Predicting positive food challenges at the introduction of nuts in sensitised children

Rationale: Children with atopic diseases in early life are frequently found with positive IgE tests to nuts, without a history of previous ingestion. We aimed to identify risk factors for reactions to nuts at their first introduction. Methods: A detailed retrospective case note and database analysis was performed. Inclusion criteria were: patients aged 3 to 16 years who had had a standardized food challenge to peanut and/or tree nuts due to primary sensitisation to the nut (positive specific IgE or SPT). A detailed assessment was performed of factors relating to food challenge outcome with univariate and multivariate logistic regression analysis. Results: There were 98 food challenges (48% peanut, 52% tree nut) with 29 positive, 67 negative and 2 inconclusive challenges. A positive maternal history and a specific IgE > 2 kU/l were strongly associated with a significantly increased risk of a positive food challenge (OR 3.54; 95% CI 1.28 to 9.81; and OR 4.82; 95% CI 1.57 to 14.86; respectively). There was no significant association between the type of nut, age, presence of other food allergies, paternal or sibling atopic history, other atopic conditions or severity of previous reaction to other foods. Conclusions: We have demonstrated an association between the presence of a maternal atopic history and a specific IgE > 2 kU/l, and a significant increase in the likelihood of a positive food challenge in children with primary sensitisation to nuts. Although requiring further prospective validation we suggest these easily identifiable components should be considered when deciding the need for a nut challenge.

Predictors of return to work after a knee injury in patients hospitalized in vocational rehabilitation

Introduction.- Knee injuries are frequent in a young and active population. Most of the patients resume their professional activity but few studies were interested in factors that predict a return to work. The aim of this study is to identify these predictors from a large panel of bio-psychosocial variables. We postulated that the return to work 3 months and 2 years after discharge is mostly predicted by psychosocial variables.Patients and methods.- Prospective study, patients hospitalized for a knee injury. Variables measured: the abbreviated injury score (AIS) for the gravity of the injuries, analog visual scale for the intensity of pain, INTERMED for the bio-psychosocial complexity, SF-36 for the quality of life, HADs for the anxiety/depression symptoms and IKDC score for the knee function. Univariate logistic regressions, adjusted for age and gender, were performed in order to predict return to work.Results.- One hundred and twenty-six patients hospitalized during 8 months after the accident were included into this prospective study. A total of 73 (58%) and 75 (59%) questionnaires were available after 3 months and 2 years, respectively. The SF-36 pain was the sole predictor of return to work at 3 months (odds Ratio 1.06 [1.02-1.10], P = 0.01; for a one point increase) and 2 years (odds Ratio 1.06 [1.02-1.10], P = 0.01). At three months, other factors are SF-36 (physic sub-scale), IKDC score, the presence of a work contract and the presence of litigation. The bio-psychosocial complexity, the presence of depressive symptoms predicts the return to work at two years.Discussion.- Our working hypothesis was partially confirmed: some psychosocial factors (i.e. depressive symptoms, work contract, litigation, INTERMED) predict the return to work but the physical health and the knee function, perceived by the patient, are also correlated. Pain is the sole factor isolated at both times (i.e. 3 months and 2 years) and, consequently, appears a key element in the prediction of the return to work. Some factors are accessible to the rehabilitation program but only if an interdisciplinary approach is performed.

The selective migration of young graduates : which of them return to their rural home region and which do not?

This paper addresses the migration behaviours of young university graduates from a rural region in Switzerland. Based on a questionnaire survey, it compares graduates' current place of residence (i.e. whether or not they returned to their home region) with characteristics related to their socio-familial, migration and professional trajectories. The propensity to return varies not only according to labour market variables (employment opportunities), but also to other factors, some of which have even more influence than job opportunities. The graduates' life course position (kind of household), their partners' characteristics (level of education and home region) and their family background (socio-economic status and history of migration) all play a central role. On the whole, results show that migration appears as a selective and complex process embedded in the life course of graduates.

Predicting global change impacts on plant species' distributions: Future challenges

Given the rate of projected environmental change for the 21st century, urgent adaptation and mitigation measures are required to slow down the on-going erosion of biodiversity. Even though increasing evidence shows that recent human-induced environmental changes have already triggered species' range shifts, changes in phenology and species' extinctions, accurate projections of species' responses to future environmental changes are more difficult to ascertain. This is problematic, since there is a growing awareness of the need to adopt proactive conservation planning measures using forecasts of species' responses to future environmental changes. There is a substantial body of literature describing and assessing the impacts of various scenarios of climate and land-use change on species' distributions. Model predictions include a wide range of assumptions and limitations that are widely acknowledged but compromise their use for developing reliable adaptation and mitigation strategies for biodiversity. Indeed, amongst the most used models, few, if any, explicitly deal with migration processes, the dynamics of population at the "trailing edge" of shifting populations, species' interactions and the interaction between the effects of climate and land-use. In this review, we propose two main avenues to progress the understanding and prediction of the different processes A occurring on the leading and trailing edge of the species' distribution in response to any global change phenomena. Deliberately focusing on plant species, we first explore the different ways to incorporate species' migration in the existing modelling approaches, given data and knowledge limitations and the dual effects of climate and land-use factors. Secondly, we explore the mechanisms and processes happening at the trailing edge of a shifting species' distribution and how to implement them into a modelling approach. We finally conclude this review with clear guidelines on how such modelling improvements will benefit conservation strategies in a changing world. (c) 2007 Rubel Foundation, ETH Zurich. Published by Elsevier GrnbH. All rights reserved.

SESAM - a new framework integrating macroecological and species distribution models for predicting spatio-temporal patterns of species assemblages

Two different approaches currently prevail for predicting spatial patterns of species assemblages. The first approach (macroecological modelling, MEM) focuses directly on realised properties of species assemblages, whereas the second approach (stacked species distribution modelling, S-SDM) starts with constituent species to approximate assemblage properties. Here, we propose to unify the two approaches in a single 'spatially-explicit species assemblage modelling' (SESAM) framework. This framework uses relevant species source pool designations, macroecological factors, and ecological assembly rules to constrain predictions of the richness and composition of species assemblages obtained by stacking predictions of individual species distributions. We believe that such a framework could prove useful in many theoretical and applied disciplines of ecology and evolution, both for improving our basic understanding of species assembly across spatio-temporal scales and for anticipating expected consequences of local, regional or global environmental changes. In this paper, we propose such a framework and call for further developments and testing across a broad range of community types in a variety of environments.

Predictive factors of adrenal insufficiency in patients admitted to acute medical wards: a case control study.

BACKGROUND: Adrenal insufficiency is a rare and potentially lethal disease if untreated. Several clinical signs and biological markers are associated with glucocorticoid failure but the importance of these factors for diagnosing adrenal insufficiency is not known. In this study, we aimed to assess the prevalence of and the factors associated with adrenal insufficiency among patients admitted to an acute internal medicine ward. METHODS: Retrospective, case-control study including all patients with high-dose (250 μg) ACTH-stimulation tests for suspected adrenal insufficiency performed between 2008 and 2010 in an acute internal medicine ward (n = 281). Cortisol values <550 nmol/l upon ACTH-stimulation test were considered diagnostic for adrenal insufficiency. Area under the ROC curve (AROC), sensitivity, specificity, negative and positive predictive values for adrenal insufficiency were assessed for thirteen symptoms, signs and biological variables. RESULTS: 32 patients (11.4%) presented adrenal insufficiency; the others served as controls. Among all clinical and biological parameters studied, history of glucocorticoid withdrawal was the only independent factor significantly associated with patients with adrenal insufficiency (Odds Ratio: 6.71, 95% CI: 3.08 -14.62). Using a logistic regression, a model with four significant and independent variable was obtained, regrouping history of glucocorticoid withdrawal (OR 7.38, 95% CI [3.18 ; 17.11], p-value <0.001), nausea (OR 3.37, 95% CI [1.03 ; 11.00], p-value 0.044), eosinophilia (OR 17.6, 95% CI [1.02; 302.3], p-value 0.048) and hyperkalemia (OR 2.41, 95% CI [0.87; 6.69], p-value 0.092). The AROC (95% CI) was 0.75 (0.70; 0.80) for this model, with 6.3 (0.8 - 20.8) for sensitivity and 99.2 (97.1 - 99.9) for specificity. CONCLUSIONS: 11.4% of patients with suspected adrenal insufficient admitted to acute medical ward actually do present with adrenal insufficiency, defined by an abnormal response to high-dose (250 μg) ACTH-stimulation test. A history of glucocorticoid withdrawal was the strongest factor predicting the potential adrenal failure. The combination of a history of glucocorticoid withdrawal, nausea, eosinophilia and hyperkaliemia might be of interest to suspect adrenal insufficiency.

Integrated Analysis of Molecular and Clinical Prognostic Factors in Stage II/III Colon Cancer.

Background The prognostic potential of individual clinical and molecular parameters in stage II/III colon cancer has been investigated, but a thorough multivariable assessment of their relative impact is missing. Methods Tumors from patients (N = 1404) in the PETACC3 adjuvant chemotherapy trial were examined for BRAF and KRAS mutations, microsatellite instability (MSI), chromosome 18q loss of heterozygosity (18qLOH), and SMAD4 expression. Their importance in predicting relapse-free survival (RFS) and overall survival (OS) was assessed by Kaplan-Meier analyses, Cox regression models, and recursive partitioning trees. All statistical tests were two-sided. Results MSI-high status and SMAD4 focal loss of expression were identified as independent prognostic factors with better RFS (hazard ratio [HR] of recurrence = 0.54, 95% CI = 0.37 to 0.81, P = .003) and OS (HR of death = 0.43, 95% CI = 0.27 to 0.70, P = .001) for MSI-high status and worse RFS (HR = 1.47, 95% CI = 1.19 to 1.81, P < .001) and OS (HR = 1.58, 95% CI = 1.23 to 2.01, P < .001) for SMAD4 loss. 18qLOH did not have any prognostic value in RFS or OS. Recursive partitioning identified refinements of TNM into new clinically interesting prognostic subgroups. Notably, T3N1 tumors with MSI-high status and retained SMAD4 expression had outcomes similar to stage II disease. Conclusions Concomitant assessment of molecular and clinical markers in multivariable analysis is essential to confirm or refute their independent prognostic value. Including molecular markers with independent prognostic value might allow more accurate prediction of prognosis than TNM staging alone.

Predicting adverse events in children with fever and chemotherapy-induced neutropenia: the prospective multicenter SPOG 2003 FN study.

PURPOSE To develop a score predicting the risk of adverse events (AEs) in pediatric patients with cancer who experience fever and neutropenia (FN) and to evaluate its performance. PATIENTS AND METHODS Pediatric patients with cancer presenting with FN induced by nonmyeloablative chemotherapy were observed in a prospective multicenter study. A score predicting the risk of future AEs (ie, serious medical complication, microbiologically defined infection, radiologically confirmed pneumonia) was developed from a multivariate mixed logistic regression model. Its cross-validated predictive performance was compared with that of published risk prediction rules. Results An AE was reported in 122 (29%) of 423 FN episodes. In 57 episodes (13%), the first AE was known only after reassessment after 8 to 24 hours of inpatient management. Predicting AE at reassessment was better than prediction at presentation with FN. A differential leukocyte count did not increase the predictive performance. The score predicting future AE in 358 episodes without known AE at reassessment used the following four variables: preceding chemotherapy more intensive than acute lymphoblastic leukemia maintenance (weight = 4), hemoglobin > or = 90 g/L (weight = 5), leukocyte count less than 0.3 G/L (weight = 3), and platelet count less than 50 G/L (weight = 3). A score (sum of weights) > or = 9 predicted future AEs. The cross-validated performance of this score exceeded the performance of published risk prediction rules. At an overall sensitivity of 92%, 35% of the episodes were classified as low risk, with a specificity of 45% and a negative predictive value of 93%. CONCLUSION This score, based on four routinely accessible characteristics, accurately identifies pediatric patients with cancer with FN at risk for AEs after reassessment.

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

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

The evolution of helping and harming on graphs: the return of the inclusive fitness effect.

Evolutionary graph theory has been proposed as providing new fundamental rules for the evolution of co-operation and altruism. But how do these results relate to those of inclusive fitness theory? Here, we carry out a retrospective analysis of the models for the evolution of helping on graphs of Ohtsuki et al. [Nature (2006) 441, 502] and Ohtsuki & Nowak [Proc. R. Soc. Lond. Ser. B Biol. Sci (2006) 273, 2249]. We show that it is possible to translate evolutionary graph theory models into classical kin selection models without disturbing at all the mathematics describing the net effect of selection on helping. Model analysis further demonstrates that costly helping evolves on graphs through limited dispersal and overlapping generations. These two factors are well known to promote relatedness between interacting individuals in spatially structured populations. By allowing more than one individual to live at each node of the graph and by allowing interactions to vary with the distance between nodes, our inclusive fitness model allows us to consider a wider range of biological scenarios leading to the evolution of both helping and harming behaviours on graphs.

Prognostic factors in early-stage leiomyosarcoma of the uterus.

Uterine leiomyosarcomas (LMSs) are rare cancers representing less than 1% of all uterine malignancies. Clinical International Federation of Gynecology and Obstetrics (FIGO) stage is the most important prognostic factor. Other significant prognostic factors, especially for early stages, are difficult to establish because most of the published studies have included localized and extra-pelvian sarcomas. The aim of our study was to search for significant prognostic factors in clinical stage I and II uterine LMS. The pathologic features of 108 uterine LMS including 72 stage I and II lesions were reviewed using standardized criteria. The prognostic significance of different pathologic features was assessed. The median follow-up in the whole group was 64 months (range, 6-223 months). The 5-year overall survival (OS) and metastasis-free interval and local relapse-free interval rates in the whole group and early-stage group (FIGO stages I and II) were 40% and 57%, 42% and 50%, 56% and 62%, respectively. Clinical FIGO stage was the most important prognostic factor for OS in the whole group (P = 4 x 10). In the stage I and II group, macroscopic circumscription was the most significant factor predicting OS (P = 0.001). In the same group, mitotic score and vascular invasion were associated with metastasis-free interval (P = 0.03 and P = 0.04, respectively). Uterine LMSs diagnosed using standardized criteria have a poor prognosis, and clinical FIGO stage is an ominous prognostic factor. In early-stage LMS, pathologic features such as mitotic score, vascular invasion, and tumor circumscription significantly impact patient outcome.

Predicting stroke through genetic risk functions: the CHARGE Risk Score Project.

BACKGROUND AND PURPOSE: Beyond the Framingham Stroke Risk Score, prediction of future stroke may improve with a genetic risk score (GRS) based on single-nucleotide polymorphisms associated with stroke and its risk factors. METHODS: The study includes 4 population-based cohorts with 2047 first incident strokes from 22,720 initially stroke-free European origin participants aged ≥55 years, who were followed for up to 20 years. GRSs were constructed with 324 single-nucleotide polymorphisms implicated in stroke and 9 risk factors. The association of the GRS to first incident stroke was tested using Cox regression; the GRS predictive properties were assessed with area under the curve statistics comparing the GRS with age and sex, Framingham Stroke Risk Score models, and reclassification statistics. These analyses were performed per cohort and in a meta-analysis of pooled data. Replication was sought in a case-control study of ischemic stroke. RESULTS: In the meta-analysis, adding the GRS to the Framingham Stroke Risk Score, age and sex model resulted in a significant improvement in discrimination (all stroke: Δjoint area under the curve=0.016, P=2.3×10(-6); ischemic stroke: Δjoint area under the curve=0.021, P=3.7×10(-7)), although the overall area under the curve remained low. In all the studies, there was a highly significantly improved net reclassification index (P<10(-4)). CONCLUSIONS: The single-nucleotide polymorphisms associated with stroke and its risk factors result only in a small improvement in prediction of future stroke compared with the classical epidemiological risk factors for stroke.

Predicting root defence against herbivores during succession

P>1. Root herbivores and pathogens interfere with basic below-ground plant function, and can thereby affect plant fitness and spatial and temporal patterns in natural plant communities. However, there has been little development of concepts and theories on below-ground plant defence, a deficit that is in contrast to the abundance of theorizing for above-ground plant parts.2. A review of the past 10 years of research on below-ground plant-herbivore interactions has revealed that, similar to above-ground tissues, root defences can be expressed constitutively or induced upon herbivore attack, and can be classified into direct and indirect traits, tolerance, and escape. Indeed, it has been shown that roots tolerate herbivory by outgrowing or re-growing lost tissues, or resist it by producing secondary metabolites that are toxic to herbivores or attract natural enemies of herbivores.3. We propose that, similar to above-ground plant-herbivore theories, the partition of abiotic and biotic factors over ecological succession can serve as the basis for predicting investment in defence strategies below-ground.4. Investigation of herbivore pressure and root responses along primary and secondary successional gradients suggests that: (i) roots are often fast growing, thinner and softer in early compared to later succession. (ii) Insect and nematode herbivore pressure increases until mid-succession and later decreases. (iii) Mycorrhizal abundance increases with succession, and the composition of fungal species changes through succession, often shifting from arbuscular mycorrhizae to ecto-mycorrhizae.5. Based on these findings, and on classical (above-ground) plant defence theory, we suggest the following set of testable hypotheses for below-ground plant defence: (i) During succession, early plants invest most of their resources in growth and less in defences (associated with a general lack of herbivores and pathogens, and with limited availability of resources in the system), therefore relying more on re-growth (tolerance) strategies. (ii) During mid-succession, a buildup of herbivore pressure facilitates replacement by plant species that exhibit greater direct and indirect defence strategies. (iii) Constitutive and inducible levels of defences may trade-off, and early successional plants should rely more on induction of defences after herbivore attack, whereas late successional plants will increasingly rely on constitutively produced levels of physical and chemical defence. (iv) Successional changes in microbial associations have consequences for root defence by improving plant nutrition and defence expression as well as directly competing for root space; however, toxic or impenetrable root defences may also limit association with root symbionts, and so may constrain the expression of root defence.

There and back again? Combining habitat suitability modelling and connectivity analyses to assess a potential return of the otter to Switzerland

After a steady decline in the early 20th century, several terrestrial carnivore species have recently recovered in Western Europe, either through reintroductions or natural recolonization. Because of the large space requirements of these species and potential conflicts with human activities, ensuring their recovery requires the implementation of conservation and management measures that address the environmental, landscape and social dimensions of the problem. Few examples exist of such integrated management. Taking the case of the otter (Lutra lutra) in Switzerland, we propose a multi-step approach that allows to (1) identify areas with potentially suitable habitat, (2) evaluate their connectivity, (3) verify the potentiality of the species recolonization from populations in neighbouring countries. We showed that even though suitable habitat is available for the species and the level of structural connectivity within Switzerland is satisfactory, the level of connectivity with neighbouring populations is crucial to prioritize strategies that favour the species recovery in the field. This research is the first example integrating habitat suitability and connectivity assessment at different scales with other factors in a multi-step assessment for species recovery.

Predicting potential distribution of the jaguar (Panthera onca) in Mexico: identification of priority areas for conservation

Aim The jaguar, Panthera onca, is a species of global conservation concern. In Mexico, the northernmost part of its distribution range, its conservation status, is particularly critical, while its potential and actual distribution is poorly known. We propose an ensemble model (EM) of the potential distribution for the jaguar in Mexico and identify the priority areas for conservation.Location Mexico.Methods We generated our EM based on three presence-only methods (Ecological Niche Factor Analysis, Mahalanobis distance, Maxent) and considering environmental, biological and anthropogenic factors. We used this model to evaluate the efficacy of the existing Mexican protected areas (PAs), to evaluate the adequacy of the jaguar conservation units (JCUs) and to propose new areas that should be considered for conservation and management of the species in Mexico.Results Our results outline that 16% of Mexico (c. 312,000 km2) can be considered as suitable for the presence of the jaguar. Furthermore, 13% of the suitable areas are included in existing PAs and 14% are included in JCUs (Sanderson et al., 2002).Main conclusions Clearly much more should be carried out to establish a proactive conservation strategy. Based on our results, we propose here new jaguar conservation and management areas that are important for a nationwide conservation blueprint.