Search

Knowledge of migration behaviour and spatio-temporal habitat use is important for management and conservation, not least for diadromous species where population dynamics are affected by processes occurring in both freshwater and marine habitats. Sampling from a commercial capture fishery for the ecologically and economically important salmonid Salmo trutta L. we genotyped 189 single nucleotide polymorphisms and carried out genetic assignment of origin for 916 migratory sea trout sampled along ∼500 km of Britain's North Sea coast. Population contributions to stocks showed strong geographical differences. Trout from rivers in the northern part of this coast (Tweed, Aln, Coquet, and Tyne) contributed the majority of migrants, irrespective of location, but fish from local rivers contributed to catches in most locations. Almost all (99%) trout assigned to native British populations and a large proportion (34%) of the sampled catches originated in rivers more than 100 km from capture sites, suggesting long-distance migration to be a common trait, confirming and enlarging historical trends from tagging data. Repeated sampling across years indicated short-term stability in migration patterns. Findings illustrate the scope for genetic stock identification to identify marine habitat use and monitor population-specific migration behaviours in species where stock assessment has not traditionally incorporated marine phase dynamics. [ABSTRACT FROM AUTHOR]

In this study, we identify 11 Kepler systems (KIC 5255552, 5653126, 5731312, 7670617, 7821010, 8023317, 10268809, 10296163, 11519226, 11558882, and 12356914) with a flip-flop effect in the eclipse timing variations O − C diagrams of the systems, report on what these systems have in common and whether these systems are dynamically stable. These systems have previously reported high eccentric binary stars with highly eccentric third bodies/outer companions. We find that all of the additional bodies in the system are dynamically stable for the configurations previously reported and are therefore likely to exist as described. We also provide additional evidence of KIC 5255552 being a quadruple star system composed of an eclipsing binary pair and non-eclipsing binary pair with the possibility of a fifth body in the system. With the advent of the NASA's Transiting Exoplanet Survey Satellite (TESS) exoplanet survey, its precision photometric monitoring offers an opportunity to help confirm more local eclipsing binary star companions, including planets. [ABSTRACT FROM AUTHOR]

Second-hand smoke (SHS) exposure is high among UK Bangladeshi and Pakistani populations, reflecting higher male smoking prevalence and fewer home smoking restrictions than the general population. The Muslim Communities Learning About Second-hand Smoke (MCLASS) study explored the feasibility and acceptability of implementing SHS education in 14 UK mosques. Religious teachers (RTs) in seven intervention mosques were trained and provided with a culturally appropriate educational package. After the intervention, mosque leaders, RTs and congregants' experiences and perceptions of the intervention were explored through interviews and focus group discussions. Delivery of the intervention varied across mosques. Facilitators and barriers included: mosque diversity (congregation size, organizational structure, educational activities, women's role and involvement); degree of trust between researchers and personnel; and views on SHS. Most participants thought mosques' involvement in SHS health promotion was appropriate, but the perceived importance of SHS differed. We found that a health promotion programme delivered within Islamic religious settings that engages RTs in the process of facilitation, can be acceptable and feasible, but care must be taken to explore the culture and ethos of the institution, including its organizational structure, management committee, RTs and congregation. [ABSTRACT FROM AUTHOR]

In this paper, we report the evidence for a planetary mass body orbiting the close binary star KIC 5095269. This detection arose from a search for eclipse timing variations amongst the more than 2000 eclipsing binaries observed by Kepler. Light curve and periodic eclipse time variations have been analysed using SYSTEMIC and a custom BINARY ECLIPSE TIMINGS code based on the TRANSIT ANALYSIS PACKAGE which indicates a 7.70 ± 0.08MJup object orbiting every 237.7 ± 0.1 d around a 1.2M⊙ primary and a 0.51M⊙ secondary in an 18.6 d orbit. A dynamical integration over 107 yr suggests a stable orbital configuration. Radial velocity observations are recommended to confirm the properties of the binary star components and the planetary mass of the companion. [ABSTRACT FROM AUTHOR]

We present a spectropolarimetric snapshot survey of solar-type planet-hosting stars. In addition to 14 planet-hosting stars observed as part of the BCool magnetic snapshot survey, we obtained magnetic observations of a further 19 planet-hosting solar-type stars in order to see if the presence of close-in planets had an effect on the measured surface magnetic field (|Bl|). Our results indicate that the magnetic activity of this sample is congruent with that of the overall BCool sample. The effects of the planetary systems on the magnetic activity of the parent star, if any, are too subtle to detect compared to the intrinsic dispersion and correlations with rotation, age and stellar activity proxies in our sample. Four of the 19 newly observed stars, two of which are subgiants, have unambiguously detected magnetic fields and are future targets for Zeeman-Doppler mapping. [ABSTRACT FROM AUTHOR]

Background Sickness certification poses significant challenges to most general practitioners (GPs). As an alternative form of certification, in 2010, the UK implemented the 'fit note', which focuses on returning to work after illness. It has been well received in the UK but little is known of non-UK GP attitudes towards the fit note. Aims To evaluate the challenges Irish GPs experience with the current sickness certification system and their attitudes towards the fit note. Methods A questionnaire assessing attitudes, practices and preferences regarding the fit note was developed, piloted and posted to a representative sample of Irish GPs selected by systematic sampling. Descriptive statistics, chi-square tests and binary logistic regression were used to analyse the results. Results Of 305 GPs surveyed, 64% (196) completed the survey. Ninety per cent (177) of responders reported a lack of available rehabilitation services for patients on sick leave and 66% (124) reported adverse effects of sickness certification on therapeutic relationships with patients. Those who indicated a preference for introducing the fit note (53%; 104) were significantly more likely to endorse both an excessive focus on disability [odds ratio (OR) = 3.16] and lack of GP training (OR = 2.04) in the sickness certification process. Conclusions Difficulties associated with sickness certification are apparent at GP-patient, GP-employer and GP-health service levels. Addressing these will require intervention at each of these levels and may be facilitated by challenging the assumption that illness equates to disability. [ABSTRACT FROM AUTHOR]

There is increasing evidence that the complement system plays an important role in diabetes and the development of diabetic vascular complications. In particular, mannan-binding lectin ( MBL) levels are elevated in diabetes patients, and diabetes patients with diabetic nephropathy have higher MBL levels than diabetes patients with normal renal function. The MBL-associated serine proteases ( MASPs) MASP-1, MASP-2 and MASP-3 and MBL-associated protein MAp44 have not yet been studied in diabetes patients. We therefore measured plasma levels of MASP-1, MASP-2, MASP-3 and MAp44 in 30 children with type 1 diabetes mellitus ( T1DM) and 17 matched control subjects, and in 45 adults with T1DM and 31 matched control subjects. MASP-1 and MASP-2 levels were significantly higher in children and adults with T1DM than in their respective control groups, whereas MASP-3 and MAp44 levels did not differ between patients and controls. MASP-1 and MASP-2 levels correlated with HbA1c, and MASP levels decreased when glycaemic control improved. Because MASP-1 and MASP-2 have been shown to interact directly with blood coagulation, elevated levels of these proteins may play a role in the enhanced thrombotic environment and consequent vascular complications in diabetes. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the effect of pre-treatment verification imaging with megavoltage X-rays on cancer and normal cell survival in vitro and to compare the findings with theoretically modelled data. Since the dose received from pre-treatment imaging can be significant, the incorporation of this dose at the planning stage of treatment has been suggested. Methods: The impact of imaging dose incorporation on cell survival was investigated by clonogenic assay of irradiated DU-145 prostate cancer, H460 non-small-cell lung cancer and AGO-1522b normal tissue fibroblast cells. Clinically relevant imaging-to-treatment times of 7.5 and 15 min were chosen for this study. The theoretical magnitude of the loss of radiobiological efficacy due to sublethal damage repair was investigated using the Lea-Catcheside dose protraction factor model. Results: For the cell lines investigated, the experimental data showed that imaging dose incorporation had no significant impact on cell survival. These findings were in close agreement with theoretical results. Conclusion: For the conditions investigated, the results suggest that allowance for the imaging dose at the planning stage of treatment should not adversely affect treatment efficacy. Advances in knowledge: There is a paucity of data in the literature on imaging effects in radiotherapy. This article presents a systematic study of imaging dose effects on cancer and normal cell survival, providing both theoretical and experimental evidence for clinically relevant imaging doses and imaging-to-treatment times. The data provide a firm foundation for further study into this highly relevant area of research. [ABSTRACT FROM AUTHOR]

The emergence of Vibrio cholerae ( Vc) lipopolysaccharide ( LPS) as a lead protective antigen for a cholera subunit vaccine has increased the interest in what type of B cell is best suited to generate anti- Vc LPS antibodies. A related question is what form of LPS is the most immunogenic. C57 Bl/6 ( B6) neonatal mice (10 days old) whose marginal zone ( MZ) B cell compartment is still maturing and two lines of knockout mice that either lack the signaling mechanism required for the maturation of MZ B cells or that lack a receptor required for MZ B cell retention in the MZ were used to determine the role of MZ B cells in anti- Vc LPS antibody responses. Data support the conclusion that MZ B cells play a significant role in the anti- Vc LPS antibody response. Serum and vibriocidal antibody titers also depend on whether the Vc LPS is purified or bacterial cell-associated. [ABSTRACT FROM AUTHOR]

Background: Sarcoidosis is a multisystem granulomatous disease of unknown aetiology. Proteins present within the alveolar space early in sarcoidosis disease may provide an insight into novel mechanisms for the development of fibrotic disease and in particular pulmonary fibrosis.Methods: A modified two-dimensional difference gel electrophoresis protocol was applied to the human bronchoalveolar lavage fluid (hBALF) of four patients with non-persistent pulmonary interstitial disease at 4-year follow-up (defined as mild disease) and four patients who developed pulmonary interstitial disease at 4-year follow-up (defined as severe disease). The protein β-actin was identified by LC-MS/MS from a preparative gel and found to be significantly elevated in early lavages from the severe disease group. To look at the potential pro-fibrotic effects of this protein, primary human pulmonary fibroblasts (CCD-19Lu) were treated with recombinant β-actin following which qPCR and ELISA assays were used to measure any effects.Results: We found that β-actin levels were significantly elevated in early hBALF samples in patients who subsequently developed severe disease when compared to the mild group. Treating primary human pulmonary fibroblasts with recombinant β-actin led to enhanced gene expression of the pro-fibrotic markers alpha smooth muscle actin and collagen 1 as well as the increased secretion of interleukin-13 and metalloproteinases 3 and 9.Conclusion: Free β-actin within the lungs of sarcoidosis patients potentially may contribute to disease pathogenesis particularly in the context of abnormal remodelling and the development of pulmonary fibrosis. [ABSTRACT FROM PUBLISHER]

Our objective was to evaluate a near-infrared reflectance spectroscopy (NIRS) used in the feed industry to estimate the potential for grains to increase the risk of ruminal acidosis. The existing NIRS calibration was developed from in sacco and in vitro measures in cattle and grain chemical composition measurements. To evaluate the existing model, 20 cultivars of 5 grain types were fed to 40 Holstein heifers using a grain challenge protocol and changes in rumen VFA, ammonia, lactic acids, and pH that are associated with acidosis were measured. A method development study was performed to determine a grain feeding rate sufficient to induce non-life threatening but substantial ruminal changes during grain challenge. Feeding grain at a rate of 1.2% of BW met these criteria, lowering rumen pH (P = 0.01) and increasing valerate (P < 0.01) and propionate concentrations (P = 0.01). Valerate was the most discriminatory measure indicating ruminal change during challenge. Heifers were assigned using a row by column design in an in vivo study to 1 of 20 grain cultivars and were reassigned after a 9 d period (n = 4 cattle/treatment). The test grains were dry rolled oats (n = 3), wheat (n = 6), barley (n = 4), triticale (n = 4), and sorghum (n = 3) cultivars. Cattle were adapted to the test grain and had ad libitum access to grass silage 11 d before the challenge. Feed was withheld for 14 h before challenge feeding with 0.3 kg DM of silage followed by the respective test grain fed at 1.2% of BW. A rumen sample was taken by stomach tube 5, 65, 110, 155, and 200 rain after grain consumption. The rumen is not homogenous and samples of rumen fluid obtained by stomach tube will differ from those gained by other methods. Rumen pH was measured immediately; individual VFA, ammonia, and D- and L-lactate concentrations were analyzed later. Rumen pH (P = 0.002) and all concentrations of fermentation products differed among grains (P = 0.001). A previously defined discriminant score calculated at 200 rain after challenge was used to rank grains for acidosis risk. A significant correlation between the discriminant score and the NIRS ranking (r = 0.731, P = 0.003) demonstrated the potential for using NIRS calibrations for predicting acidosis risk of grains in cattle. The overall rankings of grains for acidosis risk were wheat > triticale > barley > oats > sorghum. [ABSTRACT FROM AUTHOR]

Establishing status and trend for an endangered species is critical to recovery, especially when it is faced with a nascent extinction agent. We calculated, with hierarchical log-linear change-point models, hibernaculum-level population trends between 1983 and 2009 for the endangered Indiana bat (Myotis soda Us) now subjected to the fast-spreading fungal disease white-nose syndrome. We combined trends from 222 wintering populations before and after onset of the disease to determine trend for clusters of interacting wintering populations, recovery units, and the species. Before onset of the disease, a west-to-east gradient in trends existed, with westernmost populations declining and easternmost populations increasing in abundance. The species as a whole, however, was stationary between 1983 and 2005 (-0.5% mean annual change; 95% confidence interval [C7] = -2.8, +1.8%). Estimated mean population size in 2009 was 377,124 bats (195,398-957,348), with large variance apparently caused by white-nose syndrome. With the onset of white-nose syndrome (2006-2009), the species exhibited a 10.3% annual decline (95% CI = -21.1, +2.0%). White-nose syndrome is having an appreciable influence on the status and trends of Indiana bat populations, stalling and in some cases reversing population gains made in recent years. [ABSTRACT FROM AUTHOR]

SUMMARY The Pyrenees mountain belt, which separates the Iberian Peninsula from the rest of the European continent, is part of the Alpine-Himalayan orogenic belt, formed as a result of a collision between the African and Eurasian Plates. Although the instrumental seismicity in the Pyrenees is moderate, in the past centuries a number of destructive earthquakes have occurred, which could indicate continuing tectonic activity of the area. We analyse GPS observations spanning 3.5 yr from 35 continuous stations in the Pyrenees region and find significant on-going extension perpendicular to the range at 2.5 ± 0.5 nstrain yr-1, with the possibility of higher strain rates concentrated in the westernmost part of the range. This finding is in agreement with the predominantly normal faulting focal mechanisms of earthquakes that occur in the area and suggests a recurrence time for magnitude 6.5 earthquakes of 2200-2500 yr. [ABSTRACT FROM AUTHOR]

In Mencius iia6 all humans are said to have 'a heart that does not bear the suffering of others'. I argue that this statement is illustrated, rather than proven, by the example of our reaction to a child about to fall into a well. This illustration can be located at the most basic level of ethical universals (it is a universal example): basic ethical training; further steps in a ladder of reflection are universal reflection on ethical norms themselves, which may finally be related universally to non-ethical concerns. [ABSTRACT FROM AUTHOR]

Measurement of the rate of phenotypic or genetic change provides data bearing on many questions of fundamental interest to biologists, including how fast changes can proceed, whether shifts occur gradually or in bursts and how long high rates of change can be sustained. Because traits exist in functionally and genetically correlated suites, studies tracking many traits are likely to be the most informative. We quantify very rapid phenotypic changes in egg size (now smaller), clutch size (larger) and the age/size of both breeding females and males (younger, smaller) in an Alaskan population, with these traits shifting at rates from 0.13 to 0.30 haldanes over a 10-year period. In contrast, female reproductive effort and the allometric relationship of clutch size to body size changed little. These shifts appear to be caused by an altered selective landscape, with the presumed selective agent being increasing lake productivity. Some of the traits undoubtedly have at heritable component and thus represent genetic evolution as well as phenotypic. [ABSTRACT FROM AUTHOR]

The UK Infrared Telescope Infrared Deep Sky Survey (UKIDSS) is the first of a new generation of infrared surveys. Here, we combine the data from two UKIDSS components, the Large Area Survey (LAS) and the Galactic Cluster Survey (GCS), with Two-Micron All-Sky Survey (2MASS) data to produce an infrared proper motion survey for low-mass stars and brown dwarfs. In total, we detect 267 low-mass stars and brown dwarfs with significant proper motions. We recover all 10 known single L dwarfs and the one known T dwarf above the 2MASS detection limit in our LAS survey area and identify eight additional new candidate L dwarfs. We also find one new candidate L dwarf in our GCS sample. Our sample also contains objects from 11 potential common proper motion binaries. Finally, we test our proper motions and find that while the LAS objects have proper motions consistent with absolute proper motions, the GCS stars may have proper motions which are significantly underestimated. This is possibly due to the bulk motion of some of the local astrometric reference stars used in the proper motion determination. [ABSTRACT FROM AUTHOR]

We consider the issue of analyzing complex ecological data in the presence of covariate information and model uncertainty. Several issues can arise when analyzing such data, not least the need to take into account where there are missing covariate values. This is most acutely observed in the presence of time-varying covariates. We consider mark-recapture-recovery data, where the corresponding recapture probabilities are less than unity, so that individuals are not always observed at each capture event. This often leads to a large amount of missing time-varying individual covariate information, because the covariate cannot usually be recorded if an individual is not observed. In addition, we address the problem of model selection over these covariates with missing data. We consider a Bayesian approach, where we are able to deal with large amounts of missing data, by essentially treating the missing values as auxiliary variables. This approach also allows a quantitative comparison of different models via posterior model probabilities, obtained via the reversible jump Markov chain Monte Carlo algorithm. To demonstrate this approach we analyze data relating to Soay sheep, which pose several statistical challenges in fully describing the intricacies of the system. [ABSTRACT FROM AUTHOR]

We consider the estimation of the size of a closed population, often of interest for wild animal populations, using a capture–recapture study. The estimate of the total population size can be very sensitive to the choice of model used to fit to the data. We consider a Bayesian approach, in which we consider all eight plausible models initially described by Otis et al. (1978, Wildlife Monographs 62, 1–135) within a single framework, including models containing an individual heterogeneity component. We show how we are able to obtain a model-averaged estimate of the total population, incorporating both parameter and model uncertainty. To illustrate the methodology we initially perform a simulation study and analyze two datasets where the population size is known, before considering a real example relating to a population of dolphins off northeast Scotland. [ABSTRACT FROM AUTHOR]

This article presents a Bayesian analysis of mark-recapture-recovery data on Soay sheep. A reversible jump Markov chain Monte Carlo technique is used to determine age classes of common survival, and to model the survival probabilities in those classes using logistic regression. This involves environmental and individual covariates, as well as random effects. Auxiliary variables are used to impute missing covariates measured on individual sheep. The Bayesian approach suggests different models from those previously obtained using classical statistical methods. Following model averaging, features that were not previously detected, and which are of ecological importance, are identified. [ABSTRACT FROM AUTHOR]

The authors present findings from a Bayesian analysis of Scotland's four primary capture-recapture data sources for 2000 that was carried out to estimate numbers of current injecting drug users by region (Greater Glasgow vs. elsewhere in Scotland), sex (male vs. female), and age group (15-34 years vs. > or =35 years). A secondary goal of the analysis was to obtain Bayesian estimates and credible intervals for the demographic influences on Scotland's drug-related death rate per 100 current injectors. Incorporation of informative priors altered the models with highest posterior probability. Expert opinion on how demography influenced Scottish drug injectors' propensity to be listed in different data sources was taken into account, along with external information about European injectors' drug-related death rates and male:female ratios. Higher drug-related mortality was confirmed in older drug injectors and those outside of Greater Glasgow. Female injectors' lower drug-related death rate was not sustained beyond 34 years of age. The authors recommend that demographic influences be accommodated in behavioral capture-recapture estimation, especially when it is a prelude to secondary analysis, such as the analysis of drug-related death rates presented here. [ABSTRACT FROM AUTHOR]

Summary. The classical approach to statistical analysis is usually based upon finding values for model parameters that maximize the likelihood function. Model choice in this context is often also based on the likelihood function, but with the addition of a penalty term for the number of parameters. Though models may be compared pairwise by using likelihood ratio tests for example, various criteria such as the Akaike information criterion have been proposed as alternatives when multiple models need to be compared. In practical terms, the classical approach to model selection usually involves maximizing the likelihood function associated with each competing model and then calculating the corresponding criteria value(s). However, when large numbers of models are possible, this quickly becomes infeasible unless a method that simultaneously maximizes over both parameter and model space is available. We propose an extension to the traditional simulated annealing algorithm that allows for moves that not only change parameter values but also move between competing models. This transdimensional simulated annealing algorithm can therefore be used to locate models and parameters that minimize criteria such as the Akaike information criterion, but within a single algorithm, removing the need for large numbers of simulations to be run. We discuss the implementation of the transdimensional simulated annealing algorithm and use simulation studies to examine its performance in realistically complex modelling situations. We illustrate our ideas with a pedagogic example based on the analysis of an autoregressive time series and two more detailed examples: one on variable selection for logistic regression and the other on model selection for the analysis of integrated recapture–recovery data. [ABSTRACT FROM AUTHOR]

Extending the work of Dupuis (1995), we motivate a range of biologically plausible models for multiple‐site capture‐recapture and show how the original Gibbs sampling algorithm of Dupuis can be extended to obtain posterior model probabilities using reversible jump Markov chain Monte Carlo. This model selection procedure improves upon previous analyses in two distinct ways. First, Bayesian model averaging provides a robust parameter estimation technique which properly incorporates model uncertainty in the resulting intervals. Secondly, by discriminating among perhaps millions of competing models, we are able to discern fine structure within the data and thereby answer questions of primary biological importance. We demonstrate how reversible jump Markov chain Monte Carlo methods provide the only viable method for exploring model spaces of this size. We examine the lizard data discussed in Dupuis (1995) and show that most of the posterior mass is placed upon models not previously considered for these data. We discuss model discrimination and model averaging and focus upon the increased scientific understanding of the data obtained via the Bayesian model comparison procedure. [ABSTRACT FROM PUBLISHER]

We consider the problem of estimating the total size of a population from a series of incomplete census data. We observe that inference is typically highly sensitive to the choice of model and we demonstrate how Bayesian model averaging techniques easily overcome this problem. We combine and extend the work of Madigan & York (1997) and Dellaportas & Forster (1999) using reversible jump Markov chain Monte Carlo simulation to calculate posterior model probabilities which can then be used to estimate model‐averaged statistics of interest. We provide a detailed description of the simulation procedures involved and consider a wide variety of modelling issues, such as the range of models considered, their parameterisation, both prior choice and sensitivity, and computational efficiency. We consider a detailed example concerning adolescent injuries in Pennsylvania on the basis of medical, school and survey data. In the context of this example, we discuss the relationship between posterior model probabilities and the associated information criteria values for model selection. We also discuss cost‐efficiency issues with particular reference to inclusion and exclusion of sources on the grounds of cost. We consider a decision‐theoretic approach, which balances the cost and accuracy of different combinations of data sources to guide future decisions on data collection. [ABSTRACT FROM PUBLISHER]

Focuses on a study which monitored dispersing juvenile western burrowing owls using radiotelemetry within a migratory population in southwestern Idaho during 1994 and 1995. Documentation and description of post-fledging dispersal behavior and movements prior to their first migration; Methods; Results.

To determine whether a priming course of lymphoblastoid interferon-alpha (IFN-alpha) enhances the efficacy of subsequent IFN-alpha therapy in the treatment of chronic hepatitis B, a randomized trial was conducted to compare IFN-alpha priming (IFN-alpha for one month; no treatment for one month) followed by IFN-alpha therapy for three months, with IFN-alpha therapy (10 MU thrice-weekly) given for three months. Thirty-seven patients seropositive for more than six months for HBsAg, HBeAg and HBV DNA, and with histological evidence of active liver inflammation, were recruited. Eight patients (40%) treated with a priming course of IFN-alpha responded to subsequent IFN-alpha therapy for three months with loss of HBV DNA and HBe seroconversion. This compared with five patients (29%), treated only with IFN-alpha therapy for three months, who lost HBV DNA and HBeAg (but only two [12%] developed anti-HBe). IFN-alpha was well tolerated, with only three patients withdrawing from the study because of 'flu'-like symptoms or inconvenience in the early phase. The better response, although not significant, may suggest a place for a short priming course of IFN-alpha in addition to the current IFN-alpha treatment regimen. [ABSTRACT FROM AUTHOR]

To determine whether a priming course of lymphoblastoid interferon-alpha (IFN-α) enhances the efficacy of subsequent IFN-α therapy in the treatment of chronic hepatitis B, a randomized trial was conducted to compare IFN-α priming (IFN-α for one month; no treatment for one month) followed by IFN-α therapy for three months, with IFN-α therapy (10 MU thrice-weekly) given for three months. Thirty-seven patients seropositive for more than six months for HBsAg, HBeAg and HBV DNA, and with histological evidence of active liver inflammation, were recruited. Eight patients (40%) treated with a priming course of IFN-α responded to subsequent IFN-α therapy for three months with loss of HBV DNA and HBe seroconversion. This compared with five patients (29%), treated only with IFN-α therapy for three months, who lost HBV DNA and HBeAg (but only two [12%] developed anti-HBe). IFN-α was well tolerated, with only three patients withdrawing from the study because of 'flu'-like symptoms or inconvenience in the early phase. The better response, although not significant, may suggest a place for a short priming course of IFN-α in addition to the current IFN-α treatment regimen. [ABSTRACT FROM PUBLISHER]

The sulfation of primary N-hydroxy arylamines is a critical intermediate step in the bioactivation of many carcinogenic arylamines, arylamides and nitroaromatics. However, the study of this reaction in vitro is often complicated by the chemical instability of these molecules. We have examined the stability of two highly purified N-hydroxy arylamines, N-hydroxyaniline and N-hydroxy-2-aminofluorene, under different oxidative reaction conditions pertinent to the assay of sulfotransferases. Furthermore, these compounds, as well as the products of their oxidative degradation, were examined for their interactions with homogeneous aryl sulfotransferase (AST) IV. Under reaction conditions where oxidative degradation of the N-hydroxy arylamines occurred, N-hydroxyaniline and N-hydroxy-2-aminofluorene produced time-dependent and irreversible inhibition of AST IV. While this inhibition was not dependent upon the presence of 3'-phosphoadenosine 5'-phosphosulfate in the reaction mixture, analysis of the N-hydroxy arylamines by UV spectroscopy showed that the inhibition of AST IV did require non-enzymatic oxidation of the N-hydroxy arylamine. Under reaction conditions that prevented the oxidative degradation of N-hydroxyaniline, this N-hydroxy arylamine was a substrate for AST IV. Likewise, under similar conditions, 4-chloro-N-hydroxyaniline was also a substrate for the enzyme. In contrast, no AST IV catalyzed sulfation of N-hydroxy-2-aminofluorene was detected under conditions that prevented the oxidation of N-hydroxy-2-aminofluorene. Adequate protection of these N-hydroxy arylamines from oxidative degradation required the addition of L-ascorbic acid to reaction mixtures that had also been degassed and purged with argon. The irreversible inhibition of AST IV exhibited by these N-hydroxy arylamines, even in reaction mixtures where attempts were made to limit oxidative degradation by degassing and purging with argon, emphasized the importance of completely preventing such degradation when utilizing in vitro assays to assess the potential for an N-hydroxy arylamine to serve as a substrate for a specific sulfotransferase. [ABSTRACT FROM PUBLISHER]

Haemophilus ducreyi is a major cause of genital ulcer disease in many developing countries and is associated with augmented transmission of human immunodeficiency virus (HIV). However, the mechanisms through which H. ducreyi produces ulceration are poorly understood. The characteristics of the host response to H. ducreyi and the pathobiology of its potential contribution to increased HIV susceptibility are not known. Chancroid ulcer biopsies from 8 patients were analyzed histologically and immunohistochemically. All biopsies had perivascular and interstitial mononuclear cell infiltrates that extended deep into the dermis. The infiltrate, which contained macrophages and CD4 and CD8 lymphocytes, was consistent with a delayed hypersensitivity type cell-mediated immune response. The recruitment of CD4 T lymphocytes and macrophages may in part explain the facilitation of HIV transmission in patients with chancroid. [ABSTRACT FROM PUBLISHER]