A mutation in the FAM83G gene in dogs with hereditary footpad hyperkeratosis (HFH)

Hereditary footpad hyperkeratosis (HFH) represents a palmoplantar hyperkeratosis, which is inherited as a monogenic autosomal recessive trait in several dog breeds, such as e.g. Kromfohrländer and Irish Terriers. We performed genome-wide association studies (GWAS) in both breeds. In Kromfohrländer we obtained a single strong association signal on chromosome 5 (p(raw) = 1.0×10(-13)) using 13 HFH cases and 29 controls. The association signal replicated in an independent cohort of Irish Terriers with 10 cases and 21 controls (p(raw) = 6.9×10(-10)). The analysis of shared haplotypes among the combined Kromfohrländer and Irish Terrier cases defined a critical interval of 611 kb with 13 predicted genes. We re-sequenced the genome of one affected Kromfohrländer at 23.5× coverage. The comparison of the sequence data with 46 genomes of non-affected dogs from other breeds revealed a single private non-synonymous variant in the critical interval with respect to the reference genome assembly. The variant is a missense variant (c.155G>C) in the FAM83G gene encoding a protein with largely unknown function. It is predicted to change an evolutionary conserved arginine into a proline residue (p.R52P). We genotyped this variant in a larger cohort of dogs and found perfect association with the HFH phenotype. We further studied the clinical and histopathological alterations in the epidermis in vivo. Affected dogs show a moderate to severe orthokeratotic hyperplasia of the palmoplantar epidermis. Thus, our data provide the first evidence that FAM83G has an essential role for maintaining the integrity of the palmoplantar epidermis.

A boundary value problem approach to too-short arc optical track association

Given a short-arc optical observation with estimated angle-rates, the admissible region is a compact region in the range / range-rate space defined such that all likely and relevant orbits are contained within it. An alternative boundary value problem formulation has recently been proposed where range / range hypotheses are generated with two angle measurements from two tracks as input. In this paper, angle-rate information is reintroduced as a means to eliminate hypotheses by bounding their constants of motion before a more computationally costly Lambert solver or differential correction algorithm is run.

Suicide tourism: a pilot study on the swiss phenomenon

While assisted suicide (AS) is strictly restricted in many countries, it is not clearly regulated by law in Switzerland. This imbalance leads to an influx of people —‘suicide tourists’—coming to Switzerland, mainly to the Canton of Zurich, for the sole purpose of committing suicide. Political debate regarding ‘suicide tourism’ is taking place in many countries. Swiss medicolegal experts are confronted with these cases almost daily, which prompted our scientific investigation of the phenomenon. The present study has three aims: (1) to determine selected details about AS in the study group (age, gender and country of residence of the suicide tourists, the organisation involved, the ingested substance leading to death and any diseases that were the main reason for AS); (2) to find out the countries from which suicide tourists come and to review existing laws in the top three in order to test the hypothesis that suicide tourism leads to the amendment of existing regulations in foreign countries; and (3) to compare our results with those of earlier studies in Zurich. We did a retrospective data analysis of the Zurich Institute of Legal Medicine database on AS of on-Swiss residents in the last 5 years (2008–2012), and internet research for current legislation and political debate in the three foreign countries most concerned. We analysed 611 cases from 31 countries all over the world. Non-terminal conditions such as neurological and rheumatic diseases are increasing among suicide tourists. The unique phenomenon of suicide tourism in Switzerland may indeed result in the amendment or supplementary guidelines to existing regulations in foreign countries.

Regional differences of physical activity and sedentary behaviour in Swiss children are not explained by socio-demographics or the built environment

Objective We evaluated whether regional differences in physical activity (PA) and sedentary behaviour (SB) existed along language boundaries within Switzerland and whether potential differences would be explained by socio-demographics or environmental characteristics. Methods We combined data of 611 children aged 4 to 7 years from four regional studies. PA and SB were assessed by accelerometers. Information about the socio-demographic background was obtained by questionnaires. Objective neighbourhood attributes could be linked to home addresses. Multivariate regression models were used to test associations between PA and SB and socio-demographic characteristics and neighbourhood attributes. Results Children from the German compared to the French-speaking region were more physically active and less sedentary (by 10–15 %, p < 0.01). Although German-speaking children lived in a more favourable environment and a higher socioeconomic neighbourhood (differences p < 0.001), these characteristics did not explain the differences in PA behaviour between French and German speaking. Conclusions Factors related to the language region, which might be culturally rooted were among the strongest correlates of PA and SB among Swiss children, independent of individual, social and environmental factors.

Exploring occasion specificity in the assessment of DSM-5 maladaptive personality traits: A latent state-trait theory analysis.

The alternative classification system for personality disorders in DSM-5 features a hierarchical model of maladaptive personality traits. This trait model comprises five broad trait domains and 25 specific trait facets that can be reliably assessed using the Personality Inventory for DSM-5 (PID-5). Although there is a steadily growing literature on the validity of the PID-5, issues of temporal stability and situational influences on test scores are currently unexplored. We addressed these issues using a sample of 611 research participants who completed the PID-5 three times, with time intervals of two months. Latent state-trait (LST) analyses for each of the 25 PID-5 trait facets showed that, on average, 79.5% of the variance was due to stable traits (i.e., consistency), and 7.7% of the variance was due to situational factors (i.e., occasion specificity). Our findings suggest that the PID-5 trait facets predominantly capture individual differences that are stable across time.

Tracking the trajectory of shame, guilt, and pride across the life span

The authors examined age differences in shame, guilt, and 2 forms of pride (authentic and hubristic) from age 13 years to age 89 years, using cross-sectional data from 2,611 individuals. Shame decreased from adolescence into middle adulthood, reaching a nadir around age 50 years, and then increased in old age. Guilt increased from adolescence into old age, reaching a plateau at about age 70 years. Authentic pride increased from adolescence into old age, whereas hubristic pride decreased from adolescence into middle adulthood, reaching a minimum around age 65 years, and then increased in old age. On average, women reported experiencing more shame and guilt; Blacks reported experiencing less shame and Asians more hubristic pride than other ethnicities. Across the life span, shame and hubristic pride tended to be negatively related to psychological well-being, and shame-free guilt and authentic pride showed positive relations with well-being. Overall, the findings support the maturity principle of personality development and suggest that as people age they become more prone to experiencing psychologically adaptive self-conscious emotions, such as guilt and authentic pride, and less prone to experiencing psychologically maladaptive ones, such as shame and hubristic pride.

Ein nicht alltägliches türkisches Souvenir

Schlussfolgerungen für die Praxis Bei entsprechender Exposition in einem Endemiegebiet und typischer Klinik mit schmerzlosem, zentral nekrotischem, kutanen Ulkus sollte an einen kutanen Anthrax gedacht werden. Bei Einsendung einer Probe in das Primärlabor sollte unbedingt über die Verdachtsdiagnose informiert werden, damit die entsprechenden Biosicherheitsvorgaben eingehalten und eine Gefährdung von Personal und Umwelt ausgeschlossen werden können. Nach Abnahme eines Wundabstrichs bzw. einer Biopsie sollte unverzüglich eine antibiotische Therapie mit Ciprofloxacin oder Clindamycin für sieben Tage eingeleitet werden. Schon der Verdachtsfall ist in der Schweiz innerhalb von zwei Stunden meldepflichtig.

Benchmark problems for reactive transport modeling of the generation and attenuation of acid rock drainage

Acid rock drainage (ARD) is a problem of international relevance with substantial environmental and economic implications. Reactive transport modeling has proven a powerful tool for the process-based assessment of metal release and attenuation at ARD sites. Although a variety of models has been used to investigate ARD, a systematic model intercomparison has not been conducted to date. This contribution presents such a model intercomparison involving three synthetic benchmark problems designed to evaluate model results for the most relevant processes at ARD sites. The first benchmark (ARD-B1) focuses on the oxidation of sulfide minerals in an unsaturated tailing impoundment, affected by the ingress of atmospheric oxygen. ARD-B2 extends the first problem to include pH buffering by primary mineral dissolution and secondary mineral precipitation. The third problem (ARD-B3) in addition considers the kinetic and pH-dependent dissolution of silicate minerals under low pH conditions. The set of benchmarks was solved by four reactive transport codes, namely CrunchFlow, Flotran, HP1, and MIN3P. The results comparison focused on spatial profiles of dissolved concentrations, pH and pE, pore gas composition, and mineral assemblages. In addition, results of transient profiles for selected elements and cumulative mass loadings were considered in the intercomparison. Despite substantial differences in model formulations, very good agreement was obtained between the various codes. Residual deviations between the results are analyzed and discussed in terms of their implications for capturing system evolution and long-term mass loading predictions.

Chemical compositions of solid particles present in the Greenland NEEM ice core over the last 110,000 years

This study reports the chemical composition of particles present along Greenland’s North Greenland Eemian Ice Drilling (NEEM) ice core, back to 110,000 years before present. Insoluble and soluble particles larger than 0.45 μm were extracted from the ice core by ice sublimation, and their chemical composition was analyzed using scanning electron microscope and energy dispersive X-ray spectroscopy and micro-Raman spectroscopy. We show that the dominant insoluble components are silicates, whereas NaCl, Na₂SO₄, CaSO ₄, and CaCO₃ represent major soluble salts. For the first time, particles of CaMg(CO₃)₂ and Ca(NO₃)₂ 4H₂O are identified in a Greenland ice core. The chemical speciation of salts varies with past climatic conditions. Whereas the fraction of Na salts (NaCl + Na₂SO₄) exceeds that of Ca salts (CaSO₄+ CaCO₃) during the Holocene (0.6–11.7 kyr B.P.), the two fractions are similar during the Bølling-Allerød period (12.9–14.6 kyr B.P.). During cold climate such as over the Younger Dryas (12.0–12.6 kyr B.P.) and the Last Glacial Maximum (15.0–26.9 kyr B.P.), the fraction of Ca salts exceeds that of Na salts, showing that the most abundant ion generally controls the salt budget in each period. High-resolution analyses reveal changing particle compositions: those in Holocene ice show seasonal changes, and those in LGM ice show a difference between cloudy bands and clear layers, which again can be largely explained by the availability of ionic components in the atmospheric aerosol body of air masses reaching Greenland.

Recurrence-free survival, but not surgical therapy per se, determines 583 patients' long-term satisfaction following primary pilonidal sinus surgery.

PURPOSE With pilonidal sinus disease (PSD) incidence increasing and patients freely choosing their surgeon, patients' interest issues have been brought forward estimating patient satisfaction following pilonidal sinus surgery. The influence of wound healing time and long-term recurrence rate on patient satisfaction in primary PSD surgery has not been investigated yet. METHODS Five hundred eighty-three patients (German military cohort) were interviewed, compiling wound healing time, aesthetic satisfaction, long-term recurrence-free survival and patient satisfaction having undergone primary open (PO) treatment, marsupialization (MARS) or primary midline closure (PMC) treatment. Recurrence rate was determined by Kaplan-Meier calculation following up to 20 years after primary PSD surgery. RESULTS Patient satisfaction ranking from 1 to 10 (10 = max. satisfied) showed an average satisfaction of 8.2 (range 0-10; 95% confidence interval (CI) 7891-8250). In-hospital stay time was significantly longer in primary open (PO) and marsupialization (MARS) group as compared to primary midline closure (PMC; p < 0.0001, Kruskal-Wallis test). Satisfaction was comparable between treatment groups, and was neither linked to in-hospital stay time nor to longer outpatient wound care period or total treatment time. Recurrence-free survival, as seen in the PO and PMC treatment group, revealed a highly significant difference for all patients. Improvement in MARS patients with versus without recurrence was low, as satisfaction with primary treatment was lower as the other groups. CONCLUSIONS Neither choice of surgical treatment nor treatment duration within hospital or after hospital influences patient satisfaction, as long as recurrence-free survival can be provided. Marsupialization was ranked lower in both groups (with or without recurrence), and should be abandoned, as patients are significantly less satisfied with either results, independent of recurrence.

Eosinophilic esophagitis is characterized by a non-IgE-mediated food hypersensitivity.

Eosinophilic esophagitis (EoE) is a chronic disease characterized clinically by symptoms of esophageal dysfunction and histologically by eosinophil-predominant inflammation. EoE is frequently associated with concomitant atopic diseases and immunoglobulin E (IgE) sensitization to food allergens in children as well as to aeroallergens and cross-reactive plant allergen components in adults. Patients with EoE respond well to elemental and empirical food elimination diets. Recent research has, however, indicated that the pathogenesis of EoE is distinct from IgE-mediated food allergy. In this review, we discuss the individual roles of epithelial barrier defects, dysregulated innate and adaptive immune responses, and of microbiota in the pathogenesis of EoE. Although food has been recognized as a trigger factor of EoE, the mechanism by which it initiates or facilitates eosinophilic inflammation appears to be largely independent of IgE and needs to be further investigated. Understanding the pathogenic role of food in EoE is a prerequisite for the development of specific diagnostic tools and targeted therapeutic procedures. This article is protected by copyright. All rights reserved.