Predictors of normotension on withdrawal of antihypertensive drugs in elderly patients: prospective study in second Australian national blood pressure study cohort

Objectives: To identify simple long term predictors of maintenance of normotension after withdrawal of antihypertensive drugs in elderly patients in general practice. Design: Prospective cohort study. Setting: 169 general practices in Victoria, Australia. Participants: 503 patients aged 65-84 with treated hypertension who were withdrawn from all antihypertensive drugs and remained drug free and normotensive for an initial two week period; all were followed for a further 12 months. Main outcome measures: Relative likelihood of maintaining normotension 12 months after drug withdrawal; relative likelihood of early return to hypertension after drug withdrawal. Results: The likelihood of remaining normotensive at 12 months was greater among younger patients (65-74 years), patients with lower "on-treatment" systolic blood pressure, patients on single agent treatment, and patients with a greater waist:hip ratio. The likelihood of return to hypertension was greatest for patients with higher "on-treatment" systolic blood pressure. Conclusions: Age, blood pressure control, and the number of antihypertensive drugs are important factors in the clinical decision to withdraw drug treatment. Because of consistent rates of return to antihypertensive treatment, all patients from whom such treatment is withdrawn should be monitored indefinitely to detect a recurrence of hypertension.Mark R Nelson, Chris M Reid, Henry Krum, Tui Muir, Philip Ryan, John J McNei

HELLS and CDCA7 comprise a bipartite nucleosome remodeling complex defective in ICF syndrome

Mutations in CDCA7, the SNF2 family protein HELLS (LSH), or the DNA methyltransferase DNMT3b cause immunodeficiency–centro-meric instability–facial anomalies (ICF) syndrome. While it has been speculated that DNA methylation defects cause this disease, little is known about the molecular function of CDCA7 and its functional relationship to HELLS and DNMT3b. Systematic analysis of how the cell cycle, H3K9 methylation, and the mitotic kinase Aurora B affect proteomic profiles of chromatin in Xenopus egg extracts revealed that HELLS and CDCA7 form a stoichiometric complex on chromatin, in a manner sensitive to Aurora B. Although HELLS alone fails to remodel nucleosomes, we demonstrate that the HELLS–CDCA7 complex possesses nucleosome remodeling activity. Furthermore, CDCA7 is essential for loading HELLS onto chromatin, and CDCA7 harboring patient ICF mutations fails to recruit the complex to chromatin. Together, our study identifies a unique bipartite nucleosome remodeling complex where the functional remodeling activity is split between two proteins and thus delineates the defective pathway in ICF syndrome

Quantitative Risk Assessment as Applied to Natural Terrain Landslide Hazard Management in a Mid-levels Catchment, Hong Kong

This paper presents a case study of the application of quantitative risk assessment techniques to a site-specific natural terrain hazard study in Hong Kong. The development of the landslide hazard and susceptibility models is described and salient details of the consequence model are given, including the assessment of debris flowpaths and runout using state-of-the-art Geographic Information System (GIS) tools and debris runout computer models. A synthesis of the risk quantification process and schematic design of risk mitigation works is presented

Higher analogues of the discrete-time Toda equation and the quotient-difference algorithm

The discrete-time Toda equation arises as a universal equation for the relevant Hankel determinants associated with one-variable orthogonal polynomials through the mechanism of adjacency, which amounts to the inclusion of shifted weight functions in the orthogonality condition. In this paper we extend this mechanism to a new class of two-variable orthogonal polynomials where the variables are related via an elliptic curve. This leads to a `Higher order Analogue of the Discrete-time Toda' (HADT) equation for the associated Hankel determinants, together with its Lax pair, which is derived from the relevant recurrence relations for the orthogonal polynomials. In a similar way as the quotient-difference (QD) algorithm is related to the discrete-time Toda equation, a novel quotient-quotient-difference (QQD) scheme is presented for the HADT equation. We show that for both the HADT equation and the QQD scheme, there exists well-posed $s$-periodic initial value problems, for almost all \s\in\Z^2. From the Lax-pairs we furthermore derive invariants for corresponding reductions to dynamical mappings for some explicit examples.Comment: 38 page

Enhancement of the Deuteron-Fusion Reactions in Metals and its Experimental Implications

Recent measurements of the reaction d(d,p)t in metallic environments at very low energies performed by different experimental groups point to an enhanced electron screening effect. However, the resulting screening energies differ strongly for divers host metals and different experiments. Here, we present new experimental results and investigations of interfering processes in the irradiated targets. These measurements inside metals set special challenges and pitfalls which make them and the data analysis particularly error-prone. There are multi-parameter collateral effects which are crucial for the correct interpretation of the observed experimental yields. They mainly originate from target surface contaminations due to residual gases in the vacuum as well as from inhomogeneities and instabilities in the deuteron density distribution in the targets. In order to address these problems an improved differential analysis method beyond the standard procedures has been implemented. Profound scrutiny of the other experiments demonstrates that the observed unusual changes in the reaction yields are mainly due to deuteron density dynamics simulating the alleged screening energy values. The experimental results are compared with different theoretical models of the electron screening in metals. The Debye-H\"{u}ckel model that has been previously proposed to explain the influence of the electron screening on both nuclear reactions and radioactive decays could be clearly excluded.Comment: 22 pages, 12 figures, REVTeX4, 2-column format. Submitted to Phys. Rev. C; accepte

Influence of dissipation on the extraction of quantum states via repeated measurements

A quantum system put in interaction with another one that is repeatedly measured is subject to a non-unitary dynamics, through which it is possible to extract subspaces. This key idea has been exploited to propose schemes aimed at the generation of pure quantum states (purification). All such schemes have so far been considered in the ideal situations of isolated systems. In this paper, we analyze the influence of non-negligible interactions with environment during the extraction process, with the scope of investigating the possibility of purifying the state of a system in spite of the sources of dissipation. A general framework is presented and a paradigmatic example consisting of two interacting spins immersed in a bosonic bath is studied. The effectiveness of the purification scheme is discussed in terms of purity for different values of the relevant parameters and in connection with the bath temperature.Comment: 10 pages, 3 figure

The new paradigm of hepatitis C therapy: integration of oral therapies into best practices.

Emerging data indicate that all-oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon-based therapies, all-oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk-based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one-time testing for all persons born during 1945-1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk-based and birth-cohort-based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels