The paper addresses the writings of St Augustine of Hippo, thus marking the 1600th anniversary of the anti-Donatist synod held in Carthage and the start of Augustine’s anti-Pelagian argument in 411 ...AD. The focus is on two orations (Sermo 272 and 227), translated into Slovenian for the first time, which explain the significance of the Eucharist as a mystery of God’s unity and a sacrament of salvation. The contextualisation of their historical and theological backgrounds sheds light on the Donatist and Pelagian controversies, as well as on their implications for Augustine’s thought on the Eucharist from the ecclesiastic and soteriological perspectives. The basic concepts of his sacramental doctrine are defined by the descriptive method. The paper thus concisely confirms the impact of individual controversies on the development of Augustine’s theology, which has exercised a decisive influence on the history of dogmas and practices up to the present.
The aim of this research is to study the factors affecting drag coefficient (C d ) innon-Newtonian fluids which are the rheological properties ,concentrations of non-Newtonian fluids, particle shape, ...size and the density difference between particle andfluid .Also this study shows drag coefficient (C d ) and particle Reynolds' number (ReP ) relationship and the effect of rheological properties on this relationship.An experimental apparatus was designed and built, which consists of Perspex pipeof length of 160 cm. and inside diameter of 7.8 cm. to calculate the settling velocity,also electronic circuit was designed to calculate the falling time of particles throughfluid.Two types of solid particles were used; glass spheres and crushed rocks asirregularly shaped particles with different diameters and compared with each other.The concept of equivalent spherical diameter (D S ) was used to calculate thediameters of irregularly shaped particles.The flow behavior for Non-Newtonian fluids was represented by Power-Law model.Two types of polymers were used, Carboxy Methyl Cellulose CMC withconcentrations of (3.71, 5, 15 and 17.5) g/l and polyacrylamide with concentrations of(2, 4 and 6) g/l.The results showed that the drag coefficient decreased with increasing settlingvelocity and particle diameters and sizes; and increased as fluid become far fromNewtonian behavior and concentrations and the density difference between particleand fluid.The results also showed that the rheological properties of Non-Newtonian fluidshave a great effect on the drag coefficient and particle Reynolds number relationship,especially in laminar-slip regime and decreases or vanishes at transition and turbulentslipregimes.New correlations were obtained which relates drag coefficient with concentrationsof polymers and with flow behavior indices for spherical and irregular shapedparticles in Carboxy Methyl Cellulose CMC and polyacrylamide solutions.
The aim of this research is to study the factors affecting the settling velocity (V S ) in Non-Newtonian fluids which are the rheological properties, concentrations of non-Newtonian fluids, particle ...shape and size. An experimental apparatus was designed and built, which consists of Perspex pipe of length of 160 cm. and inside diameter of 7.8 cm. to calculate the settling velocity, also electronic circuit was designed to calculate the falling time of particles through fluid. Two types of solid particles were used; glass spheres and crushed rocks as irregularly shaped particles with different diameters and compared with each other. The concept of equivalent spherical diameter (D S ) was used to calculate the diameters of irregularly shaped particles. The settling velocity was calculated for Non-Newtonian fluids which represented by Power- Law fluid. Two types of polymers were used, Carboxy Methyl Cellulose with concentrations of (3.71, 5, 15 and 17.5) g/l and polyacrylamide with concentrations of (2, 4 and 6) g/l. The results showed that the settling velocity decreased when fluid becomes far from Newtonian behavior (flow index n decreased) and also when concentrations of polymer solutions increased, also, the settling velocity increased with particle diameter or volume. Three sets of equations were concluded; the first relates settling velocity with flow index (n), the second relates settling velocity with concentrations, and the third relates settling velocity with particle diameter.
There is, so far, no universal definition of severe asthma. This definition usually relies on: number of exacerbations, inhaled therapy, need for oral corticosteroids, and respiratory function. The ...use of such parameters varies in the different definitions used. Thus, according to the parameters chosen, each patient may result in having severe asthma or not. The aim of this study was to evaluate how the choice of a specific definition of severe asthma can change the allocation of patients.
Data collected from the Severe Asthma Network Italy (SANI) registry were analyzed. All the patients included were then reclassified according to the definitions of U-BIOPRED, NICE, WHO, ATS/ERS, GINA, ENFUMOSA, and TENOR.
540 patients, were extracted from the SANI database. We observed that 462 (86%) met the ATS/ERS criteria as well as the GINA criteria, 259 (48%) the U-Biopred, 222 (41%) the NICE, 125 (23%) the WHO, 313 (58%) the Enfumosa, and 251 (46%) the TENOR criteria. The mean eosinophil value were similar in the ATS/ERS, U-Biopred, and Enfumosa (528, 532 and 516 cells/mcl), higher in WHO and Tenor (567 and 570 cells/mcl) and much higher in the NICE classification (624 cells/mcl). Lung function tests resulted similarly in all groups, with WHO (67%) and ATS/ERS-GINA (73%), respectively, showing the lower and upper mean FEV1 values.
The present observations clearly evidence the heterogeneity in the distribution of patients when different definitions of severe asthma are used. However, the recent definition of severe asthma, provided by the GINA document, is similar to that indicated in 2014 by ATS/ERS, allowing mirror reclassification of the patients examined. This lack of homogeneity could complicate the access to biological therapies. The definition provided by the GINA document, which reflects what suggested by ATS/ERS, could partially overcome the problem.
Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS) which worsen patients’ health and increase healthcare spending. Aim of this study was to assess the clinical ...and economic effect of adding mepolizumab (MEP) for the treatment of these patients.
Patients >18 years old, referred to 8 asthma clinics, starting MEP between May 2017 and December 2018, were enrolled and followed-up for 12 months. Information in the 12 months before mepolizumab were collected retrospectively. The evaluation parameters included: OCS use, number of exacerbations/hospitalizations, concomitant therapies, comorbidity, and annual number of working days lost due to the disease. The primary objective was to compare the annual total cost per patient pre- and post-MEP. Secondary outcomes included rates of exacerbations and number of OCS-dependent patients.
106 patients were enrolled in the study: 46 male, median age 58 years. Mean annual cost pre- and post-MEP (cost of biologic excluded) was €3996 and €1,527, respectively. Total savings due to MEP resulted in €2469 (95%CI 1945–2993), 62% due to exacerbations reduction and 33% due to productivity increase. Such savings could fund about 22% of the total cost of MEP for one year. The introduction of MEP induced a clinical benefit by reducing both OCS-dependent patients (OR = 0.12, 95%CI 0.06–0.23) and exacerbation rate (RR = 0.19, 95%CI 0.15–0.24).
Patients with severe eosinophilic asthma experienced a clinical benefit in asthma control adding MEP to standard therapy. Biologic therapy can be, partially, funded by the savings produced by patients’ improvement.
IntroductionPostoperative health-related quality of life (HRQoL) is an essential outcome in oncological surgery, particularly for elderly patients undergoing high-risk surgery. Previous studies have ...suggested that, on average, HRQoL returns to premorbid normal levels in the months following major surgery. However, the averaging of effect over a studied cohort may hide the variation of individual HRQoL changes. The proportions of patients who have a varied HRQoL response (stable, improvement, or a deterioration) after major oncological surgery is poorly understood. The study aims to describe the patterns of these HRQoL changes at 6 months after surgery, and to assess the patients and next-of-kin regret regarding the decision to undergo surgery.Methods and analysisThis prospective observational cohort study is carried out at the University Hospitals of Geneva, Switzerland. We include patients over 18 years old undergoing gastrectomy, esophagectomy, pancreas resection or hepatectomy. The primary outcome is the proportion of patients in each group with changes in HRQoL (improvement, stability or deterioration) 6 months after surgery, using a validated minimal clinically important difference of 10 points in HRQoL. The secondary outcome is to assess whether patients and their next-of-kin may regret their decision to undergo surgery at 6 months. We measure the HRQoL using the EORTC QLQ-C30 questionnaire before and 6 months after surgery. We assess regret with the Decision Regret Scale (DRS) at 6 months after surgery. Key other perioperative data include preoperative and postoperative place of residence, preoperative anxiety and depression (HADS scale), preoperative disability (WHODAS V.2.0), preoperative frailty (Clinical Frailty Scale), preoperative cognitive function (Mini-Mental State Examination) and preoperative comorbidities. A follow-up at 12 months is planned.Ethics and disseminationThe study was first approved by the Geneva Ethical Committee for Research (ID 2020-00536) on 28 April 2020. The results of this study will be presented at national and international scientific meetings, and publications will be submitted to an open-access peer-reviewed journal.Trial registration numberNCT04444544.
Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response ...to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening.
We combined new and existing genotype data for 10,516 cases and 20,772 controls from 5 European and 2 East Asian cohorts.
We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, which each play key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, JAK-STAT signalling, and differentiation of T helper (TH)1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some of which are well-established in the treatment of other autoimmune disorders.
This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders.
Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10,516 people with PBC and 20,772 healthy individuals recruited in Canada, China, Italy, Japan, the UK, or the USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these ‘candidate genes’ to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC.
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•Trans-ethnic genome-wide meta-analysis (GWMA) of susceptibility to primary biliary cholangitis (PBC).•Five cohorts of European ancestry and two East Asian cohorts (n = 10,516 cases and 20,772 controls).•Identification of 21 additional risk loci for PBC.•Preliminary evidence that the genetic architecture of PBC is broadly shared across European and East Asian populations.•Identification (using in silico drug efficacy screening) of medications potentially suitable for re-purposing to PBC.
To evaluate DNA ploidy and S-phase fraction (SPF) in non-Lynch colonic adenocarcinoma, ulcerative colitis (UC), Crohn disease (CD) which are known as risk factors, and colitis. We correlated ploidy ...and SPF with tumor grading, staging and BRAF expression.
All studied adenocarcinomas have intact mismatch repair genes as proved by immunohistochemistry. All were assessed for ploidy by automated image-based DNA cytometry and histograms were drawn. Immunostaining by anti-BRAF V600E was performed. Diagnostic laparoscopy (DL) was done as a preliminary step for staging GI cancers.
there is significant difference in DNA ploidy between groups; 77.5% and 17.5% of aneuploid cases are adenocarcinoma and UC. Groups are compared in terms of 2C, 4C, above 4C DNA content and SPF and significant difference is principally found between adenocarcinoma group and others. In adenocarcinomas, DNA ploidy is significantly correlated with tumor staging and grading. Regarding BRAF expression, there is significant difference between groups; all adenocarcinomas, 83.33% of UC were positive, while all cases of colitis, bilharzial colitis, CD were negative. There is significant relation between BRAF and SPF among all diploid cases including adenocarcinoma, and among non-neoplastic diploid cases. There is direct significant relation between BRAF intensity and adenocarcinoma staging. There is no significant difference between BRAF and ploidy among UC cases, although 75% of aneuploid UC are positive. DL helps in GI cancer staging. Routine laparoscopy before laparotomy, especially in cancers which have equivocal operability helps to avoid unnecessary laparotomies.
Based on significant difference in ploidy between adenocarcinoma and UC and between SPF and ploidy, assessment of ploidy by DNA cytometry for UC and other colitis could therefore predict impending malignant transformation before development of colonic dysplasia. Also measuring SPF in adenocarcinoma helps to select patients who could greatly benefit from chemotherapy. DL has vital role in staging GI cancers.
Abstract
The synthesis of both enantiomers of a key intermediate in the synthesis of halofuginone was accomplished by a
Candida antarctica
lipase B (CAL-B)-catalyzed kinetic resolution of the ...corresponding racemate. When the resolution was carried out in the versatile solvent cyclopentyl methyl ether (CPME) using
p
-chlorophenylbutyrate (PCPB) as the acylating reagent, the highest enantiomeric ratio (
E
) values were measured, and highly enantioenriched (95% ee) compounds could be obtained in a single iteration. As an example, one of the two enantiomers was used as a starting material to prepare (+)-halofuginone in a three-step procedure.
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