The effects of blood pressure lowering on development of cognitive impairment and dementia in patients without apparent prior cerebrovascular disease

BACKGROUND: Hypertension and cognitive impairment are prevalent in older people. It is known that hypertension is a direct risk factor for vascular dementia and recent studies have suggested hypertension also impacts upon prevalence of Alzheimer's disease. The question is therefore whether treatment of hypertension lowers the rate of cognitive decline. OBJECTIVES: To assess the effects of blood pressure lowering treatments for the prevention of dementia and cognitive decline in patients with hypertension but no history of cerebrovascular disease. SEARCH STRATEGY: The trials were identified through a search of CDCIG's Specialised Register, CENTRAL, MEDLINE, EMBASE, PsycINFO and CINAHL on 27 April 2005. SELECTION CRITERIA: Randomized, double-blind, placebo controlled trials in which pharmacological or non-pharmacological interventions to lower blood pressure were given for at least six months. DATA COLLECTION AND ANALYSIS: Two independent reviewers assessed trial quality and extracted data. The following outcomes were assessed: incidence of dementia, cognitive change from baseline, blood pressure level, incidence and severity of side effects and quality of life. MAIN RESULTS: Three trials including 12,091 hypertensive subjects were identified. Average age was 72.8 years. Participants were recruited from industrialised countries. Mean blood pressure at entry across the studies was 170/84 mmHg. All trials instituted a stepped care approach to hypertension treatment, starting with a calcium-channel blocker, a diuretic or an angiotensin receptor blocker. The combined result of the three trials reporting incidence of dementia indicated no significant difference between treatment and placebo (Odds Ratio (OR) = 0.89, 95% CI 0.69, 1.16). Blood pressure reduction resulted in a 11% relative risk reduction of dementia in patients with no prior cerebrovascular disease but this effect was not statistically significant (p = 0.38) and there was considerable heterogeneity between the trials. The combined results from the two trials reporting change in Mini Mental State Examination (MMSE) did not indicate a benefit from treatment (Weighted Mean Difference (WMD) = 0.10, 95% CI -0.03, 0.23). Both systolic and diastolic blood pressure levels were reduced significantly in the two trials assessing this outcome (WMD = -7.53, 95% CI -8.28, -6.77 for systolic blood pressure, WMD = -3.87, 95% CI -4.25, -3.50 for diastolic blood pressure).Two trials reported adverse effects requiring discontinuation of treatment and the combined results indicated a significant benefit from placebo (OR = 1.18, 95% CI 1.06, 1.30). When analysed separately, however, more patients on placebo in SCOPE were likely to discontinue treatment due to side effects; the converse was true in SHEP 1991. Quality of life data could not be analysed in the three studies. There was difficulty with the control group in this review as many of the control subjects received antihypertensive treatment because their blood pressures exceeded pre-set values. In most cases the study became a comparison between the study drug against a usual antihypertensive regimen. AUTHORS' CONCLUSIONS: There was no convincing evidence from the trials identified that blood pressure lowering prevents the development of dementia or cognitive impairment in hypertensive patients with no apparent prior cerebrovascular disease. There were significant problems identified with analysing the data, however, due to the number of patients lost to follow-up and the number of placebo patients given active treatment. This introduced bias. More robust results may be obtained by analysing one year data to reduce differential drop-out or by conducting a meta-analysis using individual patient data.

Atmospheric parameters and rotational velocities for a sample of Galactic B-type supergiants

High-resolution optical spectra of 57 Galactic B-type supergiant stars have been analysed to determine their rotational and macroturbulent velocities. In addition, their atmospheric parameters (effective temperature, surface gravity and microturbulent velocity) and surface nitrogen abundances have been estimated using a non-local thermodynamic equilibrium grid of model atmospheres. Comparisons of the projected rotational velocities have been made with the predictions of stellar evolutionary models and in general good agreement was found. However, for a small number of targets, their observed rotational velocities were significantly larger than predicted, although their nitrogen abundances were consistent with the rest of the sample. We conclude that binarity may have played a role in generating their large rotational velocities. No correlation was found between nitrogen abundances and the current projected rotational velocities. However, a correlation was found with the inferred projected rotational velocities of the main-sequence precursors of our supergiant sample. This correlation is again in agreement with the predictions of single star evolutionary models that incorporate rotational mixing. The origin of the macroturbulence and microturbulent velocity fields is discussed and our results support previous theoretical studies that link the former to subphotospheric convection and the latter to non-radial gravity mode oscillations. In addition, we have attempted to identify differential rotation in our most rapidly rotating targets.

A 60 GHz wide tuning range SiGe bipolar VCO for HDMI and wireless docking applications

A wide tuning range voltage controlled oscillator (VCO) with novel architecture is proposed in this work. The entire circuit consists of a VCO core, a summing circuit, a single-ended to differential (STD) converter and a buffer amplifier. The VCO core oscillates at half the desired frequency and the second harmonic of the VCO core is extracted by the summing circuit, which is then converted to a differential pair by the STD. The entire VCO circuit operates from 58.85 to 70.85 GHz with 20% frequency tuning range. The measured VCO gain is less than 1.6 GHz/V. The measured phase noise at 3 MHz offset is less than -78 dBc/Hz across the entire tuning range. The differential phase error of the output signals is measured by down converting the VCO output signals to low gigahertz frequency using an on-chip mixer. The measured differential phase error is less than 8°. The VCO circuit, which is constructed using 0.35 µm SiGe technology, occupies 770 × 550 µm2 die area and consumes 62 mA under 3.5 V supply.

Explaining levels of deprivation in the European Union

In this paper we seek to explain variations in levels of deprivation between EU countries. The starting-point of our analysis is the finding that the relationship between income and life-style deprivation varies across countries. Given our understanding of the manner in which the income-deprivation mismatch may arise from the limitations of current income as a measure of command over resources, the pattern of variation seems to be consistent with our expectations of the variable degree to which welfare-state regimes achieve 'decommodification' and smooth income flows. This line of reasoning suggests that cross-national differences in deprivation might, in significant part, be due not only to variation in household and individual characteristics that are associated with disadvantage but also to the differential impact of such variables across countries and indeed welfare regimes. To test this hypothesis, we have taken advantage of the ECHP (European Community Household Panel) comparative data set in order to pursue a strategy of substituting variable names for country/welfare regime names. We operated with two broad categories of variables, tapping, respectively, needs and resources. Although both sets of factors contribute independently to our ability to predict deprivation, it is the resource factors that are crucial in reducing country effects. The extent of cross-national heterogeneity depends on specifying the social class and situation in relation to long-term unemployment of the household reference person. The impact of the structural socio-economic variables that we label 'resource factors' varies across countries in a manner that is broadly consistent with welfare regime theory and is the key factor in explaining cross-country differences in deprivation. As a consequence, European homogeneity is a great deal more evident among the advantaged than the disadvantaged.

Evidence and Spatial Planning for Sustainable Development: A Model for Spatially Allocating Material Flows

The aspiration the spatial planning should act as the main coordinating function for the transition to a sustainable society is grounded on the assumption that it is capable of incorporating both a strong evidence base of environmental accounting for policy, coupled with opportunities for open, deliberative decision-making. While there are a number of increasingly sophisticated methods (such as material flow analysis and ecological footprinting) that can be used to longitudinally determine the impact of policy, there are fewer that can provide a robust spatial assessment of sustainability policy. In this paper, we introduce the Spatial Allocation of Material Flow Analysis (SAMFA) model, which uses the concept of socio-economic metabolism to extrapolate the impact of local consumption patterns that may occur as a result of the local spatial planning process at multiple spatial levels. The initial application the SAMFA model is based on County Kildare in the Republic of Ireland, through spatial temporal simulation and visualisation of construction material flows and associated energy use in the housing sector. Thus, while we focus on an Ireland case study, the model is applicable to spatial planning and sustainability research more generally. Through the development and evaluation of alternative scenarios, the model appears to be successful in its prediction of the cumulative resource and energy impacts arising from consumption and development patterns. This leads to some important insights in relation to the differential spatial distribution of disaggregated allocation of material balance and energy use, for example that rural areas have greater resource accumulation (and are therefore in a sense “less sustainable”) than urban areas, confirming that rural housing in Ireland is both more material and energy intensive. This therefore has the potential to identify hotspots of higher material and energy use, which can be addressed through targeted planning initiatives or focussed community engagement. Furthermore, due to the ability of the model to allow manipulation of different policy criteria (increased density, urban conservation etc), it can also act as an effective basis for multi-stakeholder engagement.

3D Analysis of Seepage under Hydraulic Structures with Intermediate Filters

Seepage flow under hydraulic structures provided with intermediate filters has been investigated. The flow through the banks of the canal has been included in the model. Different combinations of intermediate filter and canal width were studied. Different lengths of the floor, differential heads, and depths of the sheet pile driven beneath the floor were also investigated. The introduction of an intermediate filter to the floor of hydraulic structures reduced the uplift force acting on the downstream floor by up to 72%. The maximum uplift reduction occurred when the ratio of the distance of filter location downstream from the cutoff to the differential head was 1. Introducing a second filter in the downstream side resulted in a further reduction in the exit hydraulic gradient and in the uplift force, which reached 90%. The optimum locations of the two filters occurred when the first filter was placed just downstream of the cutoff wall and the second filter was placed nearly at the middistance between the cutoff and the end toe of the floor. The results showed significant differences between the three-dimensional (3D) and the two-dimensional (2D) analyses.

Balteatide: A Novel Antimicrobial Decapeptide from the Skin Secretion of the Purple-Sided Leaf Frog, Phyllomedusa baltea

The skin secretions of Neotropical phyllomedusine leaf frogs have proven to be a rich source of biologically-active peptides, including antimicrobials. The major families of antimicrobial peptides (AMPs) reported are the dermaseptins and phylloseptins and the minor families, the dermatoxins, phylloxins, plasticins, distinctins and the medusins. Here, we report a novel AMP of 10 amino acid residues (LRPAILVRIKamide), named balteatide, from the skin secretion of wild Peruvian purple-sided leaf frogs, Phyllomedusa baltea. Balteatide was found to exhibit a 90% sequence identity with sauvatide, a potent myotropic peptide from the skin secretion of Phyllomedusa sauvagei. However, despite both peptides exhibiting only a single amino acid difference (I/T at position 9), sauvatide is devoid of antimicrobial activity and balteatide is devoid of myotropic activity. Balteatide was found to have differential activity against the Gram-positive bacterium, Staphylococcus aureus, the Gram-negative bacterium, Escherichia coli and the yeast, Candida albicans, and unusually for phyllomedusine frog skin AMPs, was most potent (MIC 32 mg/L) against the yeast. Balteatide was also devoid of haemolytic activity up to concentrations of 512 mg/L. Phyllomedusine frog skin secretions thus continue to provide novel AMPs, some of which may provide templates for the rational design of new classes of anti-infective therapeutics.

Genome-wide association study for sight-threatening diabetic retinopathy reveals association with genetic variation near the GRB2 gene

AIMS/HYPOTHESIS: Diabetic retinopathy is a serious complication of diabetes mellitus and can lead to blindness. A genetic component, in addition to traditional risk factors, has been well described although strong genetic factors have not yet been identified. Here, we aimed to identify novel genetic risk factors for sight-threatening diabetic retinopathy using a genome-wide association study.

METHODS: Retinopathy was assessed in white Australians with type 2 diabetes mellitus. Genome-wide association analysis was conducted for comparison of cases of sight-threatening diabetic retinopathy (n = 336) with diabetic controls with no retinopathy (n = 508). Top ranking single nucleotide polymorphisms were typed in a type 2 diabetes replication cohort, a type 1 diabetes cohort and an Indian type 2 cohort. A mouse model of proliferative retinopathy was used to assess differential expression of the nearby candidate gene GRB2 by immunohistochemistry and quantitative western blot.

RESULTS: The top ranked variant was rs3805931 with p = 2.66 × 10(-7), but no association was found in the replication cohort. Only rs9896052 (p = 6.55 × 10(-5)) was associated with sight-threatening diabetic retinopathy in both the type 2 (p = 0.035) and the type 1 (p = 0.041) replication cohorts, as well as in the Indian cohort (p = 0.016). The study-wide meta-analysis reached genome-wide significance (p = 4.15 × 10(-8)). The GRB2 gene is located downstream of this variant and a mouse model of retinopathy showed increased GRB2 expression in the retina.

CONCLUSIONS/INTERPRETATION: Genetic variation near GRB2 on chromosome 17q25.1 is associated with sight-threatening diabetic retinopathy. Several genes in this region are promising candidates and in particular GRB2 is upregulated during retinal stress and neovascularisation.

Investigation of thermal resistance and bridging in examples of contemporary and vernacular solid wall architecture

Contemporary architecture has tended to increase envelope insulation levels in an unceasing effort to reduce U-values. Traditional masonry architecture in contrast was devoid of insulation, except for the inherent insulative nature of vernacular materials. Also the consistency of the outer membrane of the building skin diminished any impact due to bridging. In contemporary highly insulated walls bridges are numerous due to the necessity to bind inner and outer structural skins through insulation layers. This paper examines thermal bridging in an example of contemporary façade design and compares it with an example of traditional vernacular architecture currently being researched which is characterized by a lack of bridging elements. Focus is given to heavy weight materials of high thermal mass, which appropriately for passive architecture help moderate fluctuations in internal temperature. In an extensive experimental study samples of highly insulated precast concrete sandwich panels and lime rendered masonry walls are tested in a guarded hot-box. The building construction methods are compared for static and dynamic thermal transmittance, via heat flux and surface temperature differential measurements. Focus is given to the differential heat loss due to the thermal bridging in the sandwich panels and its associated impact on overall heat loss relative to traditional masonry construction.

Comprehensive Transcriptome Analysis of Sex-Biased Expressed Genes Reveals Discrete Biological and Physiological Features of Male and Female Schistosoma japonicum

Schistosomiasis is a chronic and debilitating disease caused by blood flukes (digenetic trematodes) of the genus Schistosoma. Schistosomes are sexually dimorphic and exhibit dramatic morphological changes during a complex lifecycle which requires subtle gene regulatory mechanisms to fulfil these complex biological processes. In the current study, a 41,982 features custom DNA microarray, which represents the most comprehensive probe coverage for any schistosome transcriptome study, was designed based on public domain and local databases to explore differential gene expression in S. japonicum. We found that approximately 1/10 of the total annotated genes in the S. japonicum genome are differentially expressed between adult males and females. In general, genes associated with the cytoskeleton, and motor and neuronal activities were readily expressed in male adult worms, whereas genes involved in amino acid metabolism, nucleotide biosynthesis, gluconeogenesis, glycosylation, cell cycle processes, DNA synthesis and genome fidelity and stability were enriched in females. Further, miRNAs target sites within these gene sets were predicted, which provides a scenario whereby the miRNAs potentially regulate these sex-biased expressed genes. The study significantly expands the expressional and regulatory characteristics of gender-biased expressed genes in schistosomes with high accuracy. The data provide a better appreciation of the biological and physiological features of male and female schistosome parasites, which may lead to novel vaccine targets and the development of new therapeutic interventions.

The influence of socio-demographic, psychological and knowledge-related variables alongside perceived cooking and food skills abilities in the prediction of diet quality in adults: a nationally representative cross-sectional study

Background: Interventions to increase cooking skills (CS) and food skills (FS) as a route to improving overall diet are popular within public health. This study tested a comprehensive model of diet quality by assessing the influence of socio-demographic, knowledge- and psychological-related variables alongside perceived CS and FS abilities. The correspondence of two measures of diet quality further validated the Eating Choices Index (ECI) for use in quantitative research.
Methods: A cross-sectional survey was conducted in a quota-controlled nationally representative sample of 1049 adults aged 20–60 years drawn from the Island of Ireland. Surveys were administered in participants’ homes via computer-assisted personal interviewing (CAPI) assessing a range of socio-demographic, knowledge- and psychological-related variables alongside perceived CS and FS abilities. Regression models were used to model factors influencing diet quality. Correspondence between 2 measures of diet quality was assessed using chi-square and Pearson correlations.
Results: ECI score was significantly negatively correlated with DINE Fat intake (r = -0.24, p < 0.001), and ECI score was significantly positively correlated with DINE Fibre intake (r = 0.38, p < 0.001), demonstrating a high agreement. Findings indicated that males, younger respondents and those with no/few educational qualifications scored significantly lower on both CS and FS abilities. The relative influence of socio-demographic, knowledge, psychological variables and CS and FS abilities on dietary outcomes varied, with regression models explaining 10–20 % of diet quality variance. CS ability exerted the strongest relationship with saturated fat intake (β = -0.296, p < 0.001) and was a significant predictor of fibre intake (β = -0.113, p < 0.05), although not for healthy food choices (ECI) (β = 0.04, p > 0.05).
Conclusion: Greater CS and FS abilities may not lead directly to healthier dietary choices given the myriad of other factors implicated; however, CS appear to have differential influences on aspects of the diet, most notably in relation to lowering saturated fat intake. Findings suggest that CS and FS should not be singular targets of interventions designed to improve diet; but targeting specific sub-groups of the population e.g. males, younger adults, those with limited education might be more fruitful. A greater understanding of the interaction of factors influencing cooking and food practices within the home is needed.