss HIV Cohort Study, from January 1996 to December 2004, was conducted. OUTCOME ANALYZED: use of chemotherapy or death. VARIABLES ANALYZED: demographics, tumor staging [T0 or T1 (16)], CD4 cell counts and HIV-1 RNA concentration, human herpesvirus 8 (HHV8) DNA in plasma and serological titers to latent and lytic antigens. RESULTS: Of 144 patients, 54 needed chemotherapy or died. In the univariate analysis, tumor stage T1, CD4 cell count below 200 cells/microl, positive HHV8 DNA and absence of antibodies against the HHV8 lytic antigen at the time of diagnosis were significantly associated with a bad outcome.Using multivariate analysis, the following variables were associated with an increased risk of unfavorable outcome: T1 [hazard ratio (HR) 5.22; 95% confidence interval (CI) 2.97-9.18], CD4 cell count below 200 cells/microl (HR 2.33; 95% CI 1.22-4.45) and positive HHV8 DNA (HR 2.14; 95% CI 1.79-2.85).We created a score with these variables ranging from 0 to 4: T1 stage counted for two points, CD4 cell count below 200 cells/microl for one point, and positive HHV8 viral load for one point. Each point increase was associated with a HR of 2.26 (95% CI 1.79-2.85). CONCLUSION: In the multivariate analysis, staging (T1), CD4 cell count (<200 cells/microl), positive HHV8 DNA in plasma, at the time of diagnosis, predict evolution towards death or the need of chemotherapy.

Inter- and intra-individual variation of oxytocin secretion in oestrous mares exposed to stallions

The neuro-peptide hormone oxytocin regulates several reproductive mechanisms in mammals, such as uterine contractions during parturition and milk ejection in the lactating mammary gland. Oxytocin may also influence behavior and behavioral strategies, e.g. pair bonding, social recognition, maternal behavior, trust building, or anxiety. Teasing oestrous mares by a stallion provokes the release of oxytocin. We therefore tested whether such elevated oxytocin levels reveal possible mate preferences as determined in typical preference tests.

Iridophores and not carotenoids account for chromatic variation of carotenoid-basedcColoration in Common lizards (Lacerta vivipara).

Abstract Carotenoids typically need reflective background components to shine. Such components, iridophores, leucophores, and keratin- and collagen-derived structures, are generally assumed to show no or little environmental variability. Here, we investigate the origin of environmentally induced variation in the carotenoid-based ventral coloration of male common lizards (Lacerta vivipara) by investigating the effects of dietary carotenoids and corticosterone on both carotenoid- and background-related reflectance. We observed a general negative chromatic change that was prevented by β-carotene supplementation. However, chromatic changes did not result from changes in carotenoid-related reflectance or skin carotenoid content but from changes in background-related reflectance that may have been mediated by vitamin A. An in vitro experiment showed that the encountered chromatic changes most likely resulted from changes in iridophore reflectance. Our findings demonstrate that chromatic variation in carotenoid-based ornaments may not exclusively reflect differences in integumentary carotenoid content and, hence, in qualities linked to carotenoid deposition (e.g., foraging ability, immune response, or antioxidant capacity). Moreover, skin carotenoid content and carotenoid-related reflectance were related to male color polymorphism, suggesting that carotenoid-based coloration of male common lizards is a multicomponent signal, with iridophores reflecting environmental conditions and carotenoids reflecting genetically based color morphs.

The application of trend surface models to the analysis of time factors in Swiss cancer mortality.

To study different temporal components on cancer mortality (age, period and cohort) methods of graphic representation were applied to Swiss mortality data from 1950 to 1984. Maps using continuous slopes ("contour maps") and based on eight tones of grey according to the absolute distribution of rates were used to represent the surfaces defined by the matrix of various age-specific rates. Further, progressively more complex regression surface equations were defined, on the basis of two independent variables (age/cohort) and a dependent one (each age-specific mortality rate). General patterns of trends in cancer mortality were thus identified, permitting definition of important cohort (e.g., upwards for lung and other tobacco-related neoplasms, or downwards for stomach) or period (e.g., downwards for intestines or thyroid cancers) effects, besides the major underlying age component. For most cancer sites, even the lower order (1st to 3rd) models utilised provided excellent fitting, allowing immediate identification of the residuals (e.g., high or low mortality points) as well as estimates of first-order interactions between the three factors, although the parameters of the main effects remained still undetermined. Thus, the method should be essentially used as summary guide to illustrate and understand the general patterns of age, period and cohort effects in (cancer) mortality, although they cannot conceptually solve the inherent problem of identifiability of the three components.

Spatial and temporal variation of natural toxicity in cnidarians, bryozoans and tunicates in Mediterranean caves

The natural toxicity of cnidarians, bryozoans and tunicates in two caves was assessed using the Microtox® technique in spring and autumn. One cave was located in the Cabrera Archipelago (Balearic Islands) and the other in the Medes Islands (Catalan littoral). The organisms analysed were good representatives of the coverage of each Phylum in the communities; however, these Phyla are less abundant than sponges which are the dominant group in these caves. Seventy-one percent of the species of cnidarians and bryozoans analysed were toxic in one of the caves, communities or seasons, which indicates the relevance of bioactive species in these groups. The tunicate Lissoclinum perforatum was the most toxic species. Although all three Phyla had some highly toxic species, a common pattern that related the caves, communities and seasons was not found. Seasonal variation of toxicity in cnidarians and bryozoans was higher in the Cabrera than in the Medes cave. Moreover, variation in toxicity either between communities or between seasons was a common trait for most cnidarians and bryozoans, whereas tunicates remained toxic throughout communities and seasons.

The recent breakthroughs in the understanding of host genomics in hepatitis C.

BACKGROUND: Hepatitis C Virus (HCV) infection is spontaneously resolved in about 30% of acutely infected individuals. In those who progress to chronic hepatitis C, HCV therapy permanently eradicates infection in about 40% of cases. It has long been suspected that host genetic factors are key determinants for the control of HCV infection. DESIGN: We will review in this study four genome-wide association studies (GWAS) and two large candidate gene studies that assessed the role of host genetic variation for the natural and treatment-induced control of HCV infection. RESULTS: The studies consistently identified genetic variation in interleukin 28B (IL28B) as the strongest predictor for the control of HCV infection. Importantly, single nucleotide polymorphisms (SNPs) in IL28B strongly predicted both spontaneous and treatment-induced HCV recovery. IL28B is located on chromosome 19 and encodes interferon-λ, a type III interferon with antiviral activity, which is mediated through the JAK-STAT pathway by inducing interferon-stimulated genes. The SNPs identified in the GWAS are in high linkage disequilibrium with coding or functional non-coding SNPs that might modulate function and/or expression of IL28B. The role of the different IL28B alleles on gene expression and cytokine function has not yet been established. CONCLUSIONS: These findings provide strong genetic evidence for the influence of interferon-λ for both the natural and treatment-induced control of HCV infection, and support the further investigation of interferon-λ for the treatment of chronic hepatitis C. Furthermore, genetic testing before HCV therapy could provide important information towards an individualized HCV treatment.

Resting heart rate and the risk of heart failure in healthy adults: the rotterdam study.

Background- An elevated resting heart rate is associated with rehospitalization for heart failure and is a modifiable risk factor in heart failure patients. We aimed to examine the association between resting heart rate and incident heart failure in a population-based cohort study of healthy adults without pre-existing overt heart disease. Methods and Results- We studied 4768 men and women aged ≥55 years from the population-based Rotterdam Study. We excluded participants with prevalent heart failure, coronary heart disease, pacemaker, atrial fibrillation, atrioventricular block, and those using β-blockers or calcium channel blockers. We used extended Cox models allowing for time-dependent variation of resting heart rate along follow-up. During a median of 14.6 years of follow-up, 656 participants developed heart failure. The risk of heart failure was higher in men with higher resting heart rate. For each increment of 10 beats per minute, the multivariable adjusted hazard ratios in men were 1.16 (95% confidence interval, 1.05-1.28; P=0.005) in the time-fixed heart rate model and 1.13 (95% confidence interval, 1.02-1.25; P=0.017) in the time-dependent heart rate model. The association could not be demonstrated in women (P for interaction=0.004). Censoring participants for incident coronary heart disease or using time-dependent models to account for the use of β-blockers or calcium channel blockers during follow-up did not alter the results. Conclusions- Baseline or persistent higher resting heart rate is an independent risk factor for the development of heart failure in healthy older men in the general population.

Spatial planning to the test of property rights in Switzerland : an innovative land management approach to coordinate spatial planning goals with property rights interests

In Switzerland, the land management regime is characterized by a liberal attitude towards the institution of property rights, which is guaranteed by the Constitution. Under the present Swiss constitutional arrangement, authorities (municipalities) are required to take into account landowners' interests when implementing their spatial planning policy. In other words, the institution of property rights cannot be restricted easily in order to implement zoning plans and planning projects. This situation causes many problems. One of them is the gap between the way land is really used by the landowners and the way land should be used based on zoning plans. In fact, zoning plans only describe how landowners should use their property. There is no sufficient provision for handling cases where the use is not in accordance with zoning plans. In particular, landowners may not be expropriated for a non-conforming use of the land. This situation often leads to the opening of new building areas in greenfields and urban sprawl, which is in contradiction with the goals set into the Federal Law on Spatial Planning. In order to identify legal strategies of intervention to solve the problem, our paper is structured into three main parts. Firstly, we make a short description of the Swiss land management regime. Then, we focus on an innovative land management approach designed to implement zoning plans in accordance with property rights. Finally, we present a case study that shows the usefulness of the presented land management approach in practice. We develop three main results. Firstly, the land management approach brings a mechanism to involve landowners in planning projects. Coordination principle between spatial planning goals and landowners' interests is the cornerstone of all the process. Secondly, the land use is improved both in terms of space and time. Finally, the institution of property rights is not challenged, since there is no expropriation and the market stays free.

The determinants of queen size in a socially polymorphic ant.

In social animals, body size can be shaped by multiple factors, such as direct genetic effects, maternal effects, or the social environment. In ants, the body size of queens correlates with the social structure of the colony: colonies headed by a single queen (monogyne) generally produce larger queens that are able to found colonies independently, whereas colonies headed by multiple queens (polygyne) tend to produce smaller queens that stay in their natal colony or disperse with workers. We performed a cross-fostering experiment to investigate the proximate causes of queen size variation in the socially polymorphic ant Formica selysi. As expected if genetic or maternal effects influence queen size, eggs originating from monogyne colonies developed into larger queens than eggs collected from polygyne colonies, be they raised by monogyne or polygyne workers. In contrast, eggs sampled in monogyne colonies were smaller than eggs sampled in polygyne colonies. Hence, eggs from monogyne colonies are smaller but develop into larger queens than eggs from polygyne colonies, independently of the social structure of the workers caring for the brood. These results demonstrate that a genetic polymorphism or maternal effect transmitted to the eggs influences queen size, which probably affects the social structure of new colonies.

Probing the role of point mutations in the cyp51A gene from Aspergillus fumigatus in the model yeast Saccharomyces cerevisiae.

Azole-resistant strains of Aspergillus fumigatus have been detected and the underlying molecular mechanisms of resistance characterized. Point mutations in the cyp51A gene have been proved to be related to azole resistance in A. fumigatus clinical strains and with different resistance profiles depending on the amino acid change (G54E, G54V, G54R, G54W, M220V, M220K, M220T, M220I). The aim of this work was to express A. fumigatus cyp51A genes in the yeast Saccharomyces cerevisiae in order to better assess the contribution of each independent amino acid substitution to resistance. A tetracycline regulatable system allowing repression of the endogenous essential ERG11 gene was used. The expression of Aspergillus cyp51A alleles could efficiently restore the absence of ERG11 in S. cerevisiae. In general, S. cerevisiae clones expressing. A. fumigatus cyp51A alleles from azole-resistant isolates showed higher MICs to all azoles tested than those expressing alleles from susceptible isolates. The azole susceptibility profiles obtained in S. cerevisiae upon expression of specific cyp51A alleles recapitulated susceptibility profiles observed from their A. fumigatus origins. In conclusion this work supports the concept that characteristics of specific A. fumigatus cyp51A alleles could be investigated in the heterologous host S. cerevisiae.

Traducción comentada de Guidelines Governing the Adoption of Children, 2011 in India

En este trabajo se analiza la variación discursiva y los diferentes criterios de estilo entre textos jurídicos normativos en inglés y español; se establecen fenómenos lingüísticos propios del discurso jurídico que generan problemas de traducción; y se comparan algunas diferencias entre sistemas jurídicos y políticos para analizar su repercusión en la traducción.

Diffusion of influenza during the winter of 1889-90 in Switzerland

The influenza of the winter of 1889-90 was one of the first epidemics to spread all over the world. At the time, several people hypothesized that the railway was one of the main vectors of diffusion of this influenza. This hypothesis was defended in Switzerland especially by Schmid, Chief of the Swiss Office of Health, who collected an impressive body of material about the spread of the epidemic in that country. These data on influenza combined with data about the structure of the railway are used in this paper in order to test the hypothesis of a mixed diffusion process, first between communes interconnected by the railway, and secondly, between those communes and neighbouring communes. An event history analysis model taking into account diffusion effects is proposed and estimated. Results show that the hypothesis is supported if the railway network in Switzerland is not taken as a whole but if a distinction between railway companies is made.

Reduction in the use of diagnostic tests in infants with risk factors for early-onset neonatal sepsis does not delay antibiotic treatment.

Despite a low positive predictive value, diagnostic tests such as complete blood count (CBC) and C-reactive protein (CRP) are commonly used to evaluate whether infants with risk factors for early-onset neonatal sepsis (EOS) should be treated with antibiotics. We investigated the impact of implementing a protocol aiming at reducing the number of diagnostic tests in infants with risk factors for EOS in order to compare the diagnostic performance of repeated clinical examination with CBC and CRP measurement. The primary outcome was the time between birth and the first dose of antibiotics in infants treated for suspected EOS. Among the 11,503 infants born at ≥35 weeks during the study period, 222 were treated with antibiotics for suspected EOS. The proportion of infants receiving antibiotics for suspected EOS was 2.1% and 1.7% before and after the change of protocol (p = 0.09). Reduction of diagnostic tests was associated with earlier antibiotic treatment in infants treated for suspected EOS (hazard ratio 1.58; 95% confidence interval [CI] 1.20-2.07; p <0.001), and in infants with neonatal infection (hazard ratio 2.20; 95% CI 1.19-4.06; p = 0.01). There was no difference in the duration of hospital stay nor in the proportion of infants requiring respiratory or cardiovascular support before and after the change of protocol. Reduction of diagnostic tests such as CBC and CRP does not delay initiation of antibiotic treatment in infants with suspected EOS. The importance of clinical examination in infants with risk factors for EOS should be emphasised.

Effects of computing parameters and measurement locations on the estimation of 3D NPS in non-stationary MDCT images.

The goal of this study was to investigate the impact of computing parameters and the location of volumes of interest (VOI) on the calculation of 3D noise power spectrum (NPS) in order to determine an optimal set of computing parameters and propose a robust method for evaluating the noise properties of imaging systems. Noise stationarity in noise volumes acquired with a water phantom on a 128-MDCT and a 320-MDCT scanner were analyzed in the spatial domain in order to define locally stationary VOIs. The influence of the computing parameters in the 3D NPS measurement: the sampling distances bx,y,z and the VOI lengths Lx,y,z, the number of VOIs NVOI and the structured noise were investigated to minimize measurement errors. The effect of the VOI locations on the NPS was also investigated. Results showed that the noise (standard deviation) varies more in the r-direction (phantom radius) than z-direction plane. A 25 × 25 × 40 mm(3) VOI associated with DFOV = 200 mm (Lx,y,z = 64, bx,y = 0.391 mm with 512 × 512 matrix) and a first-order detrending method to reduce structured noise led to an accurate NPS estimation. NPS estimated from off centered small VOIs had a directional dependency contrary to NPS obtained from large VOIs located in the center of the volume or from small VOIs located on a concentric circle. This showed that the VOI size and location play a major role in the determination of NPS when images are not stationary. This study emphasizes the need for consistent measurement methods to assess and compare image quality in CT.

The use of quantile trees in the prediction of the diameter distribution of a stand

Abstract