Gambling Treatment Diversion Court: First in Nevada

The first Gambling Treatment Diversion Court was established in Las Vegas, Nevada in fall of 2018 following more than 25 years of effort by passionately concerned non-profit Executives, therapists, lawyers and judges. This panel represents one leader from each of those areas, including Judge Cheryl Moss, the first judge to open the Gambling Treatment Diversion Court (GTDC), Dayvid Figler, the first attorney to successfully represent a gambling client and refer her to the GTDC, Carol O\u27Hare, Executive Director of the non-profit Nevada Council on Problem Gambler with 25+ years leadership and advocacy for problem gamblers, Sydney Smith, M.A., Clinical Director of RISE treatment center in Las Vegas and nationally- and state-certified gambling counselor, and Denise F. Quirk, M.A., Clinical Director of the Reno Problem Gambling Center and nationally- and Nevada-certified problem gambling counselor and instructor at the University of Nevada, Reno. The panel will share the development of gambling diversion treatment, legal challenges and victories, the process of the GTDC, case studies of individuals with Gambling Disorder who have endured and succeeded in the legal process, and discussion relevant to the impact of the gambling diversion process at all levels of evaluation, advocacy, treatment and support for gamblers and communities

How Protein Stability and New Functions Trade Off

Numerous studies have noted that the evolution of new enzymatic specificities is accompanied by loss of the protein's thermodynamic stability (ΔΔG), thus suggesting a tradeoff between the acquisition of new enzymatic functions and stability. However, since most mutations are destabilizing (ΔΔG>0), one should ask how destabilizing mutations that confer new or altered enzymatic functions relative to all other mutations are. We applied ΔΔG computations by FoldX to analyze the effects of 548 mutations that arose from the directed evolution of 22 different enzymes. The stability effects, location, and type of function-altering mutations were compared to ΔΔG changes arising from all possible point mutations in the same enzymes. We found that mutations that modulate enzymatic functions are mostly destabilizing (average ΔΔG = +0.9 kcal/mol), and are almost as destabilizing as the “average” mutation in these enzymes (+1.3 kcal/mol). Although their stability effects are not as dramatic as in key catalytic residues, mutations that modify the substrate binding pockets, and thus mediate new enzymatic specificities, place a larger stability burden than surface mutations that underline neutral, non-adaptive evolutionary changes. How are the destabilizing effects of functional mutations balanced to enable adaptation? Our analysis also indicated that many mutations that appear in directed evolution variants with no obvious role in the new function exert stabilizing effects that may compensate for the destabilizing effects of the crucial function-altering mutations. Thus, the evolution of new enzymatic activities, both in nature and in the laboratory, is dependent on the compensatory, stabilizing effect of apparently “silent” mutations in regions of the protein that are irrelevant to its function

Single-Unit Activity in the Medial Prefrontal Cortex during Immediate and Delayed Extinction of Fear in Rats

Delivering extinction trials minutes after fear conditioning yields only a short-term fear suppression that fully recovers the following day. Because extinction has been reported to increase CS-evoked spike firing and spontaneous bursting in the infralimbic (IL) division of the medial prefrontal cortex (mPFC), we explored the possibility that this immediate extinction deficit is related to altered mPFC function. Single-units were simultaneously recorded in rats from neurons in IL and the prelimbic (PrL) division of the mPFC during an extinction session conducted 10 minutes (immediate) or 24 hours (delayed) after auditory fear conditioning. In contrast to previous reports, IL neurons exhibited CS-evoked responses early in extinction training in both immediate and delayed conditions and these responses decreased in magnitude over the course of extinction training. During the retention test, CS-evoked firing in IL was significantly greater in animals that failed to acquire extinction. Spontaneous bursting during the extinction and test sessions was also different in the immediate and delayed groups. There were no group differences in PrL activity during extinction or retention testing. Alterations in both spontaneous and CS-evoked neuronal activity in the IL may contribute to the immediate extinction deficit

Evidence for Diffuse Central Retinal Edema In Vivo in Diabetic Male Sprague Dawley Rats

Background: Investigations into the mechanism of diffuse retinal edema in diabetic subjects have been limited by a lack of animal models and techniques that co-localized retinal thickness and hydration in vivo. In this study we test the hypothesis that a previously reported supernormal central retinal thickness on MRI measured in experimental diabetic retinopathy in vivo represents a persistent and diffuse edema. Methodology/Principal Findings: In diabetic and age-matched control rats, and in rats experiencing dilutional hyponatremia (as a positive edema control), whole central retinal thickness, intraretinal water content and apparent diffusion coefficients (ADC, ‘water mobility’) were measured in vivo using quantitative MRI methods. Glycated hemoglobin and retinal thickness ex vivo (histology) were also measured in control and diabetic groups. In the dilutional hyponatremia model, central retinal thickness and water content were supernormal by quantitative MRI, and intraretinal water mobility profiles changed in a manner consistent with intracellular edema. Groups of diabetic (2, 3, 4, 6, and 9 mo of diabetes), and age-matched controls were then investigated with MRI and all diabetic rats showed supernormal whole central retinal thickness. In a separate study in 4 mo diabetic rats (and controls), MRI retinal thickness and water content metrics were significantly greater than normal, and ADC was subnormal in the outer retina; the increase in retinal thickness was not detected histologically on sections of fixed and dehydrated retinas from these rats

Salinity and Simulated Herbivory Influence Spartina alterniflora Traits and Defense Strategy

Sea level rise is expected to push saline waters into previously fresher regions of estuaries, and higher salinities may expose oligohaline marshes to invertebrate herbivores typically constrained by salinity. The smooth cordgrass, Spartina alterniflora (syn. Sporobolus alterniflorus), can defend itself against herbivores in polyhaline marshes, however it is not known if S. alterniflora’s defense varies along the mesohaline to oligohaline marsh gradient in estuaries. I found that S. alterniflora from a mesohaline marsh is better defended than plants from an oligohaline marsh, supporting the optimal defense theory. Higher salinity treatments lowered carbon content, C:N, and new stem biomass production, traits associated with a tolerance strategy, suggesting that salinity may mediate the defense response of S. alterniflora. Further, simulated herbivory increased the nitrogen content and decreased C:N of S. alterniflora. This indicates that grazing may increase S. alterniflora susceptibility to future herbivory via improved forage quality. Simulated herbivory also decreased both belowground and new stem biomass production, highlighting a potential pathway in which herbivory can indirectly facilitate marsh loss, as S. alterniflora biomass is critical for vertical accretion and marsh stability under future sea level rise scenarios

Gender Differences in Myogenic Regulation along the Vascular Tree of the Gerbil Cochlea

Regulation of cochlear blood flow is critical for hearing due to its exquisite sensitivity to ischemia and oxidative stress. Many forms of hearing loss such as sensorineural hearing loss and presbyacusis may involve or be aggravated by blood flow disorders. Animal experiments and clinical outcomes further suggest that there is a gender preference in hearing loss, with males being more susceptible. Autoregulation of cochlear blood flow has been demonstrated in some animal models in vivo, suggesting that similar to the brain, blood vessels supplying the cochlea have the ability to control flow within normal limits, despite variations in systemic blood pressure. Here, we investigated myogenic regulation in the cochlear blood supply of the Mongolian gerbil, a widely used animal model in hearing research. The cochlear blood supply originates at the basilar artery, followed by the anterior inferior cerebellar artery, and inside the inner ear, by the spiral modiolar artery and the radiating arterioles that supply the capillary beds of the spiral ligament and stria vascularis. Arteries from male and female gerbils were isolated and pressurized using a concentric pipette system. Diameter changes in response to increasing luminal pressures were recorded by laser scanning microscopy. Our results show that cochlear vessels from male and female gerbils exhibit myogenic regulation but with important differences. Whereas in male gerbils, both spiral modiolar arteries and radiating arterioles exhibited pressure-dependent tone, in females, only radiating arterioles had this property. Male spiral modiolar arteries responded more to L-NNA than female spiral modiolar arteries, suggesting that NO-dependent mechanisms play a bigger role in the myogenic regulation of male than female gerbil cochlear vessels

Reliability of dynamic contrast-enhanced magnetic resonance imaging data in primary brain tumours: a comparison of Tofts and shutter speed models

Purpose To investigate the robustness of pharmacokinetic modelling of DCE-MRI brain tumour data and to ascertain reliable perfusion parameters through a model selection process and a stability test. Methods DCE-MRI data of 14 patients with primary brain tumours were analysed using the Tofts model (TM), the extended Tofts model (ETM), the shutter speed model (SSM) and the extended shutter speed model (ESSM). A no-effect model (NEM) was implemented to assess overfitting of data by the other models. For each lesion, the Akaike Information Criteria (AIC) was used to build a 3D model selection map. The variability of each pharmacokinetic parameter extracted from this map was assessed with a noise propagation procedure, resulting in voxel-wise distributions of the coefficient of variation (CV). Results The model selection map over all patients showed NEM had the best fit in 35.5% of voxels, followed by ETM (32%), TM (28.2%), SSM (4.3%) and ESSM (<0.1%). In analysing the reliability of Ktrans, when considering regions with a CV<20%, ≈25% of voxels were found to be stable across all patients. The remaining 75% of voxels were considered unreliable. Conclusions The majority of studies quantifying DCE-MRI data in brain tumours only consider a single model and whole-tumour statistics for the output parameters. Appropriate model selection, considering tissue biology and its effects on blood brain barrier permeability and exchange conditions, together with an analysis on the reliability and stability of the calculated parameters, is critical in processing robust brain tumour DCE-MRI data

Overview of the ID, EPI and REL tasks of BioNLP Shared Task 2011

We present the preparation, resources, results and analysis of three tasks of the BioNLP Shared Task 2011: the main tasks on Infectious Diseases (ID) and Epigenetics and Post-translational Modifications (EPI), and the supporting task on Entity Relations (REL). The two main tasks represent extensions of the event extraction model introduced in the BioNLP Shared Task 2009 (ST'09) to two new areas of biomedical scientific literature, each motivated by the needs of specific biocuration tasks. The ID task concerns the molecular mechanisms of infection, virulence and resistance, focusing in particular on the functions of a class of signaling systems that are ubiquitous in bacteria. The EPI task is dedicated to the extraction of statements regarding chemical modifications of DNA and proteins, with particular emphasis on changes relating to the epigenetic control of gene expression. By contrast to these two application-oriented main tasks, the REL task seeks to support extraction in general by separating challenges relating to part-of relations into a subproblem that can be addressed by independent systems. Seven groups participated in each of the two main tasks and four groups in the supporting task. The participating systems indicated advances in the capability of event extraction methods and demonstrated generalization in many aspects: from abstracts to full texts, from previously considered subdomains to new ones, and from the ST'09 extraction targets to other entities and events. The highest performance achieved in the supporting task REL, 58% F-score, is broadly comparable with levels reported for other relation extraction tasks. For the ID task, the highest-performing system achieved 56% F-score, comparable to the state-of-the-art performance at the established ST'09 task. In the EPI task, the best result was 53% F-score for the full set of extraction targets and 69% F-score for a reduced set of core extraction targets, approaching a level of performance sufficient for user-facing applications. In this study, we extend on previously reported results and perform further analyses of the outputs of the participating systems. We place specific emphasis on aspects of system performance relating to real-world applicability, considering alternate evaluation metrics and performing additional manual analysis of system outputs. We further demonstrate that the strengths of extraction systems can be combined to improve on the performance achieved by any system in isolation. The manually annotated corpora, supporting resources, and evaluation tools for all tasks are available from http://www.bionlp-st.org and the tasks continue as open challenges for all interested parties

Lack of cortico-limbic coupling in bipolar disorder and schizophrenia during emotion regulation

Bipolar disorder (BD) and schizophrenia (Sz) share dysfunction in prefrontal inhibitory brain systems, yet exhibit distinct forms of affective disturbance. We aimed to distinguish these disorders on the basis of differential activation in cortico-limbic pathways during voluntary emotion regulation. Patients with DSM-IV diagnosed Sz (12) or BD-I (13) and 15 healthy control (HC) participants performed a well-established emotion regulation task while undergoing functional magnetic resonance imaging. The task required participants to voluntarily upregulate or downregulate their subjective affect while viewing emotionally negative images or maintain their affective response as a comparison condition. In BD, abnormal overactivity (hyperactivation) occurred in the right ventrolateral prefrontal cortex (VLPFC) during up- and downregulation of negative affect, relative to HC. Among Sz, prefrontal hypoactivation of the right VLPFC occurred during downregulation (opposite to BD), whereas upregulation elicited hyperactivity in the right VLPFC similar to BD. Amygdala activity was significantly related to subjective negative affect in HC and BD, but not Sz. Furthermore, amygdala activity was inversely coupled with the activity in the left PFC during downregulation in HC (r=−0.76), while such coupling did not occur in BD or Sz. These preliminary results indicate that differential cortico-limbic activation can distinguish the clinical groups in line with affective disturbance: BD is characterized by ineffective cortical control over limbic regions during emotion regulation, while Sz is characterized by an apparent failure to engage cortical (hypofrontality) and limbic regions during downregulation