Cholesterol and coronary heart disease: screening and treatment

Coronary heart disease (CHD) is a major cause of morbidity and mortality in the United Kingdom, accounting for just under one quarter of all deaths in 1995: 27% among men and 21% among women.1 Although many CHD deaths occur among elderly people, CHD accounts for 31% of male and 13% of female deaths within the 45–64 age group

The development of a ε-polycaprolactone (PCL) scaffold for CNS repair

Potential treatment strategies for the repair of spinal cord injury (SCI) currently favour a combinatorial approach incorporating several factors, including exogenous cell transplantation and biocompatible scaffolds. The use of scaffolds for bridging the gap at the injury site is very appealing although there has been little investigation into CNS neural cell interaction and survival on such scaffolds before implantation. Previously we demonstrated that aligned micro-grooves 12.5-25 µm wide on ε-polycaprolactone (PCL) promoted aligned neurite orientation and supported myelination. In this study we identify the appropriate substrate and its topographical features required for the design of a 3D scaffold intended for transplantation in SCI. Using an established myelinating culture system of dissociated spinal cord cells, recapitulating many of the features of the intact spinal cord, we demonstrate that astrocytes plated on the topography secrete soluble factors(s) that delay oligodendrocyte differentiation but do not prevent myelination. However, as myelination does occur after a further 10-12 days in culture this does not prevent the use of PCL as a scaffold material as part of a combined strategy for the repair of SCI

MOD-0A 200 kW wind turbine generator design and analysis report

The design, analysis, and initial performance of the MOD-OA 200 kW wind turbine generator at Clayton, NM is documented. The MOD-OA was designed and built to obtain operation and performance data and experience in utility environments. The project requirements, approach, system description, design requirements, design, analysis, system tests, installation, safety considerations, failure modes and effects analysis, data acquisition, and initial performance for the wind turbine are discussed. The design and analysis of the rotor, drive train, nacelle equipment, yaw drive mechanism and brake, tower, foundation, electricl system, and control systems are presented. The rotor includes the blades, hub, and pitch change mechanism. The drive train includes the low speed shaft, speed increaser, high speed shaft, and rotor brake. The electrical system includes the generator, switchgear, transformer, and utility connection. The control systems are the blade pitch, yaw, and generator control, and the safety system. Manual, automatic, and remote control are discussed. Systems analyses on dynamic loads and fatigue are presented

The MOD-OA 200 kilowatt wind turbine generator design and analysis report

The project requirements, approach, system description, design requirements, design, analysis, system tests, installation safety considerations, failure modes and effects analysis, data acquisition, and initial performance for the MOD-OA 200 kw wind turbine generator are discussed. The components, the rotor, driven train, nacelle equipment, yaw drive mechanism and brake, tower, foundation, electrical system, and control systems are presented. The rotor includes the blades, hub and pitch change mechanism. The drive train includes the low speed shaft, speed increaser, high speed shaft, and rotor brake. The electrical system includes the generator, switchgear, transformer, and utility connection. The control systems are the blade pitch, yaw, and generator control, and the safety system. Manual, automatic, and remote control and Dynamic loads and fatigue are analyzed

The Molecular Basis of Selective Permeability of Connexins is Complex and Includes Both Size And Charge

Although gap junction channels are still widely viewed as large, non-specific pores connecting cells, the diversity in the connexin family has led more attention to be focused on their permeability characteristics. We summarize here the current status of these investigations, both published and on-going, that reveal both charge and size selectivity between gap junction channels composed of different connexins. In particular, this review will focus on quantitative approaches that monitor the expression level of the connexins, so that it is clear that differences that are seen can be attributed to channel properties. The degree of selectivity that is observed is modest compared to other channels, but is likely to be significant for biological molecules that are labile within the cell. Of particular relevance to the in vivo function of gap junctions, recent studies are summarized that demonstrate that the connexin phenotype can control the nature of the endogenous traffic between cells, with consequent effects on biological effects of gap junctions such as tumor suppression

Comparison of Grain Sources (Barley, White Corn, and Yellow Corn) for Swine Diets and Their Effect on Production and Carcass Traits

Energy sources differ in content, quality, and availability of nutrients. The objective of this study was to identify and compare differences in production and carcass traits in pigs fed different energy sources. While pigs fed a barley-based diet had a smaller loin muscle area, there was no difference among diets when comparing fat depth or percent fat-free lean. Barley based-diets and a diet containing one-third yellow corn and two-thirds white corn had a lower lean gain per day on test. There was no significant difference in average daily gain or feed-to-gain ratios

Evaluating HIV treatment as prevention in the European context

Executive summary The goal of this project is to gather evidence regarding the population-level, and to some extent, individual-level effects of the use of antiretroviral treatment (ART) to prevent HIV infection, and to relate this to current HIV treatment guidelines. To inform the project, formal literature reviews were performed for the three main areas of interest: the effect of antiretroviral therapy in adults on preventing sexual transmission of HIV, prevention of mother-to-child transmission (pMTCT) and post exposure prophylaxis (PEP). The strongest evidence with regard to the effect of treatment of HIV positive individuals to prevent onwards sexual transmission comes from the recent randomised controlled trial (RCT), HPTN052. This study demonstrated that early versus delayed ART led to a 96% relative reduction in onwards linked transmission. Several observational studies of HIV sero-discordant heterosexual couples have also reported that transmission is rare in patients on ART, particularly in those with low HIV-RNA concentrations. However, the findings of HPTN052 and these observational studies are mainly applicable to vaginal heterosexual sex. No direct empirical evidence regarding the relationship between ART use and the risk of HIV transmission through anal intercourse is currently available. Whilst the major HIV treatment guidelines do not explicitly recommend prescribing antiretroviral treatment to prevent onwards transmission, they do not rule out individuals starting ART at a high CD4 count on a case-by-case basis. However, one must also consider the impact of earlier treatment on the HIV positive individual with regard to side effects, and development of drug resistance. Early studies showed that pMTCT regimens containing a single antiretroviral agent (short course zidovudine or single dose nevirapine) or two antiretroviral agents (zidovudine and lamivudine with or without single dose nevirapine) led to clinically important reductions in MTCT rates. However, the most substantial reductions in MTCT rates occurred when combination antiretroviral regimens (more than three antiretroviral drugs) were introduced. These regimens involve the receipt of ART before the third trimester of pregnancy, intrapartum treatment, maternal post-partum treatment and some form of neonatal treatment. There is some evidence from RCTs and extensive evidence from observational studies of the efficacy of these combination regimens, with very low rates of transmission of around 0% to 6%, in settings with no or very little breastfeeding, and 1%-9% when breastfeeding occurs. Furthermore, in settings where avoidance of breastfeeding is not possible, there are a number of studies demonstrating that receipt of maternal and/or neonatal ART during the six months after birth can reduce the risk of perinatal transmissions. All treatment guidelines recommend that HIV-positive pregnant women should receive ART to prevent MTCT, although the exact timing of when ART should begin is not always explicit. Furthermore, where mentioned, use of neonatal ART is also recommended, regardless of whether infants are breastfed. Much of the data supporting the use of PEP are based on animal models, which suggest that PEP is most efficacious if commenced as soon as possible after exposure. When considering occupational exposure to HIV, human studies are limited, as no RCTs exist for ethical reasons. Evidence for efficacy is based on one case control study which demonstrated an 81% reduction in transmission of HIV through the use of zidovudine. Other studies have demonstrated that PEP following occupational exposure is not always effective and there are cases of PEP failure. Similarly, there are also no RCTs assessing the efficacy of PEP for prevention of HIV transmission after sexual exposure, and limited evidence from observational data. Most treatment guidelines agree that PEP is not always effective and PEP policies need to emphasise the importance of risk prevention in the first place in all settings where there is a risk of HIV transmission. Side effects are not uncommon when using PEP, so it is important to consider carefully whether an individual should receive PEP and some studies have suggested that increase in availability of PEP may lead to an increase in risky sex behaviour. Antiretroviral treatment has well documented benefits in reducing transmission of HIV and, in particular, has had a major population level impact on HIV acquisition in children from HIV positive mothers. Further research is needed to help us understand how we can best use ART to prevent HIV infections through other transmission routes, and to develop evidence-based policy recommendations, particularly in the European context

Human immunodeficiency virus rebound after suppression to < 400 copies/mL during initial highly active antiretroviral therapy regimens, according to prior nucleoside experience and duration of suppression

This study evaluated 1433 human immunodeficiency virus (HIV)-infected patients starting highly active antiretroviral therapy (HAART), 409 (28%) of whom had prior nucleoside experience and achieved an HIV load of <400 copies/mL by 24 weeks of therapy. Three hundred seven patients experienced virus rebound during a total of 2773.3 person-years of follow-up. There was a higher rate of virus rebound among the patients with pre-HAART nucleoside experience (relative hazard [RH], 2.86; 95% confidence interval, 2.22-3.84; P < .0001) and a decreasing rate of virus rebound with increasing duration of virus suppression (i.e., time since achieving a virus load of <400 HIV RNA copies/mL) among both the nucleoside-experienced and naive patients (P < .0001), but the difference between the groups persisted into the third year of follow-up (P = .0007). Even patients who had experienced <2 months of nucleoside therapy before beginning HAART had an increased risk of virus rebound (RH, 1.95; P = .009). It appears that only a small period of pre-HAART nucleoside therapy is sufficient to confer a disadvantage, in terms of risk of virus rebound, that persists for several years

MOD-OA 200 kW wind turbine generator engineeringing

Engineering drawings and the detailed mechanical and electrical design of a horizontal-axis wind turbine designed for DOE at the NASA Lewis Research Center and installed in Clayton, New Mexico are discussed. The drawings show the hub, pitch change mechanism, drive train, nacelle equipment, yaw drive system, tower, foundation, electrical power systems, and the control and safety systems

Targeting MAPK phosphorylation of Connexin43 provides neuroprotection in stroke

Connexin43 (Cx43) function is influenced by kinases that phosphorylate specific serine sites located near its C-terminus. Stroke is a powerful inducer of kinase activity, but its effect on Cx43 is unknown. We investigated the impact of wild-type (WT) and knock-in Cx43 with serine to alanine mutations at the protein kinase C (PKC) site Cx43(S368A), the casein kinase 1 (CK1) sites Cx43(S325A/328Y/330A), and the mitogen-activated protein kinase (MAPK) sites Cx43(S255/262/279/282A) (MK4) on a permanent middle cerebral artery occlusion (pMCAO) stroke model. We demonstrate that MK4 transgenic animals exhibit a significant decrease in infarct volume that was associated with improvement in behavioral performance. An increase in astrocyte reactivity with a concomitant decrease in microglial reactivity was observed in MK4 mice. In contrast to WT, MK4 astrocytes displayed reduced Cx43 hemichannel activity. Pharmacological blockade of Cx43 hemichannels with TAT-Gap19 also significantly decreased infarct volume in WT animals. This study provides novel molecular insights and charts new avenues for therapeutic intervention associated with Cx43 function