Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2

Objective To develop and validate version two of the QRISK cardiovascular disease risk algorithm (QRISK2) to provide accurate estimates of cardiovascular risk in patients from different ethnic groups in England and Wales and to compare its performance with the modified version of Framingham score recommended by the National Institute for Health and Clinical Excellence (NICE).Design Prospective open cohort study with routinely collected data from general practice, 1 January 1993 to 31 March 2008.Setting 531 practices in England and Wales contributing to the national QRESEARCH database.Participants 2.3 million patients aged 35-74 (over 16 million person years) with 140 000 cardiovascular events. Overall population (derivation and validation cohorts) comprised 2.22 million people who were white or whose ethnic group was not recorded, 22 013 south Asian, 11 595 black African, 10 402 black Caribbean, and 19 792 from Chinese or other Asian or other ethnic groups.Main outcome measures First (incident) diagnosis of cardiovascular disease (coronary heart disease, stroke, and transient ischaemic attack) recorded in general practice records or linked Office for National Statistics death certificates. Risk factors included self assigned ethnicity, age, sex, smoking status, systolic blood pressure, ratio of total serum cholesterol:high density lipoprotein cholesterol, body mass index, family history of coronary heart disease in first degree relative under 60 years, Townsend deprivation score, treated hypertension, type 2 diabetes, renal disease, atrial fibrillation, and rheumatoid arthritis.Results The validation statistics indicated that QRISK2 had improved discrimination and calibration compared with the modified Framingham score. The QRISK2 algorithm explained 43% of the variation in women and 38% in men compared with 39% and 35%, respectively, by the modified Framingham score. Of the 112 156 patients classified as high risk (that is, ≥20% risk over 10 years) by the modified Framingham score, 46 094 (41.1%) would be reclassified at low risk with QRISK2. The 10 year observed risk among these reclassified patients was 16.6% (95% confidence interval 16.1% to 17.0%)—that is, below the 20% treatment threshold. Of the 78 024 patients classified at high risk on QRISK2, 11 962 (15.3%) would be reclassified at low risk by the modified Framingham score. The 10 year observed risk among these patients was 23.3% (22.2% to 24.4%)—that is, above the 20% threshold. In the validation cohort, the annual incidence rate of cardiovascular events among those with a QRISK2 score of ≥20% was 30.6 per 1000 person years (29.8 to 31.5) for women and 32.5 per 1000 person years (31.9 to 33.1) for men. The corresponding figures for the modified Framingham equation were 25.7 per 1000 person years (25.0 to 26.3) for women and 26.4 (26.0 to 26.8) for men). At the 20% threshold, the population identified by QRISK2 was at higher risk of a CV event than the population identified by the Framingham score.Conclusions Incorporating ethnicity, deprivation, and other clinical conditions into the QRISK2 algorithm for risk of cardiovascular disease improves the accuracy of identification of those at high risk in a nationally representative population. At the 20% threshold, QRISK2 is likely to be a more efficient and equitable tool for treatment decisions for the primary prevention of cardiovascular disease. As the validation was performed in a similar population to the population from which the algorithm was derived, it potentially has a “home advantage.” Further validation in other populations is therefore advised.     

Phytoremediation of lead (Pb) and Arsenic (As) by Melastoma malabathricum L. from Contaminated Soil in Separate Exposure

This study was conducted to investigate the uptake of lead (Pb) and arsenic (As) from contaminated soil using Melastoma malabathricum L. species. The cultivated plants were exposed to As and Pb in separate soils for an observation period of 70 days. From the results of the analysis, M. malabathricum accumulated relatively high range of As concentration in its roots, up to a maximum of 2800 mg/kg. The highest accumulation of As in stems and leaves was 570 mg/kg of plant. For Pb treatment, the highest concentration (13,800 mg/kg) was accumulated in the roots of plants. The maximum accumulation in stems was 880 mg/kg while maximum accumulation in leaves was 2,200 mg/kg. Only small amounts of Pb were translocated from roots to above ground plant parts (TF < 1). However, a wider range of TF values (0.01–23) for As treated plants proved that the translocation of As from root to above ground parts was greater. However, the high capacity of roots to take up Pb and As (BF > 1) is indicative this plants is a good bioaccumulator for these metals. Therefore, phytostabilisation is the mechanism at work in M. malabathricum's uptake of Pb, while phytoextraction is the dominant mechanism with As.     

Steroids from starfish

Starfish $\text{Linckia multifora, Protoreaster nodosus, Protoreaster lincki, Culcita schmideliana, Nardoa variolata}$ and $\text{Acanthaster planci}$ were examined for sterols and sapogenins. All asteroids contained cholestanol in addition to C₂₇ to C₃₀ mono and diunsaturated sterols. A planci contained largest amounts of 5α-cholesta-9(11), 20(22)-diene-3β, 6α-diol-23-one and 5α-pregn-9(11)-ene-3β,6α-diol-20-one whereas $\text{P. nodosus, P. lincki and C. schmideliana}$ contained only small amounts. Neither pregnane nor cholestane genins were detected in $\text{L. Multifora}$ and $\text{N. variolata}$.     

Development and in vitro/in vivo evaluation of artemether and lumefantrine co-loaded nanoliposomes for parenteral delivery

Combination therapy of artemether (ART) and lumefantrine (LUM) is well-established for the treatment of uncomplicated malaria worldwide. Nanoliposomes (NLs) encapsulating both drugs were prepared and freeze-dried. The lyophilized nanoliposomes exhibited high entrapment efficiency of artemether (66.18%), relatively low entrapment efficiency of lumefantrine (53.46%), low average size diameter (125.3?nm) and found to be stable at 4?°C for 60 days without significant change in mean particle diameter and drug entrapment efficiencies. In vitro drug release study has shown initial burst effect and then sustained release pattern over a time period of 30?h. In vivo toxicity study was examined by liver and kidney function test as well as histopathological examination. Nanoliposomes showed lower hemolytic potential (～10%) compared to all the components when studied individually. There was no significant change (p?>?0.05) in biochemical parametes between control and treated group of animals. Pharmacokinetic data of ART?+?LUM NLs showed higher the area under the plasma concentration–time curve (AUC) values and prolonged residence time of drug in the blood circulation compared with ART?+?LUM solution. The tissue distribution demonstrated high uptake of ART?+?LUM-NLs in RES organs particularly in liver and spleen. Biocompatibility was confirmed by hepato- and nephrotoxicity analysis showed no sign of fibrosis, fatty infiltration, centrilobular necrosis and lymphocyte infiltration confirmed the suitability of developed formulation for treatment of malaria.     

Contribution of TGFβ1 Codon 10 Polymorphism to High Myopia in an Ethnic Kashmiri Population from India

This study looks at novel variants of the TGFβ1 gene and their potential association with high myopia in an ethnic population from Kashmir, India. Allele frequencies of 247 Kashmiri subjects (from India) with high myopia and 176 ethnically matched healthy controls were tested for Hardy–Weinberg disequilibrium. The genotype and allele frequencies were evaluated using chi-square or Fisher’s exact tests. One of the three SNPs in codon 10 showed a significant difference between patients and control subjects (rs1982073: p genotype = 0.003, p allele = 0.001). There were no statistically significant differences between patients and control subjects for the other two SNPs, rs1800471 at codon 25 and a novel variant at codon 52. SNP rs1982073, substituting proline with leucine, appeared to be significantly associated with high myopia (p < 0.05). In silico predictions show that substitutions are likely to have an impact on the structure and functional properties of the protein, making it imperative to understand their functional consequences in relation to high myopia.     

N-terminal HrpE from Xanthomonas oryzae pv. oryzae mediates the regulation of growth and photosynthesis in rice

Plant Growth Regulation - Harpin proteins, produced by gram-negative bacteria, can enhance the plant growth. The growth enhancing potential of the harpins are beneficial and may be associated with...