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Rs964184 (APOA5-A4-C3-A1) Is Related to Elevated Plasma Triglyceride Levels, but Not to an Increased Risk for Vascular Events in Patients with Clinically Manifest Vascular Disease
Background: Single nucleotide polymorphisms in the APOA5-A4-C3-A1 gene complex are associated with elevated plasma triglycerides and elevated vascular risk in healthy populations. In patients with clinically manifest vascular disease, hypertriglyceridemia and metabolic syndrome are frequently present, but the contribution of these single nucleotide polymorphisms to plasma triglycerides, effect modification by obesity and risk of recurrent vascular events is unknown in these patients. Methods: Prospective cohort study of 5547 patients with vascular disease. Rs964184 (APOA5-A4-C3-A1 gene complex) was genotyped, and we evaluated the relation with plasma lipid levels, presence of metabolic syndrome and the risk for new vascular events. Results: The minor allele of rs964184 was strongly associated with log plasma triglycerides (β 0.12; 95%CI 0.10-0.15, p = 1.1*10−19), and was also associated with 0.03 mmol/L lower high-density lipoprotein-cholesterol (95%CI 0.01–0.04), and 0.14 mmol/L higher non-high-density lipoprotein-cholesterol (95%CI 0.09–0.20). The minor allele frequency increased from 10.9% in patients with plasma triglycerides 27 kg/m2, p for interaction = 0.02). The prevalence of the metabolic syndrome increased from 52% for patients with two copies of the major allele to 62% for patients with two copies of the minor allele (p = 0.01). Rs964184 was not related with recurrent vascular events (HR 0.99; 95%CI 0.86–1.13). Conclusion: The single nucleotide polymorphism rs964184 (APOA5-A4-C3-A1) is associated with elevated plasma triglycerides concentrations in patients with clinically manifest vascular disease. In carriers of one minor allele, the effect on plasma triglycerides was modified by body mass index. There is no relation between rs964184 and recurrent vascular events in these patients
Discrete approaches to quantum gravity in four dimensions
The construction of a consistent theory of quantum gravity is a problem in
theoretical physics that has so far defied all attempts at resolution. One
ansatz to try to obtain a non-trivial quantum theory proceeds via a
discretization of space-time and the Einstein action. I review here three major
areas of research: gauge-theoretic approaches, both in a path-integral and a
Hamiltonian formulation, quantum Regge calculus, and the method of dynamical
triangulations, confining attention to work that is strictly four-dimensional,
strictly discrete, and strictly quantum in nature.Comment: 33 pages, invited contribution to Living Reviews in Relativity; the
author welcomes any comments and suggestion
Frame Dependence of Spin-One Angular Conditions in Light Front Dynamics
We elaborate the frame dependence of the angular conditions for spin-1 form
factors. An extra angular condition is found in addition to the usual angular
condition relating the four helicity amplitudes. Investigating the
frame-dependence of the angular conditions, we find that the extra angular
condition is in general as complicated as the usual one, although it becomes
very simple in the frame involving only two helicity amplitudes. It
is confirmed that the angular conditions are identical in frames that are
connected by kinematical transformations. The high behaviors of the
physical form factors and the limiting behaviors in special reference frames
are also discussed.Comment: 29 pages RevTeX. submitted to Phys. Rev.
Nonlinearity in NS transport: scattering matrix approach
A general formula for the current through a disordered
normal--superconducting junction is derived, which is valid at finite
temperature and includes the full voltage dependence. The result depends on a
multichannel scattering matrix, which describes elastic scattering in the
normal region, and accounts for the Andreev scattering at the NS interface. The
symmetry of the current with respect to sign reversal in the subgap regime is
discussed. The Andreev approximation is used to derive a spectral conductance
formula, which applies to voltages both below and above the gap. In a case
study the spectral conductance formula is applied to the problem of an NINIS
double barrier junction.Comment: 26 pages, 4 Postscript figures, Latex, to be published in Phys. Rev.
Метафорична картина світу та її місце у системі світів
Статья посвящается исследованию понятия метафорической картины мира, целесообразность выделения которой автор объясняет тем, что по аналогии с языковой и концептуальной картинами мира, термин "метафорическая
картина мира" содержит информацию о сложной структуре многосмысловых
значений, которые в силу своей метафорической природе гармонически объединяются.У статті йдеться про поняття метафоричної картини світу, доцільність
виділення якої авторка пояснює тим, що за аналогією до мовної й концептуальної картин світу, термін "метафорична картина світу" вміщує інформацію про
складну структуру багатосмислових значень, що завдяки своїй метафоричній
природі гармонійно поєднуються.The article deals with the notion of metaphorical world picture connected with the
general principle of conceptualization. The term "metaphorical world picture" consists
of a complex structure of various meanings harmonically combined due to their
metaphorical nature
The Effect of Lattice Vibrations on Substitutional Alloy Thermodynamics
A longstanding limitation of first-principles calculations of substitutional
alloy phase diagrams is the difficulty to account for lattice vibrations. A
survey of the theoretical and experimental literature seeking to quantify the
impact of lattice vibrations on phase stability indicates that this effect can
be substantial. Typical vibrational entropy differences between phases are of
the order of 0.1 to 0.2 k_B/atom, which is comparable to the typical values of
configurational entropy differences in binary alloys (at most 0.693 k_B/atom).
This paper describes the basic formalism underlying ab initio phase diagram
calculations, along with the generalization required to account for lattice
vibrations. We overview the various techniques allowing the theoretical
calculation and the experimental determination of phonon dispersion curves and
related thermodynamic quantities, such as vibrational entropy or free energy. A
clear picture of the origin of vibrational entropy differences between phases
in an alloy system is presented that goes beyond the traditional bond counting
and volume change arguments. Vibrational entropy change can be attributed to
the changes in chemical bond stiffness associated with the changes in bond
length that take place during a phase transformation. This so-called ``bond
stiffness vs. bond length'' interpretation both summarizes the key phenomenon
driving vibrational entropy changes and provides a practical tool to model
them.Comment: Submitted to Reviews of Modern Physics 44 pages, 6 figure
Optical creation of vibrational intrinsic localized modes in anharmonic lattices with realistic interatomic potentials
Using an efficient optimal control scheme to determine the exciting fields,
we theoretically demonstrate the optical creation of vibrational intrinsic
localized modes (ILMs) in anharmonic perfect lattices with realistic
interatomic potentials. For systems with finite size, we show that ILMs can be
excited directly by applying a sequence of femtosecond visible laser pulses at
THz repetition rates. For periodic lattices, ILMs can be created indirectly via
decay of an unstable extended lattice mode which is excited optically either by
a sequence of pulses as described above or by a single picosecond far-infrared
laser pulse with linearly chirped frequency. In light of recent advances in
experimental laser pulse shaping capabilities, the approach is experimentally
promising.Comment: 20 pages, 7 eps figures. Accepted, Phys. Rev.
Raloxifene augmentation in men and women with a schizophrenia spectrum disorder:A study protocol
Although acute psychotic symptoms are often reduced by antipsychotic treatment, many patients with schizophrenia are impaired in daily functioning due to the persistence of negative and cognitive symptoms. Raloxifene, a Selective Estrogen Receptor Modulator (SERM) has been shown to be an effective adjunctive treatment in schizophrenia. Yet, there is a paucity in evidence for raloxifene efficacy in men and premenopausal women. We report the design of a study that aims to replicate earlier findings concerning the efficacy of raloxifene augmentation in reducing persisting symptoms and cognitive impairment in postmenopausal women, and to extend these findings to a male and peri/premenopausal population of patients with schizophrenia. The study is a multisite, placebo-controlled, double-blind, randomised clinical trial in approximately 110 adult men and women with schizophrenia. Participants are randomised 1:1 to adjunctive raloxifene 120 mg or placebo daily during 12 weeks. The treatment phase includes measurements at three time points (week 0, 6 and 12), followed by a follow-up period of two years. The primary outcome measure is change in symptom severity, as measured with the Positive and Negative Syndrome Scale (PANSS), and cognition, as measured with the Brief Assessment of Cognition in Schizophrenia (BACS). Secondary outcome measures include social functioning and quality of life. Genetic, hormonal and inflammatory biomarkers are measured to assess potential associations with treatment effects. If it becomes apparent that raloxifene reduces psychotic symptoms and/or improves cognition, social functioning and/or quality of life as compared to placebo, implementation of raloxifene in clinical psychiatric practice can be considered
The H3.3K27M oncohistone affects replication stress outcome and provokes genomic instability in pediatric glioma
While comprehensive molecular profiling of histone H3.3 mutant pediatric high-grade glioma has revealed extensive dysregulation of the chromatin landscape, the exact mechanisms driving tumor formation remain poorly understood. Since H3.3 mutant gliomas also exhibit high levels of copy number alterations, we set out to address if the H3.3K27M oncohistone leads to destabilization of the genome. Hereto, we established a cell culture model allowing inducible H3.3K27M expression and observed an increase in mitotic abnormalities. We also found enhanced interaction of DNA replication factors with H3.3K27M during mitosis, indicating replication defects. Further functional analyses revealed increased genomic instability upon replication stress, as represented by mitotic bulky and ultrafine DNA bridges. This co-occurred with suboptimal 53BP1 nuclear body formation after mitosis in vitro, and in human glioma. Finally, we observed a decrease in ultrafine DNA bridges following deletion of the K27M mutant H3F3A allele in primary high-grade glioma cells. Together, our data uncover a role for H3.3 in DNA replication under stress conditions that is altered by the K27M mutation, promoting genomic instability and potentially glioma development
Integrated approach to prevent functional decline in hospitalized elderly: the Prevention and Reactivation Care Program (PReCaP)
<p>Abstract</p> <p>Background</p> <p>Hospital related functional decline in older patients is an underestimated problem. Thirty-five procent of 70-year old patients experience functional decline during hospital admission in comparison with pre-illness baseline. This percentage increases considerably with age.</p> <p>Methods/design</p> <p>To address this issue, the Vlietland Ziekenhuis in The Netherlands has implemented an innovative program (PReCaP), aimed at reducing hospital related functional decline among elderly patients by offering interventions that are multidisciplinary, integrated and goal-oriented at the physical, social, and psychological domains of functional decline.</p> <p>Discussion</p> <p>This paper presents a detailed description of the intervention, which incorporates five distinctive elements: (1) Early identification of elderly patients with a high risk of functional decline, and if necessary followed by the start of the reactivation treatment within 48 h after hospital admission; (2) Intensive follow-up treatment for a selected patient group at the Prevention and Reactivation Centre (PRC); (3) Availability of multidisciplinary geriatric expertise; (4) Provision of support and consultation of relevant professionals to informal caregivers; (5) Intensive follow-up throughout the entire chain of care by a casemanager with geriatric expertise. Outcome and process evaluations are ongoing and results will be published in a series of future papers.</p> <p>Trial registration</p> <p>The Netherlands National Trial Register: <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2317">NTR2317</a></p
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