Inactivation of a CRF-dependent amygdalofugal pathway reverses addiction-like behaviors in alcohol-dependent rats.

The activation of a neuronal ensemble in the central nucleus of the amygdala (CeA) during alcohol withdrawal has been hypothesized to induce high levels of alcohol drinking in dependent rats. In the present study we describe that the CeA neuronal ensemble that is activated by withdrawal from chronic alcohol exposure contains ~80% corticotropin-releasing factor (CRF) neurons and that the optogenetic inactivation of these CeA CRF+ neurons prevents recruitment of the neuronal ensemble, decreases the escalation of alcohol drinking, and decreases the intensity of somatic signs of withdrawal. Optogenetic dissection of the downstream neuronal pathways demonstrates that the reversal of addiction-like behaviors is observed after the inhibition of CeA CRF projections to the bed nucleus of the stria terminalis (BNST) and that inhibition of the CRFCeA-BNST pathway is mediated by inhibition of the CRF-CRF1 system and inhibition of BNST cell firing. These results suggest that the CRFCeA-BNST pathway could be targeted for the treatment of excessive drinking in alcohol use disorder

Solubilities of Selected Metals in Mercury: Hermex Process

The solubilities of uraninm, thorium, gadelinium, sama rinm, and neodymium in mereury were determined from room temperatare to 356 deg C. Equations of the form log of solubility (wt.%) = a + b/T were developed for these metals. Integral heats of solution were calculated for each. The solubilities of ruthenium, palladium, zirconium, and molybdenum in mercury in the presence of excess uranium were determined; the low solubility of zirconium and molybdenum gave solutions with a concentration below the limit of detection in the analytical method used. Their values are reported as an upper solubility limit. Uranium solubility in a 0.1 wt.% magnesium amAlgam was approximately 1.2 to 1.5 times greater than in mercury alone. When uranium and thorium were present in the same mercury solution, their solubilities were mutually depressed. (auth

PROCESSING OF HIGH-FIRED URANIUM DIOXIDE FUELS BY A REDUCTION-MERCURY EXTRACTION-OXIDATION PROCESS

A preliminary flowsheet for the purification of uranium dioxide fuels by a magnesium reduction-- mercury extraction-- steam oxidation process is proposed. Feasibility was indicated by laboratory-scale scouting experiments. Data evaluation indicated 100% reduction of uranium dioxide by magnesium although this figure was not demonstrated, chiefly because of poor choice of materials and design of equipment. Steam oxidation of uranlum tetramercuride produced an oxide with an O/U ratio of 2.43. This ratio was decreased to 2.09 by heating the oxide in a hydrogen atmosphere at 900 deg C for 1 hr. The final product had a surface area of 3.5 m/sup 2//g, and 18% of the panticles were < 1 mu diam. A pellet of the oxide sintered at 1750 deg C had a density of 9.76 g/cc, 89% of theoretical. Decontamination factors demonstrated for ruthenium, cesium, and samarium, when present originally in amounts equivalent to 30,000 Mwd/ton fuel burnup and 60 days' decay, wer

A Transgenic Rat for Investigating the Anatomy and Function of Corticotrophin Releasing Factor Circuits.

Corticotrophin-releasing factor (CRF) is a 41 amino acid neuropeptide that coordinates adaptive responses to stress. CRF projections from neurons in the central nucleus of the amygdala (CeA) to the brainstem are of particular interest for their role in motivated behavior. To directly examine the anatomy and function of CRF neurons, we generated a BAC transgenic Crh-Cre rat in which bacterial Cre recombinase is expressed from the Crh promoter. Using Cre-dependent reporters, we found that Cre expressing neurons in these rats are immunoreactive for CRF and are clustered in the lateral CeA (CeL) and the oval nucleus of the BNST. We detected major projections from CeA CRF neurons to parabrachial nuclei and the locus coeruleus, dorsal and ventral BNST, and more minor projections to lateral portions of the substantia nigra, ventral tegmental area, and lateral hypothalamus. Optogenetic stimulation of CeA CRF neurons evoked GABA-ergic responses in 11% of non-CRF neurons in the medial CeA (CeM) and 44% of non-CRF neurons in the CeL. Chemogenetic stimulation of CeA CRF neurons induced Fos in a similar proportion of non-CRF CeM neurons but a smaller proportion of non-CRF CeL neurons. The CRF1 receptor antagonist R121919 reduced this Fos induction by two-thirds in these regions. These results indicate that CeL CRF neurons provide both local inhibitory GABA and excitatory CRF signals to other CeA neurons, and demonstrate the value of the Crh-Cre rat as a tool for studying circuit function and physiology of CRF neurons

Commentary: the role of cytologic analysis of voided urine in the work-up of asymptomatic microhematuria

Microscopic hematuria is a common finding in patients presenting to both primary care doctors as well as urologists. Sources of microscopic hematuria include infection, stones, inflammatory disorders as well as cancer of the genitourinary tract, particularly urothelial cancer. A primary focus in the urologic workup of hematuria is to rule out cancer. This is done using radiographic studies as well as procedures such as cystoscopy and bladder biopsy. As the authors state in their article titled "The utility of serial urinary cytology in the initial evaluation of the patient with microscopic hematuria", cytologic analysis of voided urine, though attractive due to its noninvasive nature, has been found to have the neither the sensitivity, cost-effectiveness, nor the ease of administration necessary to replace more invasive diagnostics in the evaluation of microscopic hematuria

A Decision Tree Approach to Predicting Recidivism in Domestic Violence

Domestic violence (DV) is a global social and public health issue that is highly gendered. Being able to accurately predict DV recidivism, i.e., re-offending of a previously convicted offender, can speed up and improve risk assessment procedures for police and front-line agencies, better protect victims of DV, and potentially prevent future re-occurrences of DV. Previous work in DV recidivism has employed different classification techniques, including decision tree (DT) induction and logistic regression, where the main focus was on achieving high prediction accuracy. As a result, even the diagrams of trained DTs were often too difficult to interpret due to their size and complexity, making decision-making challenging. Given there is often a trade-off between model accuracy and interpretability, in this work our aim is to employ DT induction to obtain both interpretable trees as well as high prediction accuracy. Specifically, we implement and evaluate different approaches to deal with class imbalance as well as feature selection. Compared to previous work in DV recidivism prediction that employed logistic regression, our approach can achieve comparable area under the ROC curve results by using only 3 of 11 available features and generating understandable decision trees that contain only 4 leaf nodes.Comment: 12 pages; Accepted at The 2018 Pacific-Asia Conference on Knowledge Discovery and Data Mining (PAKDD

The interplay between genotype, metabolic state and cofactor treatment governs phenylalanine hydroxylase function and drug response

The discovery of a pharmacological treatment for phenylketonuria (PKU) raised new questions about function and dysfunction of phenylalanine hydroxylase (PAH), the enzyme deficient in this disease. To investigate the interdependence of the genotype, the metabolic state (phenylalanine substrate) and treatment (BH4 cofactor) in the context of enzyme function in vitro and in vivo, we (i) used a fluorescence-based method for fast enzyme kinetic analyses at an expanded range of phenylalanine and BH4 concentrations, (ii) depicted PAH function as activity landscapes, (iii) retraced the analyses in eukaryotic cells, and (iv) translated this into the human system by analyzing the outcome of oral BH4 loading tests. PAH activity landscapes uncovered the optimal working range of recombinant wild-type PAH and provided new insights into PAH kinetics. They demonstrated how mutations might alter enzyme function in the space of varying substrate and cofactor concentrations. Experiments in eukaryotic cells revealed that the availability of the active PAH enzyme depends on the phenylalanine-to-BH4 ratio. Finally, evaluation of data from BH4 loading tests indicated that the patient's genotype influences the impact of the metabolic state on drug response. The results allowed for visualization and a better understanding of PAH function in the physiological and pathological state as well as in the therapeutic context of cofactor treatment. Moreover, our data underscore the need for more personalized procedures to safely identify and treat patients with BH4-responsive PAH deficienc