Numerical Studies of the Non-Linear Boltzmann Equation: Part I: Summary of Programs and Theory Used in Monte Carlo Solutions of the Boltzmann Equation

Coordinated Science Laboratory was formerly known as Control Systems LaboratoryJoint Services Electronics Program / DAAB-07-67-C-0199Office of Naval Research / N00014-67-A-0305-000

The Internal Structure of Shock Waves

Coordinated Science Laboratory was formerly known as Control Systems LaboratoryJoint Services Electronics Program / DAAB 07-67-C-0199ONR N00015-67-A-0305-000

Le risque de vivre

Myocardial constitutive No production depends on the activity of both endothelial and neuronal NOS (eNOS and nNOS, respectively). Stimulation of myocardial β(3)-adrenergic receptor (β(3)-AR) produces a negative inotropic effect that is dependent on eNOS. We evaluated whether nNOS also plays a role in β(3)-AR signaling and found that the β(3)-AR-mediated reduction in cell shortening and [Ca(2+)](i) transient amplitude was abolished both in eNOS(−/−) and nNOS(−/−) left ventricular (LV) myocytes and in wild type LV myocytes after nNOS inhibition with S-methyl-l-thiocitrulline. LV superoxide (O(2)(˙̄)) production was increased in nNOS(−/−) mice and reduced by l-N(ω)-nitroarginine methyl ester (l-NAME), indicating uncoupling of eNOS activity. eNOS S-glutathionylation and Ser-1177 phosphorylation were significantly increased in nNOS(−/−) myocytes, whereas myocardial tetrahydrobiopterin, eNOS Thr-495 phosphorylation, and arginase activity did not differ between genotypes. Although inhibitors of xanthine oxidoreductase (XOR) or NOX2 NADPH oxidase caused a similar reduction in myocardial O(2)(˙̄), only XOR inhibition reduced eNOS S-glutathionylation and Ser-1177 phosphorylation and restored both eNOS coupled activity and the negative inotropic and [Ca(2+)](i) transient response to β(3)-AR stimulation in nNOS(−/−) mice. In summary, our data show that increased O(2)(˙̄) production by XOR selectively uncouples eNOS activity and abolishes the negative inotropic effect of β(3)-AR stimulation in nNOS(−/−) myocytes. These findings provide unequivocal evidence of a functional interaction between the myocardial constitutive NOS isoforms and indicate that aspects of the myocardial phenotype of nNOS(−/−) mice result from disruption of eNOS signaling

Lamotrigine for people with borderline personality disorder: a RCT

Background: No drug treatments are currently licensed for the treatment of borderline personality disorder (BPD). Despite this, people with this condition are frequently prescribed psychotropic medications and often with considerable polypharmacy. Preliminary studies have indicated that mood stabilisers may be of benefit to people with BPD. Objective: To examine the clinical effectiveness and cost-effectiveness of lamotrigine for people with BPD. Design: A two-arm, double-blind, placebo-controlled individually randomised trial of lamotrigine versus placebo. Participants were randomised via an independent and remote web-based service using permuted blocks and stratified by study centre, the severity of personality disorder and the extent of hypomanic symptoms. Setting: Secondary care NHS mental health services in six centres in England. Participants: Potential participants had to be aged ≥ 18 years, meet diagnostic criteria for BPD and provide written informed consent. We excluded people with coexisting psychosis or bipolar affective disorder, those already taking a mood stabiliser, those who spoke insufficient English to complete the baseline assessment and women who were pregnant or contemplating becoming pregnant. Interventions: Up to 200 mg of lamotrigine per day or an inert placebo. Women taking combined oral contraceptives were prescribed up to 400 mg of trial medication per day. Main outcome measures: Outcomes were assessed at 12, 24 and 52 weeks after randomisation. The primary outcome was the total score on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) at 52 weeks. The secondary outcomes were depressive symptoms, deliberate self-harm, social functioning, health-related quality of life, resource use and costs, side effects of treatment and adverse events. Higher scores on all measures indicate poorer outcomes. Results: Between July 2013 and October 2015 we randomised 276 participants, of whom 195 (70.6%) were followed up 52 weeks later. At 52 weeks, 49 (36%) of those participants prescribed lamotrigine and 58 (42%) of those prescribed placebo were taking it. At 52 weeks, the mean total ZAN-BPD score was 11.3 [standard deviation (SD) 6.6] among those participants randomised to lamotrigine and 11.5 (SD 7.7) among those participants randomised to placebo (adjusted mean difference 0.1, 95% CI –1.8 to 2.0; p = 0.91). No statistically significant differences in secondary outcomes were seen at any time. Adjusted costs of direct care for those prescribed lamotrigine were similar to those prescribed placebo. Limitations: Levels of adherence in this pragmatic trial were low, but greater adherence was not associated with better mental health. Conclusions: The addition of lamotrigine to the usual care of people with BPD was not found to be clinically effective or provide a cost-effective use of resources. Future work: Future research into the treatment of BPD should focus on improving the evidence base for the clinical effectiveness and cost-effectiveness of non-pharmacological treatments to help policy-makers make better decisions about investing in specialist treatment services

The Grizzly, September 19, 1980

Reagan, Anderson Leading Carter In Campus Poll • Wismer Lunch Off to Optimistic Start • Explosive Bomb Found At NMD • College Van Policy Drastically Revised • Campus Expands With Enrollment • Bad Conditions Haunt New Women\u27s Dorm • Kane Appointed As New Executive Assistant • Ursinus Still Packing Them In • Ursinus News In Brief: Myrin Hosts Davison Exhibit; Davies Promoted In Admissions • TG Annex Almost Complete • Evening School Expands Services • Freshmen Class & USGA Treasurer Elections Coming Soon • Ron Baltz and Jenny Perform • Ritter Center To Open October 4 • For The Musically Inclined • WRUC - On The Air? • Yes A Maybe • Alternatives To Typical Parties • The Rush Is On • Switchboard Under New Operation • Police Rally To Cut Down Thefts • 1978 Alumnus Selected To Receive Award • Freshmen Offer Good Stats And Great Figures • Pre-Medical Evaluation Committee Reorganized • Bomberger Tower Finally To Be Replaced • Booters Sloppy in Close Call Over Drew • Delta Pi, ZX Defend Title; Intramural Football Underway • MAC Title: Cross Country Goal • Lack of Offense Hurts in Loss to Alfred • Hockey Starts Strong at Penn State Tourneyhttps://digitalcommons.ursinus.edu/grizzlynews/1040/thumbnail.jp

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

SNP array-based whole genome homozygosity mapping as the first step to a molecular diagnosis in patients with Charcot-Marie-Tooth disease

Considerable non-allelic heterogeneity for autosomal recessively inherited Charcot-Marie-Tooth (ARCMT) disease has challenged molecular testing and often requires a large amount of work in terms of DNA sequencing and data interpretation or remains unpractical. This study tested the value of SNP array-based whole-genome homozygosity mapping as a first step in the molecular genetic diagnosis of sporadic or ARCMT in patients from inbred families or outbred populations with the ancestors originating from the same geographic area. Using 10 K 2.0 and 250 K Nsp Affymetrix SNP arrays, 15 (63%) of 24 CMT patients received an accurate genetic diagnosis. We used our Java-based script eHoPASA CMT—easy Homozygosity Profiling of SNP arrays for CMT patients to display the location of homozygous regions and their extent of marker count and base-pairs throughout the whole genome. CMT4C was the most common genetic subtype with mutations detected in SH3TC2, one (p.E632Kfs13X) appearing to be a novel founder mutation. A sporadic patient with severe CMT was homozygous for the c.250G > C (p.G84R) HSPB1 mutation which has previously been reported to cause autosomal dominant dHMN. Two distantly related CMT1 patients with early disease onset were found to carry a novel homozygous mutation in MFN2 (p.N131S). We conclude that SNP array-based homozygosity mapping is a fast, powerful, and economic tool to guide molecular genetic testing in ARCMT and in selected sporadic CMT patients