Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Traveling waves in a profile of phase field: Exact analytical solutions of a hyperbolic Allen-Cahn equation

To obtain solutions of the hyperbolic Allen-Calm equation, the first integral method, which follows from well-known Hilbert Null-theorem, is used. Exact analytical solutions are obtained in a form of traveling waves, which define complete class of the hyperbolic Allen-Calm equation. It is shown that two subclasses of solutions exist within this complete class. The first subclass exhibits continual solutions and the second subclass is represented by solutions with singularity at the origin of coordinate system. Such non-uniqueness of solutions stands a question about stable attractor, i. e., about the traveling wave to which non-stationary solutions may attract. The obtained solutions include earlier solutions for the parabolic Allen-Calm equation in a form of finite number of tanh-functions

Процеси експлуатації адсорбційного регенератора теплоти та вологи на основі композитного адсорбенту «Силікагель–натрій сульфат»

Процеси експлуатації адсорбційного регенератора теплоти та вологи на основі композитного адсорбенту «Силікагель–натрій сульфат» = Оperational processes of adsorptive heat-moisture regenerator based on composite “Silicagel– sodium sulphate” / О. А. Бєляновська, Р. Д. Литовченко, М. П. Сухий, О. О. Єрьомін, М. В. Губинський, І. В. Суха // Зб. наук. пр. НУК. – Миколаїв : НУК, 2020. – № 2 (480). – С. 48–57.Анотація. Робота присвячена дослідженню процесів експлуатації адсорбційного регенератора теплоти і вологи на основі композитного адсорбенту «силікагель–натрій сульфат» для системи припливно-викидної вентиляції житлового приміщення. Розвинуто методику визначення експлуатаційних характеристик адсорбційного регенератора теплоти та вологи, що передбачає: обчислення обсягу повітря, яке пройшло через шар теплоакумулюючого матеріалу, концентрації води в повітрі на виході з теплового акумулятора, адсорбції, теплоти адсорбції, кінцевої температури холодного повітря, температури повітря після змішування холодного повітря з вулиці і теплого повітря у приміщенні під час подачі, розрахунок концентрації води в повітрі на виході з теплового акумулятора, обсягу повітря, яке пройшло через шар теплоакумулюючого матеріалу, кінцевої температури теплого повітря, температури повітря після змішування холодного повітря з вулиці і теплого повітря із приміщення під час викиду, абсолютної вологості після змішування холодного повітря на вулиці та теплого повітря із приміщення під час викиду, визначення температурного коефіцієнта корисної дії, розрахунок вологісного коефіцієнта корисної дії, сумарної адсорбції і часу досягнення максимальної адсорбції, обчислення втрат тиску під час проходження повітря через щар адсорбенту та потужність вентилятора. Показана кореляція експериментально визначених та розрахованих температур повітря й абсолютної вологості повітря біля кінців регенератора, які встановлено всередині вентильованого приміщення та назовні. Проведено моделювання процесів експлуатації адсорбційних регенераторів теплоти і вологи на основі композитів «силікагель–натрій сульфат» в умовах типової системи вентиляції житлових приміщень. Максимальні значення температурних коефіцієнтів корисної дії встановлено за швидкості вологого повітря приблизно 0,22–0,32 м/с і часу перемикання потоків до 5 хвилин. Уперше проаналізовано основні чинники, які впливають на експлуатаційні характеристики адсорбційного регенератора теплоти та вологи. Уперше розглянуто вплив конструктивних характеристик адсорбційного регенеруючого пристрою на його ефективність, а також потужності вентилятора. Результати проведеного дослідження можуть бути використані під час проєктування енергоефективних систем вентиляції і кондиціонування, а також модулів-осушувачів для житлових і складських приміщень.Abstract. The work is focused on the performance of the adsorptive regenerator of heat and moisture based on the composite adsorbent “silica gel – sodium sulphate” for the system of supply and exhaust ventilation of the living premise. The method of determining the operating characteristics of the adsorptive regenerator of heat and moisture is suggested. It involves the next stages: calculation of the volume of air that passed through the layer of heat-storage material, water concentration in the air at the outlet of the regenerator, adsorption, heat of adsorption, final cold air temperature, air temperature after mixing cold air from the street and warm air in the room when supplied, calculating the concentration of water in the air at the outlet of the heat accumulator, final temperature of warm air, air temperature after mixing cold air from the street and warm air from the room at emission, absolute humidity after mixing cold air outside and warm air from the room at emission, determination of temperature efficiency factor, calculation of moisture efficiency factor, total adsorption and time to reach maximum adsorption, calculation of pressure losses during the passage of air through the adsorbent layer and the power consumed by the fan. The correlation of experimentally determined and calculated air temperatures and absolute humidity at the ends of the regenerator, which are installed inside the ventilated room and outside, is shown. Modeling of processes of operation of adsorption regenerators of heat and moisture on the basis of composites “silica gel – sodium sulphate” under the conditions of a typical system of ventilation of premises is carried out. The maximal values of temperature efficiency are set at a humid air velocity of about 0,22–0,32 m/s and a flow switching time of up to 5 minutes. For the first time the main factors influencing the operational characteristics of the adsorption heat and moisture regenerators are analyzed. For the first time, the influence of the design characteristics of the adsorption regenerating device on its efficiency, as well as the power consumed by the fan is considered. The results of the study can be used in the design of energy-efficient ventilation and air conditioning systems, as well as dehumidifiers for residential and warehouse premises

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Deterministic Parallel Random-Number Generation for Dynamic-Multithreading Platforms

Existing concurrency platforms for dynamic multithreading do not provide repeatable parallel random-number generators. This paper proposes that a mechanism called pedigrees be built into the runtime system to enable efficient deterministic parallel randomnumber generation. Experiments with the open-source MIT Cilk runtime system show that the overhead for maintaining pedigrees is negligible. Specifically, on a suite of 10 benchmarks, the relative overhead of Cilk with pedigrees to the original Cilk has a geometric mean of less than 1%. We persuaded Intel to modify its commercial C/C++ compiler, which provides the Cilk Plus concurrency platform, to include pedigrees, and we built a library implementation of a deterministic parallel random-number generator called DOTMIX that compresses the pedigree and then “RC6-mixes ” the result. The statistical qualit