An exploration of sex-specific linkage disequilibrium on chromosome X in Caucasians from the COGA study

This paper explores the decay of linkage disequilibrium (LD) on the autosomes and chromosome X. The extent of marker-marker LD is important for both linkage and association studies. The analysis of the Caucasian sample from the Collaborative Study on the Genetics of Alcoholism study revealed the expected negative relationship between the magnitude of the marker-marker LD and distance (cM), with the male and female subgroups exhibiting similar patterns of LD. The observed extent of LD in females was less across the pseudoautosomal markers relative to the heterosomal region of chromosome X. Marked differences in LD patterns were also observed between chromosomes X and the 22 autosomes in both males and females

The Stability of Double White Dwarf Binaries Undergoing Direct Impact Accretion

We present numerical simulations of dynamically unstable mass transfer in a double white dwarf binary with initial mass ratio, q = 0.4. The binary components are approximated as polytropes of index n = 3/2 and the initially synchronously rotating, semi-detached equilibrium binary is evolved hydrodynamically with the gravitational potential being computed through the solution of Poisson's equation. Upon initiating deep contact in our baseline simulation, the mass transfer rate grows by more than an order of magnitude over approximately ten orbits, as would be expected for dynamically unstable mass transfer. However, the mass transfer rate then reaches a peak value, the binary expands and the mass transfer event subsides. The binary must therefore have crossed the critical mass ratio for stability against dynamical mass transfer. Despite the initial loss of orbital angular momentum into the spin of the accreting star, we find that the accretor's spin saturates and angular momentum is returned to the orbit more efficiently than has been previously suspected for binaries in the direct impact accretion mode. To explore this surprising result, we directly measure the critical mass ratio for stability by imposing artificial angular momentum loss at various rates to drive the binary to an equilibrium mass transfer rate. For one of these driven evolutions, we attain equilibrium mass transfer and deduce that effectively q_crit has evolved to approximately 2/3. Despite the absence of a fully developed disk, tidal interactions appear effective in returning excess spin angular momentum to the orbit.Comment: 27 pages, 6 figures. Please see http://www.phys.lsu.edu/faculty/tohline/astroph/mftd07/ for animations and full resolution figures. Accepted for publication in the Astrophysical Journa

Dopaminergic, serotonergic, and noradrenergic deficits in Parkinson disease

OBJECTIVE: People with Parkinson disease (PD) frequently develop dementia, which is associated with neocortical deposition of alpha-synuclein (α-syn) in Lewy bodies and Lewy neurites. In addition, neuronal loss and deposition of aggregated α-syn also occur in multiple subcortical nuclei that project to neocortical, limbic, and basal ganglia regions. Therefore, we quantified regional deficits in innervation from these PD-affected subcortical nuclei, by measuring the neurotransmitters and neurotransmitter transporter proteins originating from projections of dopaminergic neurons in substantia nigra pars compacta, serotonergic neurons in dorsal raphé nuclei, noradrenergic neurons in locus coeruleus, and cholinergic neurons in nucleus basalis of Meynert. METHODS: High-performance liquid chromatography and novel enzyme-linked immunosorbent assays were performed to quantify dopaminergic, serotonergic, noradrenergic, and cholinergic innervation in postmortem brain tissue. Eight brain regions from 15 PD participants (with dementia and Braak stage 6 α-syn deposition) and six age-matched controls were tested. RESULTS: PD participants compared to controls had widespread reductions of dopamine transporter in caudate, amygdala, hippocampus, inferior parietal lobule (IPL), precuneus, and visual association cortex (VAC) that exceeded loss of dopamine, which was only significantly reduced in caudate and amygdala. In contrast, PD participants had comparable deficits of both serotonin and serotonin transporter in caudate, middle frontal gyrus, IPL, and VAC. PD participants also had significantly reduced norepinephrine levels for all eight brain regions tested. Vesicular acetylcholine transporter levels were only quantifiable in caudate and hippocampus and did not differ between PD and control groups. INTERPRETATION: These results demonstrate widespread deficits in dopaminergic, serotonergic, and noradrenergic innervation of neocortical, limbic, and basal ganglia regions in advanced PD with dementia

Alcohol Misuse and Coâ Occurring Mental Disorders Among New Soldiers in the U.S. Army

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135492/1/acer13269_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135492/2/acer13269.pd

The Grizzly, February 17, 1997

Window Shopping Without the Glass • Ursinus Celebrates Diversity Week • Students Benefit from Internships • Study Abroad: They Don\u27t Call \u27Em Deadlines For Nothing • Campus Apathy on the Issue of Diversity • And the Spirit Moved Them • Caplan Addresses Ethical Issues • Dr. Scott Landis\u27 Resignation Announced • So This is What Security Does: Ursinus\u27 Security Log Returns • Opinion: Greek Speaks Out; Read This if you Think Pledging is Dumb; Come Catch a Square; Perspective from Scotland; Faces of Silence • Defend Yourself! • Keep the Tutorial Program Alive! • Wrestling Bears Win Conference Championship • Women\u27s Basketball Nets Three More Wins • Men\u27s Basketball Drops Two • Gymnasts Leap to Two More Winshttps://digitalcommons.ursinus.edu/grizzlynews/1397/thumbnail.jp

Quantifying regional α -synuclein, amyloid β, and tau accumulation in Lewy body dementia

OBJECTIVE: Parkinson disease (PD) is defined by the accumulation of misfolded α-synuclein (α-syn) in Lewy bodies and Lewy neurites. It affects multiple cortical and subcortical neuronal populations. The majority of people with PD develop dementia, which is associated with Lewy bodies in neocortex and referred to as Lewy body dementia (LBD). Other neuropathologic changes, including amyloid β (Aβ) and tau accumulation, occur in some LBD cases. We sought to quantify α-syn, Aβ, and tau accumulation in neocortical, limbic, and basal ganglia regions. METHODS: We isolated insoluble protein from fresh frozen postmortem brain tissue samples for eight brains regions from 15 LBD, seven Alzheimer disease (AD), and six control cases. We measured insoluble α-syn, Aβ, and tau with recently developed sandwich ELISAs. RESULTS: We detected a wide range of insoluble α-syn accumulation in LBD cases. The majority had substantial α-syn accumulation in most regions, and dementia severity correlated with neocortical α-syn. However, three cases had low neocortical levels that were indistinguishable from controls. Eight LBD cases had substantial Aβ accumulation, although the mean Aβ level in LBD was lower than in AD. The presence of Aβ was associated with greater α-syn accumulation. Tau accumulation accompanied Aβ in only one LBD case. INTERPRETATION: LBD is associated with insoluble α-syn accumulation in neocortical regions, but the relatively low neocortical levels in some cases suggest that other changes contribute to impaired function, such as loss of neocortical innervation from subcortical regions. The correlation between Aβ and α-syn accumulation suggests a pathophysiologic relationship between these two processes

Genomeâ wide analyses of psychological resilience in U.S. Army soldiers

Though a growing body of preclinical and translational research is illuminating a biological basis for resilience to stress, little is known about the genetic basis of psychological resilience in humans. We conducted genomeâ wide association studies (GWASs) of selfâ assessed (by questionnaire) and outcomeâ based (incident mental disorders from predeployment to postdeployment) resilience among European (EUR) ancestry soldiers in the Army study to assess risk and resilience in servicemembers. Selfâ assessed resilience (Nâ =â 11,492) was found to have significant commonâ variant heritability (h2 =â 0.162, seâ =â 0.050, pâ =â 5.37â Ã â 10â 4), and to be significantly negatively genetically correlated with neuroticism (rgâ =â â 0.388, pâ =â .0092). GWAS results from the EUR soldiers revealed a genomeâ wide significant locus on an intergenic region on Chr 4 upstream from doublecortinâ like kinase 2 (DCLK2) (four single nucleotide polymorphisms (SNPs) in LD; top SNP: rs4260523 [pâ =â 5.65â Ã â 10â 9] is an eQTL in frontal cortex), a member of the doublecortin family of kinases that promote survival and regeneration of injured neurons. A second gene, kelchâ like family member 36 (KLHL36) was detected at geneâ wise genomeâ wide significance [pâ =â 1.89â Ã â 10â 6]. A polygenic risk score derived from the selfâ assessed resilience GWAS was not significantly associated with outcomeâ based resilience. In very preliminary results, genomeâ wide significant association with outcomeâ based resilience was found for one locus (top SNP: rs12580015 [pâ =â 2.37â Ã â 10â 8]) on Chr 12 downstream from solute carrier family 15 member 5 (SLC15A5) in subjects (Nâ = 581) exposed to the highest level of deployment stress. The further study of genetic determinants of resilience has the potential to illuminate the molecular bases of stressâ related psychopathology and point to new avenues for therapeutic intervention.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149528/1/ajmgb32730.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149528/2/ajmgb32730_am.pd

X-ray absorption spectroscopy systematics at the tungsten L-edge

A series of mononuclear six-coordinate tungsten compounds spanning formal oxidation states from 0 to +VI, largely in a ligand environment of inert chloride and/or phosphine, has been interrogated by tungsten L-edge X-ray absorption spectroscopy. The L-edge spectra of this compound set, comprised of [W<sup>0</sup>(PMe<sub>3</sub>)<sub>6</sub>], [W<sup>II</sup>Cl<sub>2</sub>(PMePh<sub>2</sub>)<sub>4</sub>], [W<sup>III</sup>Cl<sub>2</sub>(dppe)<sub>2</sub>][PF<sub>6</sub>] (dppe = 1,2-bis(diphenylphosphino)ethane), [W<sup>IV</sup>Cl<sub>4</sub>(PMePh<sub>2</sub>)<sub>2</sub>], [W<sup>V</sup>(NPh)Cl<sub>3</sub>(PMe<sub>3</sub>)<sub>2</sub>], and [W<sup>VI</sup>Cl<sub>6</sub>] correlate with formal oxidation state and have usefulness as references for the interpretation of the L-edge spectra of tungsten compounds with redox-active ligands and ambiguous electronic structure descriptions. The utility of these spectra arises from the combined correlation of the estimated branching ratio (EBR) of the L<sub>3,2</sub>-edges and the L<sub>1</sub> rising-edge energy with metal Z<sub>eff</sub>, thereby permitting an assessment of effective metal oxidation state. An application of these reference spectra is illustrated by their use as backdrop for the L-edge X-ray absorption spectra of [W<sup>IV</sup>(mdt)<sub>2</sub>(CO)<sub>2</sub>] and [W<sup>IV</sup>(mdt)<sub>2</sub>(CN)<sub>2</sub>]<sup>2–</sup> (mdt<sup>2–</sup> = 1,2-dimethylethene-1,2-dithiolate), which shows that both compounds are effectively W<sup>IV</sup> species. Use of metal L-edge XAS to assess a compound of uncertain formulation requires: 1) Placement of that data within the context of spectra offered by unambiguous calibrant compounds, preferably with the same coordination number and similar metal ligand distances. Such spectra assist in defining upper and/or lower limits for metal Z<sub>eff</sub> in the species of interest; 2) Evaluation of that data in conjunction with information from other physical methods, especially ligand K-edge XAS; 3) Increased care in interpretation if strong π-acceptor ligands, particularly CO, or π-donor ligands are present. The electron-withdrawing/donating nature of these ligand types, combined with relatively short metal-ligand distances, exaggerate the difference between formal oxidation state and metal Z<sub>eff</sub> or, as in the case of [W<sup>IV</sup>(mdt)<sub>2</sub>(CO)<sub>2</sub>], add other subtlety by modulating the redox level of other ligands in the coordination sphere

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty