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A study is conducted to find a possible way to leverage the extensive genome-wide association studies (GWAS) data in the search for causal variants. The association signals detected in GWAS is attributed to the presence of multiple causal variants and hence researchers need to take caution in interpreting the true effect sizes and heritability explained by the causal variants.

Genome-wide screens were used to identify copy number variation in 3812 patients with a diverse spectrum of epilepsy syndromes and in 1299 neurologically-normal controls to evaluate the role of 16p13.11 deletions and other structural variation in epilepsy disorders. The data implicated 16p13.11 and possibly other large deletions as risk factors for a wide range of epilepsy disorders and appear to point toward haploinsufficiency as a contributor to the pathogenicity of deletions.

A more in-depth analysis of key scientific and non-scientific aspects of genetic ancestry inference in academia and industry is summarized based on the data from the 2008 ASHG Ancestry Testing. It concludes with recommendations for advancing the current debate and facilitating the development of scientifically based, ethically sound, and socially attentive guidelines concerning the use of these continually evolving technologies.

The advantage that gifted children possess for free-recall tasks is due to both strategic and nonstrategic processes. Multitrial free-recall tasks show that gifted children have higher levels of recall and strategic functioning as compared to nongifted children in initial trials. Subsequent trials, however, show that the advantage of strategic functioning to memory is more significant for nongifted children. Gifted children benefit more when the strategies used are simplified. They show a greater use of active strategies than nongifted children.

Nonrandomized data exploring pancreas stereotactic body radiation therapy (SBRT) has demonstrated excellent local control rates and low toxicity. Before commencing a randomized trial investigating pancreas SBRT, standardization of prescription dose, dose constraints, simulation technique, and clinical target volume delineation are required. Specialists in radiation oncology, medical oncology, hepatobiliary surgery, and gastroenterology attended 2 consecutive Australasian Gastrointestinal Trials Group workshops in 2017 and 2018. Sample cases were discussed during workshop contact with specifically invited international speakers highly experienced in pancreas SBRT. Furthermore, sample cases were contoured and planned between workshop contact to finalize dose constraints and clinical target volume delineation. Over 2 separate workshops, consensus was reached on dose and simulation technique. The working group recommended a dose prescription of 40 Gy in 5 fractions. Treatment delivery during end-expiratory breath hold with triple-phase contrast enhanced computed tomography was recommended. In addition, dose constraints, stepwise contouring guidelines, and an anatomic atlas for pancreatic SBRT were developed. Pancreas SBRT is emerging as a promising treatment modality requiring prospective evaluation in randomized studies. This work attempts to standardize dose, simulation technique, and volume delineation to support the delivery of high quality SBRT in a multicenter study. [ABSTRACT FROM AUTHOR]

The long-term health-related quality-of-life implications of treating low-risk differentiated thyroid cancer with total thyroidectomy or hemithyroidectomy is important to patients but remains poorly understood. Using a cross-sectional mailed survey, we compared long-term health-related quality-of-life in low-risk differentiated thyroid cancer survivors treated with hemithyroidectomy to those treated with total thyroidectomy between 2005 and 2016 at a university hospital. European Organisation for Research and Treatment of Cancer Quality of Life core Questionnaire version 3.0, the supplementary Thyroid Cancer specific questionnaire module version 2.0, and the Assessment of Survivor Concerns (ASC) questionnaires were used. Our primary outcome was the global scale of quality of life. Exploratory outcomes included differences among other health-related quality-of-life items corrected for potential confounders in multivariable regression analyses. The response rate was 51.0% (270 of 529), of which 59 patients (21.9%) were treated with hemithyroidectomy. Main outcome score global quality of life did not differ between groups (76.9 hemithyroidectomy vs 77.7 total thyroidectomy, P =.450). Exploratory analyses showed hemithyroidectomy to be associated with more worry about recurrence on the Assessment of Survivor Concerns questionnaire (2.4 hemithyroidectomy vs 2.1 total thyroidectomy, P =.021). Long-term quality of life was not significantly different between low-risk differentiated thyroid cancer patients treated with total thyroidectomy compared with hemithyroidectomy. In secondary analyses, worry about recurrence appeared to be higher in individuals treated with hemithyroidectomy. These data highlight previously unreported impact of surgical regimen to the health-related quality-of-life for low-risk differentiated thyroid cancer patients. [ABSTRACT FROM AUTHOR]

Context: Efficient and accurate clinical screening for treatment-related toxicities is a critical component of optimal patient management. A number of alternate screening tools for chemotherapy-induced peripheral neuropathy (CIPN) have been proposed in response to demonstrated limitations with standard clinical screening, although their relative diagnostic value is unclear.Objectives: The aim of this study is to evaluate the relative construct validity and discriminant properties of available CIPN screening tools.Methods: Patients treated with known potentially neurotoxic therapies underwent CIPN evaluation at one or multiple timepoints (N = 316 patients; age = 56 ± 13 years). At each testing session (N = 644 testing sessions), patients were evaluated using screening tools and comprehensive CIPN assessments. Comprehensive assessments were clinician-rated (Total Neuropathy Score, reduced) or patient-reported outcome (PRO; Functional Assessment of Cancer Therapy-Gynecologic Oncology Group/Neurotoxicity questionnaire). Similarly, screening tools were clinician-rated (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE]) or PRO (Patient Neurotoxicity Questionnaire, PRO-CTCAE).Results: Analyses revealed moderate-to-high correlations between screening tools and comprehensive assessments (0.55 ≤ rho ≤ 0.75; P < 0.001) and similar discriminant properties across screening tools (P > 0.01). Screening tool grading corresponding to clinically significant (grade 2/3) vs. low-grade (grade 0/1) CIPN would correspond to greater ratings of CIPN severity by more comprehensive assessments in a predicted 77%-91% of cases (c-statistic = 0.77-0.91; P < 0.01).Conclusions: PRO screening tools provide adequate CIPN screening while avoiding potential biases demonstrated to limit currently used clinician-rated screening tools. Addition of a brief objective test did not add value to PRO screening. Up to 23% of patients would be misidentified through screening, providing quantitative evidence of the limitations of available screening tools. More extensive CIPN evaluations are critical in patients at risk of serious neurotoxicity. [ABSTRACT FROM AUTHOR]

Abstract Purpose When deforming pathology limits intraoperative plating of the mandible, three-dimensional (3D) models can be generated by digitally replacing the deformed segment of bone with an inverted segment from the contralateral unaffected mandible to adapt a reconstruction plate. The purpose of this study was to use 3D conformance analysis to evaluate the degree of accuracy of this "segmental mirroring" technique. Methods Using a pre-existing melanoma database (January 1, 2005–September 20, 2015), high-resolution computed tomography (CT) scans of the head and neck were obtained from patients without evidence of bony disease or defects involving the mandible. Using 3D software (Mimics, Materialise, Leuven, Belgium), each mandible was segmented based on four defect classes (Ic, II, IIc and III) of the Brown et al. (2016) classification system. An inverted, or "mirrored", image of each segment was digitally created and manually co-registered with the corresponding contralateral segment of the mandible. Conformance analysis was performed by calculating the root-mean-square (RMS) conformance distance and through evaluating 3D generated conformance maps. The primary outcome was degree of conformance. Data were analyzed using descriptive statistics and tests of statistical significance. The significance level was set at a p-value less than or equal to.05. Results A high degree of conformance (mean RMS < 1 mm) was observed when comparing all classes of simulated reconstruction. The closest conformance was observed for class III simulated reconstructions (mean RMS: 0.4 ± 0.2 mm). Inclusion of the condyle resulted in a reduced mean RMS conformance (class II: 0.5 ± 0.3 mm vs class IIc: 0.7 ± 0.5 mm; p = 0.01). There was no significant difference between RMS conformance distances when comparing side of simulated reconstruction. Evaluation of 3D mapping demonstrated reduced conformance with simulated reconstruction of the condyle and coronoid process. Conclusion The segmental mirroring technique can be used reliably to generate highly accurate three-dimensional models that may assist with mandibular reconstruction in circumstances where bony deformity limits intraoperative adaptation of a reconstruction plate. This technique is less accurate where pathology involves the mandibular condyle and, to a lesser degree, the coronoid process. [ABSTRACT FROM AUTHOR]

Highlights • This review provides an update about cardiac denervation in Lewy body diseases. • There is decreased storage of catecholamines in the residual terminals. • The catecholaldehyde hypothesis: DOPAL contributes catecholamine neuronal death. • Decreasing DOPAL production and oxidation might slow the neurodegeneration. • Tracking cardiac sympathetic innervation could be used in a clinical trial. Abstract This review provides an update about cardiac sympathetic denervation in Lewy body diseases. The family of Lewy body diseases includes Parkinson's disease (PD), pure autonomic failure (PAF), and dementia with Lewy bodies (DLB). All three feature intra-neuronal cytoplasmic deposits of the protein, alpha-synuclein. Multiple system atrophy (MSA), the parkinsonian form of which can be difficult to distinguish from PD with orthostatic hypotension, involves glial cytoplasmic inclusions that contain alpha-synuclein. By now there is compelling neuroimaging, neuropathologic, and neurochemical evidence for cardiac sympathetic denervation in Lewy body diseases. In addition to denervation, there is decreased storage of catecholamines in the residual terminals. The degeneration develops in a centripetal, retrograde, "dying back" sequence. Across synucleinopathies the putamen and cardiac catecholaminergic lesions seem to occur independently of each other, whereas non-motor aspects of PD (e.g., anosmia, dementia, REM behavior disorder, OH) are associated with each other and with cardiac sympathetic denervation. Cardiac sympathetic denervation can be caused by synucleinopathy in inherited PD. According to the catecholaldehyde hypothesis, 3,4-dihydroxyphenylacetaldehyde (DOPAL), an intermediary metabolite of dopamine, causes or contributes to the death of catecholamine neurons, especially by interacting with proteins such as alpha-synuclein. DOPAL oxidizes spontaneously to DOPAL-quinone, which probably converts alpha-synuclein to its toxic oligomeric form. Decreasing DOPAL production and oxidation might slow the neurodegenerative process. Tracking cardiac sympathetic innervation over time could be the basis for a proof of principle experimental therapeutics trial targeting DOPAL. [ABSTRACT FROM AUTHOR]

The circumplanetary flow of Io's [SO.sub.2] atmosphere is modeled using the direct simulation Monte Carlo (DSMC) method. This flow develops as gas sublimates from [SO.sub.2] frost in the warm subsolar region and flows toward the colder night-side, where it condenses. The axisymmetric model presented extends from the subsolar point past the terminator into the night-side. The remaining portion of the night-side atmosphere is assumed to be static. The DSMC method solves the fully viscous and compressible, non-local thermal equilibrium (non-LTE), rarefied flow problem by statistically extrapolating from the motions and collisions of representative molecules. Heating due to neutral plasma bombardment and cooling by non-LTE radiation are modeled. Quantities of a second, non-condensible gas are also added to simulate the possible effects of [H.sub.2]S or [O.sub.2] in the atmosphere. It is found that, except in the subsolar region, the flows are predominately rarefied. For high subsolar temperatures, the atmospheric flow may become supersonic and then decelerate through a diffuse, oblique shock upstream of the terminator. Appreciable local condensation occurs below the shock while the atmosphere above the shock is significantly inflated. These hydrodynamic features, among others, have implications for the observations of frost cover, atmospheric flow, and the ionosphere. [C] 2000 Academic Press Key Words: Io; atmospheres, dynamics; atmospheres, structure; satellites, atmospheres; satellites of Jupiter.