bluuebunny/crossref_metadata_2025 huggingface dataset:
Large-scale Characterization of Drug Responses of Clinically Relevant Proteins in Cancer Cell Lines
Authors: Zhao Wei , Li Jun , Chen Mei-Ju , Ju Zhenlin , Nesser Nicole K. , Johnson-Camacho Katie , Boniface Christopher T. , Lawrence Yancey , Pande Nupur T. , Davies Michael A. , Herlyn Meenhard , Muranen Taru , Zervantonakis Ioannis , Von Euw Erika , Schultz Andre , Kumar Shwetha V. , Korkut Anil , Spellman Paul T. , Akbani Rehan , Slamon Dennis J. , Gray Joe W. , Brugge Joan S. , Lu Yiling , Mills Gordon B. , Liang Han
Published: July 2020

Perturbation biology is a powerful approach to developing quantitative models of cellular behaviors and gaining mechanistic insights into disease development. In recent years, large-scale resources for phenotypic and mRNA responses of cancer cell lines to perturbations have been generated. However, similar large-scale protein response resources are not available, resulting in a critical knowledge gap for elucidating oncogenic mechanisms and developing effective cancer therapies. Here we generated and compiled perturbed expression profiles of ~210 clinically relevant proteins in >12,000 cancer cell-line samples in response to >150 drug compounds using reverse-phase protein arrays. We show that integrating protein response signals substantially increases the predictive power for drug sensitivity and aids in gaining insights into mechanisms of drug resistance. We build a systematic map of protein-drug connectivity and develop an open-access, user-friendly data portal for community use. Our study provides a valuable information resource for a broad range of quantitative modeling and biomedical applications.

Highlights

A large collection of cancer cell line protein responses to drug perturbations

Perturbed protein responses greatly increase predictive power for drug sensitivity

Build a systematic map of protein-drug connectivity based on response profiles

Develop a user-friendly, interactive data portal for community use
Optogenetics inSinorhizobium melilotienables spatial control of exopolysaccharide production and biofilm structure
Authors: Pirhanov Azady , Bridges Charles M. , Goodwin Reed A. , Guo Yi-Syuan , Furrer Jessica , Shor Leslie M. , Gage Daniel J. , Cho Yong Ku
Published: July 2020

Microorganisms play a vital role in shaping the soil environment and enhancing plant growth by interacting with plant root systems. Due to the vast diversity of cell types involved, combined with dynamic and spatial heterogeneity, identifying the causal contribution of a defined factor, such as a microbial exopolysaccharide (EPS), remains elusive. Synthetic approaches that enable orthogonal control of microbial pathways are a promising means to dissect such complexity. Here we report the implementation of a synthetic, light-activated, transcriptional control platform in the nitrogen fixing soil bacteriumSinorhizobium meliloti.By fine tuning the system, we successfully achieved optical control of an EPS production pathway without significant basal expression under non-inducing (dark) conditions. Optical control of EPS recapitulated important behaviors such as a mucoid plate phenotype and formation of structured biofilms, enabling spatial control of biofilm structures inS. meliloti.The successful implementation of optically controlled gene expression inS. melilotienables systematic investigation of how genotype and microenvironmental factors together shape phenotypein situ.

Significance

Microorganisms are key players in sustaining the soil environment and plant growth. Symbiotic associations of soil microbes and plants provide a major source of nitrogen in agricultural systems, prevent water contamination from synthetic fertilizer application, and support crop growth in marginal soils. However, measuring the impact of microbial gene products on beneficial function remains a major challenge. This work provides a critical step toward addressing this challenge by implementing external gene regulation in a well characterized nitrogen fixing soil bacterium. We show that light exposure enables spatial and temporal control of the extracellular polysaccharide production functionality essential for symbiosis. Remote control of genes enables the benefits of candidate microorganisms to be systematically measured and enhanced within complex natural settings.
The Impact of COVID-19 on Adjusted Mortality Risk in Care Homes for Older Adults in Wales, United Kingdom: A retrospective population-based cohort study for mortality in 2016-2020
Authors: Hollinghurst Joe , Lyons Jane , Fry Richard , Akbari Ashley , Gravenor Mike , Watkins Alan , Verity Fiona , Lyons Ronan A
Published: July 2020

Background

Mortality in care homes has had a prominent focus during the COVID-19 outbreak. Multiple and interconnected challenges face the care home sector in the prevention and management of outbreaks of COVID-19, including adequate supply of personal protective equipment, staff shortages, and insufficient or lack of timely COVID-19 testing. Care homes are particularly vulnerable to infectious diseases.

Aim

To analyse the mortality of older care home residents in Wales during COVID-19 lockdown and compare this across the population of Wales and the previous 4-years.

Study Design and Setting

We used anonymised Electronic Health Records (EHRs) and administrative data from the Secure Anonymised Information Linkage (SAIL) Databank to create a cross-sectional cohort study. We anonymously linked data for Welsh residents to mortality data up to the 14th June 2020.

Methods

We calculated survival curves and adjusted Cox proportional hazards models to estimate hazard ratios (HRs) for the risk of mortality. We adjusted hazard ratios for age, gender, social economic status and prior health conditions.

Results

Survival curves show an increased proportion of deaths between 23rd March and 14th June 2020 in care homes for older people, with an adjusted HR of 1·72 (1·55, 1·90) compared to 2016. Compared to the general population in 2016-2019, adjusted care home mortality HRs for older adults rose from 2·15 (2·11,2·20) in 2016-2019 to 2·94 (2·81,3·08) in 2020.

Conclusions

The survival curves and increased HRs show a significantly increased risk of death in the 2020 study periods.
A mathematical model formulation to design a traditional Indian agri-fresh food supply chain: a case study problem
Authors: Patidar Rakesh , Agrawal Sunil
Published: July 2020

Purpose

The purpose of this paper is to study and develop supply chain structure of traditional Indian agri-fresh food supply chain (AFSC). This paper proposes a mathematical model to design a traditional Indian AFSC to minimize total distribution cost and post-harvest losses in the chain.

Design/methodology/approach

This paper formulates two mathematical models to structure and represent the flow of products in the existing chain. First, a three-echelon, multi-period, multi-product, mixed-integer linear programming (MILP) model is formulated to minimize the total distribution cost incurred in the chain. Further, the developed formulation is extended by considering the perishability of products in the second model.

Findings

A real case study problem of Mandsaur district (India) is solved in LINGO 17.0 package to check the validity of the formulated models. The perishable (second) model of AFSC reports better results in terms of costs and post-harvest losses minimization. The results revealed that 92% of the total distribution cost incurred in the transportation of products from farmers to the hubs.

Research limitations/implications

This paper includes implications for redesigning an existing supply chain network by incorporating an appropriate transportation strategy from farmers to hubs to minimize transportation inefficiency and enhance the profitability of farmers.

Practical implications

The formulated AFSC model would help managers and policymakers to identify optimal locations for hubs where required infrastructure would be developed.

Originality/value

According to the author's best knowledge, this paper is the first to design traditional Indian AFSC by considering the perishability of products.
Understanding the relationship between general and middle-range theorizing
Authors: Swanson David , Goel Lakshmi , Francisco Kristoffer , Stock James
Published: July 2020

Purpose

General theories have been criticized for their inability to explore the mechanics of more specific domain knowledge and understand how, when and where general theory applies to and extends domain knowledge in supply chain management (SCM). Middle-range theorizing (MRT) is a potential solution to this limitation. This paper aims to assist researchers in understanding the relationship between MRT and general theorizing (GT) and connecting MRT research findings to general theory.

Design/methodology/approach

This research provides a structured literature review of 518 articles, from eight journals in logistics, SCM and operations management. Theoretically based articles are analyzed by primary domain and SCM context.

Findings

There are frameworks for conducting MRT; however, the literature does not sufficiently assist researchers in understanding how middle-range (MR) theory should relate to general theory. Findings include a better understanding of underserved areas in SCM, guideline frameworks for understanding when to apply MRT, when to apply GT and how MRT knowledge can be connected to SCM domain knowledge.

Originality/value

This study provides a timely and appropriate compilation of theory research in SCM, including significant implications for both theory and practice, by helping to articulate the evolving philosophy of science in SCM.
Performance indicators for measuring the effects of Smart Maintenance
Authors: Lundgren Camilla , Bokrantz Jon , Skoogh Anders
Published: July 2020

Purpose

The purpose of this study is to ensure productive, robust and sustainable production systems and realise digitalised manufacturing trough implementation of Smart Maintenance – “an organizational design for managing maintenance of manufacturing plants in environments with pervasive digital technologies”. This paper aims to support industry practitioners in selecting performance indicators (PIs) to measure the effects of Smart Maintenance, and thus facilitate its implementation.

Design/methodology/approach

Intercoder reliability and negotiated agreement were used to analyse 170 maintenance PIs. The PIs were structurally categorised according to the anticipated effects of Smart Maintenance.

Findings

Companies need to revise their set of PIs when changing manufacturing and/or maintenance strategy (e.g. reshape the maintenance organisation towards Smart Maintenance). This paper suggests 13 categories of PIs to facilitate the selection of PIs for Smart Maintenance. The categories are based on 170 PIs, which were analysed according to the anticipated effects of Smart Maintenance.

Practical implications

The 13 suggested categories bring clarity to the measuring potential of the PIs and their relation to the Smart Maintenance concept. Thereby, this paper serves as a guide for industry practitioners to select PIs for measuring the effects of Smart Maintenance.

Originality/value

This is the first study evaluating how maintenance PIs measure the anticipated effects of maintenance in digitalised manufacturing. The methods intercoder reliability and negotiated agreement were used to ensure the trustworthiness of the categorisation of PIs. Such methods are rare in maintenance research.
Evaluation of risks in foodgrains supply chain using failure mode effect analysis and fuzzy VIKOR
Authors: Rathore Rishabh , Thakkar J. J. , Jha J. K.
Published: July 2020

Purpose

This paper investigates the risks involved in the Indian foodgrain supply chain (FSC) and proposes risk mitigation taxonomy to enable decision making.

Design/methodology/approach

This paper used failure mode and effect analysis (FMEA) for risk estimation. In the traditional FMEA, risk priority number (RPN) is evaluated by multiplying the probability of occurrence, severity and detection. Because of some drawbacks of the traditional FMEA, instead of calculating RPN, this paper prioritizes the FSC risk factors using fuzzy VIKOR. VIKOR is a multiple attribute decision-making technique which aims to rank FSC risk factors with respect to criteria.

Findings

The findings indicate that “technological risk” has a higher impact on the FSC, followed by natural disaster, communication failure, non-availability of procurement centers, malfunctioning in PDS and inadequate storage facility. Sensitivity analysis is performed to check the robustness of the results.

Practical implications

The outcomes of the study can help in deriving detailed risk mitigation strategy and risk mitigation taxonomy for the improved resilience of FSC.

Originality/value

Specifically, this research investigates the risks for foodgrains supply chain system for a developing country such as India, an area which has received limited attention in the present literature.
Six Sigma Project Procurement application in public procurement
Authors: Ottou Jemima Antwiwaa , Baiden Bernard Kofi , Nani Gabriel
Published: July 2020

Purpose

Project management tools and techniques have been widely adopted in the construction industry; however, its combination with Six Sigma and application in construction procurement has not been widely researched. This paper explores the use of Six Sigma Project Procurement (SSPP) and its potential applications in public sector construction procurement.

Design/methodology/approach

The role of Six Sigma and project management in construction is critically evaluated using three case studies to demonstrate their application in public procurement.

Findings

The use of SSPP by public sector organisations creates efficient and effective construction procurement processes by addressing delays. The proposed timelines for competitive tendering in the Ghanaian Public Procurement Manual are not realistic.

Research limitations/implications

This paper contributes to and broadens the limited body of evidence and knowledge of applying SSPP to public procurement processes and identifies areas for further research.

Practical implications

Project management will continue to expand in the global construction industry. However, what will eventually determine if SSPP is embraced by public sector construction depends on the leadership and success of its execution. The application of SSPP to public construction procurement will address delays and lead to significant time reduction of the process. This will eliminate the major issue (delay) accounting for deficiencies in the process.

Originality/value

The paper yields immense value to construction project management researchers and practitioners, especially in the public sector. It recommends the inclusion of Six Sigma to promote focus on actual instead of perceived problems and advocates for decisions-making based on facts which will ensure continuous improvement.
Disruptive Maintenance Engineering 4.0
Authors: Navas Miguel Angel , Sancho Carlos , Carpio Jose
Published: July 2020

Purpose

The purpose of this paper is to present a new disruptive maintenance model based on new technologies.

Design/methodology/approach

The approach is carrying out through the impact of the Industry 4.0, Internet of things, big data, virtual reality and additive manufacturing on maintenance.

Findings

The findings are that new technologies are an evolutionary challenge that is immediately affecting maintenance engineering. It presents a unique opportunity to make a disruptive evolution of maintenance.

Research limitations/implications

The correct development of Maintenance 4.0 relates to the correct implementation of Industry 4.0.

Practical implications

Maintenance 4.0 will greatly improve the main operating indicators: safety, reliability, availability and cost.

Social implications

Maintenance 4.0 will contribute to a circular and sustainable economy.

Originality/value

For the first time, a complete new Maintenance Engineering 4.0 model is proposed. The application of the new technologies appears in each specific maintenance process of the product life cycle.
Sustainable manufacturing and industry 4.0: what we know and what we don't
Authors: Sharma Rohit , Jabbour Charbel José Chiappetta , Lopes de Sousa Jabbour Ana Beatriz
Published: July 2020

Purpose

The emergence the fourth industrial revolution, known as well as industry 4.0, and its applications in the manufacturing sector ushered a new era for the business entities. It not only promises enhancement in operational efficiency but also magnify sustainable operations practices. This current paper provides a thorough bibliometric and network analysis of more than 600 articles highlighting the benefits in favor of the sustainability dimension in the industry 4.0 paradigm.

Design/methodology/approach

The analysis begins by identifying over 1,000 published articles in Scopus, which were then refined to works of proven influence and those authored by influential researchers. Using rigorous bibliometric software, established and emergent research clusters were identified for intellectual network analysis, identification of key research topics, interrelations and collaboration patterns.

Findings

This bibliometric analysis of the field helps graphically to illustrate the publications evolution over time and identify areas of current research interests and potential directions for future research. The findings provide a robust roadmap for mapping the research territory in the field of industry 4.0 and sustainability.

Originality/value

As the literature on sustainability and industry 4.0 expands, reviews capable of systematizing the main trends and topics of this research field are relevant.
Effects of comparability of promotions on inaction inertia
Authors: Liu Hsin-Hsien , Chou Hsuan-Yi
Published: July 2020

Purpose

Based on mental accounting theory, this study explored whether the comparability of missed and subsequent promotional formats/frames affects inaction inertia.

Design/methodology/approach

Four experiments with imaginary and incentive-compatible designs were conducted to test the hypotheses.

Findings

Consumers are more likely to express inaction inertia after having missed a comparable promotion than after having missed a noncomparable promotion. Devaluation of the promoted target mediates the impact of comparability on inaction inertia, while referent others' actions do not moderate the comparability effect. Finally, when consumers accept a subsequent inferior promotion, they prefer using a different payment format because it reduces comparability of the two promotions.

Practical implications

Companies should use different promotional formats/frames to reduce comparability and inaction inertia when a new promotion is relatively inferior to a recent previous one. Companies should offer different payment options to help customers actively avoid comparing a current promotion with a missed promotion.

Originality/value

This study provides a more comprehensive conceptual structure for understanding the relationship between psychological comparability and inaction inertia. It provides insights into what actions companies should take to reduce inaction inertia. Furthermore, this study empirically tests the influence of multiple comparison referents, which provides a reference point for future studies on the factors affecting inaction inertia. A new method to examine whether consumers actively avoid comparisons is used, which clarifies the internal mechanism of inaction inertia.
Alpha‐lipoic acid: A possible pharmacological agent for treating dry eye disease and retinopathy in diabetes
Authors: Ajith Thekkuttuparambil A.
Published: July 2020

Alpha‐lipoic acid (ALA) is a naturally occurring dithiol micronutrient which acts as a cofactor for mitochondrial enzyme activity. Due to its potential antioxidant activity, it is considered as “universal antioxidant”. Previous studies reported the pharmacological benefits of ALA such as glycaemic control, improved insulin sensitivity and alleviation of diabetic complications such as neuropathy and cardiovascular diseases. Dry eye disease and retinopathy are prevalent in diabetic patients. Experimental studies demonstrated the beneficial effects of ALA in dry eye and diabetic retinopathy. ALA can prevent the dry eye by down regulating the expression of matrix metalloproteinase‐9 in the corneal epithelial cells and activating the antioxidant status of the ocular surface. Furthermore, its direct antioxidant effect can also prevent oxidative stress‐induced corneal surface erosion and lachrymal gland damage. ALA prevents diabetic retinopathy through inhibition of O‐linked β‐N‐acetylglucosamine transferase and nuclear factor‐kappa B activity and alleviation of oxidative stress. It can activate the nuclear factor erythroid‐2‐related factor 2 and AMP‐activated protein kinase in retinal ganglion cells. Clinical trials conducted in pre‐retinopathic diabetic patients showed ALA with genistein and vitamins could protect the retinal cells and decline the inflammatory effect in diabetic patients. However, studies are scant to explore its beneficial effects in dry eye disease and diabetic retinopathy. Therefore, this review article discusses an update on the role of ALA in dry eye disease and diabetic retinopathy, two ocular diseases prevalent in diabetic patients.
Serum uric acid and incident atrial fibrillation: A systematic review and dose–response meta‐analysis
Authors: Zhang Jiayong , Zheng Ruiping , Li Hejun , Guo Jin
Published: July 2020

The exposure‐effect association between serum uric acid and atrial fibrillationis not well known. We conduct a meta‐analysis to quantitatively examine the exposure‐effect relationship between serum uric acid and atrial fibrillation. Prospective studies (including cohort or nested case‐control) that reported the serum uric acid and atrial fibrillation were identified through electronic searches using EMBASE, PubMed, and the Cochrane Library database. The exposure‐effect analysis was performed using a stage robust error meta‐regression. Eleven studies were included, with a total of 6831 cases of atrial fibrillation among 527 908 individuals. Both the highest (risk ratio (RR), 1.9; 95% confidence interval (CI), 1.64–2.23;I2 = 0%) and intermediate (RR, 1.36; 95% CI, 1.16–1.59;I2 = 36%) level of serum uric acid were associated with increased risks of atrial fibrillation compared to the patients with the lowest level of serum uric acid. In the exposure‐effect analysis, for each 1 mg/dL increase in serum uric acid level, the incidence of atrial fibrillation increased by 21% (RR, 1.21; 95% CI, 1.12–1.32;I2 = 78%). Furthermore, a significant positive linear relationship between serum uric acid and the risk of atrial fibrillation, Pnonlinearity = 0.47 was found. The exposure‐effect analysis demonstrated that serum uric acid over 5.0 mg/dL significantly increased the risk of atrial fibrillation. There was a positive linear association between serum uric acid and risk of atrial fibrillation, both in subjects with noruricaemia and hyperuricaemia. More studies are needed to explore the impact of serum uric acid reduction on the incidence of atrial fibrillation.
Vocabulary accessibility and acquisition: do you get more from a financestor or a sociophite?
Authors: Binder Katherine S. , Tremblay Kathryn A. , Joseph Alison
Published: July 2020

Background

The purpose of the current study was to examine how the morphological structure of a real word or novel word affected the incidental vocabulary learning of participants and to examine how these target items are processed as they are read. In addition, we examined the roles of vocabulary depth and breadth in the process of incidental vocabulary learning.

Methods

We had participants read short passages that contained real words or novel words that differed on their morphological accessibility as we collected eye movement data. Participants also completed several vocabulary depth and breadth measures.

Results

Accessible real words and novel words were learned better than inaccessible and less accessible items, but there was a processing cost associated with accessible real words compared with inaccessible real words. In contrast, participants spent more time on the less accessible novel words compared with accessible novel words, but that extra processing time did not translate into better acquisition scores. Finally, both vocabulary breadth and depth explained variance in incidental vocabulary acquisition, while breadth explained variance in gaze duration and depth explained variance in regressive eye movements.

Conclusions

Accessibility of the targets affected both acquisition and reading time, and depth and breadth are both individual differences that explain variance in incidental acquisition and the processing of those words.
Significance of granuloma and granulomatous lymphangitis in the differential diagnosis of Crohn's disease
Authors: Qian Yun , He Wei , Zheng Chu Yi , Xue Jin Hui , Fang Jing Yuan , Chen Xiao Yu , Cui Yun
Published: July 2020

Objective

To clarify the pathological characteristics of granuloma and granulomatous lymphangitis in patients with non‐neoplastic bowel diseases and to compare their significance in the differential diagnosis of Crohn's disease (CD) and intestinal tuberculosis (ITB).

Methods

Altogether 78 cases with CD, 11 with ITB and 33 suffering from other non‐neoplastic bowel diseases were included. All patients underwent a partial enterectomy and histopathological examination. Pathological sections were reviewed retrospectively. Detailed morphological features and the distribution of granulomas and granulomatous lymphangitis in the three groups were analyzed and compared.

Results

Significant differences in the features of granuloma were observed in CD compared with ITB, including the presence of Langhans giant cells, caseous necrosis, coalescence, hyaline change, onionskin changes, and their frequency and size. Granulomatous lymphangitis was significantly more frequent in CD than in other non‐neoplastic bowel diseases (P < 0.0001). The rate was also higher than that of granuloma in CD (P = 0.0004). It more often manifested within the mucosal layer of the small bowel (55.4%) in CD whereas it tended to be located within the deep layers of the intestinal wall in other diseases. It can be divided into four types, but types 1 and 2 appeared relatively specific to CD.

Conclusions

Granuloma and granulomatous lymphangitis were not specific in CD. However, by combining morphology and distribution, their manifestations could assist in the differentiation of CD from other non‐neoplastic bowel diseases. Furthermore, granulomatous lymphangitis showed better diagnostic performance than granulomas in the mucosal layer of the small bowel.
Application of genotyping methods in the investigation of sources of dermatophytosis associated with vaccination in cattle
Authors: Łagowski Dominik , Gnat Sebastian , Nowakiewicz Aneta , Osińska Marcelina , Zięba Przemysław
Published: July 2020

Vaccines against trichophytosis introduced over 60 years ago contributed to a significant reduction in the prevalence of dermatophyte infections on cattle farms. Currently, vaccination is not obligatory but commonly used and recommended by veterinarians, which is associated with the renaissance of dermatophyte infections in farm animals. Importantly, vaccine administration may cause clinical lesions imitating a virulent form of dermatophytosis. Correct determination of a possible correlation of superficial changes with the vaccine strain plays a key role in taking therapeutic measures. In this study, the usefulness of genotyping methods (melting‐point‐PCR and amplified fragment length polymorphism) in identification of the source of dermatophyte infection in cases correlated with vaccine administration is examined. The results revealed that dermatophytes isolated from skin lesions in calves temporarily associated with vaccine administration had an identical electrophoretic profile with the vaccine strain and differed from the reference strain of Trichophyton verrucosum CBS365.53. In conclusion, genotyping methods are a useful tool for rapid and reliable identification of the vaccine source of superficial lesions in calves. Their high resolution, speed of execution and low costs are undoubted advantages in the implementation for routine use in similar cases of dermatophyte infections.
Cannabis use disorder trajectories and their prospective predictors in a large population‐based sample of young Swiss men
Authors: Marmet Simon , Studer Joseph , Wicki Matthias , Gmel Gerhard
Published: July 2020

Background and Aims

Cannabis use disorder (CUD) is frequent in adolescence and often goes into remission towards adulthood. This study aimed to estimate trajectories of CUD severity (CUDS) in Swiss men aged from 20 to 25 years and to identify prospective predictors of these trajectories.

Design

Latent class growth analysis of self‐reported CUDS in a cohort study with three data collection waves.

Setting

A general population sample of young Swiss men.

Participants

A total of 5987 Swiss men assessed longitudinally at the mean ages of 20, 21.5 and 25 years.

Measurements

Latent CUDS in the last 12 months was measured at each wave with the Cannabis Use Disorders Identification Test–Revised (CUDIT‐R). Predictors of CUDS trajectories, measured at age 20, were from six domains: factors related to cannabis use, family, peers, other substance use, mental health and personality.

Findings

We distinguished four CUDS trajectories: stable–low (88.2%), decreasing (5.2%), stable–high (2.6%) and increasing (4.0%). Predictors were generally associated with higher odds of membership in the decreasing and stable–high trajectory (versus the stable–low), and to a lesser degree with higher odds of membership in the increasing trajectory. Bivariate predictors of persistent high CUDS (stable–high versus decreasing trajectory) were major depression severity [odds ratio (OR) = 1.19, 95% confidence interval (CI) = 1.01, 1.40], attention deficit hyperactivity disorder severity (OR = 1.25, 95% CI = 1.04, 1.51), antisocial personality disorder severity (OR = 1.18, 95 % CI = 1.04, 1.34), relationship with parents (OR = 0.74, 95% CI = 0.63, 0.88), number of friends with drug problems (OR = 1.33, 95% CI = 1.11, 1.60) and the personality dimensions neuroticism–anxiety (OR = 1.35, 95% CI = 1.11, 1.65) and sociability (OR = 0.78, 95% CI = 0.62, 0.97).

Conclusions

Factors associated with persistent cannabis use disorder in young Swiss men include cannabis use, cannabis use disorder severity, mental health problem severity, relationship with parents (before the age of 18), peers with drug problems and the personality dimensions neuroticism–anxiety and sociability at or before age 20. Effect sizes may be small, and predictors are mainly associated with persistence via higher severity at age 20 years.
Changes in alcoholic beverage preference and consumption in Taiwan following accession to the World Trade Organization
Authors: Chen Cheng‐Che , Cheng Kai‐Wen , Chang Hsin‐Yi , Chang Shu‐Sen
Published: July 2020

Background and Aims

Given the growing concerns that international trade agreements may increase the supply of health‐harming commodities, including alcohol, this study aimed to investigate the changes in alcoholic beverage preference and consumption after Taiwan's accession to the World Trade Organization (WTO).

Design

A before‐and‐after comparison analysis using data from two waves (1993–1996 and 2005–2008) of the Nutrition and Health Survey in Taiwan (NAHSIT), before and after Taiwan's accession to the WTO in 2002.

Setting

Taiwan.

Participants

A total of 5031 and 2910 participants aged 19 years or older in NAHSIT 1993–1996 and 2005–2008, respectively.

Measurements

Alcohol measures included beverage‐specific preference, mean daily ethanol consumption, and heavy drinking. Logistic regression was used to estimate the prevalence rate ratios and rate differences of beverage preferences between the two waves and the risk ratios of heavy drinking associated with different beverage preferences.

Findings

A reduced prevalence rate of drinkers who preferred rice spirits (prevalence rate ratio [PRR] = 0.47; 95% confidence interval [CI] = 0.24, 0.91) and Asian wine (PRR = 0.11; 95% CI = 0.04, 0.29) was found in contrast to an increase in the preference for fruit wine (PRR = 2.90; 95% CI = 1.75, 4.79); the preference for Asian spirits showed a non‐significant increase (PRR = 1.63; 95% CI = 0.88, 3.02). Similarly, the mean daily ethanol consumption decreased for Asian wine and increased for Asian spirits. Compared with beer, an increased risk of heavy drinking was associated with rice spirits (adjusted risk ratio [aRR] = 3.30; 95% CI = 1.68, 6.47) and Asian spirits (aRR = 2.64; 95% CI = 1.38, 5.01).

Conclusions

After Taiwan became a member of the World Trade Organization and abolished its alcohol monopoly in 2002, the pattern of alcoholic beverage preference changed markedly, including a decrease in drinkers who preferred rice spirits and Asian wine (53% and 89% decrease, respectively) and an increase in drinkers who preferred fruit wine and Asian spirits (2.9‐fold and 1.6‐fold increase, respectively).
Fetal safety of nicotine replacement therapy in pregnancy: systematic review and meta‐analysis
Authors: Taylor Lauren , Claire Ravinder , Campbell Katarzyna , Coleman‐Haynes Tom , Leonardi‐Bee Jo , Chamberlain Catherine , Berlin Ivan , Davey Mary‐Ann , Cooper Sue , Coleman Tim
Published: July 2020

Background and aims

Smoking in pregnancy causes substantial avoidable harm to mothers and offspring; nicotine replacement therapy (NRT) may prevent this, and is used to help women to quit. A recently updated Cochrane Review of randomized controlled trials (RCTs) investigating impacts of NRT in pregnancy focuses primarily on efficacy data, but also reports adverse impacts from NRT. Here we identify and summarize NRT impacts on adverse pregnancy outcomes reported in non‐randomized controlled trials (non‐RCTs).

Methods

Systematic reviews and meta‐analyses of RCTs and non‐RCT studies of NRT in pregnancy, with design‐specific risk of bias assessment and grading of recommendations, assessment, development and evaluations (GRADE) criteria applied to selected outcomes.

Findings

Relevant Cochrane Review findings are reported alongside those from this new review. Seven RCTs were included; n = 2340. Nine meta‐analyses were performed; non‐statistically significant estimates indicated potentially reduced risk from NRT compared with smoking for mean birth weight, low birth weight, preterm birth, intensive care admissions, neonatal death, congenital anomalies and caesarean section and potentially increased risks for miscarriage and stillbirth. GRADE assessment for mean birth weight and miscarriage outcomes indicated ‘low’ confidence in findings.

Twenty‐three non‐RCTs were included; n = 931 163. Eleven large studies from five routine health‐care cohorts reported clinical outcomes; 12 small studies investigated mainly physiological outcomes within in‐patient women given NRT. Findings from meta‐analyses for congenital anomalies, stillbirth and preterm birth were underpowered and not in a consistent direction; GRADE assessment of confidence in findings was ‘very low’. Routine health‐care studies were of higher quality, but implications of reported findings were unclear as there was inadequate measurement and reporting of women's smoking.

Conclusions

Available evidence from randomized controlled trials and non‐randomized comparative studies does not currently provide clear evidence as to whether maternal use of nicotine replacement therapy during pregnancy is harmful to the fetus.
Quadratus lumborum block vs. transversus abdominis plane block for caesarean delivery: a systematic review and network meta‐analysis*
Authors: El‐Boghdadly K. , Desai N. , Halpern S. , Blake L. , Odor P. M. , Bampoe S. , Carvalho B. , Sultan P.
Published: July 2020

Caesarean delivery is the most commonly performed inpatient surgical procedure globally. Pain after caesarean delivery is moderate to severe if not adequately treated, and is a primary anaesthetic concern for patients. Transversus abdominis plane and quadratus lumborum blocks are fascial plane blocks that have the potential to improve analgesia following caesarean delivery. Although proponents of the quadratus lumborum block suggest that this technique may provide better analgesia compared with transversus abdominis plane block, there are limited data directly comparing these two techniques. We, therefore, performed a systematic review and network meta‐analysis to compare transversus abdominis plane and quadratus lumborum block approaches, seeking randomised controlled trials comparing both techniques to each other, or to control, with or without intrathecal morphine. In all, 31 trials with 2188 patients were included and our primary outcome, the cumulative intravenous morphine equivalent consumption at 24 h, was reported in 12 trials. In the absence of intrathecal morphine, transversus abdominis plane and quadratus lumborum blocks were equivalent, and both were superior to control (moderate‐quality evidence). In the presence of intrathecal morphine, no differences were found between control, transversus abdominis plane and quadratus lumborum blocks (moderate‐quality evidence). Similar results were found for resting and active pain scores at 4–6 h, 8–12 h, 24 h and 36 h, although quadratus lumborum block was associated with lower pain scores at 36 h when compared with transversus abdominis plane block (very low‐quality evidence). However, transversus abdominis plane block was associated with a reduced incidence of postoperative nausea and vomiting (moderate‐quality evidence) and sedation when compared with inactive control following intrathecal morphine administration (low‐quality evidence). There are insufficient data to draw definitive conclusions, but transversus abdominis plane and quadratus lumborum block appear to be superior to control in the absence of intrathecal morphine, but provide limited additional benefit over inactive control when intrathecal morphine is also used.
Equals in Solidarity: Orfanotrofio’s Housing Squat as a Site for Political Subjectification Across Differences Amid the “Greek Crisis”
Authors: Karaliotas Lazaros , Kapsali Matina
Published: July 2020

This article engages with the political struggles staged by illegalised migrants and activists in solidarity amid the long summer of migration and the “Greek crisis”. Grounding its analysis on Orfanotrofio’s housing squat in Thessaloniki, it narrates how such struggles are articulated to politicise migration and stage the equality of newcomers—migrants and refugees—and locals. Drawing on Jacques Rancière’s political writings and contemporary geographical work on solidarity, the article argues that such struggles not only disrupt the exclusionary ordering of our cities but also construct political spaces and infrastructures of dissensus wherein equals in solidarity discuss common political problems and devise common political strategies. Through the notion of equals in solidarity, the article investigates how the performative enactment of equality can form the basis for solidarities across differences and analyses how some of the tensions that emerge around collective political subjectification are negotiated. Building on this, it explores some of the challenges and limitations that these struggles face in their efforts to transform the existing order of the city.
On precision dosing of oral small molecule drugs in oncology
Authors: Lyashchenko Alex K. , Cremers Serge
Published: July 2020

Personalization of oral small molecule anticancer drug doses based on individual patient blood drug levels, also known as therapeutic drug monitoring (TDM), has the potential to significantly improve the effectiveness of treatment by maximizing drug efficacy and minimize toxicity. However, this option has not yet been widely embraced by the oncology community. Some reasons for this include increased logistical complexity of dose individualization, the lack of clinical laboratories that measure small molecule drug concentrations in support of patient care, and the lack of reimbursement of costs. However, the main obstacle may be the lack of studies clearly demonstrating that monitoring of oral small molecule anticancer drug levels actually improves clinical outcomes. Without unequivocal evidence in support of TDM‐guided dose individualization, especially demonstration of improved survival with TDM in randomized controlled trials, wide acceptance of this approach by oncologists and reimbursement by insurance companies is unlikely, and patients may continue to suffer as a result of receiving incorrect drug doses. This article reviews the current status of TDM of oral small molecule drugs in oncology and intends to provide strategic insights into the design of studies for evaluating the utility of TDM in this clinical context.
Inhibition of CYP2D6 with low dose (5 mg) paroxetine in patients with high 10‐hydroxynortriptyline serum levels‐A prospective pharmacokinetic study
Authors: Jessurun Naomi T. , Vermeulen Windsant Annemieke , Mikes Oenone , van Puijenbroek Eugène P. , van Marum Rob J. , Grootens Koen , Derijks Hieronymus J.
Published: July 2020

The antidepressant nortriptyline is metabolized by cytochrome P450 2D6 (CYP2D6) to the less active and more cardiotoxic drug metabolite, 10‐hydroxynortriptyline. High serum levels of this metabolite (>200 μg/L) may lead to withdrawal of nortriptyline therapy. Adding CYP2D6 inhibitors reduce the metabolic activity of CYP2D6 (phenoconversion) and so decrease the forming of hydroxynortriptyline. In this study, 5 mg paroxetine is administered to patients with high hydroxynortriptyline concentrations (>200 μg/L). The shift in number of patients to therapeutic nortriptyline (50–150 μg/L) and safe hydroxynortriptyline (<200 μg/L) concentrations, and the degree of phenoconversion, expressed as the change in ratio nortriptyline/hydroxynortriptyline concentrations before and after paroxetine addition, are prospectively observed and described. After paroxetine addition, 12 patients (80%) had therapeutic nortriptyline and safe hydroxynortriptyline concentrations. Hydroxynortriptyline concentrations decreased in all patients. The average nortriptyline/hydroxynortriptyline concentrations ratio increased from 0.32 to 0.59. This study shows that 5 mg paroxetine addition is able to lower high hydroxynortriptyline serum levels to safe ranges.
The influence of stage of illness on functional outcomes after psychological treatment in bipolar disorder: A systematic review
Authors: Tremain Hailey , Fletcher Kathryn , Scott Jan , McEnery Carla , Berk Michael , Murray Greg
Published: July 2020

Objectives

The aim of this study was to advance understanding of stage of illness in bipolar disorder (BD), by interrogating the literature for evidence of an influence of stage of illness on functional (ie non‐symptom) outcomes following psychosocial intervention.

Methods

A systematic literature search following PRISMA guidelines was conducted to identify empirical studies of psychosocial interventions for established BD. To investigate stage as a predictor of three functional outcomes (general/social functioning, cognitive functioning and quality of life [QoL]), study samples were dichotomised into earlier and later stage using proxy measures identified in existing staging models. Findings were integrated using data‐based convergent synthesis.

Results

A total of 88 analyses from 62 studies were identified. Synthesis across studies suggested that psychosocial intervention was more likely to be effective for general functioning outcomes earlier in the course of established BD. No stage‐related differences were found for cognitive or QoL outcomes. Exploratory investigations found some evidence of an interaction between specific intervention type and stage of illness in predicting outcomes.

Conclusions

A novel systematic review provided preliminary evidence that benefits general/social functioning may be more pronounced in earlier versus later stages of established BD. The review also generated hypotheses about a potential three‐way interaction, whereby specific psychosocial interventions may be best placed to target functional outcomes in earlier versus later stage BD. The strength of conclusions is limited by the overall low‐quality and significant heterogeneity of studies. Further research is urgently required to understand the impact of illness stage on the effectiveness of psychosocial interventions.
Students' perception of corporate social responsibility: Analyzing the influence of gender, academic status, and exposure to business ethics education
Authors: Ugwuozor Felix Okechukwu
Published: July 2020

Studies on students' perception of corporate social responsibility (CSR) have been growing in western scholarship. For students in African countries, such as Nigeria, there is little that is known about how and whether gender, level of study, and being enrolled in business education courses impact their perception of and disposition towards CSR. This study explores the significance of gender, academic status or level of study, and exposure to business ethics education (BEE) on Nigerian students' perception of CSR as a veritable business ethic. Specifically, the effects of these factors on students' perception of CSR are examined using analysis of variance. The results show a significant effect of exposure to BEE and gender on CSR‐sensitivity, and a mild, but significant effect of academic status. This implies that male students and female students had different perspectives on CSR issues. Students who took ethics courses and those who did not would run businesses differently. However, age and experience on campus did not influence students' perception or position on CSR. The study recommends that more behavioral models be estimated with the inclusion of more demographic and socioeconomic variables to elicit more robust results.
FDG‐PET/CT after two cycles of R‐CHOP in DLBCL predicts complete remission but has limited value in identifying patients with poor outcome – final result of a UK National Cancer Research Institute prospective study
Authors: Mikhaeel N. George , Cunningham David , Counsell Nicholas , McMillan Andrew , Radford John A. , Ardeshna Kirit M. , Lawrie Anthony , Smith Paul , Clifton‐Hadley Laura , O'Doherty Michael J. , Barrington Sally F.
Published: July 2020

The UK National Cancer Research Institute initiated a prospective study (UKCRN‐ID 1760) to assess the prognostic value of early fluorodeoxyglucose (FDG)‐positron emission tomography (PET)/computed tomography (CT) in diffuse large B‐cell lymphoma (DLBCL). In total, 189 patients with DLBCL treated with R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) had baseline and post‐cycle‐2 PET (PET2) within a quality assurance framework. Treatment decisions were based on CT; PET2 was archived for central blinded reporting after treatment completion. The association of PET2 response with end‐of‐treatment CT, progression‐free (PFS) and overall survival (OS) was explored. The end‐of‐treatment complete response rate on CT was 83·9%, 75·0%, 70·5%, 40·4% and 36·4% for Deauville score (DS) 1 (n = 34), 2 (n = 39), 3 (n = 46), 4 (n = 56) and 5 (n = 14) (P < 0·001); and 64·1% and 50·0% for the maximum standardised uptake value (∆SUVmax) of ≥66% (n = 168) and <66% (n = 21), respectively (P = 0·25). After a median 5·4 years of follow‐up, the 5‐year PFS was 69·4%, 72·8%, 76·7%, 71·2% and 47·6% by DS 1–5 (P = 0·01); and 72·6% and 57·1% by ∆SUVmax of ≥66% and <66% (P = 0·03), respectively. The association with DS remained in multivariable analyses, and was consistent for OS. Early complete metabolic response (DS 1–3) at interim PET/CT after two cycles of R‐CHOP in DLBCL was associated with a higher end‐of‐treatment complete and overall response rate; however, only DS‐5 patients had inferior PFS and OS.