A comparison between diuretics and angiotensin-receptor blocker agents in patients with stage I hypertension (PREVER-treatment trial): study protocol for a randomized double-blind controlled trial

Abstract Background Cardiovascular disease is the leading cause of death in Brazil, and hypertension is its major risk factor. The benefit of its drug treatment to prevent major cardiovascular events was consistently demonstrated. Angiotensin-receptor blockers (ARB) have been the preferential drugs in the management of hypertension worldwide, despite the absence of any consistent evidence of advantage over older agents, and the concern that they may be associated with lower renal protection and risk for cancer. Diuretics are as efficacious as other agents, are well tolerated, have longer duration of action and low cost, but have been scarcely compared with ARBs. A study comparing diuretic and ARB is therefore warranted. Methods/design This is a randomized, double-blind, clinical trial, comparing the association of chlorthalidone and amiloride with losartan as first drug option in patients aged 30 to 70 years, with stage I hypertension. The primary outcomes will be variation of blood pressure by time, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new subclinical atherosclerosis and sudden death. The study will last 18 months. The sample size will be of 1200 participants for group in order to confer enough power to test for all primary outcomes. The project was approved by the Ethics committee of each participating institution. Discussion The putative pleiotropic effects of ARB agents, particularly renal protection, have been disputed, and they have been scarcely compared with diuretics in large clinical trials, despite that they have been at least as efficacious as newer agents in managing hypertension. Even if the null hypothesis is not rejected, the information will be useful for health care policy to treat hypertension in Brazil. Clinical trials registration number ClinicalTrials.gov: NCT00971165

Distribution of Rickettsia rickettsii in ovary cells of Rhipicephalus sanguineus (Latreille1806) (Acari: Ixodidae)

Abstract Background Considering the fact that the dog tick, Rhipicephalus sanguineus, has a great potential to become the vector of Brazilian Spotted Fever (BSF) for humans, the present study aimed to describe the distribution of the bacterium Rickettsia rickettsii, the etiological agent of BSF, in different regions of the ovaries of R. sanguineus using histological techniques. The ovaries were obtained from positive females confirmed by the hemolymph test and fed in the nymph stage on guinea pigs inoculated with R. rickettsii. Results The results showed a general distribution of R. rickettsii in the ovary cells, being found in oocytes in all stages of development (I, II, III, IV and V) most commonly in the periphery of the oocyte and also in the cytoplasm of pedicel cells. Conclusions The histological analysis of the ovaries of R. sanguineus infected females confirmed the presence of the bacterium, indicating that the infection can interfere negatively in the process of reproduction of the ticks, once alterations were detected both in the shape and cell structure of the oocytes which contained bacteria.

A two-stage economic succession at the inception of farming in central Portugal. Preliminary examination of possible causes and consequences

[EN]Notwithstanding their scarcity and uneven distribution, zooarchaeological and stable isotope data sets on the Early and Middle Neolithic (5500–3200 cal BC) in the region of Estremadura in Central Portugal strongly suggest that two succeeding stages in subsistence strategies took place: sheep and goat itinerant pastoralism (across large areas) and/or renewed focus on wild food sources (cervid hunting, harvesting marine and freshwater food) which replaced livestock farming within smaller areas and less specialised hunting practices. This economic shift seems to have coincided with two other dramatic changes: the 5.9 kyr cal BP climate event and the onset of megalithism. Possible correlations between these past cultural and palaeoenvironmental phenomena are herein preliminarily outlined. [ES] A pesar de su escasez y distribución desigual, el conjunto de datos arqueozoológicos y de isótopos estables para el Neolítico Antiguo y Medio de la región de Estremadura en el centro de Portugal (5500-3200 a. C. cal), sugiere con claridad dos etapas sucesivas en las estrategias de subsistencia: pastoreo itinerante de ovejas y cabras (ocupando grandes territorios) y/o un renovado interés por los recursos alimenticios silvestres (caza de cérvidos, recolección de alimentos marinos y de agua dulce), que reemplazó otras formas de ganadería más confinadas en el espacio acciones con regímenes de mantenimiento reducidos y unas prácticas de caza menos especializadas. Este cambio económico parece haber ocurrido junto con otros dos cambios dramáticos, el evento climático 5.9 k BP (cal.) y el inicio del megalitismo. Aquí se esbozan de forma preliminar las posibles correlaciones entre estos fenómenos culturales y paleoambientales del pasado.

Dental arch relationship in children with complete unilateral cleft lip and palate following one-stage and three-stage surgical protocols

The objective of this study is to compare dental arch relationship following one-stage and three-stage surgical protocols of unilateral cleft lip and palate. Dental casts of 61 children (mean age, 11.2 years; SD, 1.7), consecutively treated in one center with one-stage closure of the complete cleft at 9.2 months (SD, 2.0), were compared with a sample of 97 patients (mean age, 8.7 years; SD, 0.9), consecutively treated with a three-stage protocol including delayed hard palate closure in another center. The dental casts were assigned random numbers to blind their origin. Four raters graded dental arch relationship and palatal morphology using the EUROCRAN index. The strength of agreement of rating was assessed with kappa statistics. Independent t tests were run to compare the EUROCRAN scores between one-stage and three-stage samples, and Fisher's exact tests were performed to evaluate differences of distribution of the EUROCRAN grades. The intra- and inter-rater agreement was moderate to very good. Dental arch relationship in the one-stage sample was less favorable than in three-stage group (mean scores, 2.58 and 1.97 for one-stage and three-stage samples, respectively; p?stage sample was more favorable than in the three-stage group (mean scores, 1.79 and 1.96 for one-stage and three-stage samples, respectively; p?=?0.047). The dental arch relationship following one-stage repair was less favorable than the outcome of three-stage repair. The palatal morphology following one-stage repair, however, was more favorable than the outcome of three-stage repair.

Accurate and robust reconstruction of proximal femur from sparse intraoperative data and dense point distribution model for surgical navigation

Constructing a 3D surface model from sparse-point data is a nontrivial task. Here, we report an accurate and robust approach for reconstructing a surface model of the proximal femur from sparse-point data and a dense-point distribution model (DPDM). The problem is formulated as a three-stage optimal estimation process. The first stage, affine registration, is to iteratively estimate a scale and a rigid transformation between the mean surface model of the DPDM and the sparse input points. The estimation results of the first stage are used to establish point correspondences for the second stage, statistical instantiation, which stably instantiates a surface model from the DPDM using a statistical approach. This surface model is then fed to the third stage, kernel-based deformation, which further refines the surface model. Handling outliers is achieved by consistently employing the least trimmed squares (LTS) approach with a roughly estimated outlier rate in all three stages. If an optimal value of the outlier rate is preferred, we propose a hypothesis testing procedure to automatically estimate it. We present here our validations using four experiments, which include 1 leave-one-out experiment, 2 experiment on evaluating the present approach for handling pathology, 3 experiment on evaluating the present approach for handling outliers, and 4 experiment on reconstructing surface models of seven dry cadaver femurs using clinically relevant data without noise and with noise added. Our validation results demonstrate the robust performance of the present approach in handling outliers, pathology, and noise. An average 95-percentile error of 1.7-2.3 mm was found when the present approach was used to reconstruct surface models of the cadaver femurs from sparse-point data with noise added.

Nectar distribution and its relation to food quality in honeybee (Apis mellifera) colonies

In honeybees (Apis niellifera), the process of nectar collection is considered a straightforward example of task partitioning with two subtasks or two intersecting cycles of activity: (1) foraging and (2) storing of nectar, linked via its transfer between foragers and food processors. Many observations suggest, however, that nectar colleclion and processing in honeybees is a complex process, involving workers of other sub-castes and depending on variables such as resource profitability or the amount of stored honey. It has been observed that food processor bees often distribute food to other hive bees after receiving it from incoming foragers, instead of storing it immediately in honey cells. While there is little information about the sub-caste affiliation and the behaviour of these second-order receivers, this stage may be important for the rapid distribution of nutrients and related information. To investigate the identity of these second-order receivers, we quantified behaviours following nectar transfer and compared these behaviours with the behaviour of average worker hive-bees. Furthermore, we tested whether food quality (sugar concentration) affects the behaviour of the second-order receivers. Of all identified second-order receivers, 59.3% performed nurse duties, 18.5% performed food-processor duties and 22.2% performed forager duties. After food intake, these bees were more active, had more trophallaxes (especially offering contacts) compared to average workers and they were found mainly in the brood area, independent of food quality. Our results show that the liquid food can be distributed rapidly among many bees of the three main worker sub-castes, without being stored in honey cells first. Furthermore, the results suggest that the rapid distribution of food partly depends on the high activity of second-order receivers.

Afghanistan connection : heroin production, distribution, and consumption

Heroin prices are a reflection of supply and demand, and similar to any other market, profits motivate participation. The intent of this research is to examine the change in Afghan opium production due to political conflict affecting Europe’s heroin market and government policies. If the Taliban remain in power, or a new Afghan government is formed, the changes will affect the heroin market in Europe to a certain degree. In the heroin market, the degree of change is dependent on many socioeconomic forces such as law enforcement, corruption, and proximity to Afghanistan. An econometric model that examines the degree of these socioeconomic effects has not been applied to the heroin trade in Afghanistan before. This research uses a two-stage least squares econometric model to reveal the supply and demand of heroin in 36 different countries from the Middle East to Western Europe in 2008. An application of the two-stage least squares model to the heroin market in Europe will attempt to predict the socioeconomic consequences of Afghanistan opium production.

Time to renal disease and end-stage renal disease in PROFILE: a multiethnic lupus cohort.

BACKGROUND: Renal involvement is a serious manifestation of systemic lupus erythematosus (SLE); it may portend a poor prognosis as it may lead to end-stage renal disease (ESRD). The purpose of this study was to determine the factors predicting the development of renal involvement and its progression to ESRD in a multi-ethnic SLE cohort (PROFILE). METHODS AND FINDINGS: PROFILE includes SLE patients from five different United States institutions. We examined at baseline the socioeconomic-demographic, clinical, and genetic variables associated with the development of renal involvement and its progression to ESRD by univariable and multivariable Cox proportional hazards regression analyses. Analyses of onset of renal involvement included only patients with renal involvement after SLE diagnosis (n = 229). Analyses of ESRD included all patients, regardless of whether renal involvement occurred before, at, or after SLE diagnosis (34 of 438 patients). In addition, we performed a multivariable logistic regression analysis of the variables associated with the development of renal involvement at any time during the course of SLE.In the time-dependent multivariable analysis, patients developing renal involvement were more likely to have more American College of Rheumatology criteria for SLE, and to be younger, hypertensive, and of African-American or Hispanic (from Texas) ethnicity. Alternative regression models were consistent with these results. In addition to greater accrued disease damage (renal damage excluded), younger age, and Hispanic ethnicity (from Texas), homozygosity for the valine allele of FcgammaRIIIa (FCGR3A*GG) was a significant predictor of ESRD. Results from the multivariable logistic regression model that included all cases of renal involvement were consistent with those from the Cox model. CONCLUSIONS: Fcgamma receptor genotype is a risk factor for progression of renal disease to ESRD. Since the frequency distribution of FCGR3A alleles does not vary significantly among the ethnic groups studied, the additional factors underlying the ethnic disparities in renal disease progression remain to be elucidated.

Estimating Spatial Distribution of American Lobster Homarus Americanus Using Habitat Variables

The spatial distribution of the American lobster Homarus americanus is influenced by many factors, which are often difficult to quantify. We implemented a modeling approach for quantifying season-, size-, and sex-specific lobster spatial distribution in the Gulf of Maine with respect to environmental and spatial variables including bottom temperature, bottom salinity, latitude, longitude, depth, distance offshore, and 2 substratum features. Lobster distribution was strongly associated with temperature and depth, and differed seasonally by sex. In offshore waters in the fall, females were dominant at higher latitudes and males at lower latitudes. This segregation was not apparent in the spring although females were still dominant at higher latitudes in offshore waters. Juveniles and adults were also distributed differently; juveniles were more abundant at the lower latitudes in inshore waters, while adults were more widespread along the entire coast. These patterns are consistent with the ecology of the American lobster. This study provides a tool to evaluate changes in lobster spatial distribution with respect to changes in key habitat and other environmental variables, and consequently could be of value for the management of the American lobster.

Spatial Distribution of Stem Cell-Like Keratinocytes in Dissected Compound Hair Follicles of the Dog

Hair cycle disturbances are common in dogs and comparable to some alopecic disorders in humans. A normal hair cycle is maintained by follicular stem cells which are predominately found in an area known as the bulge. Due to similar morphological characteristics of the bulge area in humans and dogs, the shared particularity of compound hair follicles as well as similarities in follicular biomarker expression, the dog is a promising model to study human hair cycle and stem cell disorders. To gain insight into the spatial distribution of follicular keratinocytes with stem cell potential in canine compound follicles, we microdissected hair follicles in anagen and telogen from skin samples of freshly euthanized dogs. The keratinocytes isolated from different locations were investigated for their colony forming efficiency, growth and differentiation potential as well as clonal growth. Our results indicate that i) compound and single hair follicles exhibit a comparable spatial distribution pattern with respect to cells with high growth potential and stem cell-like characteristics, ii) the lower isthmus (comprising the bulge) harbors most cells with high growth potential in both, the anagen and the telogen hair cycle stage, iii) unlike in other species, colonies with highest growth potential are rather small with an irregular perimeter and iv) the keratinocytes derived from the bulbar region exhibit characteristics of actively dividing transit amplifying cells. Our results now provide the basis to conduct comparative studies of normal dogs and those with hair cycle disorders with the possibility to extend relevant findings to human patients.

Expression and distribution of a vacuolar aquaporin in young and mature leaf tissues of Brassica napus in relation to water fluxes

Recently, it has been shown that water fluxes across biological membranes occur not only through the lipid bilayer but also through specialized water-conducting proteins, the so called aquaporins. In the present study, we investigated in young and mature leaves of Brassica napus L. the expression and localization of a vacuolar aquaporin homologous to radish γ-tonoplast intrinsic protein/vacuolar-membrane integral protein of 23 kDa (TIP/VM 23). In-situ hybridization showed that these tonoplast aquaporins are highly expressed not only in developing but also in mature leaves, which export photosynthates. No substantial differences could be observed between different tissues of young and mature leaves. However, independent of the developmental stage, an immunohistochemical approach revealed that the vacuolar membrane of bundle-sheath cells contained more protein cross-reacting with antibodies raised against radish γ-TIP/VM 23 than the mesophyll cells. The lowest labeling was detected in phloem cells. We compared these results with the distribution of plasma-membrane aquaporins cross-reacting with antibodies detecting a domain conserved among members of the plasma-membrane intrinsic protein 1 (PIP1) subfamily. We observed the same picture as for the vacuolar aquaporins. Furthermore, a high density of gold particles labeling proteins of the PIP1 group could be observed in plasmalemmasomes of the vascular parenchyma. Our results indicate that γ-TIP/VM 23 and PIP1 homologous proteins show a similar expression pattern. Based on these results it is tempting to speculate that bundle-sheath cells play an important role in facilitating water fluxes between the apoplastic and symplastic compartments in close proximity to the vascular tissue.

The liver stage of Plasmodium berghei inhibits host cell apoptosis.

Plasmodium berghei is the causative agent of rodent malaria and is widely used as a model system to study the liver stage of Plasmodium parasites. The entry of P. berghei sporozoites into hepatocytes has extensively been studied, but little is known about parasite-host interaction during later developmental stages of the intracellular parasite. Growth of the parasite far beyond the normal size of the host cell is an important stress factor for the infected cell. Cell stress is known to trigger programmed cell death (apoptosis) and we examined several apoptotic markers in P. berghei-infected cells and compared their level of expression and their distribution to that of non-infected cells. As none of the apoptotic markers investigated were found altered in infected cells, we hypothesized that parasite infection might confer resistance to apoptosis of the host cell. Treatment with peroxide or serum deprivation induced apoptosis in non-infected HepG2 cells, whereas P. berghei-infected cells appeared protected, indicating that the parasite interferes indeed with the apoptotic machinery of the host cell. To prove the physiological relevance of these results, mice were infected with high numbers of P. berghei sporozoites and treated with tumour necrosis factor (TNF)-alpha/D-galactosamine to induce massive liver apoptosis. Liver sections of these mice, stained for degraded DNA, confirmed that infected cells containing viable parasites were protected from programmed cell death. However, in non-treated control mice as well as in TNF-alpha-treated mice a small proportion of dead intracellular parasites with degraded DNA were detected. Most hepatocytes containing dead parasites provoked an infiltration of immunocompetent cells, indicating that these cells are no longer protected from cell death.

An individual based model spatial distribution, production and biomass for Calanus finmarchicus in the Norwegian Sea

The copepod Calanus finmarchicus is the dominant species of the meso-zooplankton in the Norwegian Sea, and constitutes an important link between the phytoplankton and the higher trophic levels in the Norwegian Sea food chain. An individualbased model for C. finmarchicus, based on super-individuals and evolving traits for behaviour, stages, etc., is two-way coupled to the NORWegian ECOlogical Model system (NORWECOM). One year of modelled C. finmarchicus spatial distribution, production and biomass are found to represent observations reasonably well. High C. finmarchicus abundance is found along the Norwegian shelf-break in the early summer, while the overwintering population is found along the slope and in the deeper Norwegian Sea basins. The timing of the spring bloom is generally later than in the observations. Annual Norwegian Sea production is found to be 29 million tonnes of carbon and a production to biomass (P/B) ratio of 4.3 emerges. Sensitivity tests show that the modelling system is robust to initial values of behavioural traits and with regards to the number of super-individuals simulated given that this is above about 50,000 individuals. Experiments with the model system indicate that it provides a valuable tool for studies of ecosystem responses to causative forces such as prey density or overwintering population size. For example, introducing C. finmarchicus food limitations reduces the stock dramatically, but on the other hand, a reduced stock may rebuild in one year under normal conditions. The NetCDF file contains model grid coordinates and bottom topography.

Mineralogy and nannoplankton distribution in ODP Hole 194-1195A

Significant synchronous shifts in the chemistry, mineralogy, grain sizes and color of the sediments at 6 m below sea floor (mbsf) at ODP Site 1195 on the Marion Plateau (NE Australia) are interpreted to reflect a major regional paleoceanographic change: the initiation of the southern province of the Great Barrier Reef (GBR). The onset of this massive carbonate production centre nearby resulted primarily in increased deposition of carbonate-rich sediments of neritic origin. Both sedimentation rate and terrigenous input record a coincident decline attributed to inshore trapping of materials behind the reefs. Our best estimate places the development of reef framework in the southern part of the GBR between 560 and 670 kyr B.P., based on an age model combining magnetostratigraphic and biostratigraphic data. The proposed estimation agrees with previous studies reporting an age between 500 and 930 kyr B.P., constraining more tightly their results. However, it does not support research placing the birth of the GBR in Marine Isotope Stage (MIS) 11 (~400 kyr), nor the theory of a worldwide modern barrier reef development at that time.

(Appendix) Benthic foraminifera distribution of upper Creatceous and Paleocene at DSDP Hole 72-516F

Benthic foraminifers of the Coniacian-Santonian through the Paleocene were recovered from a continuous pelagic carbonate section from Hole 516F on the Rio Grande Rise. Sixty-five genera and 153 species have been identified, most of which have been reported from other localities. Bathyal depths are reflected in the benthic assemblages dominated by gavelinellids (Gavelinella beccariiformis, G. velascoensis), Nuttallides truempyi, and various gyroidinids and buliminids. Rapid subsidence during the Coniacian-Santonian from nearshore to upper to middle bathyal depths was followed by much reduced subsidence, with the Campanian-Paleocene interval accumulating at middle bathyal to lower bathyal depths. A census study based on detailed sampling reveals major changes in benthic faunal composition at the Cretaceous/Tertiary boundary transition. It was a time of rapid turnover, with the extinctions of numerous species and the introduction of many new species. Overall, species diversity decreases about 20%, and approximately one-third of latest Maestrichtian species do not survive to the end of the Cretaceous. This shift indicates a significant environmental change in the deep sea, the precise nature of which is not apparent from the foraminifers or their enclosing sediments.