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

No abstract available

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

Gaia Early Data Release 3: The celestial reference frame (Gaia-CRF3)

Context. Gaia-CRF3 is the celestial reference frame for positions and proper motions in the third release of data from the Gaia mission, Gaia DR3 (and for the early third release, Gaia EDR3, which contains identical astrometric results). The reference frame is defined by the positions and proper motions at epoch 2016.0 for a specific set of extragalactic sources in the (E)DR3 catalogue. Aims. We describe the construction of Gaia-CRF3 and its properties in terms of the distributions in magnitude, colour, and astrometric quality. Methods. Compact extragalactic sources in Gaia DR3 were identified by positional cross-matching with 17 external catalogues of quasi-stellar objects (QSO) and active galactic nuclei (AGN), followed by astrometric filtering designed to remove stellar contaminants. Selecting a clean sample was favoured over including a higher number of extragalactic sources. For the final sample, the random and systematic errors in the proper motions are analysed, as well as the radio-optical offsets in position for sources in the third realisation of the International Celestial Reference Frame (ICRF3). Results. Gaia-CRF3 comprises about 1.6 million QSO-like sources, of which 1.2 million have five-parameter astrometric solutions in Gaia DR3 and 0.4 million have six-parameter solutions. The sources span the magnitude range G = 13-21 with a peak density at 20.6 mag, at which the typical positional uncertainty is about 1 mas. The proper motions show systematic errors on the level of 12 μas yr-1 on angular scales greater than 15 deg. For the 3142 optical counterparts of ICRF3 sources in the S/X frequency bands, the median offset from the radio positions is about 0.5 mas, but it exceeds 4 mas in either coordinate for 127 sources. We outline the future of Gaia-CRF in the next Gaia data releases. Appendices give further details on the external catalogues used, how to extract information about the Gaia-CRF3 sources, potential (Galactic) confusion sources, and the estimation of the spin and orientation of an astrometric solution

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation