150 research outputs found

    Securities Law: A Conservative Approach

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    Soft-Wall Stabilization

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    We propose a general class of five-dimensional soft-wall models with AdS metric near the ultraviolet brane and four-dimensional Poincar\'e invariance, where the infrared scale is determined dynamically. A large UV/IR hierarchy can be generated without any fine-tuning, thus solving the electroweak/Planck scale hierarchy problem. Generically, the spectrum of fluctuations is discrete with a level spacing (mass gap) provided by the inverse length of the wall, similar to RS1 models with Standard Model fields propagating in the bulk. Moreover two particularly interesting cases arise. They can describe: (a) a theory with a continuous spectrum above the mass gap which can model unparticles corresponding to operators of a CFT where the conformal symmetry is broken by a mass gap, and; (b) a theory with a discrete spectrum provided by linear Regge trajectories as in AdS/QCD models.Comment: 27 pages, 6 figures, 1 table. v2: references added, version to appear in NJP Focus Issue on Extra Dimension

    Five millennia of surface temperatures and ice core bubble characteristics from the WAIS Divide deep core, West Antarctica

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    Bubble number densities from the West Antarctic Ice Sheet (WAIS) Divide deep core in West Antarctica record relatively stable temperatures during the middle Holocene followed by late Holocene cooling. We measured bubble number density, shape, size, and arrangement on new samples of the main WAIS Divide deep core WDC06A from similar to 580m to similar to 1600 depth. The bubble size, shape, and arrangement data confirm that the samples satisfy the requirements for temperature reconstructions. A small correction for cracks formed after core recovery allows extension of earlier work through the brittle ice zone, and a site-specific calibration reduces uncertainties. Using an independently constructed accumulation rate history and a steady state bubble number density model, we determined a temperature reconstruction that agrees closely with other independent estimates, showing a stable middle Holocene, followed by a cooling of similar to 1.25 degrees C in the late Holocene. Over the last similar to 5 millennia, accumulation has been higher during warmer times by similar to 12%degrees C-1, somewhat stronger than for thermodynamic control alone, suggesting dynamic processes

    Prioritisation of patients on waiting lists for hip and knee arthroplasties and cataract surgery: Instruments validation

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    <p>Abstract</p> <p>Background</p> <p>Prioritisation instruments were developed for patients on waiting list for hip and knee arthroplasties (AI) and cataract surgery (CI). The aim of the study was to assess their convergent and discriminant validity and inter-observer reliability.</p> <p>Methods</p> <p>Multicentre validation study which included orthopaedic surgeons and ophthalmologists from 10 hospitals. Participating doctors were asked to include all eligible patients placed in the waiting list for the procedures under study during the medical visit. Doctors assessed patients' priority through a visual analogue scale (VAS) and administered the prioritisation instrument. Information on socio-demographic data and health-related quality of life (HRQOL) (HUI3, EQ-5D, WOMAC and VF-14) was obtained through a telephone interview with patients. The correlation coefficients between the prioritisation instrument score and VAS and HRQOL were calculated. For the reliability study a self-administered questionnaire, which included hypothetic patients' scenarios, was sent via postal mail to the doctors. The priority of these scenarios was assessed through the prioritisation instrument. The intraclass correlation coefficient (ICC) between doctors was calculated.</p> <p>Results</p> <p>Correlations with VAS were strong for the AI (0.64, CI95%: 0.59–0.68) and for the CI (0.65, CI95%: 0.62–0.69), and moderate between the WOMAC and the AI (0.39, CI95%: 0.33–0.45) and the VF-14 and the CI (0.38, IC95%: 0.33–0.43). The results of the discriminant analysis were in general as expected. Inter-observer reliability was 0.79 (CI95%: 0.64–0.94) for the AI, and 0.79 (CI95%: 0.63–0.95) for the CI.</p> <p>Conclusion</p> <p>The results show acceptable validity and reliability of the prioritisation instruments in establishing priority for surgery.</p

    The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

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    Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

    Quantum Entanglement of Localized Excited States at Finite Temperature

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    In this work we study the time evolutions of (Renyi) entanglement entropy of locally excited states in two dimensional conformal field theories (CFTs) at finite temperature. We consider excited states created by acting with local operators on thermal states and give both field theoretic and holographic calculations. In free field CFTs, we find that the growth of Renyi entanglement entropy at finite temperature is reduced compared to the zero temperature result by a small quantity proportional to the width of the localized excitations. On the other hand, in finite temperature CFTs with classical gravity duals, we find that the entanglement entropy approaches a characteristic value at late time. This behaviour does not occur at zero temperature. We also study the mutual information between the two CFTs in the thermofield double (TFD) formulation and give physical interpretations of our results.Comment: 1+28 pages, 12 figures, v2 reference adde

    Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

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    We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

    Prevalence and architecture of de novo mutations in developmental disorders.

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    The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year
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