High specificity of line-immunoassay based algorithms for recent HIV-1 infection independent of viral subtype and stage of disease

Background Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have shown that a patient's antibody reaction in a confirmatory line immunoassay (INNO-LIATM HIV I/II Score, Innogenetics) provides information on the duration of infection. Here, we sought to further investigate the diagnostic specificity of various Inno-Lia algorithms and to identify factors affecting it. Methods Plasma samples of 714 selected patients of the Swiss HIV Cohort Study infected for longer than 12 months and representing all viral clades and stages of chronic HIV-1 infection were tested blindly by Inno-Lia and classified as either incident (up to 12 m) or older infection by 24 different algorithms. Of the total, 524 patients received HAART, 308 had HIV-1 RNA below 50 copies/mL, and 620 were infected by a HIV-1 non-B clade. Using logistic regression analysis we evaluated factors that might affect the specificity of these algorithms. Results HIV-1 RNA <50 copies/mL was associated with significantly lower reactivity to all five HIV-1 antigens of the Inno-Lia and impaired specificity of most algorithms. Among 412 patients either untreated or with HIV-1 RNA ≥50 copies/mL despite HAART, the median specificity of the algorithms was 96.5% (range 92.0-100%). The only factor that significantly promoted false-incident results in this group was age, with false-incident results increasing by a few percent per additional year. HIV-1 clade, HIV-1 RNA, CD4 percentage, sex, disease stage, and testing modalities exhibited no significance. Results were similar among 190 untreated patients. Conclusions The specificity of most Inno-Lia algorithms was high and not affected by HIV-1 variability, advanced disease and other factors promoting false-recent results in other STARHS. Specificity should be good in any group of untreated HIV-1 patients.

General and specific components of depression and anxiety in an adolescent population

Background Depressive and anxiety symptoms often co-occur resulting in a debate about common and distinct features of depression and anxiety. Methods An exploratory factor analysis (EFA) and a bifactor modelling approach were used to separate a general distress continuum from more specific sub-domains of depression and anxiety in an adolescent community sample (n = 1159, age 14). The Mood and Feelings Questionnaire and the Revised Children's Manifest Anxiety Scale were used. Results A three-factor confirmatory factor analysis is reported which identified a) mood and social-cognitive symptoms of depression, b) worrying symptoms, and c) somatic and information-processing symptoms as distinct yet closely related constructs. Subsequent bifactor modelling supported a general distress factor which accounted for the communality of the depression and anxiety items. Specific factors for hopelessness-suicidal thoughts and restlessness-fatigue indicated distinct psychopathological constructs which account for unique information over and above the general distress factor. The general distress factor and the hopelessness-suicidal factor were more severe in females but the restlessness-fatigue factor worse in males. Measurement precision of the general distress factor was higher and spanned a wider range of the population than any of the three first-order factors. Conclusions The general distress factor provides the most reliable target for epidemiological analysis but specific factors may help to refine valid phenotype dimensions for aetiological research and assist in prognostic modelling of future psychiatric episodes.

Effect of Methodological and Ecological Approaches on Heterogeneity of Nest-Site Selection of a Long-Lived Vulture

The application of scientific-based conservation measures requires that sampling methodologies in studies modelling similar ecological aspects produce comparable results making easier their interpretation. We aimed to show how the choice of different methodological and ecological approaches can affect conclusions in nest-site selection studies along different Palearctic meta-populations of an indicator species. First, a multivariate analysis of the variables affecting nest-site selection in a breeding colony of cinereous vulture (Aegypius monachus) in central Spain was performed. Then, a meta-analysis was applied to establish how methodological and habitat-type factors determine differences and similarities in the results obtained by previous studies that have modelled the forest breeding habitat of the species. Our results revealed patterns in nesting-habitat modelling by the cinereous vulture throughout its whole range: steep and south-facing slopes, great cover of large trees and distance to human activities were generally selected. The ratio and situation of the studied plots (nests/random), the use of plots vs. polygons as sampling units and the number of years of data set determined the variability explained by the model. Moreover, a greater size of the breeding colony implied that ecological and geomorphological variables at landscape level were more influential. Additionally, human activities affected in greater proportion to colonies situated in Mediterranean forests. For the first time, a meta-analysis regarding the factors determining nest-site selection heterogeneity for a single species at broad scale was achieved. It is essential to homogenize and coordinate experimental design in modelling the selection of species' ecological requirements in order to avoid that differences in results among studies would be due to methodological heterogeneity. This would optimize best conservation and management practices for habitats and species in a global context.

Gene expression in cortex and hippocampus during acute pneumococcal meningitis

BACKGROUND: Pneumococcal meningitis is associated with high mortality (approximately 30%) and morbidity. Up to 50% of survivors are affected by neurological sequelae due to a wide spectrum of brain injury mainly affecting the cortex and hippocampus. Despite this significant disease burden, the genetic program that regulates the host response leading to brain damage as a consequence of bacterial meningitis is largely unknown.We used an infant rat model of pneumococcal meningitis to assess gene expression profiles in cortex and hippocampus at 22 and 44 hours after infection and in controls at 22 h after mock-infection with saline. To analyze the biological significance of the data generated by Affymetrix DNA microarrays, a bioinformatics pipeline was used combining (i) a literature-profiling algorithm to cluster genes based on the vocabulary of abstracts indexed in MEDLINE (NCBI) and (ii) the self-organizing map (SOM), a clustering technique based on covariance in gene expression kinetics. RESULTS: Among 598 genes differentially regulated (change factor > or = 1.5; p < or = 0.05), 77% were automatically assigned to one of 11 functional groups with 94% accuracy. SOM disclosed six patterns of expression kinetics. Genes associated with growth control/neuroplasticity, signal transduction, cell death/survival, cytoskeleton, and immunity were generally upregulated. In contrast, genes related to neurotransmission and lipid metabolism were transiently downregulated on the whole. The majority of the genes associated with ionic homeostasis, neurotransmission, signal transduction and lipid metabolism were differentially regulated specifically in the hippocampus. Of the cell death/survival genes found to be continuously upregulated only in hippocampus, the majority are pro-apoptotic, while those continuously upregulated only in cortex are anti-apoptotic. CONCLUSION: Temporal and spatial analysis of gene expression in experimental pneumococcal meningitis identified potential targets for therapy.

Validity and reliability of the German version of the short understanding of substance abuse scale

This paper presents the German version of the Short Understanding of Substance Abuse Scale (SUSS) [Humphreys et al.: Psychol Addict Behav 1996;10:38-44], the Verstandnis von Storungen durch Substanzkonsum (VSS), and evaluates its psychometric properties. The VSS assesses clinicians' beliefs about the nature and treatment of substance use disorders, particularly their endorsement of psychosocial and disease orientation. The VSS was administered to 160 treatment staff members at 12 substance use disorder treatment programs in the German-speaking part of Switzerland. Because the confirmatory factor analysis of the VSS did not completely replicate the factorial structure of the SUSS, an exploratory factor analysis was undertaken. This analysis identified two factors: the Psychosocial model factor and a slightly different Disease model factor. The VSS Disease and Psychosocial subscales showed convergent and discriminant validity, as well as sufficient reliability.

Transient dominance in a central African rain forest

The large-crowned emergent tree Microberlinia bisulcata dominates rain forest groves at Korup National Park, Cameroon, along with two codominants, Tetraberlinia bifoliolata and T. korupensis. M. bisulcata has a pronounced modal size frequency distribution around 110 cm stem diameter: its recruitment potential is very poor. It is a long-lived light-demanding species, one of many found in African forests. Tetraberlinia species lack modality, are more shade tolerant, and recruit better. All three species are ectomycorrhizal. M. bisulcata dominates grove basal area, even though it has similar numbers of trees (≥50 cm stem diameter) as each of the other two species. This situation presented a conundrum that prompted a long-term study of grove dynamics. Enumerations of two plots (82.5 and 56.25 ha) between 1990 and 2010 showed mortality and recruitment of M. bisulcata to be very low (both rates 0.2% per year) compared with Tetraberlinia (2.4% and 0.8% per year), and M. bisulcata grows twice as fast as the Tetraberlinia. Ordinations indicated that these three species determined community structure by their strong negative associations while other species showed almost none. Ranked species abundance curves fitted the Zipf-Mandelbrot model well and allowed “overdominance” of M. bisulcata to be estimated. Spatial analysis indicated strong repulsion by clusters of large (50 to <100 cm) and very large (≥100 cm) M. bisulcata of their own medium-sized (10 to <50 cm) trees and all sizes of Tetraberlinia. This was interpreted as competition by M. bisulcata increasing its dominance, but also inhibition of its own replacement potential. Stem coring showed a modal age of 200 years for M. bisulcata, but with large size variation (50–150 cm). Fifty-year model projections suggested little change in medium, decreases in large, and increases in very large trees of M. bisulcata, accompanied by overall decreases in medium and large trees of Tetraberlinia species. Realistically increasing very-large-tree mortality led to grove collapse without short-term replacement. M. bisulcata most likely depends on climatic events to rebuild its stands: the ratio of disturbance interval to median species' longevity is important. A new theory of transient dominance explains how M. bisulcata may be cycling in abundance over time and displaying nonequilibrium dynamics.

Ecotypes and genetic structure of Rhinanthus alectorolophus (Orobanchaceae) in southwestern Germany

European annual species of the genus Rhinanthus often exhibit seasonal ecotypic variation, a phenomenon also known from related genera of hemiparasitic Orobanchaceae. Populations with different flowering times exist, correlated with differences in a number of morphological characters. The present study evaluates the correlation of morphological characters and genetic differentiation of populations of Rhinanthus alectorolophus. Thirty-nine populations of three different subspecies from southwestern Germany were sampled. A total of 798 individuals were used for morphological analyses and 187 of these for AFLP analyses. Principal component analysis showed that morphological variation is mostly continuous. In a discriminant analysis based on morphological characters, only 89.7 % of all individuals were correctly assigned to their previously determined subspecies, indicating that subspecies identification is ambiguous for some populations. Using AFLP data and Bayesian assignment analysis, the sampled individuals could be grouped in three genetic clusters which do not correspond to the three subspecies. Instead, the clustering shows a clear geographic pattern and a Mantel test likewise revealed a significant correlation between genetic and geographic distances. Correlations of genetic distances with differences in morphological characters were weak and mostly insignificant. The results indicate that the subspecies of R. alectorolophus do not form discrete entities and that the character combinations distinguishing them are homoplastic.

Landscape connectivity, habitat structure and activity of bat guilds in farmland-dominated matrices

Agricultural intensification has caused a decline in structural elements in European farmland, where natural habitats are increasingly fragmented. The loss of habitat structures has a detrimental effect on biodiversity and affects bat species that depend on vegetation structures for foraging and commuting. We investigated the impact of connectivity and configuration of structural landscape elements on flight activity, species richness and diversity of insectivorous bats and distinguished three bat guilds according to species-specific bioacoustic characteristics. We tested whether bats with shorter-range echolocation were more sensitive to habitat fragmentation than bats with longer-range echolocation. We expected to find different connectivity thresholds for the three guilds and hypothesized that bats prefer linear over patchy landscape elements. Bat activity was quantified using repeated acoustic monitoring in 225 locations at 15 study plots distributed across the Swiss Central Plateau, where connectivity and the shape of landscape elements were determined by spatial analysis (GIS). Spectrograms of bat calls were assigned to species with the software batit by means of image recognition and statistical classification algorithms. Bat activity was significantly higher around landscape elements compared to open control areas. Short- and long-range echolocating bats were more active in well-connected landscapes, but optimal connectivity levels differed between the guilds. Species richness increased significantly with connectivity, while species diversity did not (Shannon's diversity index). Total bat activity was unaffected by the shape of landscape elements. Synthesis and applications. This study highlights the importance of connectivity in farmland landscapes for bats, with shorter-range echolocating bats being particularly sensitive to habitat fragmentation. More structurally diverse landscape elements are likely to reduce population declines of bats and could improve conditions for other declining species, including birds. Activity was highest around optimal values of connectivity, which must be evaluated for the different guilds and spatially targeted for a region's habitat configuration. In a multi-species approach, we recommend the reintroduction of structural elements to increase habitat heterogeneity should become part of agri-environment schemes.

Extended kalman filter for estimation of parameters in nonlinear state-space models of biochemical networks.

It is system dynamics that determines the function of cells, tissues and organisms. To develop mathematical models and estimate their parameters are an essential issue for studying dynamic behaviors of biological systems which include metabolic networks, genetic regulatory networks and signal transduction pathways, under perturbation of external stimuli. In general, biological dynamic systems are partially observed. Therefore, a natural way to model dynamic biological systems is to employ nonlinear state-space equations. Although statistical methods for parameter estimation of linear models in biological dynamic systems have been developed intensively in the recent years, the estimation of both states and parameters of nonlinear dynamic systems remains a challenging task. In this report, we apply extended Kalman Filter (EKF) to the estimation of both states and parameters of nonlinear state-space models. To evaluate the performance of the EKF for parameter estimation, we apply the EKF to a simulation dataset and two real datasets: JAK-STAT signal transduction pathway and Ras/Raf/MEK/ERK signaling transduction pathways datasets. The preliminary results show that EKF can accurately estimate the parameters and predict states in nonlinear state-space equations for modeling dynamic biochemical networks.

Developmental Changes in the Structure and Composition of the Postsynaptic Density

The development of the brain and its underlying circuitry is dependent on the formation of trillions of chemical synapses, which are highly specialized contacts that regulate the flow of information from one neuron to the next. It is through these synaptic connections that neurons wire together into networks capable of performing specific tasks, and activity-dependent changes in their structural and physiological state is one way that the brain is thought to adapt and store information. At the ultrastructural level, developmental and activity-dependent changes in the size and shape of dendritic spines have been well documented, and it is widely believed that structural changes in spines are a hallmark sign of synapse maturation and alteration of synaptic physiology. While changes in spine structure have been studied extensively, changes in one of its most prominent components, the postsynaptic density (PSD), have largely evaded observation. The PSD is a protein-rich organelle on the cytoplasmic side of the postsynaptic membrane, where it sits in direct opposition to the presynaptic terminal. The PSD functions both to cluster neurotransmitter receptors at the cell surface as well as organize the intracellular signaling molecules responsible for transducing extracellular signals to the postsynaptic cell. Much is known about the chemical composition of the PSD, but the structural arrangement of its molecular components is not well documented. Adding to the difficulty of understanding such a complex mass of protein machinery is the fact that its protein composition is known to change in response to synaptic activity, meaning that its structure is plastic and no two PSDs are identical. Here, immuno-gold labeling and electron tomography of PSDs isolated throughout development was used to track changes in both the structure and molecular composition of the PSD. State-of-the-art cryo-electron tomography was used to study the fine structure of the PSD during development, and provides an unprecedented glimpse into its molecular architecture in an un-fixed, unstained and hydrated state. Through this analysis, large structural and compositional changes are apparent and suggest a model by which the PSD is first assembled as a mesh-like lattice of proteins that function as support for the later recruitment of various PSD components. Spatial analysis of the recruitment of proteins into the PSD demonstrated that its assembly has an underlying order.

Total IgE and allergen-specific IgE and IgG antibody levels in sera of atopic dermatitis affected and non-affected Labrador- and Golden retrievers.

Canine atopic dermatitis (CAD) is an allergic skin disease associated with IgE and IgG antibodies (Ab) to environmental allergens. The aim of this study was to determine which other factors influence serum Ab levels in CAD-affected and non-affected dogs as this has only been poorly investigated in dogs so far. Total and allergen-specific IgE levels and Dermatophagoides farinae (DF)-specific IgG1 and IgG4 were measured by ELISA in sera of 145 CAD-affected and 271 non-affected Labrador- and Golden retrievers. A multivariable logistic regression analysis including the factors age, breed, gender, castration, clinical CAD status and allergen-specific immunotherapy (ASIT) was performed. Golden retrievers had more frequently total (OR=1.87, 95% CI=1.26-2.87, p<0.01) and specific IgE levels above the threshold value than Labrador retrievers, suggesting that genetic factors influence IgE levels in dogs. Castration was generally associated with low Ab levels (OR=0.43-0.65, p<0.05). Surprisingly, dogs with CAD did not have increased odds for high IgE against any of the allergens tested. ASIT with DF was associated with high DF-specific IgG1 (OR=4.32, 95% CI 1.46-12.8, p<0.01) but was not associated with DF-specific IgG4 or decreased IgE levels. Further studies are needed to understand the role of allergen-specific IgE in CAD and of IgG1 in ASIT.

Who Supports Minority Rights in Popular Votes? Empirical Evidence from Switzerland

Recent research shows that well-educated citizens are more supportive of minority rights in direct democratic votes than people with less education. This article however suggests that educational effects on minority rights only emerge under certain conditions. A Bayesian multilevel analysis of 39 referendums and initiatives on minority rights in Switzerland (1981–2009) shows that educational effects are particularly strong when the rights of lesser-known cultural minorities are to be extended. They are entirely absent, however, when referenda address the curtailment of rights for well-known minority groups.

Serosurveillance of Schmallenberg virus in Switzerland using bulk tank milk samples.

Infections with Schmallenberg virus (SBV), a novel Orthobunyavirus transmitted by biting midges, can cause abortions and malformations of newborns and severe symptoms in adults of domestic and wild ruminants. Understanding the temporal and spatial distribution of the virus in a certain territory is important for the control and prevention of the disease. In this study, seroprevalence of antibodies against SBV and the spatial spread of the virus was investigated in Swiss dairy cattle applying a milk serology technique on bulk milk samples. The seroprevalence in cattle herds was significantly higher in December 2012 (99.5%) compared to July 2012 (19.7%). This high between-herd seroprevalence in cattle herds was observed shortly after the first detection of viral infections. Milk samples originating from farms with seropositive animals taken in December 2012 (n=209; mean 160%) revealed significantly higher S/P% ratios than samples collected in July 2012 (n=48; mean 103.6%). This finding suggests a high within-herd seroprevalence in infected herds which makes testing of bulk tank milk samples for the identification farms with past exposures to SBV a sensitive method. It suggests also that within-herd transmission followed by seroconversion still occurred between July and December. In July 2012, positive bulk tank milk samples were mainly restricted to the western part of Switzerland whereas in December 2012, all samples except one were positive. A spatial analysis revealed a separation of regions with and without positive farms in July 2012 and no spatial clustering within the regions with positive farms. In contrast to the spatial dispersion of bluetongue virus, a virus that is also transmitted by Culicoides midges, in 2008 in Switzerland, the spread of SBV occurred from the western to the eastern part of the country. The dispersed incursion of SBV took place in the western part of Switzerland and the virus spread rapidly to the remaining territory. This spatial pattern is consistent with the hypothesis that transmission by Culicoides midges was the main way of spreading.

Watershed classification in the Lower Mekong Basin: Rapid economic growth - a source of increasing potential for conflict over resource use

In the Lower Mekon Basin the extraordinary pace of economic development and growth contradicts with environmental protection. On base of the Watershed Classification Project (WSCP) and the inclusion of a DTM for the entire LMB the potential degradation risk was derived for each land unit. The risks were grouped into five classes, where classes one and two are considered critical with regard to soil erosion when the land is cleared of natural resources. For practical use the database has an enormous potential for further spatial analysis in combination with other datasets, as for example the NCCR North-South uses the WSCP within two research projects.

Marginal lands or marginal people? Analysing key processes determining the outcomes of large-scale land acquisitions in Lao PDR and Cambodia

This chapter aims to overcome the gap existing between case study research, which typically provides qualitative and process-based insights, and national or global inventories that typically offer spatially explicit and quantitative analysis of broader patterns, and thus to present adequate evidence for policymaking regarding large-scale land acquisitions. Therefore, the chapter links spatial patterns of land acquisitions to underlying implementation processes of land allocation. Methodologically linking the described patterns and processes proved difficult, but we have identified indicators that could be added to inventories and monitoring systems to make linkage possible. Combining complementary approaches in this way may help to determine where policy space exists for more sustainable governance of land acquisitions, both geographically and with regard to processes of agrarian transitions. Our spatial analysis revealed two general patterns: (i) relatively large forestry-related acquisitions that target forested landscapes and often interfere with semi-subsistence farming systems; and (ii) smaller agriculture-related acquisitions that often target existing cropland and also interfere with semi-subsistence systems. Furthermore, our meta-analysis of land acquisition implementation processes shows that authoritarian, top-down processes dominate. Initially, the demands of powerful regional and domestic investors tend to override socio-ecological variables, local actors’ interests, and land governance mechanisms. As available land grows scarce, however, and local actors gain experience dealing with land acquisitions, it appears that land investments begin to fail or give way to more inclusive, bottom-up investment models.