Early Detection and Treatment of Psychosis: The Bern Child and Adolescent Psychiatric Perspective

Commonly conceptualized as neurodevelopmental disorders of yet poorly understood aetiology, schizophrenia and other nonorganic psychoses remain one of the most debilitating illnesses with often poor outcome despite all progress in treatment of the manifest disorder. Drawing on the frequent poor outcome of psychosis and its association with the frequently extended periods of untreated first-episode psychosis (FEP) including its prodrome, an early detection and treatment of both the FEP and the preceding at-risk mental state (ARMS) have been increasingly studied. Thereby both approaches are confronted with different problems, for example, treatment engagement in FEP and predictive accuracy in ARMS. They share, however, the problems related to the lack of understanding of developmental, that is, age-related, peculiarities and of the presentation and natural course of their cardinal symptoms in the community. Most research on early detection and intervention in FEP and ARMS is still related to clinical psychiatric samples, and little is known about symptom presentation and burden and help-seeking in the general population related to these experiences. Furthermore, in particular in the early detection of an ARMS, studies often address adolescents and young adults alike without consideration of developmental characteristics, thereby applying risk criteria that have been developed predominately in adults. Combining our earlier experiences described in this paper in child and adolescent, and general psychiatry as well as in both lines of research, that is, on early psychosis and its treatment and on the early detection of psychosis, in particular in its very early states by subjective disturbances in terms of basic symptoms, age-related developmental and epidemiological aspects have therefore been made the focus of our current studies in Bern, thus making our line of research unique

Detection and quantification of leptospires in urine of dogs: a maintenance host for the zoonotic disease leptospirosis.

Leptospirosis is a global zoonotic disease. Pathogenic Leptospira species, the causative agent of leptospirosis, colonize the renal tubules of chronically infected maintenance hosts such as dogs, rats and cattle. Maintenance hosts typically remain clinically asymptomatic and shed leptospires into the environment via urine. In contrast, accidental hosts such as humans can suffer severe acute forms of the disease. Infection results from direct contact with infected urine or indirectly, through contaminated water sources. In this study, a quantitative real-time PCR specific for lipL32 was designed to detect the urinary shedding of leptospires from dogs. The sensitivity and specificity of the assay was evaluated using both a panel of pathogenic Leptospira species and clinical microbial isolates, and samples of urine collected from experimentally infected rats and non-infected controls. The lower limit of detection was approximately 3 genome equivalents per reaction. The assay was applied to canine urine samples collected from local dog sanctuaries and the University Veterinary Hospital (UVH) at University College Dublin. Of 525 canine urine samples assayed, 37 were positive, indicating a prevalence of urinary shedding of leptospires of 7.05%. These results highlight the need to provide effective canine vaccination strategies and raise public health awareness.

Simultaneous detection and discrimination of virulent and benign Dichelobacter nodosus in sheep of flocks affected by foot rot and in clinically healthy flocks by competitive real-time PCR.

Ovine foot rot caused by Dichelobacter nodosus is affecting sheep worldwide. The current diagnostic methods are difficult and cumbersome. Here, we present a competitive real-time PCR based on allelic discrimination of the protease genes aprV2 and aprB2. This method allows direct detection and differentiation of virulent and benign D. nodosus from interdigital skin swabs in a single test. Clinically affected sheep harbored high loads of only virulent strains, whereas healthy sheep had lower loads of predominantly benign strains.

Detection and functional portrayal of a novel class of dihydrotestosterone derived selective progesterone receptor modulators (SPRM).

In early pregnancy, abortion can be induced by blocking the actions of progesterone receptors (PR). However, the PR antagonist, mifepristone (RU38486), is rather unselective in clinical use because it also cross-reacts with other nuclear receptors. Since the ligand-binding domain of human progesterone receptor (hPR) and androgen receptor (hAR) share 54% identity, we hypothesized that derivatives of dihydrotestosterone (DHT), the cognate ligand for hAR, might also regulate the hPR. Compounds designed and synthesized in our laboratory were investigated for their affinities for hPRB, hAR, glucocorticoid receptor (hGRα) and mineralocorticoid receptor (hMR), using whole cell receptor competitive binding assays. Agonistic and antagonistic activities were characterized by reporter assays. Nuclear translocation was monitored using cherry-hPRB and GFP-hAR chimeric receptors. Cytostatic properties and apoptosis were tested on breast cancer cells (MCF7, T-47D). One compound presented a favorable profile with an apparent neutral hPRB antagonistic function, a selective cherry-hPRB nuclear translocation and a cytostatic effect. 3D models of human PR and AR with this ligand were constructed to investigate the molecular basis of selectivity. Our data suggest that these novel DHT-derivatives provide suitable templates for the development of new selective steroidal hPR antagonists.

Automatic X-ray landmark detection and shape segmentation via data-driven joint estimation of image displacements

In this paper, we propose a new method for fully-automatic landmark detection and shape segmentation in X-ray images. To detect landmarks, we estimate the displacements from some randomly sampled image patches to the (unknown) landmark positions, and then we integrate these predictions via a voting scheme. Our key contribution is a new algorithm for estimating these displacements. Different from other methods where each image patch independently predicts its displacement, we jointly estimate the displacements from all patches together in a data driven way, by considering not only the training data but also geometric constraints on the test image. The displacements estimation is formulated as a convex optimization problem that can be solved efficiently. Finally, we use the sparse shape composition model as the a priori information to regularize the landmark positions and thus generate the segmented shape contour. We validate our method on X-ray image datasets of three different anatomical structures: complete femur, proximal femur and pelvis. Experiments show that our method is accurate and robust in landmark detection, and, combined with the shape model, gives a better or comparable performance in shape segmentation compared to state-of-the art methods. Finally, a preliminary study using CT data shows the extensibility of our method to 3D data.

NA61/SHINE facility at the CERN SPS: beams and detector system

NA61/SHINE (SPS Heavy Ion and Neutrino Experiment) is a multi-purpose experimental facility to study hadron production in hadron-proton, hadron-nucleus and nucleus-nucleus collisions at the CERN Super Proton Synchrotron. It recorded the first physics data with hadron beams in 2009 and with ion beams (secondary 7Be beams) in 2011. NA61/SHINE has greatly profited from the long development of the CERN proton and ion sources and the accelerator chain as well as the H2 beamline of the CERN North Area. The latter has recently been modified to also serve as a fragment separator as needed to produce the Be beams for NA61/SHINE. Numerous components of the NA61/SHINE set-up were inherited from its predecessors, in particular, the last one, the NA49 experiment. Important new detectors and upgrades of the legacy equipment were introduced by the NA61/SHINE Collaboration. This paper describes the state of the NA61/SHINE facility — the beams and the detector system — before the CERN Long Shutdown I, which started in March 2013.

Unified detection and tracking of instruments during retinal microsurgery

Methods for tracking an object have generally fallen into two groups: tracking by detection and tracking through local optimization. The advantage of detection-based tracking is its ability to deal with target appearance and disappearance, but it does not naturally take advantage of target motion continuity during detection. The advantage of local optimization is efficiency and accuracy, but it requires additional algorithms to initialize tracking when the target is lost. To bridge these two approaches, we propose a framework for unified detection and tracking as a time-series Bayesian estimation problem. The basis of our approach is to treat both detection and tracking as a sequential entropy minimization problem, where the goal is to determine the parameters describing a target in each frame. To do this we integrate the Active Testing (AT) paradigm with Bayesian filtering, and this results in a framework capable of both detecting and tracking robustly in situations where the target object enters and leaves the field of view regularly. We demonstrate our approach on a retinal tool tracking problem and show through extensive experiments that our method provides an efficient and robust tracking solution.

Detection and quantification of 56 new psychoactive substances in whole blood and urine by LC-MS/MS

BACKGROUND New psychoactive substances (NPS) have become increasingly prevalent and are sold in internet shops as 'bath salts' or 'research chemicals' and comprehensive bioanalytical methods are needed for their detection. METHODOLOGY We developed and validated a method using LC and MS/MS to quantify 56 NPS in blood and urine, including amphetamine derivatives, 2C compounds, aminoindanes, cathinones, piperazines, tryptamines, dissociatives and others. Instrumentation included a Synergi Polar-RP column (Phenomenex) and a 3200 QTrap mass spectrometer (AB Sciex). Run time was 20 min. CONCLUSION A novel method is presented for the unambiguous identification and quantification of 56 NPS in blood and urine samples in clinical and forensic cases, e.g., intoxications or driving under the influence of drugs.

Cold Microwave-Enabled Protein Detection and Quantification.

Protein screening/detection is an essential tool in many laboratories. Owing to the relatively large time investments that are required by standard protocols, the development of methods with higher throughput while maintaining an at least comparable signal-to-noise ratio is highly beneficial in many research areas. This chapter describes how cold microwave technology can be used to enhance the rate of molecular interactions and provides protocols for dot blots, Western blots, and ELISA procedures permitting a completion of all incubation steps (blocking and antibody steps) within 24-45 min.

Sustainable development in international law making and trade: International food governance and trade in agriculture

This timely book provides an accessible insight into how the concept of sustainable development can be made operational through its translation into legal terms. Understood as a multidimensional legal principle, sustainable development facilitates coherent international law making. Using this notion as an analytical lens on the WTO Agreement on Agriculture, the book considers the unresolved question of what a sustainable and coherent agricultural trade agreement could look like.

Balanced bilinguals favor lexical processing in their opaque language and conversion system in their shallow language

Referred to as orthographic depth, the degree of consistency of grapheme/phoneme correspondences varies across languages from high in shallow orthographies to low in deep orthographies. The present study investigates the impact of orthographic depth on reading route by analyzing evoked potentials to words in a deep (French) and shallow (German) language presented to highly proficient bilinguals. ERP analyses to German and French words revealed significant topographic modulations 240-280ms post-stimulus onset, indicative of distinct brain networks engaged in reading over this time window. Source estimations revealed that these effects stemmed from modulations of left insular, inferior frontal and dorsolateral regions (German>French) previously associated to phonological processing. Our results show that reading in a shallow language was associated to a stronger engagement of phonological pathways than reading in a deep language. Thus, the lexical pathways favored in word reading are reinforced by phonological networks more strongly in the shallow than deep orthography.

The HARPS search for southern extra-solar planets XXXVII. Five new long-period giant planets and a system update

We describe radial-velocity time series obtained by HARPS on the 3.60 m telescope in La Silla (ESO, Chile) over ten years and report the discovery of five new giant exoplanets in distant orbits; these new planets orbit the stars HD 564, HD 30669, HD 108341, and BD -114672. Their periods range from 492 to 1684 days, semi-major axes range from 1.2 to 2.69 AU, and eccentricities range from 0 to 0.85. Their minimum mass ranges from 0.33 to 3.5 MJup. We also refine the parameters of two planets announced previously around HD 113538, based on a longer series of measurements. The planets have a period of 663 ± 8 and 1818 ± 25 days, orbital eccentricities of 0.14 ± 0.08 and 0.20 ± 0.04, and minimum masses of 0.36 ± 0.04 and 0.93 ± 0.06 MJup. Finally, we report the discovery of a new hot-Jupiter planet around an active star, HD 103720; the planet has a period of 4.5557 ± 0.0001 days and a minimum mass of 0.62 ± 0.025 MJup. We discuss the fundamental parameters of these systems and limitations due to stellar activity in quiet stars with typical 2 m s-1 radial velocity precision.