A percentile‐based approach to rainfall scenario construction for surface‐water flood forecasts

A novel technique to produce reasonable worst‐case rainfall scenarios from ensemble forecasts is presented. This type of scenario is relevant for predicting the risk of localized, intense rainfall events with a duration between 15 min and several hours. Such rainfall events can cause surface‐water (pluvial) flooding. Producing useful forecasts of these events at lead times of more than a few hours is challenging due to the precision and accuracy in rainfall intensity, duration and location that is required. The technique described here addresses these challenges by constructing appropriate scenarios using a neighbourhood technique in combination with ensemble forecasting. It is similar to the distance‐dependent depth–duration analysis described in earlier studies, but it introduces an additional post‐processing step based on probability distribution functions of rainfall accumulation near a location of interest. This additional step makes the reasonable worst‐case scenarios less dependent on grid‐scale behaviour, and helps to generate scenarios with a consistent interpretation. The method is used to compare forecasts with a lead time of 6–36 hr to radar data for several case studies that occurred in Yorkshire. These comparisons also introduce new techniques to present maps of the reasonable worst‐case rainfall accumulation at each location

When Do Objects Become Landmarks? A VR Study of the Effect of Task Relevance on Spatial Memory

We investigated how objects come to serve as landmarks in spatial memory, and more specifically how they form part of an allocentric cognitive map. Participants performing a virtual driving task incidentally learned the layout of a virtual town and locations of objects in that town. They were subsequently tested on their spatial and recognition memory for the objects. To assess whether the objects were encoded allocentrically we examined pointing consistency across tested viewpoints. In three experiments, we found that spatial memory for objects at navigationally relevant locations was more consistent across tested viewpoints, particularly when participants had more limited experience of the environment. When participants’ attention was focused on the appearance of objects, the navigational relevance effect was eliminated, whereas when their attention was focused on objects’ locations, this effect was enhanced, supporting the hypothesis that when objects are processed in the service of navigation, rather than merely being viewed as objects, they engage qualitatively distinct attentional systems and are incorporated into an allocentric spatial representation. The results are consistent with evidence from the neuroimaging literature that when objects are relevant to navigation, they not only engage the ventral “object processing stream”, but also the dorsal stream and medial temporal lobe memory system classically associated with allocentric spatial memory

Scaling Up Towards International Targets for AIDS, Tuberculosis, and Malaria: Contribution of Global Fund-Supported Programs in 2011–2015

OBJECTIVE: The paper projects the contribution to 2011-2015 international targets of three major pandemics by programs in 140 countries funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria, the largest external financier of tuberculosis and malaria programs and a major external funder of HIV programs in low and middle income countries. DESIGN: Estimates, using past trends, for the period 2011-2015 of the number of persons receiving antiretroviral (ARV) treatment, tuberculosis case detection using the internationally approved DOTS strategy, and insecticide-treated nets (ITNs) to be delivered by programs in low and middle income countries supported by the Global Fund compared to international targets established by UNAIDS, Stop TB Partnership, Roll Back Malaria Partnership and the World Health Organisation. RESULTS: Global Fund-supported programs are projected to provide ARV treatment to 5.5-5.8 million people, providing 30%-31% of the 2015 international target. Investments in tuberculosis and malaria control will enable reaching in 2015 60%-63% of the international target for tuberculosis case detection and 30%-35% of the ITN distribution target in sub-Saharan Africa. CONCLUSION: Global Fund investments will substantially contribute to the achievement by 2015 of international targets for HIV, TB and malaria. However, additional large scale international and domestic financing is needed if these targets are to be reached by 2015

Bioassay design and length of time in the laboratory affect intercolonial interactions of the Formosan subterranean termite (Isoptera, Rhinotermitidae)

This study examined the effect of diet, experimental design, and length of time in the laboratory on intercolonial agonism among Formosan subterranean termite, Coptotermes formosanus Shiraki, colonies. In pairings of 12 C. formosanus Shiraki colonies collected in an urban forest, there was no significant reduction in survival of termites in 30 out of 59 colony pairs compared to colony controls, but there was <50% survival in 18 colony pairs and <10% survival in six colony pairs. There was no correlation between the level of aggressive behavior and the laboratory diet of the termites. Effect of bioassay design and length of time in the laboratory was evaluated in three colony pairs where tests were first conducted on the day of field collection, then colony pairs were retested every 7 days. Aggressive behavior decreased over time in both bioassays, but it tended to decrease more rapidly in the Petri dish tests. The rapid loss of agonism in groups of termites kept in the laboratory demonstrates that changes in environmental factors affect intercolonial agonism

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Perceiving What Is Reachable Depends on Motor Representations: Evidence from a Transcranial Magnetic Stimulation Study

Background: Visually determining what is reachable in peripersonal space requires information about the egocentric location of objects but also information about the possibilities of action with the body, which are context dependent. The aim of the present study was to test the role of motor representations in the visual perception of peripersonal space. Methodology: Seven healthy participants underwent a TMS study while performing a right-left decision (control) task or perceptually judging whether a visual target was reachable or not with their right hand. An actual grasping movement task was also included. Single pulse TMS was delivered 80 % of the trials on the left motor and premotor cortex and on a control site (the temporo-occipital area), at 90 % of the resting motor threshold and at different SOA conditions (50ms, 100ms, 200ms or 300ms). Principal Findings: Results showed a facilitation effect of the TMS on reaction times in all tasks, whatever the site stimulated and until 200ms after stimulus presentation. However, the facilitation effect was on average 34ms lower when stimulating the motor cortex in the perceptual judgement task, especially for stimuli located at the boundary of peripersonal space. Conclusion: This study provides the first evidence that brain motor area participate in the visual determination of what is reachable. We discuss how motor representations may feed the perceptual system with information about possibl

The immunopathology of canine vector-borne diseases

The canine vector-borne infectious diseases (CVBDs) are an emerging problem in veterinary medicine and the zoonotic potential of many of these agents is a significant consideration for human health. The successful diagnosis, treatment and prevention of these infections is dependent upon firm understanding of the underlying immunopathology of the diseases in which there are unique tripartite interactions between the microorganism, the vector and the host immune system. Although significant advances have been made in the areas of molecular speciation and the epidemiology of these infections and their vectors, basic knowledge of the pathology and immunology of the diseases has lagged behind. This review summarizes recent studies of the pathology and host immune response in the major CVBDs (leishmaniosis, babesiosis, ehrlichiosis, hepatozoonosis, anaplasmosis, bartonellosis and borreliosis). The ultimate application of such immunological investigation is the development of effective vaccines. The current commercially available vaccines for canine leishmaniosis, babesiosis and borreliosis are reviewed

Huntington's disease and its therapeutic target genes: a global functional profile based on the HD Research Crossroads database.

BACKGROUND: Huntington's disease (HD) is a fatal progressive neurodegenerative disorder caused by the expansion of the polyglutamine repeat region in the huntingtin gene. Although the disease is triggered by the mutation of a single gene, intensive research has linked numerous other genes to its pathogenesis. To obtain a systematic overview of these genes, which may serve as therapeutic targets, CHDI Foundation has recently established the HD Research Crossroads database. With currently over 800 cataloged genes, this web-based resource constitutes the most extensive curation of genes relevant to HD. It provides us with an unprecedented opportunity to survey molecular mechanisms involved in HD in a holistic manner. METHODS: To gain a synoptic view of therapeutic targets for HD, we have carried out a variety of bioinformatical and statistical analyses to scrutinize the functional association of genes curated in the HD Research Crossroads database. In particular, enrichment analyses were performed with respect to Gene Ontology categories, KEGG signaling pathways, and Pfam protein families. For selected processes, we also analyzed differential expression, using published microarray data. Additionally, we generated a candidate set of novel genetic modifiers of HD by combining information from the HD Research Crossroads database with previous genome-wide linkage studies. RESULTS: Our analyses led to a comprehensive identification of molecular mechanisms associated with HD. Remarkably, we not only recovered processes and pathways, which have frequently been linked to HD (such as cytotoxicity, apoptosis, and calcium signaling), but also found strong indications for other potentially disease-relevant mechanisms that have been less intensively studied in the context of HD (such as the cell cycle and RNA splicing, as well as Wnt and ErbB signaling). For follow-up studies, we provide a regularly updated compendium of molecular mechanism, that are associated with HD, at http://hdtt.sysbiolab.eu Additionally, we derived a candidate set of 24 novel genetic modifiers, including histone deacetylase 3 (HDAC3), metabotropic glutamate receptor 1 (GRM1), CDK5 regulatory subunit 2 (CDK5R2), and coactivator 1ß of the peroxisome proliferator-activated receptor gamma (PPARGC1B). CONCLUSIONS: The results of our study give us an intriguing picture of the molecular complexity of HD. Our analyses can be seen as a first step towards a comprehensive list of biological processes, molecular functions, and pathways involved in HD, and may provide a basis for the development of more holistic disease models and new therapeutics

Quantitative cardiovascular magnetic resonance for molecular imaging

Cardiovascular magnetic resonance (CMR) molecular imaging aims to identify and map the expression of important biomarkers on a cellular scale utilizing contrast agents that are specifically targeted to the biochemical signatures of disease and are capable of generating sufficient image contrast. In some cases, the contrast agents may be designed to carry a drug payload or to be sensitive to important physiological factors, such as pH, temperature or oxygenation. In this review, examples will be presented that utilize a number of different molecular imaging quantification techniques, including measuring signal changes, calculating the area of contrast enhancement, mapping relaxation time changes or direct detection of contrast agents through multi-nuclear imaging or spectroscopy. The clinical application of CMR molecular imaging could offer far reaching benefits to patient populations, including early detection of therapeutic response, localizing ruptured atherosclerotic plaques, stratifying patients based on biochemical disease markers, tissue-specific drug delivery, confirmation and quantification of end-organ drug uptake, and noninvasive monitoring of disease recurrence. Eventually, such agents may play a leading role in reducing the human burden of cardiovascular disease, by providing early diagnosis, noninvasive monitoring and effective therapy with reduced side effects