768 research outputs found

    Probability of improvement methods for constrained multi-objective optimization

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    This paper shows how the simultaneous consideration of multiple Kriging models can lead to useful metrics for the selection of design vectors in constrained multiobjective optimization. The savings in computational cost with such methods make them particularly useful for optimal electromagnetic design

    Peroxisome Proliferator-activated receptor alpha gene variation influences age of onset and progression of type 2 diabetes

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    Dysregulation of fatty acid metabolism is important in the pathogenesis of type 2 diabetes. Peroxisome proliferator-activated receptor (PPAR) is a master regulator of fatty acid catabolism, and PPAR activators delay the onset of type 2 diabetes. We examined association between three PPAR gene polymorphisms (an AC variant in intron 1, the L162V variant, and the intron 7 GC variant) and age at diagnosis of type 2 diabetes in 912 Caucasian type 2 diabetic subjects. Individually, PPAR gene variants did not influence age at diagnosis, but in combination, the rare alleles of both the intron 1 AC (P < 0.001) and intron 7 GC (P = 0.025) variants synergistically lowered age at diagnosis (interaction P < 0.001). Overall, the PPAR haplotype signficantly influenced age at diagnosis (P = 0.027), with the C-L-C and C-V-C haplotypes (intron 1-L162V-intron 7) accelerating onset of diabetes by 5.9 (P = 0.02) and 10 (P = 0.03) years, respectively, as compared with the common A-L-G haplotype, and was associated with an odds ratio for early-onset diabetes (age at diagnosis 45 years) of 3.75 (95% CI 1.65–8.56, P = 0.002). Intron 1 C-allele carriers also progressed more rapidly to insulin monotherapy (AA 9.4 ± 1.5 and AC + CC 5.3 ± 1.1 years, P = 0.002). These data indicate that PPAR gene variation influences the onset and progression of type 2 diabetes

    Deep learning approach to estimate the optimal number of piles and beams from architectural floorplans

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    The traditional process of estimating piles and beams from architectural floor plans is a manual, time-consuming task that is prone to human error. Accurate estimation is vital for effective planning and execution of construction projects. It helps in scheduling, resource allocation, and logistics, ensuring that the construction process is smooth and efficient. The need for an automated process to enhance efficiency and accuracy is a primary problem being addressed. This paper presents an innovative framework for automating the estimation of the optimal number of piles and beams from architectural floor plans using advanced image processing and structural analysis techniques. Leveraging a deep segmentation network with a context-aware classifier, we enhance the accuracy of identifying key structural elements in floor plans. Our method involves a three-stage process: extracting structural elements, vectorizing floor plans, and identifying load-bearing walls. We employ a thinning algorithm and contour reduction techniques for precise vectorization, and our approach in determining room spans assists in accurately locating load-bearing walls. This methodology not only streamlines the estimation process of foundationalelements but also introduces a novel way of integrating deep learning with architectural engineering, setting a new standard in construction planning. Preliminary results demonstrate a significant reduction in time and error margins compared to traditional methods, showcasing the potential of our frameworkto revolutionize construction planning and execution

    The eVALuate study: two parallel randomised trials, one comparing laparoscopic with abdominal hysterectomy, the other comparing laparoscopic with vaginal hysterectomy

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    OBJECTIVE: To compare the effects of laparoscopic hysterectomy and abdominal hysterectomy in the abdominal trial, and laparoscopic hysterectomy and vaginal hysterectomy in the vaginal trial. DESIGN: Two parallel, multicentre, randomised trials. Setting 28 UK centres and two South African centres. Participants 1380 women were recruited; 1346 had surgery; 937 were followed up at one year. PRIMARY OUTCOME: outcome Rate of major complications. RESULTS: In the abdominal trial laparoscopic hysterectomy was associated with a higher rate of major complications than abdominal hysterectomy (11.1% v 6.2%, P = 0.02; difference 4.9%, 95% confidence interval 0.9% to 9.1%) and the number needed to treat to harm was 20. Laparoscopic hysterectomy also took longer to perform (84 minutes v 50 minutes) but was less painful (visual analogue scale 3.51 v 3.88, P = 0.01) and resulted in a shorter stay in hospital after the operation (3 days v 4 days). Six weeks after the operation, laparoscopic hysterectomy was associated with less pain and better quality of life than abdominal hysterectomy (SF-12, body image scale, and sexual activity questionnaires). In the vaginal trial we found no evidence of a difference in major complication rates between laparoscopic hysterectomy and vaginal hysterectomy (9.8% v 9.5%, P = 0.92; difference 0.3%, − 5.2% to 5.8%), and the number needed to treat to harm was 333.We found no evidence of other differences between laparoscopic hysterectomy and vaginal hysterectomy except that laparoscopic hysterectomy took longer to perform (72 minutes v 39 minutes) and was associated with a higher rate of detecting unexpected pathology (16.4% v 4.8%, P = < 0.01). However, this trial was underpowered. CONCLUSIONS: Laparoscopic hysterectomy was associated with a significantly higher rate of major complications than abdominal hysterectomy. It also took longer to perform but was associated with less pain, quicker recovery, and better short term quality of life. The trial comparing vaginal hysterectomy with laparoscopic hysterectomy was underpowered and is inconclusive on the rate of major complications; however, vaginal hysterectomy took less time

    A New Strategy to Stabilize Oxytocin in Aqueous Solutions: I. The Effects of Divalent Metal Ions and Citrate Buffer

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    In the current study, the effect of metal ions in combination with buffers (citrate, acetate, pH 4.5) on the stability of aqueous solutions of oxytocin was investigated. and divalent metal ions (Ca2+, Mg2+, and Zn2+) were tested all as chloride salts. The effect of combinations of buffers and metal ions on the stability of aqueous oxytocin solutions was determined by RP-HPLC and HP-SEC after 4 weeks of storage at either 4°C or 55°C. Addition of sodium or potassium ions to acetate- or citrate-buffered solutions did not increase stability, nor did the addition of divalent metal ions to acetate buffer. However, the stability of aqueous oxytocin in aqueous formulations was improved in the presence of 5 and 10 mM citrate buffer in combination with at least 2 mM CaCl2, MgCl2, or ZnCl2 and depended on the divalent metal ion concentration. Isothermal titration calorimetric measurements were predictive for the stabilization effects observed during the stability study. Formulations in citrate buffer that had an improved stability displayed a strong interaction between oxytocin and Ca2+, Mg2+, or Zn2+, while formulations in acetate buffer did not. In conclusion, our study shows that divalent metal ions in combination with citrate buffer strongly improved the stability of oxytocin in aqueous solutions

    Vitamin D as a Neuroactive Substance: Review

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    The objectives of this paper were (1) to review recent research on the actions of vitamin D as a steroid derivative with neuroactive properties and (2) to highlight clinical relevance and need for more research. Our methods included review of research from current journals, Medline, and Cochrane Reviews; theoretical discussion. Scientific research has had a justifiably strong emphasis on how vitamin D affects calcium metabolism and bone. This appears to have eclipsed its fundamental actions on several other important systems, including the central nervous system. Vitamin D as a neuroactive compound, a prohormone, is highly active in regulating cell differentiation, proliferation, and peroxidation in a variety of structures, including the brain. Vitamin D insufficiency is not rare. Historically, focus has been on bone metabolism, which appears to have caused research bias and evidence bias, distorting physiological importance. The central nervous system is increasingly recognized as a target organ for vitamin D via its wide-ranging hormonal effects, including the induction of proteins such as nerve growth factor. We need more research on this important neuroactive substance because it may play a role as a relatively safe and inexpensive pharmaceutical in the prevention and treatment of a number of common neuropsychiatric conditions

    Human paraoxonase gene cluster polymorphisms as predictors of coronary heart disease risk in the prospective Northwick Park Heart Study II

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    AbstractThe anti-atherogenic effect of HDL has been suggested to be partly due to the action of HDL-associated paraoxonase (PON). Three distinct enzymes have been identified, encoded by PON1, PON2 and PON3, clustered on chromosome 7q21–q22. Two cSNPs in PON1 (L55M and Q192R) and one in PON2 (S311C) have been implicated as independent risk factors for coronary heart disease (CHD) in some, but not all, studies. A PON3 SNP (A99A) was identified and the effect of these four PON SNPs on HDL levels and CHD risk was examined in the prospective Northwick Park Heart Study II (NPHSII). Genotype frequencies did not differ between cases and controls but the CHD risk associated with smoking was significantly modified by PON1 L55M genotype. Compared to LL non-smokers, LL smokers had a hazard ratio (HR) of 1.30 (95% CI 0.81–2.06) while M-allele carriers had a HR of 1.76 (1.17–2.67). When genotypes were analysed in combination, men with the genotype PON1 55 LM/MM+PON2 311 CC, had HR of 3.54 (1.81–6.93) compared to PON1 LL+PON2 SS/SC men (interaction P=0.004). These effects were independent of classical risk factors. These data demonstrate the importance of stratifying by environmental factors and the use of multiple SNPs for genetic analysis

    Capillary electrophoresis-mass spectrometry using noncovalently coated capillaries for the analysis of biopharmaceuticals

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    In this work, the usefulness of capillary electrophoresis–electrospray ionization time-of-flight–mass spectrometry for the analysis of biopharmaceuticals was studied. Noncovalently bound capillary coatings consisting of Polybrene-poly(vinyl sulfonic acid) or Polybrene-dextran sulfate-Polybrene were used to minimize protein and peptide adsorption, and achieve good separation efficiencies. The potential of the capillary electrophoresis-mass spectrometry (CE-MS) system to characterize degradation products was investigated by analyzing samples of the drugs, recombinant human growth hormone (rhGH) and oxytocin, which had been subjected to prolonged storage, heat exposure, and/or different pH values. Modifications could be assigned based on accurate masses as obtained with time-of-flight–mass spectrometry (TOF-MS) and migration times with respect to the parent compound. For heat-exposed rhGH, oxidations, sulfonate formation, and deamidations were observed. Oxytocin showed strong deamidation (up to 40%) upon heat exposure at low pH, whereas at medium and high pH, mainly dimer (>10%) and trisulfide formation (6–7%) occurred. Recombinant human interferon-β-1a (rhIFN-β) was used to evaluate the capability of the CE-MS method to assess glycan heterogeneity of pharmaceutical proteins. Analysis of this N-glycosylated protein revealed a cluster of resolved peaks which appeared to be caused by at least ten glycoforms differing merely in sialic acid and hexose N-acetylhexosamine composition. Based on the relative peak area (assuming an equimolar response per glycoform), a quantitative profile could be derived with the disialytated biantennary glycoform as most abundant (52%). Such a profile may be useful for in-process and quality control of rhIFN-β batches. It is concluded that the separation power provided by combined capillary electrophoresis and TOF-MS allows discrimination of highly related protein species

    Screening families of patients with premature coronary heart disease to identify avoidable cardiovascular risk: a cross-sectional study of family members and a general population comparison group

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    &lt;b&gt;Background:&lt;/b&gt; Primary prevention should be targeted at individuals with high global cardiovascular risk, but research is lacking on how best to identify such individuals in the general population. Family history is a good proxy measure of global risk and may provide an efficient mechanism for identifying high risk individuals. The aim was to test the feasibility of using patients with premature cardiovascular disease to recruit family members as a means of identifying and screening high-risk individuals. &lt;b&gt;Findings:&lt;/b&gt; We recruited family members of 50 patients attending a cardiology clinic for premature coronary heart disease (CHD). We compared their cardiovascular risk with a general population control group, and determined their perception of their risk and current level of screening. 103 (36%) family members attended screening (27 siblings, 48 adult offspring and 28 partners). Five (5%) had prevalent CHD. A significantly higher percentage had an ASSIGN risk score &#62;20% compared with the general population (13% versus 2%, p &#60; 0.001). Only 37% of family members were aware they were at increased risk and only 50% had had their blood pressure and serum cholesterol level checked in the previous three years. &lt;b&gt;Conclusions:&lt;/b&gt; Patients attending hospital for premature CHD provide a mechanism to contact family members and this can identify individuals with a high global risk who are not currently screened
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