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BACKGROUND: Diagnosing coeliac disease (CD) in patients on a gluten-free diet (GFD) is difficult. Ingesting gluten elevates circulating interleukin (IL)-2, IL-8 and IL-10 in CD patients on a GFD. OBJECTIVE: We tested whether cytokine release after gluten ingestion differentiates patients with CD from those with self-reported gluten sensitivity (SR-GS). METHODS: Australian patients with CD (n = 26) and SR-GS (n = 18) on a GFD consumed bread (estimated gluten 6 g). Serum at baseline and at 3 and 4 h was tested for IL-2, IL-8 and IL-10. Separately, Norwegian SR-GS patients (n = 49) had plasma cytokine assessment at baseline and at 2, 4 and 6 h after food bars containing gluten (5.7 g), fructan or placebo in a previous double-blind crossover study. RESULTS: Gluten significantly elevated serum IL-2, IL-8 and IL-10 at 3 and 4 h in patients with CD but not SR-GS. The highest median fold-change from baseline at 4 h was for IL-2 (8.06, IQR: 1.52–24.0; P

Background In patients with coeliac disease, FODMAPs in gluten-containing foods, and participant anticipation of a harmful ('nocebo') effect, may contribute to acute symptoms after gluten challenge. Aim To establish acute gluten-specific symptoms linked to immune activation in coeliac disease Methods We included 36 coeliac disease patients on a gluten-free diet receiving placebo in the RESET CeD trial. Double-blind, bolus vital wheat gluten (similar to 6-g gluten protein) and sham challenges low in FODMAPs were consumed 2 weeks apart. Assessments included daily Coeliac Disease Patient Reported Outcome (CeD PRO) symptom scores (0-10), adverse events and serum interleukin-2 (baseline and 4 hours). Results Median CeD PRO score for nausea increased most (sham: 0 vs gluten: 5.5; P < .001). Apart from tiredness (1 vs 4, P = .005) and headache (0 vs 2, P = .002), changes in other symptoms were small or absent. Only nausea increased significantly in occurrence with gluten (11% vs 69%, P < .001). Without nausea, only tiredness and flatulence were common after gluten. Nausea (6% vs 61%, P < .001; median onset: 1:34 hours) and vomiting (0% vs 44%, P < .001; 1:51 hours) were the only adverse events more common with gluten than sham. Interleukin-2 was always below the level of quantitation (0.5 pg/mL) at baseline, and after sham. Interleukin-2 was elevated after gluten in 97% of patients (median fold-change: 20), and correlated with severity of nausea (r(s) = .49, P = .0025) and occurrence of vomiting (P = .0005). Conclusions Nausea and vomiting are relatively specific indicators of acute gluten ingestion, and correlate with immune activation. IBS-like symptoms without nausea are unlikely to indicate recent gluten exposure.

Background: Coeliac disease patients on a gluten-free diet experience reactions to gluten, but these are not well characterised or understood. Systemic cytokine release was recently linked to reactivation of gluten immunity in coeliac disease. Aim: To define the nature and time-course of symptoms and interleukin-2 changes specific for coeliac disease patients. Methods: 25 coeliac disease patients on a gluten-free diet and 25 healthy volunteers consumed a standardised 6 gram gluten challenge. Coeliac Disease Patient-Reported Outcome survey and global digestive symptom assessment were completed hourly up to 6 hours after gluten. Adverse events over 48 hours were recorded. Serum interleukin-2 was measured at baseline, and 2, 4 and 6 hours. Results: Serum interleukin-2 was always undetectable in healthy controls, whereas it was undetectable at baseline and elevated >0.5 pg/ml at 4 hours in 92% of coeliac disease patients. All patient-reported outcome severity scores increased significantly after gluten in coeliac disease patients (P

Background Nexvax2 contains three gluten-derived peptides, intended to tolerize coeliac disease patients to gluten. Sequences cover six epitopes that trigger immune activation in human leucocyte antigen-DQ2.5-positive patients, most notably after an initial dose. Patients experience gastrointestinal symptoms with increases in serum interleukin-2. Consistent with Nexvax2's induction of non-responsiveness, reactivity disappears after repeated doses, or is avoided with gradual dose escalation. Early clinical trials used intradermal dosing, but pharmacokinetics and rapid onset of effect suggest that subcutaneous delivery may also be effective. Aims To document the relative bioavailability of Nevax2 peptides after subcutaneous and intradermal dosing, and the tolerability and ability of subcutaneous dosing to induce non-responsiveness to Nexvax2 peptides. Methods A randomised, double-blind, placebo-controlled study was conducted to assess plasma pharmacokinetics after subcutaneous and intradermal Nexvax2 dosing in HLA DQ2.5-positive patients, who had symptoms after an oral gluten challenge. Randomisation was to semi-weekly Nexvax2 (n = 12) or placebo (n = 2) injections, over a 5-week subcutaneous dose escalation and 2-week maintenance period, the latter with four doses of 900 mu g, two subcutaneous and two intradermal. Post-dose circulating peptide and interleukin-2 levels were assessed. Investigators recorded adverse events experienced by patients. Results Subcutaneous dosing resulted in slightly greater exposure. Interleukin-2 responses were seen with the gluten challenge but not after subcutaneous or intradermal dosing of 900 mu g. Adverse events were generally mild and self-limited. Conclusions Subcutaneous and intradermal dosing of Nexvax2 yield similar bioavailability of constituent peptides; subcutaneous dose escalation avoids an immune response to dominant gluten epitopes.

AIM: Ecological niche modelling requires robust estimation of model performance and significance, but common evaluation approaches often yield biased estimates. Null models provide a solution but are rarely used in this field. We implemented an important modification to existing null model tests, evaluating null models with the same withheld records that were used to evaluate the real model. We built and evaluated models across a range of modelling scenarios and for various performance measures using the algorithm Maxent and the monk parakeet (Myiopsitta monachus). LOCATION: Native range in Southern America and global invasions predominantly in North/Central America and Europe. METHODS: We tested the ability of models built under 15 scenarios (five sets of calibration records and three settings that varied the level of model complexity) to predict spatially independent evaluation data in the invaded range (in effect, testing the models under spatial transfer). We quantified performance with measures of discriminatory ability and overfitting based on area under the receiver operating characteristic curve (AUC) and the omission error rate. We estimated null distributions of these measures and calculated effect size and significance. We determined how these estimates varied across modelling scenarios, comparing with two tests existing in the literature. RESULTS: Performance varied starkly across modelling scenarios. As expected, the measures of overfitting agreed with each other and provided different information than that of discriminatory ability. However, high performance per se did not show strong association with high effect size and significance. MAIN CONCLUSIONS: Ecological niche models should be assessed with measures of effect size and significance based on appropriate null distributions, in contrast to several approaches existing in the literature. The proposed approach using independent evaluation data, implemented with our accompanying code and R package, allows such estimates for either the same or a different region/time period, and it merits use and continued development.

１．Quantitative evaluations to optimize complexity have become standard for avoiding overfitting of ecological niche models (ENMs) that estimate species’ potential geographic distributions. ENMeval was the first R package to make such evaluations (often termed model tuning) widely accessible for the Maxent algorithm. It also provided multiple methods for partitioning occurrence data and reported various performance metrics.２．Requests by users, recent developments in the field, and needs for software compatibility led to a major redesign and expansion. We additionally conducted a literature review to investigate trends in ENMeval use (2015–2019).３．ENMeval 2.0 has a new object-oriented structure for adding other algorithms, enables customizing algorithmic settings and performance metrics, generates extensive metadata, implements a null-model approach to quantify significance and effect sizes, and includes features to increase the breadth of analyses and visualizations. In our literature review, we found insufficient reporting of model performance and parameterization, heavy reliance on model selection with AICc and low utilization of spatial cross-validation; we explain how ENMeval 2.0 can help address these issues.４．This redesigned and expanded version can promote progress in the field and improve the information available for decision-making.

Abtract 1.Scientific research increasingly calls for open-source software that is flexible, interactive, and expandable, while providing methodological guidance and reproducibility. Currently, many analyses in ecology are implemented with “black box” graphical user interfaces that lack flexibility or command-line interfaces that are infrequently used by non-specialists. 2.To help remedy this situation in the context of species distribution modeling, we created Wallace, an open and modular application with a richly documented graphical user interface to underlying R scripts that is flexible and highly interactive. 3.Wallace guides users from acquiring and processing data to building models and examining predictions. Additionally, it is designed to grow via community contributions of new modules to expand functionality. All results are downloadable, along with code to reproduce the analysis. 4.Wallace provides an example of an innovative platform to increase access to cutting-edge methods and encourage plurality in science and collaboration in software development. This article is protected by copyright. All rights reserved.

This software note announces a new open-source release of the Maxent software for modeling species distributions from occurrence records and environmental data, and describes a new R package for fitting such models. The new release (ver. 3.4.0) will be hosted online by the American Museum of Natural History, along with future versions. It contains small functional changes, most notably use of a complementary log-log (cloglog) transform to produce an estimate of occurrence probability. The cloglog transform derives from the recently-published interpretation of Maxent as an inhomogeneous Poisson process (IPP), giving it a stronger theoretical justification than the logistic transform which it replaces by default. In addition, the new R package, maxnet, fits Maxent models using the glmnet package for regularized generalized linear models. We discuss the implications of the IPP formulation in terms of model inputs and outputs, treating occurrence records as points rather than grid cells and interpreting the exponential Maxent model (raw output) as as an estimate of relative abundance. With these two open-source developments, we invite others to freely use and contribute to the software.

Objectives Understanding the T cell receptor (TCR) repertoire of regulatory CD4+ T‐cell (Treg) populations is important for strategies aiming to re‐establish tolerance in autoimmune diseases. We studied circulating deamidated gluten‐epitope‐specific CD39+ Tregs in patients with coeliac disease following an oral gluten challenge, and we used cytomegalovirus (CMV)‐specific CD39+ Tregs from healthy controls as a comparator population. Methods We used the OX40 assay to isolate antigen‐specific Tregs by induced surface co‐expression of CD25, OX40 and CD39. RACE PCR amplification and Sanger sequencing of the TCR β chain were used to analyse repertoire diversity. Results We found that, following oral gluten challenge, circulating gluten‐specific CD39+ Tregs had an oligoclonal TCR repertoire that contained public clonotypes. Conversely, the TCR repertoire of CMV‐epitope‐specific CD39+ Tregs from healthy controls was polyclonal. Discussion These data indicate that a biased TCR repertoire is not inherent to CD39+ Tregs, and, in this case, is apparently driven by the HLA‐DQ2.5‐restricted deamidated gluten peptide in coeliac disease patients. Conclusion This is the first assessment of the TCR repertoire within circulating human Tregs specific for foreign antigen. These data enhance our understanding of antigen‐specific CD4+ responses in the settings of chronic inflammation and infection and may help guide immunomonitoring strategies for CD4+ T cell‐based therapies, particularly for coeliac disease.

Aim Ecological niche models (ENMs) are used widely in ecology, evolution, global change biology, but model uncertainty remains an underappreciated issue. Generally, either a single model from one algorithm or an ensemble of single models from different algorithms is used to provide a prediction. In addition to variability among algorithms, recent studies have shown the need to consider variability within a single algorithm, for example optimizing model complexity by tuning model settings. We present an ensemble ENM using a single-algorithm approach, while adjusting model settings to maximize performance. Location Madagascar. Methods We used maxent, bioclimatic variables and occurrence records of four species of Malagasy tenrecs (Family Tenrecidae). We calibrated and evaluated preliminary models using a jackknife approach, tuning two model settings to estimate optimal model complexity. We chose a suite of top-performing preliminary models and then generated a consensus prediction. Furthermore, we calculated the variability among predictions of the co-optimal models to indicate variation in geography (i.e. uncertainty). We then did the same after projecting the predictions to climatic estimates for the Last Glacial Maximum and the year 2070. Results The default settings were never identified as optimal for any of the four species. The model settings considered as the co-optimal solutions essentially led to the same evaluation statistics; however, they showed high variation in their geographic predictions for three of the four species. Additionally, variation among such models was greater when transferred across time. Main conclusions This approach likely can provide better predictions for a single algorithm as well as quantifications of within-algorithm uncertainty, qualities that are highly useful in interpreting reconstructed suitable areas or forecasts of potential range shifts under future climate change. Finally, this within-algorithm uncertainty can be integrated into a larger framework that considers variability due to other factors (e.g. related to input data, alternate algorithms or various Global circulation models).

Biotic interactions can influence the ranges and abundances of species, but no clear guidelines exist for integrating them into correlative models of niches and distributions. Niche/distributional models characterize environmental/habitat suitability or species presence using predictor variables unaffected by (= unlinked to) the population of the focal species. Such variables (termed ‘scenopoetic’) typically have been considered to include only abiotic factors. In contrast, population–demographic approaches model the abundance of the focal species by including linked predictor variables, which frequently are biotic interactors. Nevertheless, a focal species might hold no, or negligible, population-level effects on its biotic interactors. Hence, contrary to current theory, such interactors would represent unlinked variables valid and potentially very useful for niche/distributional models. Consideration of population-level effects indicates that facilitators and affecting amensals (species that negatively affect another species but are not affected by it) constitute unlinked variables, but commensals and affected amensals do not. For competitors, mutualists, predators/prey, consumers/resources, and parasites/hosts, additional information is necessary. Specifically, available ecological/natural history information for the particular species involved (e.g. regarding specificity) and theory regarding ecological networks can allow identification of interactors that are likely to be unlinked or nearly so. Including an unlinked biotic interactor as a predictor variable in a niche/distributional model should improve predictions when the effects of the biotic interactor vary across the study region, or in another place or time period. Other relevant interactors must be taken into account by post-processing a niche/distributional model, or via population–demographic models that require abundance data over time. This framework should improve current correlative models and highlights areas requiring progress.

Summary Remote sensing techniques offer an opportunity to improve biodiversity modelling and prediction world-wide. Yet, to date, the weather station-based WorldClim data set has been the primary source of temperature and precipitation information used in correlative species distribution models. WorldClim consists of grids interpolated from in situ station data recorded primarily from 1960 to 1990. Those data sets suffer from uneven geographic coverage, with many areas of Earth poorly represented. Here, we compare two remote sensing data sources for the purposes of biodiversity prediction: MERRA climate reanalysis data and AMSR-E, a pure remote sensing data source. We use these data to generate novel temperature-based bioclimatic information and to model the distributions of 20 species of vertebrates endemic to four regions of South America: Amazonia, the Atlantic Forest, the Cerrado and Patagonia. We compare the bioclimatic data sets derived from MERRA and AMSR-E information with in situ station data and contrast species distribution models based on these two products to models built with WorldClim. Surface temperature estimates provided by MERRA and AMSR-E showed warm temperature biases relative to the in situ data fields, but the reliability of these data sets varied in geographic space. Species distribution models derived from the MERRA data performed equally well (in Cerrado, Amazonia and Patagonia) or better (Atlantic Forest) than models built with the WorldClim data. In contrast, the performance of models constructed with the AMSR-E data was similar to (Amazonia, Atlantic Forest, Cerrado) or worse than (Patagonia) that of models built with WorldClim data. Whereas this initial comparison assessed only temperature fields, efforts to estimate precipitation from remote sensing information hold great promise; furthermore, other environmental data sets with higher spatial and temporal fidelity may improve upon these results.

Summary Recent studies have demonstrated a need for increased rigour in building and evaluating ecological niche models (ENMs) based on presence-only occurrence data. Two major goals are to balance goodness-of-fit with model complexity (e.g. by ‘tuning’ model settings) and to evaluate models with spatially independent data. These issues are especially critical for data sets suffering from sampling bias, and for studies that require transferring models across space or time (e.g. responses to climate change or spread of invasive species). Efficient implementation of procedures to accomplish these goals, however, requires automation. We developed ENMeval, an R package that: (i) creates data sets for k-fold cross-validation using one of several methods for partitioning occurrence data (including options for spatially independent partitions), (ii) builds a series of candidate models using Maxent with a variety of user-defined settings and (iii) provides multiple evaluation metrics to aid in selecting optimal model settings. The six methods for partitioning data are n−1 jackknife, random k-folds ( = bins), user-specified folds and three methods of masked geographically structured folds. ENMeval quantifies six evaluation metrics: the area under the curve of the receiver-operating characteristic plot for test localities (AUCTEST), the difference between training and testing AUC (AUCDIFF), two different threshold-based omission rates for test localities and the Akaike information criterion corrected for small sample sizes (AICc). We demonstrate ENMeval by tuning model settings for eight tree species of the genus Coccoloba in Puerto Rico based on AICc. Evaluation metrics varied substantially across model settings, and models selected with AICc differed from default ones. In summary, ENMeval facilitates the production of better ENMs and should promote future methodological research on many outstanding issues.

Based on our own empirical data and a literature review, we explore the possibility that biotic interactions, specifically competition, might be responsible for creating, and/or maintaining, geographic isolation. Ecological niche modeling was first used to test whether the distributions of 2 species of Neotropical marsupials (Marmosa robinsoni and M. xerophila) fit the predicted geographic pattern of competitive exclusion: one species predominates in areas environmentally suitable for both species along real contact zones. Secondly, we examined the connectivity among populations of each species, interpreted in the light of the niche models. The results show predominance of M. xerophila along its contact zone with M. robinsoni in the Peninsula de Paraguana in northwestern Venezuela. There, M. robinsoni has an extremely restricted distribution despite climatic conditions suitable for both species across the peninsula and its isthmus. The latter two results suggest that M. xerophila may be responsible for the geographic isolation of the peninsular populations of M. robinsoni with respect to other populations of the latter species in northwestern Venezuela. These results may represent an example of allopatry caused, or at least maintained, by competition. Our results and a review of numerous studies in which biotic interactions restrict species distributions (including at the continental scale) support a previously overlooked phenomenon: biotic interactions can isolate populations of a species. We propose 2 general mechanisms, intrusion and contraction, to classify allopatric conditions caused by various classes of biotic interactions. We present a necessary modification of the concept of ecological vicariance to include biotic interactions as possible vicariant agents regardless of whether genetic differentiation occurs or not.

Aim We introduce and evaluate the potential effect of spatially marginal localities (specifically those protruding into unsuitable regions), in overestimating species niches and distributions when using ecological niche models (ENMs). Location North-western South America. Methods We built an ENM for the Caribbean spiny pocket mouse (Heteromys anomalus) using MaxEnt and climatic variables. This species typically inhabits extensive tropical forests but can also range into drier habitats through patches of mesic vegetation. We ranked occurrence records according to the suitability value they received, and retrieved habitat information from collectors' field notes and the literature to determine whether those receiving lower values correspond to spatially marginal localities protruding into unsuitable regions. We then built a model excluding a subset of such localities and compared its geographic and environmental prediction with that of the original model. Results Models differed substantially in their estimates of suitability. The original model resulted in an overly extensive prediction, considering as suitable hot and dry regions dominated by xerophytic vegetation. Records receiving the lowest suitability values in this model corresponded mainly to captures in patches of mesic forest surrounded by thorn scrub or savannas. The model calibrated without such records restricted suitability mostly to regions characterized by the typical habitat of the species. Main conclusions When it is not possible to use variables that are more proximal or have finer resolutions, we recommend building complementary models that, together, can provide a more realistic estimate of the species' niche and corresponding geographic distribution. Jointly interpreting these models, researchers may better differentiate between areas harbouring typical habitat and those where the species can be found only if locally favourable conditions exist. Such a distinction is of relevance for a wide range of applications relying on inferences obtained from ENMs.

Aim Models of species niches and distributions have become invaluable to biogeographers over the past decade, yet several outstanding methodological issues remain. Here we address three critical ones: selecting appropriate evaluation data, detecting overfitting, and tuning program settings to approximate optimal model complexity. We integrate solutions to these issues for Maxent models, using the Caribbean spiny pocket mouse, Heteromys anomalus, as an example. Location North-western South America. Methods We partitioned data into calibration and evaluation datasets via three variations of k-fold cross-validation: randomly partitioned, geographically structured and masked geographically structured (which restricts background data to regions corresponding to calibration localities). Then, we carried out tuning experiments by varying the level of regularization, which controls model complexity. Finally, we gauged performance by quantifying discriminatory ability and overfitting, as well as via visual inspections of maps of the predictions in geography. Results Performance varied among data-partitioning approaches and among regularization multipliers. The randomly partitioned approach inflated estimates of model performance and the geographically structured approach showed high overfitting. In contrast, the masked geographically structured approach allowed selection of high-performing models based on all criteria. Discriminatory ability showed a slight peak in performance around the default regularization multiplier. However, regularization levels two to four times higher than the default yielded substantially lower overfitting. Visual inspection of maps of model predictions coincided with the quantitative evaluations. Main conclusions Species-specific tuning of model parameters can improve the performance of Maxent models. Further, accurate estimates of model performance and overfitting depend on using independent evaluation data. These strategies for model evaluation may be useful for other modelling methods as well.

Predicting species geographic distributions in the future is an important yet exceptionally challenging endeavor. Overall, it requires a two-step process: (1) a niche model characterizing suitability, applied to projections of future conditions and linked to (2) a dispersal/demographic simulation estimating the species' future occupied distribution. Despite limitations, for the vast majority of species, correlative approaches are the most feasible avenue for building niche models. In addition to myriad technical issues regarding model building, researchers should follow critical principles for selecting predictor variables and occurrence data, demonstrating effective performance in prediction across space, and extrapolating into nonanalog conditions. Many of these principles relate directly to the niche space, dispersal/demographic noise, biotic noise, and human noise assumptions defined here. Issues requiring progress include modeling interactions between abiotic variables, integrating biotic variables, considering genetic heterogeneity, and quantifying uncertainty. Once built, the niche model identifying currently suitable conditions must be processed to approximate the areas that the species occupies. That estimate serves as a seed for the simulation of persistence, dispersal, and establishment in future suitable areas. The dispersal/demographic simulation also requires data regarding the species' dispersal ability and demography, scenarios for future land use, and the capability of considering multiple interacting species simultaneously.

Recent advances allow harnessing enormous stores of biological and environmental data to model species niches and geographic distributions. Natural history museums hold specimens that represent the only information available for most species. Ecological niche models (sometimes termed species distribution models) combine such information with digital environmental data (especially climatic) to offer key insights for conservation biology, management of invasive species, zoonotic human diseases, and other pressing environmental problems. Five major pitfalls seriously hinder such research, especially for cross-space or cross-time uses: (1) incorrect taxonomic identifications; (2) lacking or inadequate databasing and georeferences; (3) effects of sampling bias across geography; (4) violation of assumptions related to selection of the study region; and (5) problems regarding model evaluation to identify optimal model complexity. Large-scale initiatives regarding data availability and quality, technological development, and capacity building should allow high-quality modeling on a scale commensurate with the enormous potential of and need for these techniques.

Aliment Pharmacol Ther 2010; 32: 1184–1191 Summary Background Wheat, rye and barley prolamins are toxic to patients with coeliac disease. Barley is diploid with pure inbred cultivars available, and is attractive for genetic approaches to detoxification. Aim To identify barley hordein fractions which activated the interferon-γ (IFN-γ) secreting peripheral blood T-cells from coeliac volunteers, and compare immunotoxicity of hordeins from experimental barley lines. Methods To reactivate a T-cell response to hordein, volunteers underwent a 3-day oral barley challenge. Peripheral blood mononuclear cells (PBMC) were isolated from twenty-one HLA DQ2+ patients with confirmed coeliac disease. IFN-γ ELISpot assays enumerated T-cells activated by purified prolamins and positive controls. Results Hordein-specific T-cells were induced by oral barley challenge. All prolamin fractions were immunotoxic, but D- and C-hordeins were most active. Barley lines lacking B- and C-hordeins had a 5-fold reduced hordein-content, and immunotoxicity of hordein extracts were reduced 20-fold compared with wild-type barley. Conclusions In vivo oral barley challenge offers a convenient and rapid approach to test the immunotoxicity of small amounts of purified hordeins using fresh T-cells from patients in high throughput overnight assays. Barley lines that did not accumulate B- and C-hordeins were viable, yet had substantially reduced immunotoxicity. Creation of hordein-free barley may therefore be possible.

Aim Various techniques model a species’ niche and potential distribution by comparing the environmental conditions of occurrence localities with those of the overall study region (via a background or pseudoabsence sample). Here, we examine how changes in the extent of the study region (ignored or under-appreciated in most studies) affect models of two rodents, Nephelomys caracolus and Nephelomys meridensis. Location North-central South America. Methods We used Maxent to model the species' potential distributions via two methods of defining the study region. In Method 1 (typical of most studies to date), we calibrated the model in a large study region that included the ranges of both species. In Method 2, we calibrated the model using a smaller study region surrounding the localities of the focal species, and then applied it to the larger region. Because the study region of Method 1 is likely to include areas of suitable conditions that are unoccupied because of dispersal limitations and/or biotic interactions, this approach is prone to overfitting to conditions found near the occupied localities. In contrast, Method 2 should avoid such problems but may require further assumptions (‘clamping’ in Maxent) to make predictions for areas with environmental conditions beyond those found in the smaller study region. For each method, we calculated several measures of geographic interpredictivity between predictions for the species (cross-species AUC, cross-species omission rate, and proportional geographic overlap). Results Compared with Method 1, Method 2 revealed a larger predicted area for each species, less concentrated around known localities (especially for N. caracolus). It also led to higher cross-species AUC values, lower cross-species omission rates and higher proportions of geographic overlap. Clamping was minimal and occurred primarily in regions unlikely to be suitable. Main conclusions Method 2 led to more realistic predictions and higher estimates of niche conservatism. Conclusions reached by many studies depend on the selection of an appropriate study region. Although detailed information regarding dispersal limitations and/or biotic interactions will typically be difficult to obtain, consideration of coarse distributional patterns, topography and vegetational zones often should permit delimitation of a much more reasonable study region than the extremely large ones currently in common use.

Public anxiety over gluten has fuelled widespread demand for gluten-free food, yet coeliac disease remains significantly underdiagnosed and some confusion remains regarding optimal diagnostic practices. Small bowel histology is the gold standard for diagnosis. High-quality commercial enzyme-linked immunosorbent assays for transglutaminase immunoglobulin A and deamidated gliadin immunoglobulin A and G are sensitive tools for screening, but almost 10% of coeliac disease is seronegative and serological testing is unreliable in the very young, in people already following a gluten-reduced diet, and those using immunosuppressive medications. HLA DQA and DQB genotyping to show that alleles encoding HLA DQ2 and DQ8 are absent virtually excludes coeliac disease. Confirming histological remission reduces the risks of later complications, such as osteoporosis and cancer. Monitoring remission by serology is unreliable. Because gluten is an exogenous antigen and the small intestine is readily accessible, the immunopathogenesis of coeliac disease is better understood than other strongly major histocompatibility complex class II-associated diseases, such as type 1 diabetes mellitus. Therapeutic targets have been identified and drugs are under development to supplement or even replace gluten-free diet. With greater awareness and non-dietary therapeutics, diagnosis and treatment of coeliac disease will be increasingly prominent in medical practice.

Aim Numerous geographical information system (GIS)-based techniques for estimating a species' potential geographical distribution now exist. While a species' potential distribution is more extensive than its documented range, the lack of records from some suitable regions may simply derive from inadequate sampling there. Using occurrence records of both the study species and the more inclusive overall target group, I propose a

Geographic studies addressing the role of competition in determining species’ macrodistributions have been limited by only simple or subjective means of identifying regions of suitable habitat. Now, ecological-niche models of species’ potential distributions present a possible approach to testing for the geographic patterns predicted under competitive exclusion and competitive release. Previously, we modeled the potential distributions of two spiny pocket mice (Heteromys australis and H. anomalus) in northwestern South America using specimen localities, environmental data, and the Genetic Algorithm for Rule-Set Prediction (GARP). Here we superimpose the models to examine known distributional records in areas of potential sympatry between the two species, thus testing the geographic predictions of competitive exclusion. In addition, we examine environmental characteristics of known localities, testing for data consistent with competitive release. Areas of potential sympatry are minimal, lying in regions of intermediate water balance. Only records of H. australis are known from areas of potential sympatry in regions where the species’ ranges meet, consistent with exclusion of H. anomalus by H. australis. Heteromys anomalus inhabits areas ecologically suitable for both species only in the isolated Sierra Nevada de Santa Marta, in which H. australis is not present (most likely for historical reasons). Furthermore, environmental characteristics of localities of H. anomalus in biogeographic regions where H. australis is absent fit the pattern predicted under competitive release. In contrast, localities of H. australis show no indication of competitive release. Although the results of present analyses do not conclusively demonstrate competitive exclusion or release, they provide directional hypotheses that can now be tested in experimental field and laboratory studies.

Aim Predictive models of species’ distributions use occurrence records and environmental data to produce a model of the species’ requirements and a map of its potential distribution. To determine regions of suitable environmental conditions and assess biogeographical questions regarding their ranges, we modelled the potential geographical distributions of two spiny pocket mice (Rodentia: Heteromyidae) in northwestern South America.

A model of hyperkinesis is introduced based on an ecological conception. The antecedents of hyperkinetic behavior are provided by a child's family environment, academic environment, and physiologic environment. These factors influence cognitive processes of the child. The consequences of hyperkinetic behavior often are undesirable, and so professional treatment is sought. Based on the ecological approach, effective treatment is multimodal and can involve the child, the family, and the school. No single approach to treatment is effective with all children.

Fifty-four alcoholics and 30 nonalcoholics were tested on Russell's (1975) revision of the Wechsler Memory Scale (RWMS). Subjects were dichotomized into groups of old and young, and alcoholics were divided further into groups of short- and long-term abusers. Groups were matched on socioeconomic status. Significant group differences were found on three of the four RWMS measures as a function of abuse status and on two of the measures as a function of age. In terms of severity of impairment, alcoholics were found to demonstrate only mild verbal and figural memory deficits when compared to age-matched controls. Results are discussed with regard to the clinical utility of the RWMS as a memory screening instrument with alcoholic patients and in terms of treatment implications.

This paper examines modes of behavior across different ethnic groups of children rated as hyperactive on a behavior rating scale. The experimenters questioned the similarity in behavior patterns or modes displayed by 132 black, white, and Mexican-American children who had been rated as hyperactive. Using the Abbreviated Conners Teacher Rating Scale, score patterns of these children were examined through analysis of variance. The results revealed differences across ethnic groups: black children scored significantly higher than the white and Mexican-American children on three scale items and also scored significantly higher than the other two groups in terms of mean total scale score. These findings are interpreted from a sociological perspective.

N-formylated chemotactic peptides are produced by intestinal bacteria in vitro and Can be detected in intestinal luminal fluids. The healthy intestine must have mechanisms for preventing absorption of such peptides which can induce an inflammatory response when introduced systemically. Synthetic formyl-methionyl-leucyl-phenylalanine (F-met-leu-3H-phe) has been used as a model bacterial chemotactic peptide to investigate intestinal absorption and metabolism of such peptides in the rat. Disappearance of tritium-activity was rapid from jejunal and ileal loops and substantial hydrolysis of peptide occurred with only labelled metabolites appearing in portal blood. Less absorption and less metabolism occurred in the colon. Degradation of F-met-leu-phe was due to a mucosal carboxypeptidase and was inhibited by benzylsuccinate, a potent inhibitor of the enzyme. In the presence of inhibitor, luminal disappearance from ileal loops was abolished and F-met-leu-3H-phe was not detected in portal blood indicating that healthy gut mucosa is ‘impermeable’ to intact peptide. The intestinal ‘barrier’ preventing mucosal penetration and the inflammatory effects of luminal bacterial peptides have two components: restricted mucosal permeability and a carboxypeptidase capable of hydrolysing such peptides with loss of their bioactivity.

This paper examines the relationship between ethnicity and hyperactivity, an area largely neglected in research on hyperactivity. The assumption that hyperactivity is uniformly distributed across ethnic groups is challenged, based on a large (N = 1719) sample of white, black, and Mexican-American elementary school children. The Abbreviated Conners Teacher Rating Scale was used to identify the hyperactive group. Two important findings emerged. First, the 15% overall incidence rate is substantially higher than previously reported in the literature for large samples. Second, in those schools with nonwhite majorities, teachers rated black children as significantly more often hyperactive and Mexican-American children as significantly less often hyperactive than would be expected, based on their representation in the general student body. These findings are interpreted from a sociological perspective.

This study investigated the efficacy of using a behavioral feedback procedure as a means of reducing the nonattending behavior in children with attentional deficits and/or motoric restlessness. It was hypothesized that children with an attentional deficit would be able to learn to attend to classroom work when provided information about their behavior. Subjects consisted of 4 children with attentional deficits and motoric restlessness, 4 with motoric restlessness alone, and 8 without attentional deficits or motoric restlessness. A modified operant design was used to demonstrate the effectiveness of the feedback procedure. Significant changes were evidenced by all groups of subjects. Initial results and follow-up observations indicated that the attending behavior of the experimental subjects increased, and was manitained, without the use of tangible reinforcers.

N-formyl methionyl leucyl 3H-phenylalanine was used as a model bacterial chemotactic peptide to study the systemic metabolism and excretory pathways for such peptides in the rat. After intravenous bolus infusion, the peptide was rapidly cleared from the systemic circulation with a mean of 22% of the dose being excreted in bile over 2 h. In bile, 53% of radioactivity existed as intact peptide, the remainder was its degradation product, 3H-phenylalanine. No intact peptide was detected in urine. While previous studies have shown no significant absorption of F-met-leu-phe from normal rat intestine, in the current studies ileal loop infusions of F-met-leu-phe in hyperosmolar solution, to increase gut permeability, resulted in absorption of intact peptide which was recovered in bile. These studies show that bile is a major pathway for excretion of bacterial chemotactic peptide in the rat and confirm the potential for an enterohepatic circulation of peptides from the gut lumen under conditions of increased intestinal mucosal permeability.

Raven's Colored Progressive Matrices were adapted to a tactual format, thus making possible the insightful solution of the test items without the use of vision. In order to determine the validity of this test as a measure of intelligence in blind children, tactual Progressive Matrices scores of 115 blind students were correlated with WISC Verbal Scale IQ scores, academic achievement, and chronological age. Subjects ranged from 6 to 15 years of age, and all had a 99 per cent or greater loss of visual efficiency. The tactual test correlated with validity criteria in a positive and significant manner. Kuder-Richardson reliability of the tactual Progressive Matrices was found to be adequate in children age 9 years and older. It was concluded that this test shows promise as a non-verbal intelligence test for the child of 9–15 years of age, but that further development is necessary before it can be considered a useful supplement to the standard tests used with the blind.