Bone density of first and second segments of normal and dysmorphic sacra

BACKGROUND: Iliosacral screw fixation is safe and effective but can be complicated by loss of fixation, particularly in patients with osteopenic bone. Sacral morphology dictates where iliosacral screws may be placed when stabilizing pelvic ring injuries. In dysmorphic sacra, the safe osseous corridor of the upper sacral segment (S1) is smaller and lacks a transsacral corridor, increasing the need for fixation in the second sacral segment (S2). Previous evidence suggests that S2 is less dense than S1. The aim of this cross-sectional study is to further evaluate bone mineral density (BMD) of the S1 and S2 iliosacral osseous pathways through morphology stratification into normal and dysmorphic sacra. MATERIALS AND METHODS: Pelvic computed tomography scans of 50 consecutive trauma patients, aged 18 to 50 years, from a level 1 trauma center were analyzed prospectively. Five radiographic features (upper sacral segment not recessed in the pelvis, mammillary bodies, acute alar slope, residual S1 disk, and misshapen sacral foramen) were used to identify dysmorphic characteristics, and sacra with four or five features were classified as dysmorphic. Hounsfield unit values were used to estimate the regional BMD of S1 and S2. Student\u27s t-test was utilized to compare the mean values at each segment, with statistical significance being set at p \u3c 0.05. No change in clinical management occurred as a result of inclusion in this study. RESULTS: A statistical difference in BMD was appreciated between S1 and S2 in both normal and dysmorphic sacra (p \u3c 0.0001), with 28.4% lower density in S2 than S1. Further, S1 in dysmorphic sacra tended to be 4% less dense than S1 in normal sacra (p = 0.047). No difference in density was appreciated at S2 based on morphology. CONCLUSIONS: Our results would indicate that, based on BMD alone, fixation should be maximized in S1 prior to fixation in S2. In cases where S2 fixation is required, we recommend that transsacral fixation should be strongly considered if possible to bypass the S2 body and achieve fixation in the cortical bone of the ilium and sacrum. LEVEL OF EVIDENCE: Level III

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M&gt;70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0&lt;e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Landscape of Preterm Birth Therapeutics and a Path Forward

Preterm birth (PTB) remains the leading cause of infant morbidity and mortality. Despite 50 years of research, therapeutic options are limited and many lack clear efficacy. Tocolytic agents are drugs that briefly delay PTB, typically to allow antenatal corticosteroid administration for accelerating fetal lung maturity or to transfer patients to high-level care facilities. Globally, there is an unmet need for better tocolytic agents, particularly in low- and middle-income countries. Although most tocolytics, such as betamimetics and indomethacin, suppress downstream mediators of the parturition pathway, newer therapeutics are being designed to selectively target inflammatory checkpoints with the goal of providing broader and more effective tocolysis. However, the relatively small market for new PTB therapeutics and formidable regulatory hurdles have led to minimal pharmaceutical interest and a stagnant drug pipeline. In this review, we present the current landscape of PTB therapeutics, assessing the history of drug development, mechanisms of action, adverse effects, and the updated literature on drug efficacy. We also review the regulatory hurdles and other obstacles impairing novel tocolytic development. Ultimately, we present possible steps to expedite drug development and meet the growing need for effective preterm birth therapeutics

Regulation Theories in Retrospect and Prospect.

This chapter critically assesses the regulation approach to the critique of political economy. It starts with the theoretical background to regulation theories; moves on to compare the main approaches and their various fields of application; and then offers some methodological and epistemological criticisms of the leading schools. Then come some more general methodological remarks on the object and subject of regulation and some specific comments on one of the weakest areas of regulation theory - its account of the state. Thus this chapter focuses on methodology and general theory rather than empirical analysis