Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer

Diversification into novel habitats in the Africa clade of Dioscorea (Dioscoreaceae): erect habit and elephant’s foot tubers

Background: Dioscorea is a widely distributed and highly diversified genus in tropical regions where it is represented by ten main clades, one of which diversified exclusively in Africa. In southern Africa it is characterised by a distinct group of species with a pachycaul or “elephant’s foot” structure that is partially to fully exposed above the substrate. In contrast to African representatives of the genus from other clades, occurring mainly in forest or woodland, the pachycaul taxa and their southern African relatives occur in diverse habitats ranging from woodland to open vegetation. Here we investigate patterns of diversification in the African clade, time of transition from forest to more open habitat, and morphological traits associated with each habitat and evaluate if such transitions have led to modification of reproductive organs and mode of dispersal. Results: The Africa clade originated in the Oligocene and comprises four subclades. The Dioscorea buchananii subclade (southeastern tropical Africa and South Africa) is sister to the East African subclade, which is respectively sister to the recently evolved sister South African (e. g., Cape and Pachycaul) subclades. The Cape and Pachycaul subclades diversified in the east of the Cape Peninsula in the mid Miocene, in an area with complex geomorphology and climate, where the fynbos, thicket, succulent karoo and forest biomes meet. Conclusions: Diversification out of forest is associated with major shifts in morphology of the perennial tuber (specifically an increase in size and orientation which presumably led them to become pachycaul) and rotation of stem (from twining to non-twining). The iconic elephant's foot morphology, observed in grasslands and thicket biomes, where its corky bark may offer protection against fire and herbivory, evolved since mid Miocene. A shift in pollination trait is observed within the forest, but entry into open habitat does not show association with reproductive morphology, except in the seed wing, which has switched from winged all round the seed margin to just at the base or at the apex of it, or has been even replaced by an elaiosome

Addressing Surgical Instrument Oversupply: A Focused Literature Review and Case-Study in Orthopedic Hand Surgery

Background Instrument oversupply drives cost in the operating room (OR). We review previously reported methodologies for surgical instrument reduction and report a pilot methodology for optimizing instrument supply via ethnographic instrument tracking of thumb carpometacarpal (CMC) arthroplasties. Additionally, we report a cost analysis of instrument oversupply and potential savings of tray optimization methods. Methods Instrument utilization was tracked over 8 CMC arthroplasties conducted by 2 surgeons at an ambulatory surgery center of a large academic hospital. An optimized supply methodology was designed. A cost analysis was conducted using health-system-specific data and previously published research. Results After tracking instrument use in 8 CMC arthroplasties, a cumulative total of 59 out of the 120 instruments in the Hand &amp; Foot (H&amp;F) tray were used in at least 1 case. Two instruments were used in all cases, and another 20 instruments were used in at least 50% of the cases. Using a reduced tray with 59 instruments, potential cost savings for tray reduction in 60 cases were estimated to be $2086 without peel-packing and$2356 with peel-packing. The estimated cost savings were lower than those reported in literature due to a reduced scope and exclusion of OR time cost in the analysis. Conclusions Instrument oversupply drives cost at our institution’s ambulatory surgery center. Ethnography is a cost-effective method to track instrument utilization and determine optimal tray composition for small services but is not scalable to large health systems. The time and cost required to observe sufficient surgeries to enable supply reduction to motivate the need for more efficient methods to determine instrument utility. </jats:sec