Accuracy of screening women at familial risk of breast cancer without a known gene mutation:individual patient data meta-analysis

Introduction Women with a strong family history of breast cancer (BC) and without a known gene mutation have an increased risk of developing BC. We aimed to investigate the accuracy of screening using annual mammography with or without magnetic resonance imaging (MRI) for these women outside the general population screening program. Methods An individual patient data (IPD) meta-analysis was conducted using IPD from six prospective screening trials that had included women at increased risk for BC: only women with a strong familial risk for BC and without a known gene mutation were included in this analysis. A generalised linear mixed model was applied to estimate and compare screening accuracy (sensitivity, specificity and predictive values) for annual mammography with or without MRI. Results There were 2226 women (median age: 41 years, interquartile range 35–47) with 7478 woman-years of follow-up, with a BC rate of 12 (95% confidence interval 9.3–14) in 1000 woman-years. Mammography screening had a sensitivity of 55% (standard error of mean [SE] 7.0) and a specificity of 94% (SE 1.3). Screening with MRI alone had a sensitivity of 89% (SE 4.6) and a specificity of 83% (SE 2.8). Adding MRI to mammography increased sensitivity to 98% (SE 1.8, P &lt; 0.01 compared to mammography alone) but lowered specificity to 79% (SE 2.7, P &lt; 0.01 compared with mammography alone). Conclusion In this population of women with strong familial BC risk but without a known gene mutation, in whom BC incidence was high both before and after age 50, adding MRI to mammography substantially increased screening sensitivity but also decreased its specificity.</p

Inner Ear Malformations in Congenital Deafness Are Not Associated with Increased Risk of Breech Presentation

Background: There is speculation that an immature vestibular system may be associated with breech presentation at delivery. Our aim was to determine whether syndromes with congenital inner ear malformations were accompanied by a higher frequency of breech presentation/malpresentations than in the general population (2%−3%). Methods: A review was conducted for published literature using PubMed/MEDLINE (1936–2016), to determine frequency of breech presentation and transverse lie in cases with congenital deafness (Michel aplasia, Wildervanck syndrome, Mondini-Alexander dysplasia, Waardenburg syndrome, CHARGE syndrome, Large vestibular aqueductal syndrome, Pendred syndrome, Oculo-aurico-vertebral spectrum, Jervel and Lange-Nielsen syndrome, Usher syndrome, and Scheibe dysplasia) and vestibular nerve aplasia. Results: Identified were total of 122 cases. The frequency of breech presentation was 1.64%, and of transverse lie 1.64%, giving a total of 3.28% malpresentations. Conclusion: The results of the study suggest that congenital malformations of the vestibular apparatus are not associated with the increased risk of breech presentation at delivery

Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis.

BACKGROUND: Increased circulating plasma urate concentration is associated with an increased risk of coronary heart disease, but the extent of any causative effect of urate on risk of coronary heart disease is still unclear. In this study, we aimed to clarify any causal role of urate on coronary heart disease risk using Mendelian randomisation analysis. METHODS: We first did a fixed-effects meta-analysis of the observational association of plasma urate and risk of coronary heart disease. We then used a conventional Mendelian randomisation approach to investigate the causal relevance using a genetic instrument based on 31 urate-associated single nucleotide polymorphisms (SNPs). To account for potential pleiotropic associations of certain SNPs with risk factors other than urate, we additionally did both a multivariable Mendelian randomisation analysis, in which the genetic associations of SNPs with systolic and diastolic blood pressure, HDL cholesterol, and triglycerides were included as covariates, and an Egger Mendelian randomisation (MR-Egger) analysis to estimate a causal effect accounting for unmeasured pleiotropy. FINDINGS: In the meta-analysis of 17 prospective observational studies (166 486 individuals; 9784 coronary heart disease events) a 1 SD higher urate concentration was associated with an odds ratio (OR) for coronary heart disease of 1·07 (95% CI 1·04-1·10). The corresponding OR estimates from the conventional, multivariable adjusted, and Egger Mendelian randomisation analysis (58 studies; 198 598 individuals; 65 877 events) were 1·18 (95% CI 1·08-1·29), 1·10 (1·00-1·22), and 1·05 (0·92-1·20), respectively, per 1 SD increment in plasma urate. INTERPRETATION: Conventional and multivariate Mendelian randomisation analysis implicates a causal role for urate in the development of coronary heart disease, but these estimates might be inflated by hidden pleiotropy. Egger Mendelian randomisation analysis, which accounts for pleiotropy but has less statistical power, suggests there might be no causal effect. These results might help investigators to determine the priority of trials of urate lowering for the prevention of coronary heart disease compared with other potential interventions. FUNDING: UK National Institute for Health Research, British Heart Foundation, and UK Medical Research Council

A high-resolution study of particle export in the southern South China Sea based on Th-234 : U-238 disequilibrium

During a spring intermonsoon cruise in 2004, depth profiles of total and particulate Th-234 in the upper 100 m were collected at 36 stations in the southern South China Sea (SCS), covering a surface area of similar to 1.0 x 10(6) km(2). Thorium-234 was sampled by using a modified small-volume MnO2 co-precipitation technique, which allows mapping the Th-234 distribution with a high spatial resolution. A stratified structure of Th-234/U-238 disequilibria was generally observed in the upper 100 m water column, suggesting that the euphotic zone of the southern SCS in this season can be separated into two layers: an upper layer with low export production rates and a lower layer with high export production rates. At the same time, we observed extensive zones of Th-234 excess within the euphotic layer, which is possibly due to intense remineralization of particulate matter. Particulate organic carbon (POC) export was estimated from a three-dimensional steady state model of Th-234 fluxes combined with measurements of the POC/Th-234 ratio on suspended particles. The POC export for this region varied from a low of -10.7 +/- 1.5 mmolC m(-2) d(-1) to a high of 12.6 +/- 1.1 mmolC m(-2) d(-1), with an average of 3.8 +/- 4.0 mmolC m(-2) d(-1). A negative flux of POC export is interpreted as the result of lateral input of particulate matter from nearby waters. Regional patterns in POC export show enhanced fluxes along the western and southern boundaries of the study region, and a "tongue'' of low export extending northwestward from similar to 7 degrees N 116 degrees E to similar to 10 degrees N 111 degrees E. This geographic distribution is consistent with the overall surface circulation pattern of the southern SCS in this season

Provenance signature of changing plate boundary conditions along a convergent margin: Detrital Record of Spreading-Ridge and Flat-Slab Subduction Processes, Cenozoic Forearc Basins, Alaska

Cenozoic strata from forearc basins in southern Alaska record deposition related to two different types of shallow subduction: Paleocene-Eocene spreading-ridge subduction and Oligocene-Recent oceanic plateau subduction. We use detrital zircon geochronology (n = 1368) and clast composition of conglomerate (n = 1068) to reconstruct the upper plate response to these two subduction events as recorded in forearc basin strata and modern river sediment. Following spreading-ridge subduction, the presence of Precambrian and Paleozoic detrital zircon ages in middle Eocene-lower Miocene arc-margin strata and Early Cretaceous ages in lower Miocene accretionary prism-margin strata indicates that sediment was transported to the basin from older terranes in interior Alaska and from the exhumed eastern part of the Cretaceous forearc system, respectively. By middle-late Miocene time, diminished abundances of these populations reflect shallow subduction of an oceanic plateau and associated exhumation that resulted in an overall contraction of the catchment area for the forearc depositional system. In the southern Alaska forearc basin system, upper plate processes associated with subduction of a spreading ridge resulted in an abrupt increase in the diversity of detrital zircon ages that reflect new sediment sources from far inboard regions. The detrital zircon signatures from strata deposited during oceanic plateau subduction record exhumation of the region above the flat slab, with the youngest detrital zircon population reflecting the last period of major arc activity prior to insertion of the flat slab. This study provides a foundation for new tectonic and provenance models of forearc basins that have been modified by shallow subduction processes, and may help to facilitate the use of U-Pb dating of detrital zircons to better understand basins that formed under changing geodynamic plate boundary conditions