In order to draw patterns in helminth parasite composition and species richness in Mexican freshwater fishes we analyse a presence-absence matrix representing every species of adult helminth parasites of freshwater fishes from 23 Mexican hydrological basins. We examine the distributional patterns of the helminth parasites with regard to the main hydrological basins of the country, and in doing so we identify areas of high diversity and point out the biotic similarities and differences among drainage basins. Our dataset allows us to evaluate the relationships among drainage basins in terms of helminth diversity. This paper shows that the helminth fauna of freshwater fishes of Mexico can characterise hydrological basins the same way as fish families do, and that the basins of south-eastern Mexico are home to a rich, predominantly Neotropical, helminth fauna whereas the basins of the Mexican Highland Plateau and the Nearctic area of Mexico harbour a less diverse Nearctic fauna, following the same pattern of distribution of their fish host families. The composition of the helminth fauna of each particular basin depends on the structure of the fish community rather than on the limnological characteristics and geographical position of the basin itself. This work shows distance decay of similarity and a clear linkage between host and parasite distributions. The helminth parasite fauna of freshwater fish of Mexico ranks amongst the best characterised parasite faunas in Latin America In this paper, we analyse the distributional patterns of adult helminth parasites of freshwater fishes of Mexico, with regard to the main hydrological basins of the country. We examine the linkage between host and parasite distributions, evaluating the relationships among drainage basins in terms of helminth diversity. Considering the points explained before, if each family of fish has a typical helminth fauna whose distribution corresponds to that of their hosts, then the ichthyological composition of the basin may be an important determinant of the patterns of distribution of the helminths. Moreover, the geographical distance amongst basins can be an important determinant of similarity in helminth faunas. Frequent contacts and exchanges of parasites between host populations of nearby basins should lead to highly homogenous faunas, we would expect the similarity in species composition among basins to decay with increasing distance between them et al.et al.et al.A presence-absence matrix, representing every species of adult helminth parasites of freshwater fishes from 23 Mexican hydrological basins , Table 1Major drainage basins of freshwater systems of Mexico, outlined in Relationships between the helminthofauna inhabiting each drainage basin were examined via a similarity matrix constructed using the Sørensen coefficient. Multivariate classification is a useful method to examine biogeographic patterns exhibited by species and to distinguish and characterise biogeographic entities. In this work, drainage basins were considered the main units of comparison, and individual species occurrence represented the attributes of the individual drainage units Bothriocephalus acheilognathi Yamaguti, 1934 (Cestoda) that was found in 12 river basins The compiled database includes a total of 170 species of adult helminths from 85 genera and 34 families recorded from 16 families of freshwater species of fishes in Mexico this database has been already examined for taxonomical composition and endemism by Salgado-Maldonado and Quiroz-Martínez Helminth species richness varies widely throughout drainage basins of the country . NeotropAnalysis of similarity, based on Sørensen’s coefficient, of the relationships between helminth faunas of the 21 drainage basins for all species (excluding introduced species) showed three large clusters that exhibit low similarity (<10%) between them at species level. Results of the analyses carried out using the full species list (with the introduced species) show a somewhat disrupted pattern. The three main groups are still clearly represented in the dendrogram and the MDS ordination . However, it is worth noting that the sampling effort has been different for each of the Mexican biogeographical provinces. The tropics have been studied far more intensively, with a greater number of basins explored, more frequency in sampling, and more fish families and species sampled et al.Our analyses allowed the distinction of Neotropical, Nearctic and Pacific Mexican drainage basins. Fish parasite fauna shows that half (11/21) of the Mexican basins analysed in this work classify as Neotropical. The close relationship between the helminths of Chiapas-Usumacinta and Tabasco hydrological systems was expected as most of these records belong indeed to the Río Usumacinta drainage basin, sampled form its middle part in Chiapas and from its lower part in Tabasco. The bodies of water sampled from the Yucatán Peninsula appeared as the area most associated with them, followed by the Río Papaloapan basin. This is further confirmed as distance between basins is taken into account: geographical proximity of the basins would allow frequent contacts and exchange of parasites that would explain high values of similarity between neighbouring basins. These similarities in helminth fauna are in accordance to the concept of the Usumacinta Ichthyological Province proposed by Miller In the same way, the close similarities observed between the second group of neotropical basins  can be explained by the helminthological and the ichthyological composition of the faunas and by the geographical proximity of the basins. All these data confirm that parasite communities show decay in compositional similarity as a function of distance separating them. As shown by our results nearby host populations tend to have many parasite species in common, whereas distant ones share few Ictalurus balsanus and the goodeid Ilyodon whitei, in the Río Balsas basin, coupled with the record of three North American generalist helminths, provide a component of nearctic species in this basin. This is counterbalanced by several neotropical species of helminths associated to the cichlid Cichlasoma istlanum and the characid Astyanax aeneus. The neotropical species component is even larger in the three remaining basins mentioned , and is responsible for the strong similarity between these basins, while the presence of an ictalurid species in each basin contributes to the nearctic component. As for the main two neotropical groups of helminths discussed previously, the composition of the helminthofauna in the Balsas, Pánuco, Ayuquila and Santiago basins is explained because the geographical distribution of the helminth fauna reflects the distribution of the ichthyological fauna. Traditionally, the Lerma and Santiago basins have been considered as a single biogeographic unit for different taxa particularly freshwater fishes The Balsas and Pánuco river basins as well as the Ayuquila and Santiago river basins have a mixture of nearctic and neotropical helminth species associated with the fish families that inhabit them. The presence of the ictalurid host I. punctatus  The helminth composition and the position in the multivariate analyses of the bodies of water of the Cuatro Ciénegas Valley, geographically located in the Nearctic realm, can be explained by the fact that only cichlids and characids have been examined in this area, and that these are essentially neotropical fish families Agonostomus monticola, which migrate along the coast, entering continental bodies of water from brackish environments. The absence of these eleotrids and mugilids from nearctic environments results in a strong differentiation of this set of basins compared to the Pacific ones. These Pacific basins can also be differentiated from the neotropical ones by the peripheral distribution and the number of species of eleotrids and mugilids, given the fact that species of either families are rarely examined in more inland neotropical basins.The third set of basins, the Pacific affinities group, includes the oases of Baja California Sur, rivers and streams near Chamela Jalisco, and bodies of water belonging to either, the Río Papagayo or Río Atoyac basins. This group can be explained by the distribution of the basins along the Pacific versant of Mexico, by the geographic proximity between the Papagayo and Atoyac basins and between the Baja California and Ayuquila basins and also by the way their fish hosts families and their parasites disperse. The records of helminths in these basins are primarily associated with eleotrids and a species of mullet What this paper shows is that the helminth fauna of freshwater fishes of Mexico can characterise hydrological basins the same way as the fish families do. The data presented above show that the basins of south-eastern Mexico harbour a predominantly Neotropical helminth fauna whereas the basins of the Mexican Highland Plateau and the Nearctic area of Mexico harbour Nearctic fauna, following the same pattern of distribution of fish host families. The analysis shows that the composition of the helminth fauna of each particular basin depends on the structure of the fish community rather than on the limnological characteristics and geographical position of the basin itself and that the similarity decreases with increasing distance between drainage basins, the same that holds for their host families Figure S1Dendrogram resulting from the similarity matrix based on the Sørensen Similarity Index for all river basins with introduced species. Groups are based on parasite species composition of the basin.(TIF)Click here for additional data file.Figure S2Non Metric multidimensional scaling (nMDS) ordination plot resulting from the resemblance matrix of the river basins, based on the Sørensen Similarity Index, with introduced species.(TIF)Click here for additional data file.Table S1Most widespread species helminths of freshwater fishes of Mexico.(DOCX)Click here for additional data file.


There are substantial geographic variations in coronary heart disease (CHD) mortality rates in England that may in part be due to differences in climate and air pollution. An ecological cross-sectional multi-level analysis of male and female CHD mortality rates in all wards in England (1999–2004) was conducted to estimate the relative strength of the association between CHD mortality rates and three aspects of the physical environment - temperature, hours of sunshine and air quality. Models were adjusted for deprivation, an index measuring the healthiness of the lifestyle of populations, and urbanicity. In the fully adjusted model, air quality was not significantly associated with CHD mortality rates, but temperature and sunshine were both significantly negatively associated (p<0.05), suggesting that CHD mortality rates were higher in areas with lower average temperature and hours of sunshine. After adjustment for the unhealthy lifestyle of populations and deprivation, the climate variables explained at least 15% of large scale variation in CHD mortality rates. The results suggest that the climate has a small but significant independent association with CHD mortality rates in England. Geographical inequalities in coronary heart disease (CHD) mortality rates in England are substantial and persistent. Since the late 1970s, male CHD mortality rates have been at least 30% higher in the North of England than in the South East, and the differences between North and South for female rates have been even larger It is unclear how much of the geographic variation in CHD in England is a result of differences in the physical environmental. This paper explores the impact of climate and air pollution on geographic variation in CHD mortality rates. Plausible mechanisms for the effect of these factors on CHD have been suggested. Cold weather increases blood pressure, blood cholesterol, blood viscosity (thereby increasing the risk of thrombosis), and could induce a mild inflammatory response thereby increasing blood coagulability st January 2003. Henceforth these areas are referred to simply as ‘wards’. There are 7,929 wards in England, which can be grouped into 355 local authorities (LAs). Mortality data were provided by the Office for National Statistics for the years 1999 to 2004 (inclusive) stratified by sex, ward and five year age group. The mortality data included all deaths in England where CHD was recorded as the primary cause of death . Change in ICD coding over the data collection period is thought to have had little impact on reporting of CHD mortalities The analyses reported in this paper utilise ecological regression models, with all standard table wards as the unit of analysis. Standard table wards are a statistical set of boundaries based on the electoral ward boundaries as of 1Data on mean maximum temperature and total hours of sunshine were provided by the Meteorological Office for 37 English weather stations for every month between 2000 and 2002. The data were used to generate model-based ward-level estimates of mean maximum temperature and total hours of sunshine for each month between 2000 and 2002 using second order trend surface modelling Air pollution data were collected in 2001 for the development of the physical environment domain of the Index of Multiple Deprivation 2004 2An index of unhealthy lifestyle was used as a measure of the behavioural risk factor profile of populations. This index was derived from a principal components analysis of five sets of ward-level synthetic estimates of the prevalence of cardiovascular risk factors, specifically consumption of less than five portions of fruit and vegetables per day Deprivation and urbanicity are other potential confounders of the relationship between climate, air pollution and CHD mortality rates. Deprivation in England is higher in the North than in the South (following a similar gradient to mean temperature and hours of sunshine), and air pollution is higher in more urban areas. The deprivation index used in these analyses was the ward-level Carstairs index Initially exploratory data analysis techniques were used to investigate correlations between the exposure variables and assess the distribution of the outcome variables. Then baseline multi-level regression models ) were built with male and female CHD mortality rates as outcome variables, in order to get a baseline measurement of residual variance at ward-level and LA-level. Then univariate and multivariate multi-level models were built with the physical environment, unhealthy lifestyle index and deprivation variables as exposure variables. Inclusion of variance at ward-level and LA-level is important as climate and air pollution vary on different spatial scales. Finally, equivalent spatial error regression models were built with the same exposure and outcome variables. These were built to assess whether the associations derived in the multi-level models were adversely affected by spatial autocorrelation bias. Results from the multi-level models were the primary outcomes, as they allow for an assessment of how much variance is explained by the exposure variables both at ward-level and LA-level. These results are used as proxies for explanation of ‘small-scale’ variation  and ‘large-scale’ variation . The estimation technique used for the multi-level modelling was iterative generalised least squares (IGLS), and the spatial error modelling used maximum likelihood techniques, ensuring that the results of the multi-level models and the spatial error models are comparable.Both male and female ward-level age-standardised CHD mortality rates were reasonably normally distributed, and hence suitable for regression analyses. The ward-level and LA-level variance in the baseline models is shown in The physical environment variables contribute little to the explanation of ward-level variation. However, they clearly contribute to the explanation of LA-level variance in mortality, even after adjustment for urbanicity, the unhealthy lifestyle and deprivation indices: the models containing only the confounding variables (model E) explained around 65% of the LA-level variance, whereas this increased to nearly 80% in the final model (model F).The spatial error univariate and multivariate models showed good agreement with the multi-level models, suggesting that spatial autocorrelation bias has not substantially affected these findings. The parameter estimates in the spatial error models tended to be closer to zero than in the multi-level models, demonstrating that spatial autocorrelation (when unaccounted for) tends to result in a bias away from the null hypothesis. The difference in the parameter estimates between the multi-level and spatial error models was generally in the region of around 10% to 20% (results not shown).Two local climate measures  and a measure of air pollution were found to explain - without accounting for other factors - nearly 60% of large scale geographic variation in CHD mortality rates but did little to explain small scale geographic variations in CHD rates. The strength of the relationships was strongly attenuated when deprivation, urbanicity and behavioural risk factor profiles of populations were added as explanatory variables. A substantial amount of large scale geographic variation in CHD rates is explained by physical environment variables even after adjustment for deprivation, urbanicity and behavioural risk factor profiles of populations – at least 10% of large scale variation in mortality rates. These models suggest that the climate has a small but independent association with CHD mortality rates in England – a ward with the lowest observed temperature had 40 more male deaths per 100,000 and 25 more female deaths per 100,000 than a ward with highest observed temperature, all else being equal. In comparison, applying excess winter mortality from CHD for England in 2004/05 This is the first instance of a study of geographic variation in small area CHD rates that accounts for behavioural risk factor profiles of populations, deprivation, and a number of measures of the physical environment within the same set of analyses. The multi-level design of the analyses allowed for the explanation of large scale and small scale geographic variation in CHD rates simultaneously, which allowed for disentanglement of the influence of variables that are effective at the different scales. The spatial error models allowed for an assessment of whether the multi-level models were prone to spatial autocorrelation bias, which was shown not to be the case. The systematic approach to building models that was utilised here allowed for a comprehensive assessment of the impact of confounding, and for some disentanglement of the amount of geographic variation that is explained by the climate and air pollution variables.The results presented in this paper are derived from ecological cross-sectional analyses. Because of the cross-sectional nature of the studies, the results cannot confirm causal relationships. The relationship between climate and CHD rates presented here may be a result of residual confounding. Economic deprivation, unhealthy lifestyles and the climate generally follow the same North-South gradient in England, and the associations shown in the analyses may be a result of errors in the measurement of economic deprivation and unhealthy lifestyles, or could be due to unmeasured and potentially confounding factors such as utilisation and quality of health care. A previous study of women in 23 towns in Great Britain suggested that controlling for aspirin and statin use  removed the residual variance in adjusted cardiovascular prevalence rates in England (but not in Scotland) The results presented here are in general agreement with the UK literature on geographic variation in CHD rates, in that not all of the variation in CHD rates can be explained by lifestyle factors alone. The British Regional Heart Study (BRHS) provides the most comparable results for the impact of climate on geographic variation in heart disease in England, despite the widely differing methodology employed in the study compared with the analyses reported here. Analysis of phase one of the BRHS  suggested that in 1969–73 climate variables had a modest effect on variation in local CHD mortality rates after adjustment for deprivation The results of this paper extend the results of phase one of the BRHS in the following ways: all wards in England were included in the analysis; a measure of the behavioural risk factor profile of populations of areas was included; an exploration of both small scale and large scale geographic variation in CHD rates was conducted; including wards from rural areas allowed for urbanicity to be included as a potential explanatory variable; more sophisticated estimates of air pollution and climate were used, which allowed for modelled estimates of these measures to be applied to all wards in England. The results of this paper complement the results of phase two of the BRHS, but extend the interpretations to women and to men of all ages. In addition, the analyses reported here were sufficiently powered at the area-level to allow for inclusion of several environmental variables in the models simultaneously.The results presented here suggest that air pollution has a small positive association with CHD mortality rates in small areas. A similar finding was shown by Maheswaran et al. in an analysis of census enumeration districts in Sheffield The analyses reported here suggest that, on top of excess winter mortality, CHD mortality rates in the coldest parts of England are generally higher compared to the warmest parts . Whilst this difference is small compared to differences in the lifestyle of populations, if the relationship is shown to be causal then it is an area which could be targeted in order to reduce geographic inequalities in CHD. Analyses of excess winter mortality in different regions of Europe have shown that the excess mortality is generally greater in countries with milder climates and this has led researchers to suggest that the impact of a cold climate on cardiovascular health can be substantially reduced if the population were better prepared for cold weather by improving household heating and insulation and wearing more appropriate clothing during cold periods of the year The work reported in this manuscript has not previously been published elsewhere, or submitted for publication elsewhere.


It is believed that immunosuppression is the sole cause for the occurrence of rhinosinusitis in hematopoietic stem cell transplant (HSCT). There is a high incidence of sinusitis in recipient's patients, especially those with Chronic Graft Versus Host disease (GVHD). Histopathological abnormalities were described in recipient's sinus mucosa comparing to the immunocompetents patients. There are also mucosal abnormalities related to the cytotoxicity in the transplanted patients with chronic GVHD, but no difference in ultrastructure between HSCT patients with and without GVHD, except increased goblet cells in patients without GVHD. The relation between the sinunasal mucosa abnormalities of patients with and without GVHD and rhinosinusitis is not well established yet.To verify the ultrastructure of the sinunasal mucosa of HSCT with and without GVHD with rhinosinusitis in order to understand the cause of high sinusitis incidence in recipients with and without GVHD.A preliminary prospective study with statistical analysis of data obtained from the evaluation of the mucosa of the uncinate process by transmission electron microscopy of those recipients with (10) and without GVHD (9) with rhinosinusitis.93% of transplanted patients with GVHD and 62% of those without GVHD had 2 or more rhinosinusitis. Only the presence of microvilli was significantly increased in patients without GVHD. There was no significant difference in the cilia number, cilia ultrastructure, squamous metaplasia, goblet cells or citoplasmatic vacuolization between those groups.The recurrence of rhinosinusitis seems to be higher in chronic GVHD patients, however no abnormalities were found in the ultrastructure of their sinunasal mucosa, except increased microvilli in those without GVHD. This is a preliminary study and an increased sample might modify statistical analysis, as well as the comparison of recipients without rhinosinusitis.


Plasmodium berghei pbNK65) the cytokine profile of infected animals is significantly altered in relation to the percent parasitemia. Preliminary data from our laboratory have shown alterations of the fatty acid profile in lungs of mice infected by pbNK65. However, it is not known if the molecular organization and lipid composition of pulmonary surfactant change during malaria ARDS. Surfactant once secreted forms organized lipid structures referred as large aggregates (LA). During respiration an inactive form of surfactant is also produced, the small aggregate form (SA). We explored the lipid profile both of the aggregates and of the lung tissue from non infected and infected animals with pbNK65 and with Plasmodium chabaudi (PcAS), a Plasmodium strain that does not induce lung pathology.One of the lethal complications of malaria is acute lung injury and in its more severe form, acute respiratory distress syndrome (ARDS). In the murine model of malaria-associated ARDS . The membrane enriched fractions of the lungs from NK65 mice are characterized by a significant increase of phosphatidylcholine and phosphatidylethanolamine. No differences are present in the other classes of PL and in the AS group.The increase in PL in the lung tissue is a common response to alveolar inflammation. This modification, absent in AS mice, appears to be correlated with malaria ARDS and consistent with the eosinophilic hyaline membrane deposition and cell infiltration observed in the alveoli of NK65 mice. The BAL fluid of NK65 mice is characterized by high increase of protein levels indicative of oedema and alveolar leakage due to the lung pathology. On the contrary, the total PL increase present also in AS groups, seems related to malaria infection but not to lung pathology. Increased total protein levels are present in the LA fraction of NK65 mice, probably due to blood-derived proteins being incorporated into or associated with these microstructures in the alveolar hypophase. The increase of LPC, a known inhibitor of surfactant activity, in the SA fraction of NK65 mice is consistent with the action of phospholipases which are known to be present in the lungs during inflammatory injury.


There is extensive research into eating disorder risk factors, and recently the focus has moved to investigating the mechanisms underlying these factors. The current study examines the interrelationships between eating disorder symptoms and two proposed risk factors: perfectionism and media internalisation. This study uses data collected as part of the Prevention Across the Spectrum randomized controlled trial, which involves approximately 2000 Grade 7 and 8 adolescents across Australia. Students were randomly allocated to one of three eating disorder prevention programs or a control group. Students were assessed in 4 waves  and the assessment included measures of perfectionism , media internalisation , and shape and weight concerns (Eating Disorder Examination Questionnaire). Preliminary analyses using a sample of baseline data suggest that the relationship between perfectionism and eating disorder symptoms is mediated by media internalisation, with differential effects depending upon the dimension of perfectionism and the outcome measure used in the analysis. Part two of this study will investigate the effects of the intervention programs on this relationship and outcome. The findings presented will have implications for our understanding of the development and prevention of eating disorder symptomatology.Prevention stream of the 2013 ANZAED Conference.This abstract was presented in the


Dear Editor,We enjoyed reading the excellent article by Abenavoli and colleagues on the clinical role of Ribavirin (RBV), and particularly the selection and maintenance of the optimal RBV dosing strategy that are required to achieve sustained viral suppression in patients with chronic hepatitis C (CHC) infection. They concluded that contemporary therapy for CHC infection is to deliver doses of both RBV and pegylated interferon-alpha (PEG-IFN) that confer optimal antiviral efficacy for a sufficient time to minimize viral relapse. At the same time, it is important to minimize the impact of side effects that might erode the effectiveness of therapy due to dose reductions below the level of therapeutic efficacy, or because the patient is unable to complete an optimal treatment course . The ear


To illustrate results of both classical and Bayesian methods of analysis, I compared Bayes and empirical Bayes esimates of abundance and density using recaptures from simulated and real populations of animals. Real populations included two iconic datasets: recaptures of tigers detected in camera-trap surveys and recaptures of lizards detected in area-search surveys. In the datasets I analyzed, classical and Bayesian methods provided similar – and often identical – inferences, which is not surprising given the sample sizes and the noninformative priors used in the analyses.In capture-recapture and mark-resight surveys, movements of individuals both within and between sampling periods can alter the susceptibility of individuals to detection over the region of sampling. In these circumstances spatially explicit capture-recapture (SECR) models, which incorporate the observed locations of individuals, allow population density and abundance to be estimated while accounting for differences in detectability of individuals. In this paper I propose two Bayesian SECR models, one for the analysis of recaptures observed in trapping arrays and another for the analysis of recaptures observed in area searches. In formulating these models I used distinct submodels to specify the distribution of individual home-range centers and the observable recaptures associated with these individuals. This separation of ecological and observational processes allowed me to derive a formal connection between Bayes and empirical Bayes estimators of population abundance that has not been established previously. I showed that this connection applies to  In capture-recapture and mark-resight surveys, movements of individuals both within and between sampling periods can alter the susceptibility of individuals to detection over the region of sampling. In these circumstances spatially explicit capture-recapture (SECR) models, which incorporate the observed locations of individuals, allow population density and abundance to be estimated while accounting for differences in detectability of individuals.http://www.mrc-bsu.cam.ac.uk/bugs/winbugs/contents.shtml) and JAGS (http://mcmc-jags.sourceforge.net)). Program SPACECAP provides a more specialized implementation of this approach A variety of SECR models have been developed to accommodate different kinds of sampling protocols and capture methods If the region occupied by the population is sufficiently large, the Poisson limit theorem suggests an asymptotic equivalence between the Poisson and binomial SECR models and their estimators of The asymptotic equivalence of binomial and Poisson SECR models may not apply in small regions or small populations. In a simulation study where recapture locations were simulated for area-search surveys The source(s) of the apparent difference in performance of classical and Bayesian estimators of density cannot be inferred from this simulation study. Were the differences associated with differences in modeling assumptions  or with differences in methods of inference and point estimators (MLE vs. posterior mean or mode)? Also, owing to the sizeable difference in number of data sets analyzed in each simulation scenario , the estimated bias and coverage of the Bayesian estimators may have included substantial Monte Carlo error, casting doubt on the statistical significance of the reported difference in performance of classical and Bayesian methods.every Poisson point-process model of SECR data and provides theoretical support for an estimator of abundance proposed for recaptures in trapping arrays To shed light on this issue and to establish a formal relationship between classical and Bayesian estimators of abundance, I developed two Bayesian models of SECR data using Poisson point processes. One model is for the analysis of recaptures observed in trapping arrays; the other is for the analysis of recapture locations observed in area searches. In formulating these models I used distinct submodels to specify the distribution of individual home-range centers and the observable recaptures associated with these individuals. This separation of ecological and observational processes allowed me to derive a formal connection between Bayes and empirical Bayes estimators of population abundance that has not been established previously. I showed that this connection applies to To illustrate the results of both classical and Bayesian methods of analysis, I compared Bayes and empirical Bayes esimates of abundance and density for both simulated and real populations of animals. Surprisingly few analyses of SECR data have assumed spatial variation in individual density In this section I describe two SECR models, one for the analysis of recaptures observed in trapping arrays and another for the analysis of recaptures observed in area searches. These models can be specified hierarchically using one component to describe the process that generates the spatial distribution of individuals in the population and a second component to describe the process that leads to an observable sample of individuals. The first component, a Poisson point-process model, is identical for both SECR models; therefore, I describe this component first and follow with descriptions of the underlying assumptions and likelihood functions of the two observation models.This component of the SECR models is similar to the model of home-range centers  proposed by I assume that the activity centers are a realization of an inhomogeneous Poisson point process parameterized by a first-order intensity function expected density of individuals  at location In the context of SECR models, We are now equipped with all of the components needed to derive the likelihood function of the model. Let In classical (non-Bayesian) statistics, the likelihood function is often written as a function of not detected in any of the In reality, only The likelihood function of the ''complete data''  locations, I assume that each individual moves randomly around its activity center jth search of region jth survey  cannot be used in the likelihood function of the observable data. Instead, we must factor the joint density into two components, one for the locations of individuals that are detected and another for the marginal probability of the non-detections obtained by integrating the unobserved recapture locations from (7).The first component of the joint density is associated with the value of The second component of the joint density is associated with the value of Note that (9) is based on the assumption that jth search of region ith individual during the jth area-search survey. Our objective is to estimate not detected during the We now have all of the elements needed to derive the likelihood function of the model. Let The likelihood function of the “complete data” (wherein The maximum-likelihood estimator (MLE) of Classical (non-Bayesian) and Bayesian estimators of population size To develop the Bayesian estimator of The MCMC algorithm used to fit this model is given in Summaries of the posterior distribution of The density of individuals can vary substantially in regions of spatially varying habitat. To mimic this situation, I simulated a population of individuals living in a square , but few individuals were observed more than twice at the same trap (average = 1.2 detections per trap).I fitted the SECR model for recaptures in trapping arrays to these data by partitioning the region occupied by the population into a grid of square pixels (width = 160 m) for numerical integration. Further reductions in pixel width did not change the value of the maximized log likelihood. I used maximum-likelihood estimates of the model's parameters to initialize the Markov chain used in the Bayesian analysis. In addition, I used  sampler  to estimClassical and Bayesian estimates of the model parameters and of their 95% confidence or credible intervals are quite similar . Strong  quality  and 3. Tognormal .I fitted the SECR model for recaptures in trapping arrays to a set of data that have been analyzed previously using both non-spatial and spatial capture-recapture models 2 (20.7 km × 37.3 km). To fit the model, I assigned In the absence of spatial covariates of tiger density, I fitted the model based on a homogeneous Poisson point process using both classical and Bayesian methods of analysis. The minimum rectangular region needed to encompass the entire trapping array spanned an area of 772 km sampler  to estim−2. The probabilities of detecting these tigers appears to be very low since the estimated maximum detection probability is only about 0.02. For comparison with a previous analysis of these data 2). 2) . The empirical Bayes and Bayes estimates of N are also quite similar since the posterior distribution appears to be approximately lognormal  within a 9-ha square plot (width = 300 m) located in southwestern Arizona, USA. During each survey, this plot was searched thoroughly for lizards, which were marked and released after noting their capture locations. A total of 14 surveys were conducted over 17 days producing 134 captures I fitted the SECR model for area-search surveys to a set of data that have been described and analyzed previously In the absence of spatial covariates of lizard density, I fitted the model based on a homogeneous Poisson point process using both classical and Bayesian methods of analysis. To fit the model, I assigned  sampler  to estim−1. For comparison with previous analyses of these data, I estimated the number of lizards present in the 9-ha surveyed plot. The empirical Bayes and Bayes estimates of Classical and Bayesian estimates of the model parameters and their 95% confidence or credible intervals are quite similar . The ave similar .I repeated the simulation study of To perform classical and Bayesian analyses of each simulated data set, I partitioned  sampler  to estimClassical and Bayes estimates of population abundance and average density were similar in most of the scenarios of the simulation study  and 8. TIn formulating the SECR models I used a Poisson point process to specify the spatial distribution of individual activity centers. This modeling assumption allowed me to derive estimators of population abundance and density for use in classical or Bayesian analyses and to compare the operating characteristics of these estimators in analyses of real and simulated data sets.every Poisson point-process model of SECR data. The only difference between models is the functional form of The Bayes and empirical Bayes estimators of population abundance are closely related. Both estimators depend on the full conditional distribution of the number An estimator of abundance proposed by An empirical Bayes approach for estimating abundance is also feasible if a binomial point-process model is fitted to SECR data. In this case the conditional distribution of the number In the datasets I analyzed, classical and Bayesian methods provided similar – and often identical – inferences, which is not surprising given the sample sizes and the noninformative priors used in the analyses. For example, in the analysis of recaptures of tigers in trapping arrays and of lizards in area searches, classical and Bayesian estimates of the model parameters and their 95% confidence or credible intervals were quite similar and were consistent with previous analyses of these data The Bayesian SECR models that I described can be extended in a variety of useful and important ways. For example, the ecological process submodel can be extended to specify stochastic sources of spatial variation in density that induce clustering of individual activity centers . The Bayesian SECR models also can be revised to include spatial or non-spatial sources of variation in detectability of individuals or alternative functional forms for models of detectability Appendix S1Derivation of empirical Bayes estimator of Var((PDF)Click here for additional data file.


Food allergies are adverse immune reactions to food proteins that can range from immediate, potentially life-threatening reactions to chronic disorders such as atopic dermatitis and allergic gastrointestinal disorders. These adverse reactions can be IgE-mediated; cells mediated or result from a combination of both. No effective preventive strategy or curative protocol is currently established. Various mouse models have been developed which mirror some of the key elements of food allergies to a high degree. These models have extended our understanding on the immunological and patho-physiological mechanisms of the allergic immune response and have been used for the initial testing of preventive and therapeutic agents. In particular the prenatal and early postnatal period seem to be a critical window for the establishment and maintenance of a normal immune response towards food allergens. This presentation will focus on the role of the maternal adaptive immune response and the nature of the diaplacental antigen transfer during the prenatal period in preventing the onset of allergies in the offspring. In addition, during the early postnatal period several host factors can influence the acquisition of oral tolerance. The interaction of the developing immune system with microbial structures seems to play a decisive role for the induction of local and systemic tolerance. Several studies demonstrated that continuous administration of live Lactobacillus rhamnosus GG (LGG) during gestation and the breastfeeding period inhibited the onset of allergen-induced sensitization and airway disease in the offspring which is associated with the induction of T-regulatory cells. Recent findings suggest that heat treated and soluble factors may also have the ability to suppress the allergic immune response. These data may help to interpret previous data from successful clinical trials and provide an outlook on future intervention strategies.


The trans-Atlantic slave trade dramatically changed the demographic makeup of the New World, with varying regions of the African coast exploited differently over roughly a 400 year period. When compared to the discrete mitochondrial haplotype distribution of historically appropriate source populations, the unique distribution within a specific source population can prove insightful in estimating the contribution of each population. Here, we analyzed the first hypervariable region of mitochondrial DNA in a sample from the Caribbean island of Jamaica and compared it to aggregated populations in Africa divided according to historiographically defined segments of the continent's coastline. The results from these admixture procedures were then compared to the wealth of historic knowledge surrounding the disembarkation of Africans on the island.In line with previous findings, the matriline of Jamaica is almost entirely of West African descent. Results from the admixture analyses suggest modern Jamaicans share a closer affinity with groups from the Gold Coast and Bight of Benin despite high mortality, low fecundity, and waning regional importation. The slaves from the Bight of Biafra and West-central Africa were imported in great numbers; however, the results suggest a deficit in expected maternal contribution from those regions.When considering the demographic pressures imposed by chattel slavery on Jamaica during the slave era, the results seem incongruous. Ethnolinguistic and ethnographic evidence, however, may explain the apparent non-random levels of genetic perseverance. The application of genetics may prove useful in answering difficult demographic questions left by historically voiceless groups. Of the estimated ten million people captured in Africa between the 16The island of Jamaica was sparsely inhabited by indigenous sea faring peoples when it was established as a Spanish settlement in 1509. These peoples either fled the island or were eradicated by the time of the English conquest of Jamaica in 1655, the result of forced labour and European diseases imposed by the Spanish . Due to th century.Between 1655 and 1807, captive Africans embarked from the most westerly shores of Senegambia and along the coast eastward, as far as Madagascar. These regions  is passed entirely matrilineally and accumulates mutations along the maternal line, providing a unique opportunity to explore the matriline of select groups. Once considering the relatively rapid mutation rate of mtDNA when compared to the nuclear genome, it is possible to create detailed phylogenies to explore the matrilineal relatedness of people . GroupinUsing historically defined geographical parameters, the distribution of mtDNA haplogroup profiles in discrete founding populations can be combined in hopes of identifying and replicating the source populations found on Jamaica during the slave trade era. This approach has been used with success in comparing great swaths of New World populations of African origin to various macro-regions in Africa, showing a concurrence with the historical literature, as well as differing contributions of African source populations in North, Central, and South America . Using aThe aim of this study is to apply similar admixture modelling to the mtDNA distribution of Jamaica with an eye toward geographic sensitivity, using historical data on the coasts of origin as source populations in an attempt to investigate the genetic vestiges of population constraints present during the slave era in Jamaica. Considering the overwhelming proportion of slaves imported from the Bight of Biafra and West-central Africa just before the end of the slave trade, as well as the continuously high levels of mortality among slaves, it is hypothesized that the mtDNA haplogroup profile distribution will resemble these latter sources more closely than regions exploited earlier in the slave trade.The mitochondrial haplogroup profiles observed in the sample of Jamaicans are presented in Additional file Only one Jamaican profile could be undoubtedly classified as belonging to typical Native American haplogroups A2; several exact matches were observed in El Salvador , Costa RAs shown in Additional file The results of the exact test of population differentiation performed on the haplogroup profile distributions confirm the discrete nature of each African coast (results not shown). In order to estimate the proportion of maternal ancestry from each major slaving coast present in the population of modern Jamaican mtDNA, admixture models using both haplogroup profiles and haplotype similarities from the African coasts were fitted to the pool of sampled Jamaicans. Combinations excluding marginal populations were also explored to investigate any contribution these groups may have on the regional haplogroup profile distribution. These estimated admixture coefficients are summarized in Tables th century and the 1790 s.Varying parts of the western coast of Africa contributed to the British trans-Atlantic slave trade in differing intensities over differing periods; however, the Gold Coast embarked slaves for the New World in consistently great numbers between the beginning of the 18Using haplogroup distributions to calculate parental population contribution, the largest admixture coefficient was associated with the Gold Coast (0.477 ± 0.12), suggesting that the people from this region may have been consistently prolific throughout the slave era on Jamaica. The diminutive admixture coefficients associated with the Bight of Biafra and West-central Africa  is striking considering the massive influx of individuals from these areas in the waning years of the British Slave trade. When excluding the pygmy groups, the contribution from the Bight of Biafra and West-central rise to their highest levels , though still far from a major contribution. When admixture coefficients were calculated by assessing shared haplotypes, the Gold Coast also had the largest contribution, though much less striking at 0.196, with a 95% confidence interval of 0.189 to 0.203. Interestingly, when haplotypes are allowed to differ by one base pair, the Jamaican matriline shows the greatest affinity with the Bight of Benin, though both Bight of Biafra and West-central Africa remain underrepresented.The results of the evaluation on genetic diversity and demography of the parental populations and of the Jamaican mitochondrial gene pool are summarized in Table The African Diaspora in Jamaica is the result of a well-documented trade in human lives for just over 150 years motivated almost entirely by the rise in demand for luxury goods in Western Europe. By taking historical African embarkation points into account, we compared estimates of maternal contribution of each parental population with historical disembarkation records. The results of the admixture analysis suggest the mtDNA haplogroup profile distribution of Jamaica more closely resembles that of aggregated populations from the modern day Gold Coast region despite an increasing influx of individuals from both the Bight of Biafra and West-central Africa during the final years of the trade. When taking what is known about the negative rate of natural population growth of slaves on Jamaica, these results add an additional layer of complexity to demographic history of Jamaica. Planters found it more economical to import new labour rather than invest in natural reproduction within their existing groups. Coupling low fecundity with the high mortality leads to the expectation of a fluid demographic shift through time to a haplogroup profile distribution more closely resembling those groups arriving later during the slave trade. Present results do not show this, hinting instead at non-random processes in the creation of modern Jamaican matrilineal demography.The admixture results may suggest a preference among Jamaican planters. Historic evidence suggests the Jamaican planting class held the Akan of the Gold Coast in very high regards , althougThe entire acclimatization process was understandably both mentally and physically stressful for newly arriving Africans. Between a quarter to a half of newly landed Africans died within the first three years on the island . The disThe slave society on Jamaica also operated in a very rigid social hierarchy; creole slaves had much greater life expectancy, fecundity, and upward social mobility than those born in Africa . The entThe development of modern Jamaican English may also provide insight into the demographic development of the island. The modern creolized English spoken on the island has been traced to relatively uneducated Northern British and Irish overseers and bookmakers and the early African slaves they interacted with. During the initial era of slavery on the island (1655-1700), slave acculturation was a process characterized by direct contact between newly arrived Africans and their European overseers. Though the Gold Coast contributed marginally to the slave trade prior to 1700, the Akan speaking groups from modern Ghana were thought to be the largest concentrated linguistic groups . These eIn summation, despite the historical evidence that an overwhelming majority of slaves were sent from the Bight of Biafra and West-central Africa near the end of the British slave trade, the mtDNA haplogroup profile of modern Jamaicans show a greater affinity with groups found in the present day Gold Coast region. Caution must be paid however to the scope of the analyses performed here. The Jamaican slave markets were the largest in the West Indies and sporadic accounts exist of slaves being purchase in Jamaica for plantations in other part of the New World; however, it is difficult to accurately trace the ancestry of the resold slaves. Additionally, after the abolition of slavery in 1834, the island is treated here as roughly a closed system with regards to the African continent. The trajectory of the mtDNA distribution is assumed to have stayed relatively consistent since emancipation; however, constraints imposed on the Jamaican population may have changed through time, influencing modern demography. The end of the slave trade in Jamaica brought about a change in economic climate, with a small albeit recognizable amount of Jamaicans emigrating to other parts of the world, as well as foreign migrant labours arriving from around the globe. Whether any these constraints have significantly affected the mtDNA distribution on the island is difficult to say.The study was approved by the local ethics committees of the University of West Indies in Mona, Jamaica. After providing informed consent, over 400 Jamaican volunteers were then asked to complete a simple questionnaire stating their birth place, their parents' birth places, and--if known--the birth places of both sets of grandparents. Individuals born outside the country or with any reported maternal relatives born outside the country were excluded from the study. Additionally, where more than one maternal relative was sampled, only one individual was used in further analysis.A database of 9,265 African first hyper variable segment (HVS-1) sequences was amassed from the literature in order to investigate any life history constraints present on the island during and after slavery. African ethnic groups were assigned locations based on present day ranges of the population imposed on the historic guidelines for the differing coasts. To account for transit of slaves from inland Africa to the coast, these regions were then segregated into the hinterland roughly perpendicularly from the coast, an assumption explored previously  is used.After exclusion criteria, analyses were preformed on 400 Jamaican individuals from around the island. Buccal swabs were collected from all subjects and stored in cell lysis solution . Total DNA was then extracted using the Qiagen buccal cell spin protocol . The HVS-1 was then amplified using PCR. A reverse primer was used to generate all sequences (for details see ). A forwAdmixture coefficients based on haplogroup profile distributions were estimated using a Markov-Chain Monte Carlo posterior sampling method assuming a multinomial distribution for the mtDNA haplogroup profiles, a method best explained in detail elsewhere . AdditioIn order to investigate the internal diversity of the studied regions' mtDNA pools, the following diversity indices were calculated: number of different haplotypes (k), number of polymorphic sites (S), mean number of pairwise differences (θπ) . DemogramtDNA: mitochondrial DNA.MLD conceived the study, performed the genetic laboratory analysis, data analysis, and drafted the manuscript. AS aided in the data analysis, interpretation and presentation. SPN assisted in the social science interpretation and validation of historical content. VAM helped in the design, conception and analysis. EYstAM aided in sample collection and help in the study design. YPP was the principal sample collector and aided in the study design. All authors reviewed and commented on the manuscript during its drafting and approved the final version.Table S1. HVS-I sequences of the Jamaican individuals analyzed in the present study.Click here for fileTable S2. Haplogroup frequencies of Jamaica, different African regions and different iterations considered and analyzed in the present study.Click here for fileTable S3. Haplotypes shared (relative frequencies) between Jamaica and the different African regions analyzed in the present study.Click here for fileTable S4. Number of shared haplotypes between the different regions considered in the present study. Numbers in the diagonal are the number of different haplotypes per region. In brackets is the proportion of the Jamaican haplotypes that are shared with each of the African regions considered.Click here for fileTable S5. Mitochondrial DNA HVS-I sequences included in this study [is study ,53-80.Click here for file


Collateral damage to esophagus with ablative therapies for atrial fibrillation (AF) remains a major concern with percutaneous catheter based therapies. Endoscopically documented thermal injuries to the esophageal mucosa such as ulcerations or hemorrhages are seen in a significant percentage of patients undergoing AF ablation. ,2 The reThe introduction of balloon based high intensity focused ultrasound therapy (HIFU) was received with considerable enthusiasm, primarily due its ability to deliver therapy without tissue contact, and absence of requirement for 3 dimensional mapping systems.  AdherencThe burden of evidence points to the mobile anatomy of the retro cardiac esophagus being responsible for the high prevalence of thermal injuries leading to LAEF which is fortunately a rare but nevertheless catastrophic complication of AF ablation. The proximity of esophagus to posterior left atrium which is accentuated in supine position contributes to mucosal thermal injury, particularly because of absence of serosa in this portion of the gut. The mobile and variable location of the esophagus with respect to each of the pulmonary veins and the source of energy is critical in determining its predilection to injury. The study by Naven et al in this issue of the journal elegantly shows the inverse relation of the luminal temperature of the esophagus to the distance from HIFU balloon.  The remo


In the last century peroxisomes were thought to have an endosymbiotic origin. Along with mitochondria and chloroplasts, peroxisomes primarily regulate their numbers through the growth and division of pre-existing organelles, and they house specific machinery for protein import. These features were considered unique to endosymbiotic organelles, prompting the idea that peroxisomes were key cellular elements that helped facilitate the evolution of multicellular organisms. The functional similarities to mitochondria within mammalian systems expanded these ideas, as both organelles scavenge peroxide and reactive oxygen species, both organelles oxidize fatty acids, and at least in higher eukaryotes, the biogenesis of both organelles is controlled by common nuclear transcription factors of the PPAR family. Over the last decade it has been demonstrated that the fission machinery of both organelles is also shared, and that both organelles act as critical signaling platforms for innate immunity and other pathways. Taken together it is clear that the mitochondria and peroxisomes are functionally coupled, regulating cellular metabolism and signaling through a number of common mechanisms. However, recent work has focused primarily on the role of the ER in the biogenesis of peroxisomes, potentially overshadowing the critical importance of the mitochondria as a functional partner. In this review, we explore the mechanisms of functional coupling of the peroxisomes to the mitochondria/ER networks, providing some new perspectives on the potential contribution of the mitochondria to peroxisomal biogenesis. Over the past decade we have learned a great deal about peroxisomal biogenesis and function, much of this using the genetic power of model organisms like yeast     and Dnm1 (in yeast)] led to elongated peroxisomes and mitochondria  lead to the oligomerization and “priming” of the mitochondrial fusion GTPases Mfn1 and Mfn2 (Shutt et al., Perhaps the most surprising links between the mitochondria and signaling pathways came a number of years ago with the identification of the mitochondrial anti-viral signaling protein MAVS. MAVS was identified from 4 independent groups simultaneously as an essential protein for the viral-induced transcription of Nf-kB (Kawai et al., MAVS has also been seen to signal even earlier from the peroxisomes, again linking these two organelles as unique signaling platforms (Dixit et al., In this review we have highlighted a series of observations that illustrate the very tight functional, spatial, and regulatory links between the peroxisomes and the mitochondria. Evolutionary analysis coupled with the emergence of a vesicular transport route between the mitochondria and peroxisomes propels us to consider a role for mitochondria in peroxisomal biogenesis. Since ER-derived pre-peroxisomes are fusogenic (Boukh-Viner et al., The critical importance of peroxisomes in physiology is chronically underappreciated within the wider scientific community. Along with their established links to the ER, we hope that increasing awareness of the obligate coupling of the peroxisomes to the mitochondria will encourage researchers to more carefully consider the contribution of peroxisomal dysfunction to disease progression. For example, a great deal of attention is currently being paid to the role of mitochondria in neurodegeneration, cancer and immunology, yet the impact of mitochondrial dysfunction on peroxisomes is virtually unexplored in these disease pathologies. There is a great deal of work to be done before we will fully understand the role of peroxisomal dysfunction in human disease. A first step will require a better characterization of the molecular mechanisms that regulate the behavior and biochemistry of peroxisomes as a dynamic and tightly integrated organelle.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The gastroesophageal reflux disease (GERD) is one of the main causes of dental erosion. The aim of this case presented is to describe the prosthetic rehabilitation of a patient with GERD after 4 years of followup. A 33-year-old male patient complained about tooth sensitivity. The lingual surface of the maxillary anterior teeth and the cusps of the upper and lower posterior teeth presented wear. It was suspected that the feeling of heartburn reported by the patient associated with the intake of sports supplements (isotonics) was causing gastroesophageal changes. The patient was referred to a gastroenterologist and was diagnosed with GERD. Dental treatment was performed with metal-free crowns and porcelain veneers after medical treatment of the disease. With the change in eating habits, the treatment of GERD and lithium disilicate ceramics provided excellent cosmetic results after 4 years and the patient reported satisfaction with the treatment. Nowadays, the incidence of dental erosion has become a clinical reality , 2 with Among the causes of dental erosion, the gastroesophageal reflux disease (GERD) can be highlighted , which bThe modalities of rehabilitator treatment vary according to the degree of tooth wear , 9. It iThe aim of this case presented is to describe the clinical manifestations of GERD, its diagnosis, and the medical and dental treatment of a patient with GERD after 4 years of followup.A 33-year-old male patient was admitted to Aracatuba Dental School-UNESP, complaining about tooth sensitivity to temperature variations caused by the ingestion of different foods and acidic substances.Wear on the lingual surface of the maxillary anterior teeth and the shortening of the cusps of upper and lower posterior teeth were observed. This change was just not observed in the lower anterior teeth. Slight reduction of occlusal vertical dimension of the patient was observed without the need of its restoration Figures , and 5. The patient was referred to a gastroenterologist and the presence of hiatal hernia and gastroesophageal reflux disease was diagnosed after performing some specific tests. The medical treatment was based on the use of 40 mg of Omeprazol, twice a day for 30 days, and also change in eating habits such as the reduction of isotonic drinks and other foods that could exacerbate the symptoms. There was a decreased sensation of heartburn after medication treatment and only a regular medical followup was required.The dental treatment could be performed once the symptoms were controlled and the patient was treating the disease with medicines. Initial photographs were taken and impressions of both arches were performed with stock trays and alginate  to obtain the study models. The models were positioned on semiadjustable articulator for drafting and proposing the treatment plan.Among the proposed treatment options, the patient chose to restore the dental anatomy with metal-free crowns and porcelain veneers. Initially, the affected teeth were prepared . SubsequThe zirconia  cores were confectioned and lithium disilicate ceramic was used as veneering ceramic for posterior crowns and laminate veneers  . The innThe porcelain veneers were cemented only with base paste of resin cement , whereas the crowns were cemented with both pastes  of dual resin cement  .The patient reported no sensitivity after dental treatment and a homemade topical application of sodium fluoride gel 2% was recommended  every 15 days. After 4 years of followup the restorations showed no visible deterioration and the periodontal tissue was free of gingival inflammation Figures , and 15.Dental erosion has become an increasingly frequent and important clinical reality with multiple causes . Among tWe could confirm that the patient regularly practiced physical activities and made abusive use of acidic drinks as a supplement and their suspension was recommended by the gastroenterologist. People with healthy lifestyles may consume acidic drinks frequently in low salivation conditions  or making excessive use of the same day by day, trying to keep body weight .Treatment for patients with GERD is to change eating habits and drug therapy to increase esophageal muscle activity or reduce the amount of stomach acid. In these cases, patients should avoid consumption of foods that irritate the gastric mucosa such as spicy and fatty foods, citrus fruits, coffee, tea, chocolate, alcohol, and soft drinks and get used to walk after meals .Some studies show that ceramics are degraded on their surface when exposed to acidic solutions, which could compromise the longevity of these materials –12. ThusIn order to achieve excellent cosmetic results associated with a good mechanical behavior, zirconia copings were chosen . LikewisMonitoring of patients and a multidisciplinary approach should be taken in rehabilitation treatments, since systemic changes might directly influence the final results of treatment. The modification of eating habits and treatment of GERD associated with the use of lithium disilicate ceramic offered excellent aesthetic result after 4 years and the patient reported satisfaction with the treatment.


The study of traveling waves of activity in neural tissue can provide deep insights into the functions of the brain during sensory processing or during abnormal states such as epilepsy, migraines or hallucinations. Computational models of these systems usually describe the tissue as a vast interconnected network of neurons comprised of large number of units with similar properties, for example integrate and fire neurons. It is also widely assumed that while the strength of the connections between neurons changes as a function of distance, this interaction does not depend on other local parameters.These assumptions allow for formulation of a set of integro-differential equations describing the propagation of the traveling wave fronts in a one-dimensional integrate-and-fire network of synaptically coupled neurons, allowing for investigation of the network dynamics during wave initiation and propagation. Equations for the transition between initiation and transition toward constant speed traveling waves have been derived for Gaussian connectivity  and finiWe extended our previous models that exhibit constant-speed traveling waves to investigate how the presence of these inhomogeneities affects the relationship between the speed of the activity propagation and its acceleration. We determine that the estimates from homogenization theory do not accurately capture the conditions for propagation failure. More precisely, just prior to stopping, the activity propagates at a higher average speed than predicted from the theoretical results of the homogenization theory. We derive more precise estimates for the conditions when propagation failure occurs. Furthermore, our study points to directions where researchers can obtain additional tools for analyzing experimental data in order to infer details of synaptic connectivity.


Resonance describes the ability of neurons to respond selectively to inputs at preferred frequencies . When meLVA voltage-dependence was linearized and the transfer impedance of in model consisting of a soma coupled to a cylindrical cable was derived analytically for each location along the dendrite. Changing the total density of KLVA, gave rise to different resonant frequencies along the dendrite. This enables us to identify the membrane features that influence the range of resonances along the dendrites to characterize the trade-off between the range of frequencies and the Q-factor .First, an analytical approach was used whereby the KSecond, we used a numerical approach to optimize dendritic features to create neuron models with a large range of resonant frequencies along their dendrites. We thus confirmed the analytical results and addressed the more complicated dendritic structures including branching. We found that dendritic branches (bifrucations) may increase the range of resonant frequencies in dendrites and, at least partially, may overcome the strong trade-off between resonant strength and the possible range of resonance frequencies found it unbranched structures.We argue that the computational complexity of neurons is increased significantly by dendrites endowed with a whole range of resonant frequencies and discuss the advantage of having a bank of differential dendritic resonances that act as dynamic filters which, following plastic processes enable neurons to resonate in a particular desirable frequencies.


The functional significance of correlations between action potentials of neurons is still a matter of vivid debate. In particular, it is presently unclear how much synchrony is caused by afferent synchronized events and how much is intrinsic due to the connectivity structure of cortex. The available analytical approaches based on the diffusion approximation do not allow to model spike synchrony, preventing a thorough analysis. Here we theoretically investigate to what extent common synaptic afferents and synchronized inputs each contribute to correlated spiking on a fine temporal scale between pairs of neurons. We employ direct simulation and extend earlier analytical methods based on the diffusion approximation to pulse-coupling, allowing us to introduce precisely timed correlations in the spiking activity of the synaptic afferents. We investigate the transmission of correlated synaptic input currents by pairs of integrate-and-fire model neurons, so that the same input covariance can be realized by common inputs or by spiking synchrony. We identify two distinct regimes: In the limit of low correlation linear perturbation theory accurately determines the correlation transmission coefficient, which is typically smaller than unity, but increases sensitively even for weakly synchronous inputs. In the limit of high input correlation, in the presence of synchrony, a qualitatively new picture arises. As the non-linear neuronal response becomes dominant, the output correlation becomes higher than the total correlation in the input. This transmission coefficient larger unity is a direct consequence of non-linear neural processing in the presence of noise, elucidating how synchrony-coded signals benefit from these generic properties present in cortical networks. Whether spike timing conveys information in cortical networks or whether the firing rate alone is sufficient is a matter of controversial debate, touching the fundamental question of how the brain processes, stores, and conveys information. If the firing rate alone is the decisive signal used in the brain, correlations between action potentials are just an epiphenomenon of cortical connectivity, where pairs of neurons share a considerable fraction of common afferents. Due to membrane leakage, small synaptic amplitudes and the non-linear threshold, nerve cells exhibit lossy transmission of correlation originating from shared synaptic inputs. However, the membrane potential of cortical neurons often displays non-Gaussian fluctuations, caused by synchronized synaptic inputs. Moreover, synchronously active neurons have been found to reflect behavior in primates. In this work we therefore contrast the transmission of correlation due to shared afferents and due to synchronously arriving synaptic impulses for leaky neuron models. We not only find that neurons are highly sensitive to synchronous afferents, but that they can suppress noise on signals transmitted by synchrony, a computational advantage over rate signals. Simultaneously recording the activity of multiple neurons provides a unique tool to observe the activity in the brain. The immediately arising question of the meaning of the observed correlated activity between different cells In the other view, on the contrary, theoretical considerations The role of correlations entails the question whether cortical neurons operate as integrators or as coincidence detectors The pivotal role of correlations distinguishing the two opposing views and the appearance of synchrony at task-specific times One particular measure for assessing the transmission of correlation by a pair of neurons is the transmission coefficient, i.e. the ratio of output to input correlation. When studying spiking neuron models, the synaptic input is typically modeled as Gaussian white noise, e.g. by applying the diffusion approximation to the leaky integrate-and-fire model Understanding the influence of synchrony among the inputs on the correlation transmission requires to extend the above mentioned methods, as Gaussian fluctuating input does not allow to represent individual synaptic events, not to mention synchrony. Therefore, in this work we introduce an input model that extends the commonly investigated Gaussian white noise model. We employ the multiple interaction process (MIP) “Understanding and Isolating the Effect of Synchrony” we study the impact of input synchrony on the firing properties of a pair of leaky integrate-and-fire neurons with current based synapses. Isolating and controlling this impact allows us to separately study the effect of input synchrony on the one hand and common input on the other hand on the correlation transmission. In section “Correlation Transmission in the Low Correlation Limit” and “Correlation Transmission in the High Correlation Limit” we present a quantitative explanation of the mechanisms involved in correlation transmission, in the limit of low and high correlation, respectively, and show how the transmission coefficient can exceed unity in the latter case. In section In section The neuronal dynamics considered in this work follows the leaky integrate-and-fire model, whose membrane potential We investigate the correlation transmission of a pair of neurons considering the following input scenario. Each neuron receives input from ng rate  . Fig. 1CLet us now consider the case of The output firing rates and output spike synchrony shown in These two observations – the increase of input correlation and output firing rate induced by input synchrony – foil our objective to understand the sole impact of synchronous input events on the correlation transmission of neurons. In the following we will therefore first provide a quantitative description of the effect of finite sized presynaptic events on the membrane potential dynamics and subsequently describe a way to isolate and control this effect.The synchronous arrival of Again, In order to isolate and control the effect of the synchrony parameter In scenario 1  suggests, that the decisive properties of the marginal input statistics are characterized by the first . In order to obtain a correlation coefficient, we need to normalize the integral of (9) by the integral of the auto-covariance of the neurons' spike trains. This integral equals Before deriving an expression for the correlation transmission by a pair of neurons, we first need the firing rate deflection of a neuron In order to understand how the neurons are able to achieve a correlation coefficient larger than one, we need to take a closer look at the neural dynamics in the high correlation regime. We refer to the strong pulses caused by synchronous firing of numerous afferents as MIP events. Let us now recapitulate these last thoughts in terms of a pair of neurons: In the regime of synchronized high input correlation . Due to the non-linearity of the neurons we expect the effect of synchronous input events on their firing to depend on the choice of this working point. We therefore performed simulations and computed (2) using four different values for the mean membrane potential  . This waconstant , inset. A further approximation of (15) and (16) confirms the intuitive expectation that the mean size of a synchronous event compared to the distance of the membrane potential to the threshold plays an important role for the output synchrony: if synchrony is sufficiently high, say Measuring the integral of the output correlation over a window of A qualitatively new behavior is observed in the intermediate range of input correlation So far, for  windows  a correlIn this work we investigate the correlation transmission by a neuron pair, using two different types of input spike correlations. One is caused solely by shared input – typically modeled as Gaussian white noise in previous studies To model correlated spiking activity among the excitatory afferents in the input to a pair of neurons we employ the Multiple Interaction Process (MIP) Given a fixed input correlation, the correlation transmission increases with Hitherto existing studies argue that neurons either loose correlation when they are in the fluctuation driven regime or at most are able to preserve the input correlation in the mean driven regime We presented a quantitative description of the increased correlation transmission by synchronous input events for the leaky integrate-and-fire model. Our analytical results explain earlier observations from a simulation study modeling synchrony by co-activation of a fixed fraction of the excitatory afferents As for our spiking model, iven by  . At the iven by  .The situation illustrated in Several aspects of this study need to be taken into account when relating the results to other studies and to biological systems. The multiple interaction process as a model for correlated neural activity might seem unrealistic at first sight. However, a similar correlation structure can easily be obtained from the activity of a population of The correlation transmission coefficient can only exceed unity if the firing of the neurons is predominantly driven by the synchronously arriving volleys and disjoint input does not contribute to firing. The threshold then acts as a noise gate, small fluctuations caused by disjoint input do not penetrate to the output side. In the mean driven regime, i.e. when The boost of output correlation by synchronous synaptic impulses relies on fast positive transients of the membrane potential and strong departures from the stationary state: An incoming packet of synaptic impulses brings the membrane potential over the threshold within short time. Qualitatively, we therefore expect similar results for short, but non-zero rise times of the synaptic currents. For long synaptic time constants compared to the neuronal dynamics, however, the instantaneous firing intensity follows the modulation of the synaptic current adiabatically The choice of the correlation measure is of importance when analyzing spike correlations. It has been pointed out recently that the time scale It has been proposed that the coordinated firing of cell assemblies provides a means for the binding of coherent stimulus features Though in the limit of weak input correlation the correlation in the output is bounded by that in the input, in agreement with previous reports We here derive an approximation for the integral of the impulse response of the firing rate with respect to a perturbing impulse in the input. A similar derivation has been presented in The first four moments of the binomial distribution


Comparative genomics has put additional demands on the assessment of similarity between sequences and their clustering as means for classification. However, defining the optimal number of clusters, cluster density and boundaries for sets of potentially related sequences of genes with variable degrees of polymorphism remains a significant challenge. The aim of this study was to develop a method that would identify the cluster centroids and the optimal number of clusters for a given sensitivity level and could work equally well for the different sequence datasets.Nocardia species) and highly variable (VP1 genomic region of Enterovirus 71) sequences and outperformed existing unsupervised machine learning clustering methods and dimensionality reduction methods. This method does not require prior knowledge of the number of clusters or the distance between clusters, handles clusters of different sizes and shapes, and scales linearly with the dataset.A novel method that combines the linear mapping hash function and multiple sequence alignment (MSA) was developed. This method takes advantage of the already sorted by similarity sequences from the MSA output, and identifies the optimal number of clusters, clusters cut-offs, and clusters centroids that can represent reference gene vouchers for the different species. The linear mapping hash function can map an already ordered by similarity distance matrix to indices to reveal gaps in the values around which the optimal cut-offs of the different clusters can be identified. The method was evaluated using sets of closely related (16S rRNA gene sequences of The combination of MSA with the linear mapping hash function is a computationally efficient way of gene sequence clustering and can be a valuable tool for the assessment of similarity, clustering of different microbial genomes, identifying reference sequences, and for the study of evolution of bacteria and viruses. The distance matrix can then be clustered using the Unweighted Pair Group Method with Arithmetic Mean (UPGMA)  ← min(distSum)centroid (i) ← sCluster (i)+idx-1elsecentroid(i) ← sCluster (i)endendk-mers) that orders the sequences by similarity as , and clusters them by UPGMA as shown in the tree. The remaining steps proposed by this method are the diagonal extraction, the conversion of these scores into hash codes, and the clustering of these codes by identifying the natural gaps between the codes based on the sensitivity parameters chosen.The main steps of this process are summarised in Figure © "princomp" function. The highest scoring first (x-axis) and second (y-axis) coordinates were used for the plotting of the sequences on a two dimensional plane, while the symbols representing the different clusters reflected the clustering results produced by the linear mapping method.To visualize the spatial distribution of the points on two-dimensional plots, Principal Component Analysis (PCA) was applied on the distance matrix using the MatlabThe authors declare that they have no competing interests.MH conceived and designed the experiments, carried out experiments and drafted the manuscript. FK participated in the design of the study, in sequence alignment and data analysis. SCAC participated in the design of the study, provided sequencing data and drafted the manuscript. FZ provided sequencing data and participated in the data analysis. DED participated in the data analysis and drafted the manuscript. JP contributed to the development of methods and data analysis. VS conceived and designed the experiments, participated in the data analysis and drafted the manuscript. All authors have read and approved the final manuscript.


This paper reports on an investigation of mass transport of blood cells at micro-scale stenosis where local strain-rate micro-gradients trigger platelet aggregation. Using a microfluidic flow focusing platform we investigate the blood flow streams that principally contribute to platelet aggregation under shear micro-gradient conditions. We demonstrate that relatively thin surface streams located at the channel wall are the primary contributor of platelets to the developing aggregate under shear gradient conditions. Furthermore we delineate a role for red blood cell hydrodynamic lift forces in driving enhanced advection of platelets to the stenosis wall and surface of developing aggregates. We show that this novel microfluidic platform can be effectively used to study the role of mass transport phenomena driving platelet recruitment and aggregate formation and believe that this approach will lead to a greater understanding of the mechanisms underlying shear-gradient dependent discoid platelet aggregation in the context of cardiovascular diseases such as acute coronary syndromes and ischemic stroke. Pathological thrombus formation underlies a number of major health problems with significant economic impact. Usually thrombus formation occurs where blood vessels become narrowed (stenosis) as a result of atherosclerosis. This narrowing produces changes in blood-flow parameters which in turn trigger cell adhesion and aggregation. The way in which the geometry of the blood vessel changes blood-flow parameters and these in turn affect blood cell responses has been the focus for decades. Clinically, however it has been difficult to investigate, under controlled conditions, the role of mechanical parameters (geometry and flow) on thrombosis and platelet aggregation. The challenge arises from the fact that the geometrical and flow parameters, are difficult to isolate in-vivo. Recent clinical studies still continue to neglect the geometry of the stenosis treams / and, twoeams //. Comparieams // presentsIn order to simplify our proof-of-concept studies and to isolate the mechanical effects of blood flow from biochemically driven platelet activation, all experiments were performed in the presence of pharmacological inhibitors of the canonical platelet amplification loops as was described in the methods section. For the first experiment with blood, a two flow geometry as presented in his case . This daThe experiments presented in the previous section were useful as a proof of concept to visualize different blood streams, to begin gaining insight into which components of the blood flow contribute to the aggregate as also to observe cell interaction. To further resolve the platelet streams contributing to aggregation and explore in greater detail the cellular interactions occurring within defined stenosis, we conducted a series of experiments to generate asymmetric streams in a ratio of 75∶25 and then 85∶15. In order to investigate the role of the hematocrit in the upper streams and the effect of red cell interactions at the stenosis, model experiments on the microfluidics platform were conducted where the upper layer was changed as a function of the amount of red cells suspended in solution. The hematocrit in the upper stream of 80% . Our miture see , demonsteamlines ). This aeamlines  288, vorThis paper presents model experiments on a microfluidic platform incorporating hydrodynamic flow focusing to examine blood cell transport investigating the mechanical flow processes governing pathological platelet aggregation at stenosis (micro-contractions). These initial proof-of-concept experiments suggests that aggregate growth in acute stenosis can generate enhanced advective transport zones within the local flow effectively increasing platelet mass transport to the wall, further accelerating aggregate growth. This feedback effect of platelet aggregation on advective transport may be a function of the change in angle of deceleration of the stenosis or the already formed aggregate. Future studies will focus on further delineating this phenomenon and in particular will focus on the effect of initial streams acceleration as a significant parameter determining platelet aggregation dynamics. We have demonstrated the importance of the effects of hemodynamic forces present in a stenosis driving platelet aggregation. The experiments presented in this manuscript reveal a significant role of role of lift forces at stenosis. These forces appear to be important in modulating the delivery rate of platelets to the vessel wall. Delivery rate is mediated by the action of red cells which because of their relative size experience a higher imbalance of lift forces in comparison to platelets. We hypothesize that this imbalance of forces, is a generalised phenomena and consequence of stenosis and that the experimental approach outlined in this study will lead to a greater understanding of the mechanisms underlying shear-gradient dependent discoid platelet aggregation. These new experimental insights suggest a complex time varying role of enhanced advection through particulate flow, in controlling the extent and rate of platelet aggregation. Although it may be speculative to apply the insight gained here to more inertial dominated flows, a more detailed understanding of these aggregation phenomena should greatly extend our understanding of the mechanical flow processes governing pathological thrombus formation in the context of coronary artery disease and stroke, with particular relevance to inertially dominated stent related thrombosis.In order to model the flow focusing behavior of the micro-fluidic devices, the mass transport equation for two species was solved numerically. For the case of this paper, no chemical reaction was considered and the only phenomena present for the chemical species was the transport of mass and momentum. The governing equation of the mass transport for different species can be expressed as:Text S1Vortex formation as a function of platelet aggregate size.(DOCX)Click here for additional data file.Video S1Supplementary Material.(AVI)Click here for additional data file.


Sir,In the past few years, a new optical intubation device, i.e. laryngeal mask airway (LMA) CTrach has emerged as a useful alternative for the facilitation of tracheal intubation in difficult airway situations provided the interdental distance is ≥25 mm. The LMA The LMA CTrach is inserted in neutral head position using one handed rotational technique. FollowinOn initial insertion, if the complete laryngeal view is not seen on the viewer, the presence of three distinct colours, i.e. red, white and black can indicate the likely causes of inadequate view. The knowledge of this tri-colour concept described below can be extremely helpful in obtaining the best laryngeal view and performing intubation successfully through the LMA CTrachOnce the best laryngeal view is achieved, the application of medial-lateral manoeuvre can help in centralizing the glottic aperture on the viewer and finally the application of Chandy’s manoeuvre  at the time of intubation can eventually influence the success of first attempt intubation.The achievement of the best laryngeal view and facilitation of tracheal intubation through the LMA CTrach can be made simpler by understanding of this tri-colour concept. We feel that the learning of tri-colour concept should be an integral part of the teaching of CTrach use as it can help in increasing the efficacy of this useful airway device in difficult airway situations.


SirSubcutaneous tunnelling of the epidural catheter is routinely practiced for anchoring the epidural catheter. There are different techniques for subcutaneous tunnelling which are associated with complications like needle stick to the clinician or shearing of the epidural catheter. Rose GL (2009) reported the efficacy of needle sheath for prevention of these complications.Still, the likelihood of shearing of the epidural catheter cannot be ruled out. Following shearing of the epidural catheter it has to be pulled out, as it cannot be used for administering medication. RecentlyFortunately, shearing of the catheter happened at an extracutaneous site so we got extra length to attach the filter and other assembly with it. Although, short length of catheter or slightly bulky assembly (filter system) or absence of loop may pose a possibility of dislodgement it is a safe and cost-effective method. We therefore suggest that this technique could be employed in cases of shearing of epidural catheter during the process of subcutaneous tunnelling.


The discovery of HIV in 1983 originated from a collective adventure, which mobilized clinicians, researchers and patients altogether. This collaboration was crucial to rapidly expand the knowledge of the virus and develop the first diagnostic tests and antiretroviral therapy (ART).More than 25 years after the discovery of the etiological agent responsible for AIDS, research priorities still remain care, treatment and prevention with the major objective of developing a preventive vaccine.Today, we have gained significant insight into the virus pathogenesis. The evolution and progression of the disease caused by HIV is closely linked to a number of determinants of the virus itself and the host. We also know today that, very early after exposure to the virus, a massive depletion of CCR5+ CD4+ T memory cells associated with microbial translocation occurs in the gastrointestinal tract of HIV infected patients. HIV infection is clearly inducing an inflammation and a generalized and persistent T cell activation, which may play a role in the persistence of HIV infection, resulting from the establishment of permanent reservoirs into host cells and in different host compartments. The reduction of the size of these reservoirs is representing one of the main challenges for the development of future therapeutic strategies.Among other challenges in therapy, we also need to better understand the mechanisms leading to the severe complications  observed in some patients on long-term ART. Again, whether the inflammatory response is contributing or not to these complications remains an opened question.The early acute phase of HIV infection appears therefore to be crucial in determining disease progression. Given the importance of the innate immune responses in this very early phase following infection and in driving adaptive immunity, further research on innate immunity in HIV infection are certainly among priorities for elaborating future therapeutic and vaccine strategies.New technologies are today available to address all these scientific challenges. But they will only be overcome with a multidisciplinary and translational research for the global benefit of humanity.


Journal of Adolescent Health is devoted to understanding the health and well-being of adolescents by taking the long view of this period of the life cycle. The articles herein analyze data collected from conception through age 15 from 4,500 individuals born in the city of Pelotas, Brazil, in 1993. The analyses provide us with not just a snapshot of adolescents' current health status, but rather an entire movie depicting the life-course trajectories and the emergence of health outcomes of this population during adolescence.This supplement to the The first four articles of the supplement focus on early-life predictors of later health and behavior The next three articles focus on the health effects of behavioral changes during adolescence The next three articles further explore environmental factors that influence obesity and perceptions of obesity from the perspective of parents and adolescents The supplement closes with a study showing an alarmingly prevalence of self-medication (29%) among 15-year-old adolescents, with girls being more likely to self-medicate than boys ∘First, several factors arise early in development. Further, the behaviors and social context of the family affects not just the young child but also the adolescent ∘Second, behaviors tend to track from childhood to adolescence, suggesting once again that interventions need to start earlier, preferably before individuals get on the wrong track ∘Third, some exposures  might have both benefits (lung function) and harmful effects (school failure), depending on the dose ∘Fourth, qualitative studies provide us with an opportunity to hear the nuances that come from adolescents and families that are difficult to extract from quantitative studies Although these studies collectively provide valuable insights into child development, it is important to note that the Pelotas cohort only provides us with information through mid-adolescence (15 years). Whereas it is clear that many of the behaviors and health outcomes examined in these studies have their roots in early childhood, the brain continues to develop well into young adulthood This collection of articles examining the Pelotas cohort provides us with a rare opportunity to understand clearly the critical role of a life-course perspective in promoting the health and well-being of adolescents. We look forward to seeing these findings replicated in other settings, but the results presented here are robust and have relevance to populations throughout the world. Consider the collective critical findings: