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Background: The formation of alpha-synuclein aggregates may be a critical event in the pathogenesis of multiple system atrophy (MSA). However, the role of this gene in the aetiology of MSA is unknown and untested.Method: The linkage disequilibrium (LD) structure of the alpha-synuclein gene was established and LD patterns were used to identify a set of tagging single nucleotide polymorphisms (SNPs) that represent 95% of the haplotype diversity across the entire gene. The effect of polymorphisms on the pathological expression of MSA in pathologically confirmed cases was also evaluated.Results and Conclusion: In 253 Gilman probable or definite MSA patients, 457 possible, probable, and definite MSA cases and 1472 controls, a frequency difference for the individual tagging SNPs or tag-defined haplotypes was not detected. No effect was observed of polymorphisms on the pathological expression of MSA in pathologically confirmed cases. [ABSTRACT FROM AUTHOR]

Post-curing is intended to improve strength, elevate glass transition, and reduce residual stress and outgassing in thermosets. Also, experiments indicate post-curing temperatures lead to ether crosslinks and backbone dehydration. These results informed molecular dynamics methods to represent them and compare the resulting thermomechanical effects. Diglycidyl ether of bisphenol A (DGEBA)-diamino diphenyl sulfone (DDS) systems were examined. Independent variables were resin length, stoichiometry, and reaction type (i.e., amine addition, etherification, and dehydration). Etherification affected excess epoxide systems most. These were strengthened and became strain hardening. Systems which were both etherified and dehydrated were most consistent with results of post-curing experiments. Dehydration stiffened and strengthened systems with the longer resin molecules due to their intermediate hydroxyl groups for crosslinking. Changes in the concavity of functions fit to the specific volume versus temperature were used to detect thermal transitions. Etherification generally increased transition temperatures. Dehydration resulted in more transitions., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

A novel method to combine quantum mechanics (QM) and molecular mechanics has been developed to accurately and efficiently account for covalent bond breaking in polymer systems under high strain without the use of predetermined break locations. Use of this method will provide a better fundamental understanding of the mechano-chemical origins of fracture in thermosets. Since classical force fields cannot accurately account for bond breaking, and QM is too demanding to simulate large systems, a hybrid approach is required. In the method presented here, strain is applied to the system using a classical force field, and all bond lengths are monitored. When a bond is stretched past a threshold value, a zone surrounding the bond is used in a QM energy minimization to determine which, if any, bonds break. The QM results are then used to reconstitute the system to continue the classical simulation at progressively larger strain until another QM calculation is triggered. In this way, a QM calculation is only computed when and where needed, allowing for efficient simulations. A robust QM method for energy minimization has been determined, as well as appropriate values for the QM zone size and the threshold bond length. Compute times do not differ dramatically from classical molecular mechanical simulations.

The use of voluntary approaches to achieve conservation goals is becoming increasingly popular. Nevertheless, few researchers have quantitatively evaluated their efficacy. In 1998 industry, government agencies, and nongovernmental organizations established a voluntary conservation program for whale watching in the northeast region of the United States, with the intent to avoid collisions with and harassment of endangered whales by commercial and recreational whale-watching vessels. One important aspect of the program was the establishment of 3 speed zones within specific distances of whales. We wanted to determine the level of compliance with this aspect of the program to gauge its efficacy and gain insights into the effectiveness of voluntary measures as a conservation tool. Inconspicuous observers accompanied 46 commercial whale-watching trips from 12 companies in 2003 (n= 35) and 2004 (n= 11). During each trip, vessel position and speed were collected at 5-second intervals with a GPS receiver. Binoculars with internal laser rangefinders and digital compasses were used to record range and bearing to sighted whales. We mapped whale locations with ArcGIS. We created speed-zone buffers around sighted whales and overlaid them with vessel-track and speed data to evaluate compliance. Speeds in excess of those recommended by the program were considered noncompliant. We judged the magnitude of noncompliance by comparing a vessel's maximum speed within a zone to its maximum recorded trip speed. The level of noncompliance was high (mean 0.78; company range 0.74-0.88), some companies were more compliant than others (p= 0.02), noncompliance was significantly higher in zones farther from whales (p < 0.001), and operators approached the maximum speed capabilities of their vessel in all zones. The voluntary conservation program did not achieve the goal of substantially limiting vessel speed near whales. Our results support the need for conservation programs to have quantifiable metrics and frequent evaluation to ensure efficacy.

The recent identification of fragile X-associated tremor ataxia syndrome (FXTAS) associated with premutations in the FMR1 gene and the possibility of clinical overlap with multiple system atrophy (MSA) has raised important questions, such as whether genetic testing for FXTAS should be performed routinely in MSA and whether positive cases might affect the specificity of current MSA diagnostic criteria. We genotyped 507 patients with clinically diagnosed or pathologically proven MSA for FMR1 repeat length. Among the 426 clinically diagnosed cases, we identified four patients carrying FMR1 premutations (0.94%). Within the subgroup of patients with probable MSA-C, three of 76 patients (3.95%) carried premutations. We identified no premutation carriers among 81 patients with pathologically proven MSA and only one carrier among 622 controls (0.16%). Our results suggest that, with proper application of current diagnostic criteria, FXTAS is very unlikely to be confused with MSA. However, slowly progressive disease or predominant tremor are useful red flags and should prompt the consideration of FXTAS. On the basis of our data, the EMSA Study Group does not recommend routine FMR1 genotyping in typical MSA patients.

A functional --1021C --> T polymorphism in the dopamine beta-hydroxylase gene has been demonstrated to regulate plasma DBH activity. We report that individuals with genetically determined low serum DBH activity (genotype T/T) have protection against Parkinson's disease (p = 0.01). In particular, we observed an underrepresentation of the T/T genotype odds ratio = 0.46 (CI = 0.27-0.8). Rather than identifying a haplotype, or a marker in linkage disequilibrium with the risk variant, this to our knowledge is the first report directly linking PD susceptibility with a proven functional variant.

Background: In the Lübeck region, as is usual in Germany, hospital-based emergency physicians are called for outside emergencies. They evaluate and stabilize patients and transfer them to hospital facilities of their choice (no emergency department system). These physicians are mainly anesthesiologists, surgeons, and internists-not pediatricians. Numerous quality management studies have shown an overall excellent performance of this system, but it has not been evaluated for pediatric emergencies., Patients and Methods: In a prospective, observational study conducted over a 1-year period, all pediatric emergencies (patient age < 15 y) treated by the emergency physician service were studied. A syllabus with standards of care for children with trauma, obstructive airway disease, and seizures was distributed. In accordance with this syllabus, the actions taken were documented by the emergency physicians, and the cases were documented as life threatening or not and were classified as "trauma," "obstructive airway disease," "seizures," or "other" by the admitting pediatric intensivists and surgeons. The admitting attending physician compared these data and evaluated whether the standard management required by the syllabus was followed., Results: A total of 422 pediatric cases out of 11,605 emergencies (3.5%) were recorded (147 [34.8%] trauma patients, 41 [9.7%] patients with obstructive airway disease, and 108 [25.6%] patients with seizures). Of the pediatric patients, 20.5% had life-threatening conditions; three children died before arrival, and the others required treatment in the intensive care unit. In 25% of trauma patients, deficiencies in primary treatment were observed: no documentation of neurologic status in 10.6%, no cervical immobilization in 15% of head trauma patients, and no adequate analgesia in 7%. In 25% of seizure patients, neurologic status was not documented, although treatment was in accordance with the standard of care. The worst results were observed in infants with obstructive airway disease: no documentation of oxygen saturation in 71.4%, no oxygen therapy despite hypoxemia in seven of 12 patients, and overall therapy not in accordance with the standard of care in 50%., Conclusions: The high quality of the emergency physician service documented for adults is not reproduced in the pediatric population. Trauma and seizures with similarities to adult cases are handled in a fair manner. However, the most important pediatric diagnostic entity of obstructive airway disease is often not treated adequately. Intensified educational programs for emergency physicians are warranted.