The waiting time paradox: population based retrospective study of treatment delay and survival of women with endometrial cancer in Scotland

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Local Damage of Plain and Reinforced Concrete Targets under Impact Load

In the present study, simplified models for calculating the penetration depth, scabbing, and perforation thicknesses for concrete targets have been proposed. These models consider the dynamic strain rate effect in the estimation of penetration parameters. The results of proposed model have been compared with the experimental data

Biological screening and docking studies of unique hybrids synthesized by conventional versus microwave assisted techniques

Purpose: To carry out the synthesis of various hybrids of 1,2,4-triazole in search of potential therapeutic enzyme inhibitory agents, and carry out docking and bovine serum albumin (BSA) binding studies on docking and bovine serum albumin (BSA) binding studies on the hybrids. Methods: The target compounds were synthesized by following a multistep protocol. Compound 1 was synthesized from 4-methoxybenzenesulfonyl chloride (a) and ethyl isonipecotate (b). Compound 1 was refluxed with hydrazine to synthesize compound 2, which was converted to compound 3 through two consecutive steps. Compound 4 and different amines (5a-5i), were utilized to synthesize an array of electrophiles (6a-6i). A series of 1,2,4-triazole hybrids (7a-7i) were synthesized at room temperature by stirring together 3 and 6a-6i. The final structures of 7a-7i were elucidated through 1H-NMR, 13C-NMR and EI-MS spectroscopy. The BSA binding studies were performed by fluorometric titration. Furthermore, antioxidant and enzyme inhibition activities were determined colorimetrically. Results: Compound 7d was the most active antioxidant agent, compared to butylated hydroxyanisole (BHA), while compounds 7d, 7e, 7f, 7g and 7i proved to be potent urease inhibitors with half-maximal inhibitory concentration (IC50) values of 19.5 ± 0.12, 21.1 ± 0.68, 18.2 ± 0.78, 19.9 ± 0.77 and 17.9 ± 0.10 µM, respectively, compared to thiourea with an IC50 of 24.3 ± 0.24 µM. Compounds 7a, 7b, 7d, and 7e exhibited high butyrylcholinesterase inhibition potential, compared to eserine. Conclusion: The synthesized compounds require studies further as potential therapeutic enzyme inhibitory agents in view of their urease inhibition as well as antioxidant activity

The prognostic value of pre-operative systemic inflammation-based scoring in patients undergoing endovascular repair of AAA

Objectives: Abdominal aortic aneurysm (AAA) is a common condition which is predominantly managed in the UK by endovascular aneurysm repair (EVAR). Activation of the systemic inflammatory response (SIR) appears to offer prognostic value in patients with vascular disease. The present study examines the relationship between the systemic inflammatory response and survival in patients undergoing standard and complex endovascular aneurysm repair (EVAR and F/B-EVAR). Methods: Consecutive patients undergoing elective EVAR and F/B-EVAR were retrospectively identified from three tertiary vascular centres over a 5-year period. Neutrophil:lymphocyte ratio (NLR) and modified Glasgow Prognostic Score (mGPS) were calculated from pre-operative blood results and combined into the systemic inflammatory grade (SIG). The primary outcome was all cause mortality during the follow-up period which was compared between sub-groups of SIG. Results: There were 506 patients included in the final study, with a median (IQR) follow-up of 68.0 (27.3) months, and there were 163 deaths during the follow-up period. Mean (95% CI) survival in the SIG 0 vs. SIG 1 vs. SIG 2 vs. SIG 3 vs. SIG 4 subgroups was 80.7 (76.5 – 85.0) vs. 78.7 (72.7 – 84.7) vs. 61.0 (51.1 - 70.8) vs. 65.1 (45.0 – 85.2) vs. 54.9 (34.4 – 75.3) months (p < 0.05). In the entire cohort, age (p < 0.001), BMI (p <0.05), high creatinine (p <0.05), and SIG (p < 0.05) were associated with survival on univariate analysis, with retained independent association for age (HR 1.72, 95% CI 1.29 – 2.31, p <0.001) and SIG (HR 1.20 95% CI 1.02 – 1.40, p <0.05) on multivariate analysis. Increasing SIG (AUC 0.68, 95% CI 0.58 – 0.78, p <0.01) predicted 1-year mortality. Conclusions: Markers of the systemic inflammatory response such the SIG may be used to identify patients at higher risk of adverse outcome in patients undergoing EVAR and F/B-EVAR for AAA. These findings warrant further investigation in large prospective cohort studies

The relationship between CT-derived body composition, systemic inflammation, and survival in patients with abdominal aortic aneurysm

Objectives: Patient selection and risk stratification for elective repair of abdominal aortic aneurysm (AAA), either by open surgical repair (OSR) or endovascular aneurysm repair (EVAR), remains challenging. CT-derived body composition analysis (CT-BC), and systemic inflammation-based scoring systems such as the systemic inflammatory grade (SIG), appear to offer prognostic value in patients with AAA undergoing EVAR. The relationship between CT-BC, systemic inflammation, and prognosis has been explored in patients with cancer, but data in non-cancer populations are lacking. The present study aimed to examine the relationship between CT-BC, SIG, and survival in patients undergoing elective intervention for AAA. Methods: 611 consecutive patients undergoing elective intervention for AAA at three large tertiary referral centres were retrospectively recruited for inclusion into the study. CT-BC was performed and analysed using the CT-sarcopenia score (CT-SS). Subcutaneous and visceral fat indices (SFI, VFI) were also recorded. SIG was calculated from pre-operative blood tests. The outcomes of interest were overall and 5-year mortality. Results: Median (IQR) follow-up was 67.0 (32) months, and there were 194 (32%) deaths during the follow-up period. There were 122 (20%) OSR cases, 558 (91%) males, and a median (IQR) age of 73.0 (11.0) years. Age (HR 1.66, 95% CI 1.28 – 2.14, p <0.001), elevated CT-SS (HR 1.58, 95% CI 1.28 – 1.94, p <0.001), and elevated SIG (HR 1.29, 95% CI 1.07 – 1.55, p <0.01) were independently associated with increased hazard of mortality. Mean (95% CI) survival in the CT-SS 0 & SIG 0 sub-group was 92.6 (84.8 – 100.4) months, compared with 44.9 (30.6 – 59.2) months in the CT-SS 2 & SIG ≥ 2 sub-group (p <0.001). Patients with CT-SS 0 & SIG 0 had 90% (SE 4%) 5-year survival, compared with 34% (SE 9%) in patients with CT-SS 2 & SIG ≥ 2 (p <0.001). Conclusions: Combining measures of radiological sarcopenia and the SIR offers prognostic value in patients undergoing elective intervention for AAA and may contribute to future clinical risk predication strategies

Rural waste generation: a geographical survey at local scale

"The paper examines the per capita waste generation rates from from rural areas of Neamț County (Romania) using thematic cartography. Geographical approach of this issue is difficult because the lack of a geostatistic database at commune scale. Spatial analysis of waste indicators reveals several disparities between localities. Comparability of data between communes located in various geographical conditions must be carrefully made according to local waste management systems. Several dysfunctionalities are outlined in order to compare these results, on the one hand, between localities and on the one hand, between recent years. Geographical analysis of waste generation rates is imperative for a proper monitoring of this sector. Data from 2009, 2010 and 2012 shows that rural waste management is in a full process of change towards a more organized, stable and efficient system." (author's abstract

Common variants at theCHEK2gene locus and risk of epithelial ovarian cancer

Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P ≤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r (2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1×10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72×10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r (2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70×10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene.Other Research Uni

Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.</p

Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.</p