Variant calling in low-coverage whole genome sequencing of a Native American population sample.

BACKGROUND: The reduction in the cost of sequencing a human genome has led to the use of genotype sampling strategies in order to impute and infer the presence of sequence variants that can then be tested for associations with traits of interest. Low-coverage Whole Genome Sequencing (WGS) is a sampling strategy that overcomes some of the deficiencies seen in fixed content SNP array studies. Linkage-disequilibrium (LD) aware variant callers, such as the program Thunder, may provide a calling rate and accuracy that makes a low-coverage sequencing strategy viable. RESULTS: We examined the performance of an LD-aware variant calling strategy in a population of 708 low-coverage whole genome sequences from a community sample of Native Americans. We assessed variant calling through a comparison of the sequencing results to genotypes measured in 641 of the same subjects using a fixed content first generation exome array. The comparison was made using the variant calling routines GATK Unified Genotyper program and the LD-aware variant caller Thunder. Thunder was found to improve concordance in a coverage dependent fashion, while correctly calling nearly all of the common variants as well as a high percentage of the rare variants present in the sample. CONCLUSIONS: Low-coverage WGS is a strategy that appears to collect genetic information intermediate in scope between fixed content genotyping arrays and deep-coverage WGS. Our data suggests that low-coverage WGS is a viable strategy with a greater chance of discovering novel variants and associations than fixed content arrays for large sample association analyses.

Abaloparatide Real-World Patient Experience Study.

Despite the availability of various osteoporosis treatments, adherence remains suboptimal. One contributing factor may be patient experience with therapy. This US, multicenter, combined retrospective chart review and patient questionnaire study included postmenopausal women at high risk for fracture and is the first study to describe real-world patient experience with abaloparatide (ABL) injection. Eight geographically diverse secondary care sites in the United States participated (n = 193). Mean ± SD age was 67.4 ±8.62 years. Most patients (86%) were satisfied with the ABL regimen, especially with ease of preparation (82%), ease of storage (87%), and storage convenience (89%), an attribute 83% of the patients thought was important. The majority of patients reported complete satisfaction with the ABL regimen allowing for their ability to conduct daily activities (85%) and convenience to fit into their daily schedule (84%). All reported taking ABL as directed, by injection in the lower abdomen, and 83% of patients reported medium or high adherence. Patients were satisfied with the needle size (76% completely satisfied), and 93% reported never deliberately missing a dose. Although injecting medication (18%) and higher out-of-pocket costs (17%) were deemed the most bothersome attributes, the majority (69%) noted their healthcare team understands how osteoporosis impacts their lives. In multivariable analyses, ease of preparation (OR = 2.62; 95% CI, 1.01-6.81; p = 0.048) and fracture history (OR = 1.72; 95% CI, 1.03-2.86; p = 0.037) were significantly associated with overall satisfaction. Ease of preparation was a predictor of higher satisfaction with treatment convenience (coefficient = 13.60; 95% CI, 8.08-19.12; p = 0.00). Remembering to take the medication was a significant predictor of self-reported adherence (OR = 16.66; 95% CI, 3.30-84.24; p = 0.001). In conclusion, the majority of patients were satisfied with ABL and found it convenient/easy to prepare and store. High self-reported adherence may be associated with positive patient experience including ease of use and adequate support from healthcare providers. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Synthesis of first row transition metal selenomaltol complexes.

We report an efficient, one-step synthesis of the chelator 3-hydroxy-2-methyl-4-selenopyrone (selenomaltol). Complexes of selenomaltol with Fe(iii), Ni(ii), Cu(ii) and Zn(ii) have been prepared and studied by NMR, X-ray crystallography, cyclic voltammetry, EPR and electronic absorption. The Ni(ii) and Cu(ii) complexes show chemically reversible oxidations which are suggested to be ligand-based. Nuclear independent chemical shifts (NICS) analysis is used to compare aromaticity of the heterocyclic rings of selenomaltol and its chelates. The compounds described here should significantly expand the scope and utility of unusual O,Se-donor chelates.

OpenMx: An Open Source Extended Structural Equation Modeling Framework.

OpenMx is free, full-featured, open source, structural equation modeling (SEM) software. OpenMx runs within the R statistical programming environment on Windows, Mac OS-X, and Linux computers. The rationale for developing OpenMx is discussed along with the philosophy behind the user interface. The OpenMx data structures are introduced - these novel structures define the user interface framework and provide new opportunities for model specification. Two short example scripts for the specification and fitting of a confirmatory factor model are next presented. We end with an abbreviated list of modeling applications available in OpenMx 1.0 and a discussion of directions for future development.

[Implementation of thrombolysis in acute stroke--10-year results of the Innsbruck stroke registry]. / Einsatz der Thrombolyse beim akut ischämischen Schlaganfall : 10-Jahres-Ergebnisse an der Stroke Unit Innsbruck.

BACKGROUND: Randomized controlled trials have yielded evidence for the efficacy and safety of intravenous alteplase in the therapy of acute ischemic stroke. A large patient registry has recently confirmed the safe implementation of this therapy in the clinical routine setting. METHODS: Between January 1998 and December 2007 302 stroke patients were treated with 0.9 mg/kg rt-PA at the stroke unit of the Innsbruck University Hospital. Severity and circumstances of the stroke event, indicators of pre- and intrahospital management as well as safety and outcome at three months were prospectively assessed in the local thrombolysis database. RESULTS: The number of patients receiving intravenous thrombolysis increased continuously from 2 patients in 1998 to 67 in 2007 and 87 patients in 2008. 43% of our patients were females. The median age and NIHSS-score on admission was 67 and 16, respectively. The mean onset-to-needle time decreased from 171 min to 110 min--mainly due to a substantial shortening of the door-to-needle time from 105 min to 45 min. A proportion of 41% of our patients were treated in the main working time while 59% received rt-PA during night and weekend service. A total of 38% of our patients were functionally independent at three months (mRS 0-2). Once considering the high initial stroke severity in our patient series and correcting the NIHSS scores to levels usually seen in randomized control trials and patient registries, 56% of our patients would reach a good outcome (mRS 0-2). The rate of symptomatic intracranial bleedings was low at 6.3%. CONCLUSION: Our data reinforce that intravenous thrombolysis is safe in the treatment of acute ischemic stroke in clinical routine setting. Establishment of modern stroke services and the implementation of structural operating procedures have contributed to an increase in the number of treated patients and a parallel decrease in door-to-needle time at our hospital. Widespread educational programs in the general community, introduction of optimized pre-hospital triage algorithms as well as the potential extension of the 3-hour window to 4.5 hours all are suitable measures to further extend the benefit of i.v. thrombolysis to large proportion of stroke patients.

[Juvenile stroke--results from the Austrian Stroke Registry]. / Juveniler Schlaganfall in Osterreich--Daten aus dem Osterreichischen Schlaganfallregister.

In recent years, many aspects of juvenile stroke have been addressed in medium-sized case series. We have analyzed stroke severity, etiology, risk factors, and outcome in different age groups in the large dataset of the Austrian Stroke Unit Registry. In the nationwide Austrian Stroke Unit Registry 13,440 men and women with ischemic stroke or transient ischemic attack were recorded between March 2003 and February 2007. A number of important disease characteristics were documented by a stroke specialist upon admission of a patient and at discharge from the stroke unit and during a 3-month follow-up interview. A total of 749 patients (5.6%) were 18 to 45 years old and 1895 (14.1%) 18 to 55 years. Arterial dissection and cardiac/paradoxical embolism were the most common causes of stroke up to an age of 45. With a steeply increasing frequency of standard vascular risk factors, micro- and macroangiopathic causes of stroke substantially gain weight after the fourth decade of life. At 3-month follow-up, good clinical outcome (mRS 0-2) and death were 88.3% and 1.4% in the young (

The new diffractometer for surface X-ray diffraction at beamline BL9 of DELTA.

The experimental endstation of the hard X-ray beamline BL9 of the Dortmund Electron Accelerator is equipped with a Huber six-circle diffractometer. It is dedicated to grazing-incidence X-ray diffraction and X-ray reflectivity experiments on solid surfaces and thin films as well as to powder diffraction measurements. A new set-up for grazing-incidence X-ray scattering of liquids has been built up using a silicon mirror to reflect the incident X-ray to the liquid surface at angles of incidence around the critical angle of total reflection of the sample. X-ray reflectivity measurements of a polymer film and grazing-incidence X-ray diffraction measurements of an epitaxically grown Gd40Y60 film, an oxidized surface of Fe-15at.%Al alloy and aqueous salt solutions are presented and discussed.