Behavioral testing and preliminary analysis of the hamster visual system

The dependence of visual orienting ability in hamsters on the axonal projections from retina to midbrain tectum provides experimenters with a good model for assessing the functional regeneration of this central nervous system axonal pathway. For reliable testing of this behavior, male animals at least 10-12 weeks old are prepared by regular pretesting, with all procedures carried out during the less active portion of the daily activity cycle. Using a sunflower seed attached to a small black ball held at the end of a stiff wire, and avoiding whisker contact, turning movements toward visual stimuli are video recorded from above. Because at the eye level, the nasal-most 30° of the visual field can be seen by both the eyes, this part of the field is avoided in assessments of a single side. Daily sessions consist of ten presentations per side. Measures are frequency of responding and detailed turning trajectories. Complete assessment of the functional return of behavior in this testing paradigm takes 3-6 months to complete.postprin

Exploring Relations Between BCG and Cluster Properties in the SPectroscopic IDentification of eROSITA Sources Survey from 0.05<z<0.30.05 < z < 0.3

We present a sample of 329 low to intermediate redshift ($0.05 < z < 0.3$) brightest cluster galaxies (BCGs) in X-ray selected clusters from the SPectroscopic IDentification of eRosita Sources (SPIDERS) survey, a spectroscopic survey within Sloan Digital Sky Survey-IV (SDSS-IV). We define our BCGs by simultaneous consideration of legacy X-ray data from ROSAT, maximum likelihood outputs from an optical cluster-finder algorithm and visual inspection. Using SDSS imaging data, we fit S\'ersic profiles to our BCGs in three bands (\textit{g}, \textit{r}, \textit{i}) with \textsc{SIGMA}, a \textsc{GALFIT}-based software wrapper. We examine the reliability of our fits by running our pipeline on ${\sim}10^{4}$ psf-convolved model profiles injected into 8 random cluster fields, we then use the results of this analysis to create a robust subsample of 198 BCGs. We outline three cluster properties of interest: overall cluster X-ray luminosity ($L_{X}$), cluster richness as estimated by \textsc{redMaPPer} ($\lambda$) and cluster halo mass ($M_{200}$), which is estimated via velocity dispersion. In general, there are significant correlations with BCG stellar mass between all three environmental properties, but no significant trends arise with either S\'ersic index or effective radius. There is no major environmental dependence on the strength of the relation between effective radius and BCG stellar mass. Stellar mass therefore arises as the most important factor governing BCG morphology. Our results indicate that our sample consists of a large number of relaxed, mature clusters containing broadly homogeneous BCGs up to $z \sim 0.3$, suggesting that there is little evidence for much ongoing structural evolution for BCGs in these systems

The operationalized psychodynamic diagnostics system. Clinical relevance, reliability and validity

In this paper, we present a multiaxial system for psychodynamic diagnosis, which has attained wide usage in Germany in the last 10 years. First we will discuss the 4 operationalized psychodynamic diagnostics (OPD) axes: illness experience and treatment assumptions, relationships, mental conflicts, and structure, then clinical applications will be outlined. Focus psychodynamic formulations can be employed both with inpatients and with outpatients. Studies show good reliability in a research context and acceptable reliability for clinical purposes. Validity will be separately summarized as content, criterion, and construct validity. Validity studies indicate good validity for the individual axes. Numerous studies on the OPD indicate areas of possible improvement, for example for clinical purposes the OPD should be more practically formulated

Differential impact of two risk communications on antipsychotic prescribing to people with dementia in Scotland: segmented regression time series analysis 2001-2011

The two risk communications were associated with reductions in antipsychotic use, in ways which were compatible with marked differences in their content and dissemination. Further research is needed to ensure that the content and dissemination of regulatory risk communications is optimal, and to track their impact on intended and unintended outcomes. Although rates are falling, antipsychotic prescribing in dementia in Scotland remains unacceptably hig

Predicting disease progression in progressive supranuclear palsy in multicenter clinical trials

INTRODUCTION: Clinical and MRI measurements can track disease progression in PSP, but many have not been extensively evaluated in multicenter clinical trials. We identified optimal measures to capture clinical decline and predict disease progression in multicenter PSP trials. METHODS: Longitudinal clinical rating scales, neuropsychological test scores, and volumetric MRI data from an international, phase 2/3 clinical trial of davunetide for PSP (intent to treat population, n = 303) were used to identify measurements with largest effect size, strongest correlation with clinical change, and best ability to predict dropout or clinical decline over one year as measured by PSP Rating Scale (PSPRS). RESULTS: Baseline cognition as measured by Repeatable Battery for Assessing Neuropsychological Status (RBANS) was associated with attrition, but had only a small effect. PSPRS and Clinical Global Impression (CGI) had the largest effect size for measuring change. Annual change in CGI, RBANS, color trails, and MRI midbrain and ventricular volumes were most strongly correlated with annual PSPRS and had the largest effect sizes for detecting annual change. At baseline, shorter disease duration, more severe depression, and lower performance on RBANS and executive function tests were associated with faster worsening of the PSPRS in completers. With dropouts included, SEADL, RBANS, and executive function tests had significant effect on PSPRS trajectory of change. CONCLUSION: Baseline cognitive status and mood influence the rate of disease progression in PSP. Multiple clinical, neuropsychological, and volumetric MRI measurements are sensitive to change over one year in PSP and appropriate for use in multicenter clinical trials

Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of meier-gorlin syndrome

Mutations in ORC1, ORC4, ORC6, CDT1, and CDC6, which encode proteins required for DNA replication origin licensing, cause Meier-Gorlin syndrome (MGS), a disorder conferring microcephaly, primordial dwarfism, underdeveloped ears, and skeletal abnormalities. Mutations in ATR, which also functions during replication, can cause Seckel syndrome, a clinically related disorder. These findings suggest that impaired DNA replication could underlie the developmental defects characteristic of these disorders. Here, we show that although origin licensing capacity is impaired in all patient cells with mutations in origin licensing component proteins, this does not correlate with the rate of progression through S phase. Thus, the replicative capacity in MGS patient cells does not correlate with clinical manifestation. However, ORC1-deficient cells from MGS patients and siRNA-mediated depletion of origin licensing proteins also have impaired centrosome and centriole copy number. As a novel and unexpected finding, we show that they also display a striking defect in the rate of formation of primary cilia. We demonstrate that this impacts sonic hedgehog signalling in ORC1-deficient primary fibroblasts. Additionally, reduced growth factor-dependent signaling via primary cilia affects the kinetics of cell cycle progression following cell cycle exit and re-entry, highlighting an unexpected mechanism whereby origin licensing components can influence cell cycle progression. Finally, using a cell-based model, we show that defects in cilia function impair chondroinduction. Our findings raise the possibility that a reduced efficiency in forming cilia could contribute to the clinical features of MGS, particularly the bone development abnormalities, and could provide a new dimension for considering developmental impacts of licensing deficiency

Prevalence of c-KIT mutations in gonadoblastoma and dysgerminomas of patients with disorders of sex development (DSD) and ovarian dysgerminomas

Activating c-KIT mutations (exons 11 and 17) are found in 10-40% of testicular seminomas, the majority being missense point mutations (codon 816). Malignant ovarian dysgerminomas represent similar to 3% of all ovarian cancers in Western countries, resembling testicular seminomas, regarding chromosomal aberrations and c-KIT mutations. DSD patients with specific Y-sequences have an increased risk for Type II Germ Cell Tumor/Cancer, with gonadoblastoma as precursor progressing to dysgerminoma. Here we present analysis of c-KIT exon 8, 9, 11, 13 and 17, and PDGFRA exon 12, 14 and 18 by conventional sequencing together with mutational analysis of c-KIT codon 816 by a sensitive and specific LightCycler melting curve analysis, confirmed by sequencing. The results are combined with data on TSPY and OCT3/4 expression in a series of 16 DSD patients presenting with gonadoblastoma and dysgerminoma and 15 patients presenting pure ovarian dysgerminomas without DSD. c-KIT codon 816 mutations were detected in five out of the total of 31 cases (all found in pure ovarian dysgerminomas). A synonymous SNP (rs 5578615) was detected in two patients, one DSD patient (with bilateral disease) and one patient with dysgerminoma. Next to these, three codon N822K mutations were detected in the group of 15 pure ovarian dysgerminomas. In total activating c-KIT mutations were found in 53% of ovarian dysgerminomas without DSD. In the group of 16 DSD cases a N505I and D820E mutation was found in a single tumor of a patient with gonadoblastoma and dysgerminoma. No PDGFRA mutations were found. Positive OCT3/4 staining was present in all gonadoblastomas and dysgerminomas investigated, TSPY expression was only seen in the gonadoblastoma/dysgerminoma lesions of the 16 DSD patients. This data supports the existence of two distinct but parallel pathways in the development of dysgerminoma, in which mutational status of c-KIT might parallel the presence of TSPY

Order-of-magnitude speedup for steady states and traveling waves via Stokes preconditioning in Channelflow and Openpipeflow

Steady states and traveling waves play a fundamental role in understanding hydrodynamic problems. Even when unstable, these states provide the bifurcation-theoretic explanation for the origin of the observed states. In turbulent wall-bounded shear flows, these states have been hypothesized to be saddle points organizing the trajectories within a chaotic attractor. These states must be computed with Newton's method or one of its generalizations, since time-integration cannot converge to unstable equilibria. The bottleneck is the solution of linear systems involving the Jacobian of the Navier-Stokes or Boussinesq equations. Originally such computations were carried out by constructing and directly inverting the Jacobian, but this is unfeasible for the matrices arising from three-dimensional hydrodynamic configurations in large domains. A popular method is to seek states that are invariant under numerical time integration. Surprisingly, equilibria may also be found by seeking flows that are invariant under a single very large Backwards-Euler Forwards-Euler timestep. We show that this method, called Stokes preconditioning, is 10 to 50 times faster at computing steady states in plane Couette flow and traveling waves in pipe flow. Moreover, it can be carried out using Channelflow (by Gibson) and Openpipeflow (by Willis) without any changes to these popular spectral codes. We explain the convergence rate as a function of the integration period and Reynolds number by computing the full spectra of the operators corresponding to the Jacobians of both methods.Comment: in Computational Modelling of Bifurcations and Instabilities in Fluid Dynamics, ed. Alexander Gelfgat (Springer, 2018