Generalized linear and generalized additive models in studies of species distributions: setting the scene

An important statistical development of the last 30 years has been the advance in regression analysis provided by generalized linear models (GLMs) and generalized additive models (GAMs). Here we introduce a series of papers prepared within the framework of an international workshop entitled: Advances in GLMs/GAMs modeling: from species distribution to environmental management, held in Riederalp, Switzerland, 6-11 August 2001.We first discuss some general uses of statistical models in ecology, as well as provide a short review of several key examples of the use of GLMs and GAMs in ecological modeling efforts. We next present an overview of GLMs and GAMs, and discuss some of their related statistics used for predictor selection, model diagnostics, and evaluation. Included is a discussion of several new approaches applicable to GLMs and GAMs, such as ridge regression, an alternative to stepwise selection of predictors, and methods for the identification of interactions by a combined use of regression trees and several other approaches. We close with an overview of the papers and how we feel they advance our understanding of their application to ecological modeling.

Detection of Optimal Models in Parameter Space with Support Vector Machines

The paper proposes an approach aimed at detecting optimal model parameter combinations to achieve the most representative description of uncertainty in the model performance. A classification problem is posed to find the regions of good fitting models according to the values of a cost function. Support Vector Machine (SVM) classification in the parameter space is applied to decide if a forward model simulation is to be computed for a particular generated model. SVM is particularly designed to tackle classification problems in high-dimensional space in a non-parametric and non-linear way. SVM decision boundaries determine the regions that are subject to the largest uncertainty in the cost function classification, and, therefore, provide guidelines for further iterative exploration of the model space. The proposed approach is illustrated by a synthetic example of fluid flow through porous media, which features highly variable response due to the parameter values' combination.

Galanin pathogenic mutations in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is a common epilepsy syndrome with a complex etiology. Despite evidence for the participation of genetic factors, the genetic basis of TLE remains largely unknown. A role for the galanin neuropeptide in the regulation of epileptic seizures has been established in animal models more than two decades ago. However, until now there was no report of pathogenic mutations in GAL, the galanin-encoding gene, and therefore its role in human epilepsy was not established. Here, we studied a family with a pair of monozygotic twins affected by TLE and two unaffected siblings born to healthy parents. Exome sequencing revealed that both twins carried a novel de novo mutation (p.A39E) in the GAL gene. Functional analysis revealed that the p.A39E mutant showed antagonistic activity against galanin receptor 1 (GalR1)-mediated response, and decreased binding affinity and reduced agonist properties for GalR2. These findings suggest that the p.A39E mutant could impair galanin signaling in the hippocampus, leading to increased glutamatergic excitation and ultimately to TLE. In a cohort of 582 cases, we did not observe any pathogenic mutations indicating that mutations in GAL are a rare cause of TLE. The identification of a novel de novo mutation in a biologically-relevant candidate gene, coupled with functional evidence that the mutant protein disrupts galanin signaling, strongly supports GAL as the causal gene for the TLE in this family. Given the availability of galanin agonists which inhibit seizures, our findings could potentially have direct implications for the development of anti-epileptic treatment.

Avian erythrocytes have functional mitochondria, opening novel perspectives for birds as animal models in the study of ageing.

BACKGROUND: In contrast to mammalian erythrocytes, which have lost their nucleus and mitochondria during maturation, the erythrocytes of almost all other vertebrate species are nucleated throughout their lifespan. Little research has been done however to test for the presence and functionality of mitochondria in these cells, especially for birds. Here, we investigated those two points in erythrocytes of one common avian model: the zebra finch (Taeniopygia guttata). RESULTS: Transmission electron microscopy showed the presence of mitochondria in erythrocytes of this small passerine bird, especially after removal of haemoglobin interferences. High-resolution respirometry revealed increased or decreased rates of oxygen consumption by erythrocytes in response to the addition of respiratory chain substrates or inhibitors, respectively. Fluorometric assays confirmed the production of mitochondrial superoxide by avian erythrocytes. Interestingly, measurements of plasmatic oxidative markers indicated lower oxidative stress in blood of the zebra finch compared to a size-matched mammalian model, the mouse. CONCLUSIONS: Altogether, those findings demonstrate that avian erythrocytes possess functional mitochondria in terms of respiratory activities and reactive oxygen species (ROS) production. Interestingly, since blood oxidative stress was lower for our avian model compared to a size-matched mammalian, our results also challenge the idea that mitochondrial ROS production could have been one actor leading to this loss during the course of evolution. Opportunities to assess mitochondrial functioning in avian erythrocytes open new perspectives in the use of birds as models for longitudinal studies of ageing via lifelong blood sampling of the same subjects.

Phylogeny of subtribe Gentianinae (Gentianaceae): biogeographic inferences despite limitations in temporal calibration points

The subtribe Gentianinae comprises ca. 425 species, most of them within the well-studied genus Gentiana and mainly distributed over the Eurasian continent. Phylogenetic relationships between Gentiana and its closest relatives, the climbing gentians (Crawfurdia, Tripterospermum) and the new genus Metagentiana, remain unclear. All three genera were recently found to be polyphyletic, possibly because of poor sampling of Tripterospermum and Crawfurdia. Highest diversity of Gentianinae occurs in the western Himalaya, but the absence of uncontroversial fossil evidence limits our understanding of its biogeography. In the present study, we generated ITS and atpB-rbcL sequences for 19 species of Tripterospermum, 9 of Crawfurdia and 11 of Metagentiana, together representing about 60 percent of the species diversity of these genera. Our results show that only Metagentiana is polyphyletic and divided into three monophyletic entities. No unambiguous synapomorphies were associated with the three Metagentiana entities. Different combinations of three approximate calibration points were used to generate three divergence time estimation scenarios. Although dating hypotheses were mostly inconsistent, they concurred in associating radiation of Gentiana to an orogenic phase of the Himalaya between 15 and 10 million years ago. Our study illustrates the conceptual difficulties in addressing the time frame of diversification in a group lacking sufficient fossil number and quality.

Exposure models in Switzerland: an overview of the present situation

A survey was undertaken among Swiss occupational health and safety specialists in 2004 to identify uses, difficulties, and possible developments of exposure models. Occupational hygienists (121), occupational physicians (169), and safety specialists (95) were surveyed with an in depth questionnaire. Results obtained indicate that models are not used very much in practice in Switzerland and are reserved to research groups focusing on specific topics. However, various determinants of exposure are often considered important by professionals (emission rate, work activity), and in some cases recorded and used (room parameters, operator activity). These parameters cannot be directly included in present models. Nevertheless, more than half of the occupational hygienists think that it is important to develop quantitative exposure models. Looking at research institutions, there is, however, a big interest in the use of models to solve problems which are difficult to address with direct measurements; i. e. retrospective exposure assessment for specific clinical cases and prospective evaluation for new situations or estimation of the effect of selected parameters. In a recent study about cases of acutepulmonary toxicity following water proofing spray exposure, exposure models have been used to reconstruct exposure of a group of patients. Finally, in the context of exposure prediction, it is also important to report about a measurement database existing in Switzerland since 1991. [Authors]

Increased epidermal expression and absence of mutations in CARD14 in a series of patients with sporadic pityriasis rubra pilaris.

Pityriasis rubra pilaris (PRP; MIM 173200) encompasses a spectrum of rare chronic papulosquamous inflammatory disorders, which have been classified into 6 subtypes(1) . Clinical features include palmoplantar keratoderma and follicular hyperkeratotic papules which coalesce into large, scaly, erythematous plaques, with frequent progression to exfoliative erythroderma. This article is protected by copyright. All rights reserved.

Concise reviews: in vitro-produced pancreas organogenesis models in three dimensions: self-organization from few stem cells or progenitors.

Three-dimensional models of organ biogenesis have recently flourished. They promote a balance between stem/progenitor cell expansion and differentiation without the constraints of flat tissue culture vessels, allowing for autonomous self-organization of cells. Such models allow the formation of miniature organs in a dish and are emerging for the pancreas, starting from embryonic progenitors and adult cells. This review focuses on the currently available systems and how these allow new types of questions to be addressed. We discuss the expected advancements including their potential to study human pancreas development and function as well as to develop diabetes models and therapeutic cells.

Combined approach for the management of large vestibular schwannomas: Planned subtotal resection followed by gamma knife surgery in a series of 20 consecutive cases.

INTRODUCTION: The management of large lesions of the skull base, such as vestibular schwannomas (VS) is challenging. Microsurgery remains the main treatment option. Combined approaches (planned subtotal resection followed by gamma knife surgery (GKS) for residual tumor long-term control) are being increasingly considered to reduce the risk of neurological deficits following complete resection. The current study aims to prospectively evaluate the safety-efficacy of combined approach in patients with large VS. MATERIALS AND METHODS: We present our experience with planned subtotal resection followed by gamma knife surgery (GKS) in a consecutive a series of 20 patients with large vestibular schwannomas, treated between 2009 and 2014 in Lausanne University Hospital, Switzerland. Clinical and radiological data and audiograms were prospectively collected for all patients, before and after surgery, before and after GKS, at regular intervals, in dedicated case-report forms. Additionally, for GKS, dose-planning parameters were registered. RESULTS: Twenty patients (6 males and 14 females) with large VS had been treated by this approach. The mean age at the time of surgery was 51.6years (range 34.4-73.4). The mean presurgical diameter was 36.7 (range 26.1-45). The mean presurgical tumor volume was 15.9cm(3) (range 534.9). Three patients (15%) needed a second surgical intervention because of high volume of the tumor remnant considered too large for a safe GKS. The mean follow-up after surgery was 27.2months (range 6-61.3). The timing of GKS was decided on the basis of the residual tumor shape and size following surgery. The mean duration between surgery and GKS was 7.6months (range 413.9, median 6months). The mean tumor volume at the time of GKS was 4.1cm(3) (range 0.5-12.8). The mean prescription isodose volume was 6.3cm(3) (range 0.8-15.5). The mean number of isocenters was 20.4 (range 11-31) and the mean marginal prescription dose was 11.7Gy (range 11-12). We did not have any major complications in our series. Postoperative status showed normal facial nerve function (House-Brackmann grade I) in all patients. Six patients with useful pre-operative hearing (GR class 1) underwent surgery with the aim to preserve cochlear nerve function; of these patients, 5 (83.3%) of them remained in GR class 1 and one (16.7%) lost hearing (GR class 5). Two patients having GR class 3 at baseline remained in the same GR class, but the tonal audiometry improved in one of them during follow-up. Eleven patients (57.8%) were in GR class 5 preoperatively; one patient improved hearing after surgery, passing to GR class 3 postoperatively. Following GKS, there were no new neurological deficits, with facial and hearing function remaining identical to that after surgery. CONCLUSION: Our data suggest that planned subtotal resection followed by GKS has an excellent clinical outcome with respect to retaining facial and cochlear nerve function. This represents a paradigm shift of the treatment goals from a complete tumor excision perspective to that of a surgery designed to preserve neural functions. As long-term results emerge, this approach of a combined treatment (microsurgery and GKS) will most probably become the standard of care in the management of large vestibular schwanomma.