The GenoChip: A New Tool for Genetic Anthropology

The Genographic Project is an international effort aimed at charting human migratory history. The project is nonprofit and nonmedical, and, through its Legacy Fund, supports locally led efforts to preserve indigenous and traditional cultures. Although the first phase of the project was focused on uniparentally inherited markers on the Y-chromosome and mitochondrial DNA (mtDNA), the current phase focuses on markers from across the entire genome to obtain a more complete understanding of human genetic variation. Although many commercial arrays exist for genome-wide single-nucleotide polymorphism (SNP) genotyping, they were designed for medical genetic studies and contain medically related markers that are inappropriate for global population genetic studies. GenoChip, the Genographic Project’s new genotyping array, was designed to resolve these issues and enable higher resolution research into outstanding questions in genetic anthropology. TheGenoChip includes ancestry informativemarkers obtained for over 450 human populations, an ancient human (Saqqaq), and two archaic hominins (Neanderthal and Denisovan) and was designed to identify all knownY-chromosome andmtDNAhaplogroups. The chip was carefully vetted to avoid inclusion ofmedically relevant markers. To demonstrate its capabilities, we compared the FST distributions of GenoChip SNPs to those of two commercial arrays. Although all arrays yielded similarly shaped (inverse J) FST distributions, the GenoChip autosomal and X-chromosomal distributions had the highestmean FST, attesting to its ability to discern subpopulations. The chip performances are illustrated in a principal component analysis for 14 worldwide populations. In summary, the GenoChip is a dedicated genotyping platform for genetic anthropology. With an unprecedented number of approximately 12,000 Y-chromosomal and approximately 3,300 mtDNA SNPs and over 130,000 autosomal and X-chromosomal SNPswithout any known health,medical, or phenotypic relevance, the GenoChip is a useful tool for genetic anthropology and population genetics

Definitions and pathophysiology of vasoplegic shock.

Vasoplegia is the syndrome of pathological low systemic vascular resistance, the dominant clinical feature of which is reduced blood pressure in the presence of a normal or raised cardiac output. The vasoplegic syndrome is encountered in many clinical scenarios, including septic shock, post-cardiac bypass and after surgery, burns and trauma, but despite this, uniform clinical definitions are lacking, which renders translational research in this area challenging. We discuss the role of vasoplegia in these contexts and the criteria that are used to describe it are discussed. Intrinsic processes which may drive vasoplegia, such as nitric oxide, prostanoids, endothelin-1, hydrogen sulphide and reactive oxygen species production, are reviewed and potential for therapeutic intervention explored. Extrinsic drivers, including those mediated by glucocorticoid, catecholamine and vasopressin responsiveness of the blood vessels, are also discussed. The optimum balance between maintaining adequate systemic vascular resistance against the potentially deleterious effects of treatment with catecholamines is as yet unclear, but development of novel vasoactive agents may facilitate greater understanding of the role of the differing pathways in the development of vasoplegia. In turn, this may provide insights into the best way to care for patients with this common, multifactorial condition

Therapeutic hypothermia: is it effective for non-VF/VT cardiac arrest?

Since 2003, therapeutic hypothermia (TH) is recommended for all comatose survivors after cardiac arrest (CA) due to VF/VT. However, only 25\u201330 % of CA patients have VF/VT as the initial recorded cardiac rhythm, and this percentage has further decreased in recent years. The benefit of TH for non-VF/VT CA are controversial. Methods: Meta-analysis. All studies evaluating the benefit of TH in adult comatose survivors from CA were included. No limitations of study design, publication date and publication status were imposed. Resuts: Two randomised trials and 15 observational studies were identified. Neither of the randomised trials was specifically designed to assess the benefit of TH in this patient population.TH-treated patients had a higher 6-mo survival rate than controls (5/22 vs. 2/22; risk ratio [RR] for mortality 0.85 [0.65\u20131.11] p = 0.24). Results of the 15 observational studies (12 reporting survival to discharge on 1,581 patients, and 13 reporting neurological outcome on 1,998 patients) showed that TH was associated to a significant reduction in the RR for both hospital mortality (0.88 [0.82\u20130.95]) and poor neurological outcome (0.95 [0.90\u20130.99]). However, several studies suggested no effect or possible harm from TH. Conclusions: in patients resuscitated from non-VF/VT CA, use of TH is associated with a significant decrease in both hospital mortality and neurological outcome. Observed heterogeneity in study results may be explained by differences in case mix or cooling protocols and the presence of uncontrolled confounders, being most of the studies observational