Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects

Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Studies of electron exchange collisions and polarized electron production in a flowing helium afterglow

A flowing helium afterglow apparatus has been used to study thermal-energy electron exchange collisions between spin-polarized electrons and O\sb2 or NO molecules. Penning ionization of CO\sb2 by spin-polarized He(2\sp3S) metastable atoms is used to produce electrons which retain the spin orientation of the metastables, and which rapidly thermalize in the CO\sb2. The reactant gas (O\sb2 or NO), when introduced into the flowstream, causes a decrease in the electron spin-polarization. The electrons are then extracted from the flowtube for measurement of the polarization they retain. The rate constant for the reaction e\sp{-}(\uparrow) + X $\to$ e\sp {-}(\downarrow) + X can then be determined, given the amount of polarization decrease, reactant-gas density, and reaction time. The rates are found to be k(O\sb2) = (8 $\pm$ 3.5) x 10\sp{-11} cm\sp3/sec and k(NO) = (9 $\pm$ 4) x 10\sp{-11} cm\sp3/sec. An upper limit to the electron attachment rate for formation of an excited negative ion is derived from these measurements, and the contribution of exchange to the total scattering is discussed. In addition, a new, non-invasive technique for measuring electron-drift velocity in the flowtube is describe. Modifications of the afterglow apparatus and use of laser radiation for He(2\sp3S) spin-orientation enable it to produce an electron beam having moderate to high current and high spin polarization. Polarizations of 80% are achieved for currents up to 1$\mu$A, with 60% polarization retained at 25$\mu$A. This compares favorably with other polarized electron sources, making the afterglow apparatus a candidate for use as a beam source in high-energy electron accelerators

Energy dependent electron polarization studies of penning ionization channels

No page 9, 12, 13, 16, 18, 21-23, 26, 30, 32, 34, 36, 45-47, 49, 53, 65Penning ionization reactions have been studied in a flowing afterglow apparatus to explore the contributions of autoionizing channels in reactions of spin-polarized He(23S) with alkali atoms. Spin polarization analysis of the Penning electrons has allowed us to identify a significant autoionizing channel for rubidium, and no such contribution for cesium and potassium. Using the results of this study, a model of the reaction process was constructed to predict the Penning electron polarization produced in He(23S) -- polarized rubidium reactions. An attempt to measure this polarization was made, but it became clear in the course of the experiment that success is possible only with a substantially upgraded apparatus. A simultaneous energy and polarization measurement of the electrons produced in reactions of polarized He(23S) with 2 has also been attempted. This initial experiment was unsuccessful but indicates that results can be obtained, again given an improved apparatus

Reporting Outcomes

How does a neurosurgeon know if their treatments work? What role does this play in how the mind of the neurosurgeon makes patient care decisions? An essential part of academic medicine has always been the critical evaluation of patient outcomes. Without this, it is impossible to understand whether a (surgical) treatment was beneficial for a patient. How outcome is measured, however, has changed considerably several times over the last decades

A Reaction Rate Study in Hydrofluoric Acid of the Dissolution of Titanium and the Alpha Solid Solution of Oxygen in Titanium

Studies were conducted into the mechanism of dissolution in hydrofluoric-hydrochloric acid mixtures of titanium and of alpha solid solution specimens of oxygen in titanium. Special precautions were taken to preserve the trivalent state of titanium. For titanium a rate order of 0.76 and an activation energy of 6.9 ± 0.5 kcal was found and for titanium in TiO x a rate order of 0.83 and an activation energy of 6.6 ± 0.5 kcal. Furthermore, the oxygen content of TiO x, within the range studied, had no effect on the rate of hydrogen evolution; all specimens evolved hydrogen at the same fixed rate per unit area for a given temperature. It is concluded that a diffusionally controlled reaction can best explain the results. © 1961

Complications, Costs, and Quality Outcomes of Patients Undergoing Cervical Deformity Surgery with Intraoperative BMP Use

STUDY DESIGN An epidemiological study using national administrative data from the MarketScan database. OBJECTIVE To identify the impact of bone morphogenetic protein (BMP) on postoperative outcomes in patients undergoing adult cervical deformity (ACD) surgery. SUMMARY OF BACKGROUND DATA BMP has been shown to stimulate bone growth and improve fusion rates in spine surgery. However, the impact of BMP on reoperation rates and postoperative complication rate is controversial. METHODS We queried the MarketScan database to identify patients who underwent ACD surgery from 2007-2015. Patients were stratified by BMP use in the index operation. Patients under 18 and those with any history of tumor or trauma were excluded. Baseline demographics and comorbidities, postoperative complication rates and reoperation rates were analyzed. RESULTS A total of 13,549 patients underwent primary ACD surgery, of which 1155 (8.5%) had intraoperative BMP use. The overall 90-day complication rate was 27.6% in the non-BMP cohort and 31.1% in the BMP cohort (p < 0.05). Patients in the BMP cohort had longer average length of stay (4.0 days vs 3.7 days, p < 0.05) but lower revision surgery rates at 90-days (14.5% vs 28.3%, p < 0.05), 6 months (14.9% vs 28.6%, p < 0.05), 1 year (15.7% vs 29.2%, p < 0.05), and 2 years (16.5% vs 29.9%, p < 0.05) postoperatively. BMP use was associated with higher payments throughout the 2-year follow-up period ($107,975 vs$97,620, p < 0.05). When controlling for baseline group differences, BMP use independently increased the odds of postoperative complication (OR 1.22, 95% CI 1.1 - 1.4) and reduced the odds of reoperation throughout 2-years of follow-up (OR 0.49, 95% CI 0.4 - 0.6). CONCLUSIONS Intraoperative BMP use has benefits for fusion integrity in ACD surgery but is associated with increased postoperative complication rate. Spine surgeons should weigh these benefits and drawbacks to identify optimal candidates for BMP use in ACD surgery. LEVEL OF EVIDENCE 3