3,275 research outputs found
The importance of keeping regular: accurate guidance to the public on low-risk drinking levels
Aim
The aim of this study was to argue that recommendations to the general public on daily amounts for low-risk alcohol consumption must retain the word ‘regular’ in order to avoid being rejected.
Method
Narrative review of the evidence-base for daily limits to alcohol consumption, the guidance the public actually receives in the UK and media reactions to this guidance.
Results
Evidence for daily limits (not more than 3–4 units for men and 2–3 units for women) rests on epidemiological surveys that enquire about ‘average’ or ‘usual’ amounts of consumption and this is reflected by the use of ‘regular’ or ‘consistent’ in the UK Government's Sensible Drinking report in 1995 and in guidance currently issued by the English Department of Health. In contrast, guidance the public actually receives often omits the word ‘regular’ and implies that the limits in question are maximum daily amounts. Media reactions to this inaccurate information suggest that the general public is likely to find these recommendations incredible and to reject them.
Conclusion
If guidance to the public on daily drinking amounts is to stand any chance of being credible and effective, it must be accurate and must therefore retain the word ‘regular’
Analytical Hartree-Fock gradients for periodic systems
We present the theory of analytical Hartree-Fock gradients for periodic
systems as implemented in the code CRYSTAL. We demonstrate how derivatives of
the integrals can be computed with the McMurchie-Davidson algorithm. Highly
accurate gradients with respect to nuclear coordinates are obtained for systems
periodic in 0,1,2 or 3 dimensions.Comment: accepted by International Journal of Quantum Chemistr
Role of Mitochondria in TNF-alpha Neurotoxicity in Stroke
TNF-alpha is known to exacerbate infarct volume in animal models and elevated levels of TNF-alpha are correlated with worse outcomes in stroke patients. However, the mechanism is not well understood. TNF-alpha has been shown to be neurotoxic at high doses and after long exposure times which is not clinically relevant. Thus, we show for the first time that TNF-alpha at clinically relevant concentrations seen in the serum of stroke patients rapidly and profoundly decreases mitochondrial function resulting in neuronal cell death through activation of caspase 8 and cytochrome c release. A slight decrease in mitochondrial function is detrimental to neurons due to their high energy demand. Since TNF-alpha is known to be increased during ischemia and correlated with negative outcomes, it is important to understand the neurotoxic mechanism of TNF-alpha to develop potential therapeutic targets for stroke. Moreover, TNF-alpha is increased during infections, and 30-40% of strokes occur during an active infection. We show that having a stroke during an active bacterial infection mimic results in an increased infarct volume, worsened neurological deficits, and prolonged sickness behavior. TNF-alpha\u27s rapid and profound effect on mitochondrial function may be one mechanism by which stroke severity is exacerbated, neurological deficits are worsened, and recovery delayed. Thus, enhancing mitochondrial function acutely post-stroke could be a potential therapeutic intervention
Microsurgical Technique of Simultaneous Pancreas/Kidney Transplantation in the Rat: Clinical Experience and Review of the Literature
Background: For experimental basic research, standardized transplantation models reflecting technical and immunologic aspects are necessary. This article describes an experimental model of combined pancreas/kidney transplantation (PKTx) in detail. Materials and Methods: Donor rats underwent en bloc pancreatectomy and nephrectomy. Revascularization was performed using the aorta with the superior mesenteric artery and the inferior vena cava with the portal vein. Exocrine drainage of the pancreas took place over a segment of the duodenum which was transplanted side-to-side to the jejunum. The kidney vessels were transplanted end-to-side. The ureter was anastomosed by patch technique. Postoperatively, serum parameters were monitored daily. Biopsies for histopathology were taken on days 5, 8 and 12. Results: All 12 recipients survived the combined PKTx without serious surgical complications. One thrombosis of the portal vein led to organ failure. Blood glucose levels were normal by the 3rd postoperative day. The transplanted duodenal segment showed slight villous atrophy, and the kidneys were well perfused without vascular complications. The anastomosis between ureter and bladder was leakproof. Conclusions: Excellent graft function and survival rates can be achieved due to simplified operation technique and short operation time. It may thus have high clinical relevance to immunologic issues within the scope of basic research. Copyright (C) 2009 S. Karger AG, Base
Moments of spectral functions: Monte Carlo evaluation and verification
The subject of the present study is the Monte Carlo path-integral evaluation
of the moments of spectral functions. Such moments can be computed by formal
differentiation of certain estimating functionals that are
infinitely-differentiable against time whenever the potential function is
arbitrarily smooth. Here, I demonstrate that the numerical differentiation of
the estimating functionals can be more successfully implemented by means of
pseudospectral methods (e.g., exact differentiation of a Chebyshev polynomial
interpolant), which utilize information from the entire interval . The algorithmic detail that leads to robust numerical
approximations is the fact that the path integral action and not the actual
estimating functional are interpolated. Although the resulting approximation to
the estimating functional is non-linear, the derivatives can be computed from
it in a fast and stable way by contour integration in the complex plane, with
the help of the Cauchy integral formula (e.g., by Lyness' method). An
interesting aspect of the present development is that Hamburger's conditions
for a finite sequence of numbers to be a moment sequence provide the necessary
and sufficient criteria for the computed data to be compatible with the
existence of an inversion algorithm. Finally, the issue of appearance of the
sign problem in the computation of moments, albeit in a milder form than for
other quantities, is addressed.Comment: 13 pages, 2 figure
Expression of a catalytically inactive mutant form of glutathione peroxidase 4 (Gpx4) confers a dominant-negative effect in male fertility.
The selenoenzyme Gpx4 is essential for early embryogenesis and cell viability for its unique function to prevent phospholipid oxidation. Recently, the cytosolic form of Gpx4 was identified as an upstream regulator of a novel form of non-apoptotic cell death, called ferroptosis, whereas the mitochondrial isoform of Gpx4 (mGpx4) was previously shown to be crucial for male fertility. Here, we generated and analyzed mice with targeted mutation of the active site selenocysteine (Sec) of Gpx4 (Gpx4_U46S). Mice homozygous for Gpx4_U46S died at the same embryonic stage (E7.5) as Gpx4-/- embryos as expected. Surprisingly, male mice heterozygous for Gpx4_U46S presented subfertility. Subfertility was manifested in a reduced number of litters from heterozygous breedings and an impairment of spermatozoa to fertilize oocytes in vitro. Morphologically, sperm isolated from heterozygous Gpx4_U46S mice revealed many structural abnormalities particularly in the spermatozoan midpiece due to improper oxidation and polymerization of sperm capsular proteins and malformation of the mitochondrial capsule surrounding and stabilizing sperm mitochondria. These findings are reminiscent of sperm isolated from selenium-deprived rodents or from mice specifically lacking mGpx4. Due to a strongly facilitated incorporation of Ser in the polypeptide chain as compared to Sec at the UGA codon, expression of the catalytically inactive Gpx4_U46S was found to be strongly increased. Since the stability of the mitochondrial capsule of mature spermatozoa depends on the moonlighting function of Gpx4 both as an enzyme oxidizing capsular protein thiols and being a structural protein, tightly controlled expression of functional Gpx4 emerges being key for full male fertility
Convergence Characteristics of the Cumulant Expansion for Fourier Path Integrals
The cumulant representation of the Fourier path integral method is examined
to determine the asymptotic convergence characteristics of the imaginary-time
density matrix with respect to the number of path variables included. It is
proved that when the cumulant expansion is truncated at order , the
asymptotic convergence rate of the density matrix behaves like .
The complex algebra associated with the proof is simplified by introducing a
diagrammatic representation of the contributing terms along with an associated
linked-cluster theorem. The cumulant terms at each order are expanded in a
series such that the the asymptotic convergence rate is maintained without the
need to calculate the full cumulant at order . Using this truncated
expansion of each cumulant at order , the numerical cost in developing
Fourier path integral expressions having convergence order is
shown to be approximately linear in the number of required potential energy
evaluations making the method promising for actual numerical implementation.Comment: 47 pages, 2 figures, submitted to PR
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