Large palaeophiid and nigerophiid snakes from Paleogene Trans-Saharan Seaway deposits of Mali

The Paleogene was a time of high diversity for snakes, and was characterized by some of the largest species known to have existed. Among these snakes were pan-Tethyan marine species of Nigerophiidae and Palaeophiidae. The latter family included the largest sea snake, Palaeophis colossaeus, known from the Trans-Saharan Seaway of Mali during the Eocene. This paper describes new material collected from Malian Trans-Saharan Seaway deposits, including additional material of Palaeophis colossaeus, a new, large species of nigerophiid, Amananulam sanogoi gen. et sp. nov., and a medium-sized snake of indeterminate affinities. The material provides new information on the intracolumnar variation of the vertebral column in Palaeophis colossaeus. We estimate the total length of each species by regression of vertebral measurements on body size. Both Palaeophis colossaeus and Amananulam sanogoi gen. et sp. nov. are the largest or among the largest members of their respective clades. The large size of Tethyan snakes may be indicative of higher temperatures in the tropics than are present today

The Race Between Stars and Quasars in Reionizing Cosmic Hydrogen

The cosmological background of ionizing radiation has been dominated by quasars once the Universe aged by ~2 billion years. At earlier times (redshifts z>3), the observed abundance of bright quasars declined sharply, implying that cosmic hydrogen was reionized by stars instead. Here, we explain the physical origin of the transition between the dominance of stars and quasars as a generic feature of structure formation in the concordance LCDM cosmology. At early times, the fraction of baryons in galaxies grows faster than the maximum (Eddington-limited) growth rate possible for quasars. As a result, quasars were not able to catch up with the rapid early growth of stellar mass in their host galaxies.Comment: 5 pages, 1 figure, Accepted for publication in JCA

The effect of Vdr gene ablation on global gene expression in the mouse placenta

Abstract not availableSam Buckberry, Fleur Spronk, Rebecca L. Wilson, Jessica A. Laurence, Tina Bianco-Miotto, Shalem Leemaqz, Sean O'Leary, Paul H. Anderson, Claire T. Robert

Fetal response to external mechanical stimuli

Peer Reviewe

Predicting oral anticoagulant response using a pharmacodynamic model

We developed a pharmacokinetic and pharmacodynamic model of warfarin absorption, metabolism, and anticoagulant action appropriate for guiding anticoagulant therapy. The model requires only two independently adjustable parameters to describe warfarin's effect on individual patients. For any given individual, these parameters are rapidly and inexpensively identified using a computer program based on the model. Test data were generated by superimposing Gaussian noise on dose-response curves calculated with the model. Then the computer program was applied to the test data. Future prothrombin complex activities (PCA's) and maintenance doses were predicted accurately early in the course of drug administration. In addition, the program accurately predicted PCA response in two groups of normal volunteers.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44006/1/10439_2006_Article_BF02363455.pd

High-spin study of rotational structures in 72Br

High-spin states in 3572Br37 were studied using the 40Ca(36Ar, 3pn) reaction. The existing level scheme has been significantly modified and extended. Evidence has been found for a spin reassignment of -1ℏh to the previously observed negative-parity band, which carries implications for the interpretation of a signature inversion in this structure. One signature of the previously assigned positive-parity band is interpreted as negative parity and has been extended to I π=(22-) and its signature partner has been observed up to Iπ = (19-) for the first time. The remaining positive-parity band has been extended to Iπ=(29+). A sequence of states observed to Iπ=(22+) may be the signature partner of this structure. Configurations have been assigned to each of these three structures through comparisons to cranked Nilsson-Strutinsky calculations

Genetics of coronary artery calcification among African Americans, a meta-analysis

Background: Coronary heart disease (CHD) is the major cause of death in the United States. Coronary artery calcification (CAC) scores are independent predictors of CHD. African Americans (AA) have higher rates of CHD but are less well-studied in genomic studies. We assembled the largest AA data resource currently available with measured CAC to identify associated genetic variants.Methods: We analyzed log transformed CAC quantity (ln(CAC + 1)), for association with ~2.5 million single nucleotide polymorphisms (SNPs) and performed an inverse-variance weighted meta-analysis on results for 5,823 AA from 8 studies. Heritability was calculated using family studies. The most significant SNPs among AAs were evaluated in European Ancestry (EA) CAC data; conversely, the significance of published SNPs for CAC/CHD in EA was queried within our AA meta-analysis.Results: Heritability of CAC was lower in AA (~30%) than previously reported for EA (~50%). No SNP reached genome wide significance (p < 5E-08). Of 67 SNPs with p < 1E-05 in AA there was no evidence of association in EA CAC data. Four SNPs in regions previously implicated in CAC/CHD (at 9p21 and PHACTR1) in EA reached

A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk

Combined analyses of gene networks and DNA sequence variation can provide new insights into the aetiology of common diseases that may not be apparent from genome-wide association studies alone. Recent advances in rat genomics are facilitating systems-genetics approaches. Here we report the use of integrated genome-wide approaches across seven rat tissues to identify gene networks and the loci underlying their regulation. We defined an interferon regulatory factor 7 (IRF7)-driven inflammatory network (IDIN) enriched for viral response genes, which represents a molecular biomarker for macrophages and which was regulated in multiple tissues by a locus on rat chromosome 15q25. We show that Epstein-Barr virus induced gene 2 (Ebi2, also known as Gpr183), which lies at this locus and controls B lymphocyte migration, is expressed in macrophages and regulates the IDIN. The human orthologous locus on chromosome 13q32 controlled the human equivalent of the IDIN, which was conserved in monocytes. IDIN genes were more likely to associate with susceptibility to type 1 diabetes (T1D)-a macrophage-associated autoimmune disease-than randomly selected immune response genes (P = 8.85 x 10(-6)). The human locus controlling the IDIN was associated with the risk of T1D at single nucleotide polymorphism rs9585056 (P = 7.0 x 10(-10); odds ratio, 1.15), which was one of five single nucleotide polymorphisms in this region associated with EBI2 (GPR183) expression. These data implicate IRF7 network genes and their regulatory locus in the pathogenesis of T1D

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

Background: Anterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability. Methods: We did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367. Findings: Between Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications. Interpretation: Surgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management. Funding: The UK National Institute for Health Research Health Technology Assessment Programme