Overcoming the rare species modelling paradox: test of a novel hierarchical framework with an Iberian endemic plant

Rare species have restricted geographic ranges, habitat specialization, and/or small population sizes. Datasets on rare species distribution usually have few observations, limited spatial accuracy and lack of valid absences; conversely they provide comprehensive views of species distributions allowing to realistically capture most of their realized environmental niche. Rare species are the most in need of predictive distribution modelling but also the most difficult to model. We refer to this contrast as the "rare species modelling paradox" and propose as a solution developing modelling approaches that deal with a sufficiently large set of predictors, ensuring that statistical models aren't overfitted. Our novel approach fulfils this condition by fitting a large number of bivariate models and averaging them with a weighted ensemble approach. We further propose that this ensemble forecasting is conducted within a hierarchic multi-scale framework. We present two ensemble models for a test species, one at regional and one at local scale, each based on the combination of 630 models. In both cases, we obtained excellent spatial projections, unusual when modelling rare species. Model results highlight, from a statistically sound approach, the effects of multiple drivers in a same modelling framework and at two distinct scales. From this added information, regional models can support accurate forecasts of range dynamics under climate change scenarios, whereas local models allow the assessment of isolated or synergistic impacts of changes in multiple predictors. This novel framework provides a baseline for adaptive conservation, management and monitoring of rare species at distinct spatial and temporal scales.

A novel method for automated classification of epileptiform activity in the human electroencephalogram-based on independent component analysis.

Diagnosis of several neurological disorders is based on the detection of typical pathological patterns in the electroencephalogram (EEG). This is a time-consuming task requiring significant training and experience. Automatic detection of these EEG patterns would greatly assist in quantitative analysis and interpretation. We present a method, which allows automatic detection of epileptiform events and discrimination of them from eye blinks, and is based on features derived using a novel application of independent component analysis. The algorithm was trained and cross validated using seven EEGs with epileptiform activity. For epileptiform events with compensation for eyeblinks, the sensitivity was 65 +/- 22% at a specificity of 86 +/- 7% (mean +/- SD). With feature extraction by PCA or classification of raw data, specificity reduced to 76 and 74%, respectively, for the same sensitivity. On exactly the same data, the commercially available software Reveal had a maximum sensitivity of 30% and concurrent specificity of 77%. Our algorithm performed well at detecting epileptiform events in this preliminary test and offers a flexible tool that is intended to be generalized to the simultaneous classification of many waveforms in the EEG.

Safety of falciparum malaria diagnostic strategy based on rapid diagnostic tests in returning travellers and migrants: a retrospective study.

BACKGROUND: Rapid diagnostic tests for malaria (RDTs) allow accurate diagnosis and prompt treatment. Validation of their usefulness in travellers with fever was needed. The safety of a strategy to diagnose falciparum malaria based on RDT followed by immediate or delayed microscopy reading at first attendance was evaluated in one referral hospital in Switzerland. METHODS: A retrospective study was conducted in the outpatient clinic and emergency ward of University Hospital, covering a period of eight years (1999-2007). The study was conducted in the outpatient clinic and emergency ward of University Hospital. All adults suspected of malaria with a diagnostic test performed were included. RDT and microscopy as immediate tests were performed during working hours, and RDT as immediate test and delayed microscopy reading out of laboratory working hours. The main outcome measure was occurrence of specific complications in RDT negative and RDT positive adults. RESULTS: 2,139 patients were recruited. 1987 had both initial RDT and blood smear (BS) result negative. Among those, 2/1987 (0.1%) developed uncomplicated malaria with both RDT and BS positive on day 1 and day 6 respectively. Among the 152 patients initially malaria positive, 137 had both RDT and BS positive, four only BS positive and five only RDT positive (PCR confirmed) (six had only one test performed). None of the four initially RDT negative/BS positive and none of the five initially BS negative/RDT positive developed severe malaria while 6/137 of both RDT and BS positive did so. The use of RDT allowed a reduction of a median of 2.1 hours to get a first malaria test result. CONCLUSIONS: A malaria diagnostic strategy based on RDTs and a delayed BS is safe in non-immune populations, and shortens the time to first malaria test result.

A novel pediatric biventricular assist device: in vitro test results.

Most ventricular assist devices (VADs) currently used in infants are extracorporeal. These VADs require long-term anticoagulation therapy and extensive surgery, and two devices are needed for biventricular support. We designed a biventricular assist device based on shape memory alloy that reproduces the hemodynamic effects of cardiomyoplasty, supporting the heart with a compressing movement, and evaluated its performance in a dedicated mockup system. Nitinol fibers are the device's key component. Ejection fraction (EF), cardiac output (CO), and generated systolic pressure were measured on a test bench. Our test bench settings were a preload range of 0-15 mm Hg, an afterload range of 0-160 mm Hg, and a heart rate (HR) of 20, 30, 40, and 60 beats/min. A power supply of 15 volts and 3.5 amperes was necessary. The EF range went from 34.4% to 1.2% as the afterload and HR increased, along with a CO from 180 to 6 ml/min. The device generated a maximal systolic pressure of 25 mm Hg. Cardiac compression for biventricular assistance in child-sized heart using shape memory alloy is technically feasible. Further testing remains necessary to assess this VAD's in vivo performance range and its reliability.

Suboptimal access to primary healthcare among street-based sex workers in southwest Switzerland.

OBJECTIVES: Street-based sex workers (SSWs) in Lausanne, Switzerland, are poorly characterised. We set out to quantify potential vulnerability factors in this population and to examine SSW healthcare use and unmet healthcare requirements. METHODS: We conducted a cross-sectional questionnaire-based survey among SSWs working in Lausanne's red light district between 1 February and 31 July 2010, examining SSW socio-demographic characteristics and factors related to their healthcare. RESULTS: We interviewed 50 SSWs (76% of those approached). A fifth conducted their interviews in French, the official language in Lausanne. 48 participants (96%) were migrants, of whom 33/48 (69%) held no residence permit. 22/50 (44%) had been educated beyond obligatory schooling. 28/50 (56%) had no health insurance. 18/50 (36%) had been victims of physical violence. While 36/50 (72%) had seen a doctor during the preceding 12 months, only 15/50 (30%) were aware of a free clinic for individuals without health insurance. Those unaware of free services consulted emergency departments or doctors outside Switzerland. Gynaecology, primary healthcare and dental services were most often listed as needed. Two individuals (of 50, 4%) disclosed positive HIV status; of the others, 24/48 (50%) had never had an HIV test. CONCLUSIONS: This vulnerable population comprises SSWs who, whether through mobility, insufficient education or language barriers, are unaware of services they are entitled to. With half the participants reporting no HIV testing, there is a need to enhance awareness of available facilities as well as to increase provision and uptake of HIV testing.

Evaluating thermal treeline indicators based on air and soil temperature using an air-to-soil temperature transfer model

In recent research, both soil (root-zone) and air temperature have been used as predictors for the treeline position worldwide. In this study, we intended to (a) test the proposed temperature limitation at the treeline, and (b) investigate effects of season length for both heat sum and mean temperature variables in the Swiss Alps. As soil temperature data are available for a limited number of sites only, we developed an air-to-soil transfer model (ASTRAMO). The air-to-soil transfer model predicts daily mean root-zone temperatures (10cm below the surface) at the treeline exclusively from daily mean air temperatures. The model using calibrated air and root-zone temperature measurements at nine treeline sites in the Swiss Alps incorporates time lags to account for the damping effect between air and soil temperatures as well as the temporal autocorrelations typical for such chronological data sets. Based on the measured and modeled root-zone temperatures we analyzed. the suitability of the thermal treeline indicators seasonal mean and degree-days to describe the Alpine treeline position. The root-zone indicators were then compared to the respective indicators based on measured air temperatures, with all indicators calculated for two different indicator period lengths. For both temperature types (root-zone and air) and both indicator periods, seasonal mean temperature was the indicator with the lowest variation across all treeline sites. The resulting indicator values were 7.0 degrees C +/- 0.4 SD (short indicator period), respectively 7.1 degrees C +/- 0.5 SD (long indicator period) for root-zone temperature, and 8.0 degrees C +/- 0.6 SD (short indicator period), respectively 8.8 degrees C +/- 0.8 SD (long indicator period) for air temperature. Generally, a higher variation was found for all air based treeline indicators when compared to the root-zone temperature indicators. Despite this, we showed that treeline indicators calculated from both air and root-zone temperatures can be used to describe the Alpine treeline position.

Practical considerations for conducting ecotoxicity test methods with manufactured nanomaterials: what have we learnt so far?

This review paper reports the consensus of a technical workshop hosted by the European network, NanoImpactNet (NIN). The workshop aimed to review the collective experience of working at the bench with manufactured nanomaterials (MNMs), and to recommend modifications to existing experimental methods and OECD protocols. Current procedures for cleaning glassware are appropriate for most MNMs, although interference with electrodes may occur. Maintaining exposure is more difficult with MNMs compared to conventional chemicals. A metal salt control is recommended for experiments with metallic MNMs that may release free metal ions. Dispersing agents should be avoided, but if they must be used, then natural or synthetic dispersing agents are possible, and dispersion controls essential. Time constraints and technology gaps indicate that full characterisation of test media during ecotoxicity tests is currently not practical. Details of electron microscopy, dark-field microscopy, a range of spectroscopic methods (EDX, XRD, XANES, EXAFS), light scattering techniques (DLS, SLS) and chromatography are discussed. The development of user-friendly software to predict particle behaviour in test media according to DLVO theory is in progress, and simple optical methods are available to estimate the settling behaviour of suspensions during experiments. However, for soil matrices such simple approaches may not be applicable. Alternatively, a Critical Body Residue approach may be taken in which body concentrations in organisms are related to effects, and toxicity thresholds derived. For microbial assays, the cell wall is a formidable barrier to MNMs and end points that rely on the test substance penetrating the cell may be insensitive. Instead assays based on the cell envelope should be developed for MNMs. In algal growth tests, the abiotic factors that promote particle aggregation in the media (e.g. ionic strength) are also important in providing nutrients, and manipulation of the media to control the dispersion may also inhibit growth. Controls to quantify shading effects, and precise details of lighting regimes, shaking or mixing should be reported in algal tests. Photosynthesis may be more sensitive than traditional growth end points for algae and plants. Tests with invertebrates should consider non-chemical toxicity from particle adherence to the organisms. The use of semi-static exposure methods with fish can reduce the logistical issues of waste water disposal and facilitate aspects of animal husbandry relevant to MMNs. There are concerns that the existing bioaccumulation tests are conceptually flawed for MNMs and that new test(s) are required. In vitro testing strategies, as exemplified by genotoxicity assays, can be modified for MNMs, but the risk of false negatives in some assays is highlighted. In conclusion, most protocols will require some modifications and recommendations are made to aid the researcher at the bench. [Authors]

Introducing a new MRI classification of lumbar spinal stenosis based on cross-sectional morphology of the dural sac : 37

Introduction: Measures of the degree of lumbar spinal stenosis (LSS) such as antero-posterior diameter of the canal, and dural sac cross sectional area vary, and do not correlate with symptoms or results of surgery. We created a grading system, comprised of seven categories, based on the morphology of the dural sac and its contents as seen on T2 axial images. The categories take into account the ratio of rootlet/ CSF content. Grade A indicates no significant compression, grade D is equivalent to a total myelograhic block. We compared this classification with commonly used criteria of severity of stenosis. Methods: Fifty T2 axial MRI images taken at disc level from 27 symptomatic LSS patients undergoing decompressive surgery were classified twice by two radiologists and three spinal surgeons working at different institutions and countries. Dural sac cross-sectional surface area and AP diameter of the canal were measured both at disc and pedicle level from DICOM images using OsiriX software. Intraand inter-observer reliability were assessed using Cohen's, Fleiss' kappa statistics, and t test. Results: For the morphological grading the average intra-and inter observer kappas were 0.76 and 0.69+, respectively, for physicians working in the study originating country. Combining all observers the kappa values were 0.57 ± 0.19. and 0.44 ± 0.19, respectively. AP diameter and dural sac cross-sectional area measurements showed no statistically significant differences between observers. No correlation between morphological grading and AP diameter or dural sac crosssectional areawas observed in 13 (26%) and 8 cases (16%), respectively. Discussion: The proposed morphological grading relies on the identification of the dural sac and CSF better seen on full MRI series. This was not available to the external observers, which might explain the lower overall kappa values. Since no specific measurement tools are needed the grading suits everyday clinical practice and favours communication of degree of stenosis between practising physicians. The absence of a strict correlation with the dural sac surface suggests that measuring the surface alone might be insufficient in defining LSS as it is essentially a mismatch between the spinal canal and its contents. This grading is now adopted in our unit and further studies concentrating on relation between morphology, clinical symptoms and surgical results are underway.

Effect of Lactobacillus paracasei ST11 on a nasal provocation test with grass pollen in allergic rhinitis.

Cite this as: J. Wassenberg, S. Nutten, R. Audran, N. Barbier, V. Aubert, J. Moulin, A. Mercenier and F. Spertini, Clinical & Experimental Allergy, 2011 (41) 565-573. SUMMARY: Background Probiotics have been associated with prevention and improvement of symptoms in atopic diseases such as atopic dermatitis. However, few studies exist that document their efficacy for upper airways allergies such as allergic rhinitis. Objective To investigate the effect of short-term oral administration of Lactobacillus paracasei ST11 on a nasal provocation test (NPT) with grass pollen. Methods Thirty-one adult volunteers with allergic rhinitis were enrolled in a randomized, double-blind, placebo-controlled study, based on two 4-week cross-over periods of product consumption (ST11-fermented milk vs. placebo), separated by a wash-out period of 6-8 weeks. Objective and subjective clinical parameters of NPT as well as systemic and nasal immunological parameters were compared between the two treatment periods (registration number: NCT 011 50 253). Results Subjects that received ST11-fermented milk had lower nasal congestion than subjects under placebo (visual analogical scale; P<0.05). Nasal pruritus followed the same trend. However, no significant change in combined nasal reaction threshold was observed between the two periods. IL-5 secretion by peripheral blood mononuclear cells and serum allergen-specific IgG4 were significantly lower in ST11-fermented milk group compared to placebo group. IL-8 and IL-10 secretion followed the same trend. Conclusion and Clinical Relevance Short-term treatment with ST11-fermented milk before NPT significantly improved a clinical marker of NPT (subjective nasal congestion) and down-regulated systemic immune markers (IL-5 from peripheral blood mononuclear cells and serum IgG4). These data strongly suggest that probiotics may down modulate key parameters of allergic rhinitis and warrant future evaluation in seasonal trials.

Meta-analysis of gene-level associations for rare variants based on single-variant statistics.

Meta-analysis of genome-wide association studies (GWASs) has led to the discoveries of many common variants associated with complex human diseases. There is a growing recognition that identifying "causal" rare variants also requires large-scale meta-analysis. The fact that association tests with rare variants are performed at the gene level rather than at the variant level poses unprecedented challenges in the meta-analysis. First, different studies may adopt different gene-level tests, so the results are not compatible. Second, gene-level tests require multivariate statistics (i.e., components of the test statistic and their covariance matrix), which are difficult to obtain. To overcome these challenges, we propose to perform gene-level tests for rare variants by combining the results of single-variant analysis (i.e., p values of association tests and effect estimates) from participating studies. This simple strategy is possible because of an insight that multivariate statistics can be recovered from single-variant statistics, together with the correlation matrix of the single-variant test statistics, which can be estimated from one of the participating studies or from a publicly available database. We show both theoretically and numerically that the proposed meta-analysis approach provides accurate control of the type I error and is as powerful as joint analysis of individual participant data. This approach accommodates any disease phenotype and any study design and produces all commonly used gene-level tests. An application to the GWAS summary results of the Genetic Investigation of ANthropometric Traits (GIANT) consortium reveals rare and low-frequency variants associated with human height. The relevant software is freely available.

Examining the Agreement of Structural Loss Measured With Heidelberg Retinal Tomograhy and Functional Loss With Standard Automated Perimetry (SAP; Octopus), Pulsar Perimetry (PP), and Moorfields Motion Displacement Test (MDT) Perimetry

Purpose: To examine the relationship of functional measurements with structural measures. Methods: 146 eyes of 83 test subjects underwent Heidelberg Retinal Tomography (HRTIII) (disc area<2.43, mphsd<40), and perimetry testing with Octopus (SAP; Dynamic), Pulsar (PP; TOP) and Moorfields MDT (ESTA). Glaucoma was defined as progressive structural or functional loss (20 eyes). Perimetry test points were grouped into 6 sectors based on the estimated optic nerve head angle into which the associated nerve fiber bundle enters (Garway-Heath map). Perimetry summary measures (PSM) (MD SAP/ MD PP/ PTD MDT) were calculated from the average total deviation of each measured threshold from the normal for each sector. We calculated the 95% significance level of the sectorial PSM from the respective normative data. We calculated the percentage agreement with group1 (G1), healthy on HRT and within normal perimetric limits, and group 2 (G2), abnormal on HRT and outside normal perimetric limits. We also examined the relationship of PSM and rim area (RA) in those sectors classified as abnormal by MRA (Moorfields Regression Analysis) of HRT. Results: The mean age was 65 (range= [37, 89]). The global sensitivity versus specificity of each instrument in detecting glaucomatous eyes was: MDT 80% vs. 88%, SAP 80% vs. 80%, PP 70% vs. 89% and HRT 80% vs. 79%. Highest percentage agreement of HRT (respectively G1, G2, sector) with PSM were MDT (89%, 57%, nasal superior), SAP (83%, 74%, temporal superior), PP (74%, 63%, nasal superior). Globally percentage agreement (respectively G1, G2) was MDT (92%, 28%), SAP (87%, 40%) and PP (77%, 49%). Linear regression showed there was no significant trend globally associating RA and PSM. However, sectorally the supero-nasal sector had a statistically significant (p<0.001) trend with each instrument, the associated r2 coefficients are (MDT 0.38 SAP 0.56 and PP 0.39). Conclusions: There were no significant differences in global sensitivity or specificity between instruments. Structure-function relationships varied significantly between instruments and were consistently strongest supero-nasally. Further studies are required to investigate these relationships in detail.

Controlled nerve growth factor release from multi-ply alginate/chitosan-based nerve conduits.

The delivery kinetics of growth factors has been suggested to play an important role in the regeneration of peripheral nerves following axotomy. In this context, we designed a nerve conduit (NC) with adjustable release kinetics of nerve growth factor (NGF). A multi-ply system was designed where NC consisting of a polyelectrolyte alginate/chitosan complex was coated with layers of poly(lactide-co-glycolide) (PLGA) to control the release of embedded NGF. Prior to assessing the in vitro NGF release from NC, various release test media, with and without stabilizers for NGF, were evaluated to ensure adequate quantification of NGF by ELISA. Citrate (pH 5.0) and acetate (pH 5.5) buffered saline solutions containing 0.05% Tween 20 yielded the most reliable results for ELISA active NGF. The in vitro release experiments revealed that the best results in terms of reproducibility and release control were achieved when the NGF was embedded between two PLGA layers and the ends of the NC tightly sealed by the PLGA coatings. The release kinetics could be efficiently adjusted by accommodating NGF at different radial locations within the NC. A sustained release of bioactive NGF in the low nanogram per day range was obtained for at least 15days. In conclusion, the developed multi-ply NGF loaded NC is considered a suitable candidate for future implantation studies to gain insight into the relationship between local growth factor availability and nerve regeneration.

Clients of sex workers in Switzerland: it makes sense to counsel and propose rapid test for HIV on the street, a preliminary report.

BACKGROUND: Clients of street sex workers may be at higher risk for HIV infection than the general population. Furthermore, there is a lack of knowledge regarding HIV testing of clients of sex workers in developed countries. METHOD: This pilot study assessed the feasibility and acceptance of rapid HIV testing by the clients of street-based sex workers in Lausanne, Switzerland. For 5 evenings, clients in cars were stopped by trained field staff for face-to-face interviews focusing on sex-related HIV risk behaviors and HIV testing history. The clients were then offered a free anonymous rapid HIV test in a bus parked nearby. Rapid HIV testing and counselling were performed by experienced nurse practitioners. Clients with reactive tests were offered confirmatory testing, medical evaluation, and care in our HIV clinic. RESULT: We intercepted 144 men, 112 (77.8%) agreed to be interviewed. Among them, 50 (46.6%) had never been tested for HIV. A total of 31 (27.7%) rapid HIV tests were performed, 16 (51.6%) in clients who had not previously been tested. None were reactive. Initially, 19 (16.9%) additional clients agreed to HIV testing but later declined due to the 40-minute queue for testing. CONCLUSION: This pilot study showed that rapid HIV testing in the red light district of Lausanne was feasible, and that the clients of sex workers accepted testing at an unexpectedly high rate. This setting seems particularly appropriate for targeted HIV screening, since more than 40% of the clients had not previously been tested for HIV even though they engaged in sex-related HIV risk behaviour.

High-resolution 3D whole-heart coronary MRA: a study on the combination of data acquisition in multiple breath-holds and 1D residual respiratory motion compensation.

OBJECT: To study a scan protocol for coronary magnetic resonance angiography based on multiple breath-holds featuring 1D motion compensation and to compare the resulting image quality to a navigator-gated free-breathing acquisition. Image reconstruction was performed using L1 regularized iterative SENSE. MATERIALS AND METHODS: The effects of respiratory motion on the Cartesian sampling scheme were minimized by performing data acquisition in multiple breath-holds. During the scan, repetitive readouts through a k-space center were used to detect and correct the respiratory displacement of the heart by exploiting the self-navigation principle in image reconstruction. In vivo experiments were performed in nine healthy volunteers and the resulting image quality was compared to a navigator-gated reference in terms of vessel length and sharpness. RESULTS: Acquisition in breath-hold is an effective method to reduce the scan time by more than 30 % compared to the navigator-gated reference. Although an equivalent mean image quality with respect to the reference was achieved with the proposed method, the 1D motion compensation did not work equally well in all cases. CONCLUSION: In general, the image quality scaled with the robustness of the motion compensation. Nevertheless, the featured setup provides a positive basis for future extension with more advanced motion compensation methods.

Revising the Cannabis Use Disorders Identification Test (CUDIT) by means of Item Response Theory.

Cannabis use among adolescents and young adults has become a major public health challenge. Several European countries are currently developing short screening instruments to identify 'problematic' forms of cannabis use in general population surveys. One such instrument is the Cannabis Use Disorders Identification Test (CUDIT), a 10-item questionnaire based on the Alcohol Use Disorders Identification Test. Previous research found that some CUDIT items did not perform well psychometrically. In the interests of improving the psychometric properties of the CUDIT, this study replaces the poorly performing items with new items that specifically address cannabis use. Analyses are based on a sub-sample of 558 recent cannabis users from a representative population sample of 5722 individuals (aged 13-32) who were surveyed in the 2007 Swiss Cannabis Monitoring Study. Four new items were added to the original CUDIT. Psychometric properties of all 14 items, as well as the dimensionality of the supplemented CUDIT were then examined using Item Response Theory. Results indicate the unidimensionality of CUDIT and an improvement in its psychometric performance when three original items (usual hours being stoned; injuries; guilt) are replaced by new ones (motives for using cannabis; missing out leisure time activities; difficulties at work/school). However, improvements were limited to cannabis users with a high problem score. For epidemiological purposes, any further revision of CUDIT should therefore include a greater number of 'easier' items.