579 research outputs found

    Gaggle on the Gavel: Designing an Interactive Website to Create a Community of Lawyers

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    Law is behind other industries and professions in its implementation of technolo-gy that could make the practice of law and the delivery of legal services more ef-fective and satisfying. Although there has been considerable development in le-gal technology over the past few years, research identified the need for an interac-tive LinkedIn-style online community for lawyers to communicate other lawyers. Such a community would be particularly beneficial for solo practitioners, lawyers in small firms and lawyers in rural communities and would also provide a con-venient way to connect with lawyers for referrals and recommendations, for spe-cialized expertise and to develop contacts in different geographic locations. Ten-tatively titled Gaggle on the Gavel is an attempt to create such a community that would gather a number of attractive features and functionality under one umbrella and be compliant with the rules of professional conduct with respect to client con-fidentiality, security, advertising and solicitation. A system has been designed, prototyped and revised based on feedback from a focus group of lawyers

    Pathway-Specific Polygenic Risk Scores as Predictors of Amyloid-beta Deposition and Cognitive Function in a Sample at Increased Risk for Alzheimer's Disease

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    Polygenic risk scores (PRSs) have been used to combine the effects of variants with small effects identified by genome-wide association studies. We explore the potential for using pathway-specific PRSs as predictors of early changes in Alzheimer’s disease (AD)-related biomarkers and cognitive function. Participants were from the Wisconsin Registry for Alzheimer’s Prevention, a longitudinal study of adults who were cognitively asymptomatic at enrollment and enriched for a parental history of AD. Using genes associated with AD in the International Genomics of Alzheimer’s Project’s meta-analysis, we identified clusters of genes that grouped into pathways involved in amyloid-β (Aβ) deposition and neurodegeneration: Aβ clearance, cholesterol metabolism, and immune response. Weighted pathway-specific and overall PRSs were developed and compared to APOE alone. Mixed models were used to assess whether each PRS was associated with cognition in 1,200 individuals, cerebral Aβ deposition measured using amyloid ligand (Pittsburgh compound B) positron emission imaging in 168 individuals, and cerebrospinal fluid Aβ deposition, neurodegeneration, and tau pathology in 111 individuals, with replication performed in an independent sample. We found that PRSs including APOE appeared to be driven by the inclusion of APOE, suggesting that the pathway-specific PRSs used here were not more predictive than an overall PRS or APOE alone. However, pathway-specific PRSs could prove to be useful as more knowledge is gained on the genetic variants involved in specific biological pathways of AD

    Cumulate causes for the low contents of sulfide-loving elements in the continental crust

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    Despite the economic importance of chalcophile (sulfide-loving) and siderophile (metal-loving) elements (CSEs), it is unclear how they become enriched or depleted in the continental crust, compared with the oceanic crust. This is due in part to our limited understanding of the partitioning behaviour of the CSEs. Here I compile compositional data for mid-ocean ridge basalts and subduction-related volcanic rocks. I show that the mantle-derived melts that contribute to oceanic and continental crust formation rarely avoid sulfide saturation during cooling in the crust and, on average, subduction-zone magmas fractionate sulfide at the base of the continental crust prior to ascent. Differentiation of mantle-derived melts enriches lower crustal sulfide- and silicate-bearing cumulates in some CSEs compared with the upper crust. This storage predisposes the cumulate-hosted compatible CSEs (such as Cu and Au) to be recycled back into the mantle during subduction and delamination, resulting in their low contents in the bulk continental crust and potentially contributing to the scarcity of ore deposits in the upper continental crust. By contrast, differentiation causes the upper oceanic and continental crust to become enriched in incompatible CSEs (such as W) compared with the lower oceanic and continental crust. Consequently, incompatible CSEs are predisposed to become enriched in subduction-zone magmas that contribute to continental crust formation and are less susceptible to removal from the continental crust via delamination compared with the compatible CSEs

    Ab initio alpha-alpha scattering

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    Processes involving alpha particles and alpha-like nuclei comprise a major part of stellar nucleosynthesis and hypothesized mechanisms for thermonuclear supernovae. In an effort towards understanding alpha processes from first principles, we describe in this letter the first ab initio calculation of alpha-alpha scattering. We use lattice effective field theory to describe the low-energy interactions of nucleons and apply a technique called the adiabatic projection method to reduce the eight-body system to an effective two-cluster system. We find good agreement between lattice results and experimental phase shifts for S-wave and D-wave scattering. The computational scaling with particle number suggests that alpha processes involving heavier nuclei are also within reach in the near future.Comment: 6 pages, 6 figure

    Laryngeal Reinnervation Using Ansa Cervicalis for Thyroid Surgery-Related Unilateral Vocal Fold Paralysis: A Long-Term Outcome Analysis of 237 Cases

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    To evaluate the long-term efficacy of delayed laryngeal reinnervation using the main branch of the ansa cervicalis in treatment of unilateral vocal fold paralysis (UVFP) caused by thyroid surgery.UVFP remains a serious complication of thyroid surgery. Up to now, a completely satisfactory surgical treatment of UVFP has been elusive.From Jan. 1996 to Jan. 2008, a total of 237 UVFP patients who underwent ansa cervicalis main branch-to-recurrent laryngeal nerve (RLN) anastomosis were enrolled as UVFP group; another 237 age- and gender-matched normal subjects served as control group. Videostroboscopy, vocal function assessment (acoustic analysis, perceptual evaluation and maximum phonation time), and electromyography were performed preoperatively and postoperatively. The mean follow-up period was 5.2±2.7 years, ranging from 2 to 12 years.>0.05, respectively). Postoperative laryngeal electromyography confirmed successful reinnervation of laryngeal muscle.Delayed laryngeal reinnervation with the main branch of ansa cervicalis is a feasible and effective approach for treatment of thyroid surgery-related UVFP; it can restore the physiological laryngeal phonatory function to the normal or a nearly normal voice quality

    How and why community hospital clinicians document a positive screen for intimate partner violence: a cross-sectional study

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    BACKGROUND: This two-part study examines primary care clinicians' chart documentation and attitudes when confronted by a positive waiting room screen for intimate partner violence (IPV). METHODS: Patients at community hospital-affiliated health centers completed a screening questionnaire in waiting rooms that primary care providers (PCPs) were subsequently given at the time of the visit. We first reviewed the medical records of patients who screened positive for IPV, evaluating the presence and quality of documentation. Next we administered a survey to PCPs that measured their knowledge, attitudes and practice regarding IPV. RESULTS: Seventy-two percent of charts contained some documentation of IPV, however only 10% contained both a referral and safety plan. PCPs were more likely to refer patients (p < .05) who screened positively for mood or anxiety disorders, disclosed that they feared for their safety or were economically disadvantaged. Those that feared for their safety or endorsed mood or anxiety disorders were more likely to have notation of a safety plan in their records. When surveyed, 81.6% of clinicians strongly agreed that it is their role to inquire about IPV, but only 68% expressed confidence in their ability to manage it. In contrast, 93% expressed confidence in managing depression. Sixty-seven percent identified time constraints as a barrier to care. Predictors of PCP confidence in treating patients who have experienced IPV (p < .05) included hours of recent training and clinical experience with IPV. CONCLUSION: Mandatory waiting room screening for IPV does not result in high levels of referral or safety planning by PCPs. Despite the implementation of a screening process, clinicians lack confidence and time to address IPV in their patient populations suggesting that alternative methods of training and supporting PCPs need to be developed

    A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus

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    <p>Abstract</p> <p>Background</p> <p>Neramexane is a new substance that exhibits antagonistic properties at α<sub>9</sub>α<sub>10 </sub>cholinergic nicotinic receptors and <it>N</it>-methyl-D-aspartate receptors, suggesting potential efficacy in the treatment of tinnitus.</p> <p>Methods</p> <p>A total of 431 outpatients with moderate to severe subjective tinnitus (onset 3-18 months before screening) were assigned randomly to receive either placebo or neramexane mesylate (25 mg/day, 50 mg/day and 75 mg/day) for 16 weeks, with assessment at 4-week intervals. The primary (intention-to-treat) efficacy analysis was based on the change from baseline in Week 16 in the total score of the adapted German short version of the validated Tinnitus Handicap Inventory questionnaire (THI-12).</p> <p>Results</p> <p>Compared with placebo, the largest improvement was achieved in the 50 mg/d neramexane group, followed by the 75 mg/d neramexane group. This treatment difference did not reach statistical significance at the pre-defined endpoint in Week 16 (<it>p </it>= 0.098 for 50 mg/d; <it>p </it>= 0.289 for 75 mg/d neramexane), but consistent numerical superiority of both neramexane groups compared with placebo was observed. Four weeks after the end of treatment, THI-12 scores in the 50 mg/d group were significantly better than those of the controls. Secondary efficacy variables supported this trend, with <it>p </it>values of < 0.05 for the 50 mg/d neramexane group associated with the functional-communicational subscores of the THI-12 and the assessments of tinnitus annoyance and tinnitus impact on life as measured on an 11-point Likert-like scale. No relevant changes were observed for puretone threshold, for tinnitus pitch and loudness match, or for minimum masking levels. The 25 mg/d neramexane group did not differ from placebo. Neramexane was generally well tolerated and had no relevant influence on laboratory values, electrocardiography and vital signs. Dizziness was the most common adverse event and showed a clear dose-dependence.</p> <p>Conclusions</p> <p>This study demonstrated the safety and tolerability of neramexane treatment in patients with moderate to severe tinnitus. The primary efficacy variable showed a trend towards improvement of tinnitus suffering in the medium- and high-dose neramexane groups. This finding is in line with consistent beneficial effects observed in secondary assessment variables. These results allow appropriate dose selection for further studies.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00405886</p

    Hospitalizations during the last months of life of nursing home residents: a retrospective cohort study from Germany

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    BACKGROUND: To describe hospitalisations of nursing home (NH) residents in Germany during their last months of life. METHODS: Retrospective cohort study on 792 NH residents in the Rhine-Neckar region in South-West Germany, newly institutionalized in the year 2000, who died until the study end (December 2001). Baseline variables were derived from a standardized medical examination routinely conducted by the medical service of the health care insurance plans in Germany. Information on hospitalisations and deaths was extracted form records of the pertinent health insurance plans. RESULTS: NH residents who died after NH stay of more than 1 year spent 5.8% of their last year of life in hospitals. Relative time spent in hospitals increased from 5.2% twelve months before death (N = 139 persons) to 24.1% in their last week of life (N = 769 persons). No major differences could be observed concerning age, gender or duration of stay in NH. Overall, 229 persons (28.9%) died in hospital. Among these, the last hospital stay lasted less than 3 days for 76 persons (31.9%). Another 25 persons (3.2%) died within three days after hospital discharge. CONCLUSION: Our study indicates that proximity of death is the most important driver of health care utilization among NH residents. The relation of age or gender to health care expenditures seem to be weak once time to death is controlled for. Duration of NH stay does not markedly change rates of hospitalisation during the last months of life

    Human cardiac tissue in a microperfusion chamber simulating extracorporeal circulation - ischemia and apoptosis studies

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    <p>Abstract</p> <p>Background</p> <p>After coronary artery bypass grafting ischemia/reperfusion injury inducing cardiomyocyte apoptosis may occur. This surgery-related inflammatory reaction appears to be of extreme complexity with regard to its molecular, cellular and tissue mechanisms and many studies have been performed on animal models. However, finding retrieved from animal studies were only partially confirmed in humans. To investigate this phenomenon and to evaluate possible therapies in vitro, adequate human cardiomyocyte models are required. We established a tissue model of human cardiomyocytes preserving the complex tissue environment. To our knowledge human cardiac tissue has not been investigated in an experimental setup mimicking extracorporeal circulation just in accordance to clinical routine, yet.</p> <p>Methods</p> <p>Cardiac biopsies were retrieved from the right auricle of patients undergoing elective coronary artery bypass grafting before cardiopulmonary bypass. The extracorporeal circulation was simulated by submitting the biopsies to varied conditions simulating cardioplegia (cp) and reperfusion (rep) in a microperfusion chamber. Cp/rep time sets were 20/7, 40/13 and 60/20 min. For analyses of the calcium homoeostasis the fluorescent calcium ion indicator FURA-2 and for apoptosis detection PARP-1 cleavage immunostaining were employed. Further the anti-apoptotic effect of carvedilol [10 μM] was investigated by adding into the perfusate.</p> <p>Results</p> <p>Viable cardiomyocytes presented an intact calcium homoeostasis under physiologic conditions. Following cardioplegia and reperfusion a time-dependent elevation of cytosolic calcium as a sign of disarrangement of the calcium homoeostasis occurred. PARP-1 cleavage also showed a time-dependence whereas reperfusion had the highest impact on apoptosis. Cardioplegia and carvedilol could reduce apoptosis significantly, lowering it between 60-70% (p < 0.05).</p> <p>Conclusions</p> <p>Our human cardiac preparation served as a reliable cellular model tool to study apoptosis in vitro. Decisively cardiac tissue from the right auricle can be easily obtained at nearly every cardiac operation avoiding biopsying of the myocardium or even experiments on animals.</p> <p>The apoptotic damage induced by the ischemia/reperfusion stimulus could be significantly reduced by the cold crystalloid cardioplegia. The additional treatment of cardiomyocytes with a non-selective β-blocker, carvedilol had even a significantly higher reduction of apoptotis.</p

    Cardiorespiratory Fitness Modifies Influence of Sleep Problems on Cerebrospinal Fluid Biomarkers in an At-Risk Cohort

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    Background: Previous studies indicate that cardiorespiratory fitness (CRF) and sleep are each favorably associated with Alzheimer’s disease (AD) pathophysiology, including reduced amyloid-β (Aβ) and tau pathology. However, few studies have examined CRF and sleep in the same analysis. Objective: To examine the relationship between sleep and core AD cerebrospinal fluid (CSF) biomarkers among at-risk healthy late-middle-aged adults and determine whether CRF modifies this association. Methods: Seventy-four adults (age = 64.38±5.48, 68.9% female) from the Wisconsin Registry for Alzheimer’s Prevention participated. Sleep was evaluated using the Medical Outcomes Study Sleep Scale, specifically the Sleep Problems Index I (SPI), which incorporates domains of sleep disturbance, somnolence, sleep adequacy, and shortness of breath. Higher scores indicate greater sleep problems. To assess CRF, participants underwent a graded exercise test. CSF was collected via lumbar puncture, from which Aβ42, total-tau (t-tau), and phosphorylated-tau (p-tau) were immunoassayed. Regression analyses examined the association between SPI and CSF biomarkers, and the interaction between SPI and CRF on these same biomarkers, adjusting for relevant covariates. Results: Higher SPI scores were associated with greater p-tau (p = 0.027) and higher t-tau/Aβ42 (p = 0.021) and p-tau/Aβ42 (p = 0.009) ratios. Analyses revealed significant SPI*CRF interactions for t-tau (p = 0.016), p-tau (p = 0.008), and p-tau/Aβ42 (p = 0.041); with a trend for t-tau/Aβ42 (p = 0.061). Specifically, the relationship between poorer sleep and these biomarkers was significant among less fit individuals, but not among those who were more fit. Conclusion: In a late-middle-aged at-risk cohort, CRF attenuated the association between poor sleep and levels of select CSF biomarkers. This suggests fitness may play an important role in preventing AD by protecting against pathology, even in impaired sleep
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