bluuebunny/crossref_metadata_2025 huggingface dataset:
Trans-ethnic genome-wide meta-analysis of 35,732 cases and 34,424 controls identifies novel genomic cross-ancestry loci contributing to lung cancer susceptibility
Authors: Byun Jinyoung , Han Younghun , Li Yafang , Xia Jun , Xiao Xiangjun , Sun Ryan , Walsh Kyle M. , Gorlov Ivan , Gorlova Olga , Zhou Wen , Pettit Rowland W , Song Zhuoyi , Rosenberg Susan M , Zhu Dakai , Wiencke John K. , Albanes Demetrius , Lam Stephan , Tardon Adonina , Chen Chu , Goodman Gary , Bojeson Stig , Brenner Hermann , Landi Maria Teresa , Johansson Mattias , Mulley Thomas , Risch Angela , Wichmann H-Erich , Bickeböller Heike , Christiani David C. , Rennert Gad , Arnold Susanne , Field John K. , Shete Sanjay , LeMarchand Loic , Melander Ole , Brunnstrom Hans , Liu Geoffrey , Andrew Angeline S. , Kiemeney Lambertius A. , Shen Hongbing , Zienolddiny Shan , Grankvist Kjell , Johansson Mikael , Caporaso Neil , Cox Angela , Hong Yun-Chul , Yuan Jian-Min , Lazarus Philip , Schabath Matthew B. , Aldrich Melinda C. , Patel Apla , Lan Qing , Rothman Nat , Taylor Fiona , Spitz Margaret , Brennan Paul , Lin Xihong , McKay James , Hung Rayjean J. , Amos Christopher I. ,   INTEGRAL Consortium
Published: October 2020

Lung cancer is the leading cause of cancer death worldwide. Genome-wide association studies have revealed genetic risk factors, highlighting the role of smoking, family history, telomere regulation, and DNA damage-repair in lung cancer etiology. Many studies have focused on a single ethnic group to avoid confounding from variability in allele frequencies across populations; however, comprehensive multi-ethnic analyses may identify variants that are more likely to be causal. This large-scale, multi- ethnic meta-analyses identified 28 novel risk loci achieving genome-wide significance. Leading candidates were further studied using single-cell methods for evaluating DNA-damage. DNA-damage promoting activities were confirmed for selected genes by knockdown genes and overexpression studies.
Business Shutdowns and COVID-19 Mortality
Authors: Ciminelli Gabriele , Garcia-Mandicó Sílvia
Published: October 2020

Governments around the world have adopted unprecedented policies to deal with COVID-19. This paper zooms in on business shutdowns and investigates their effectiveness in reducing mortality. We leverage upon highly granular death registry data for over 4,000 Italian municipalities in a diff-in-diff approach that allows us to credibly mitigate endogeneity concerns. Our results, which are robust to controlling for a host of co-factors, offer strong evidence that business shutdowns are very effective in reducing mortality. We calculate that the death toll from the first wave of COVID-19 in Italy would have been twice as high in their absence. Our findings also highlight that timeliness is key – by acting one week earlier, the government could have reduced the death toll by an additional 25%. Finally, our estimates suggest that shutdowns should be targeted: closing shops, bars and restaurants saves the most lives, while shutting down manufacturing and construction activities has only mild effects.
The smORF-containing genemille-pattesis required for moulting andTrypanosoma cruzimetacyclogenesis in the Chagas disease vectorRhodnius prolixus
Authors: Silva Carina Azevedo Oliveira , da Silveira Alves Sandy , da-Costa-Rodrigues Bruno , Egidio Jonatha Anderson Fraga , Ribeiro Lupis , Logullo Carlos , Mury Flavia Borges , da Silva José Roberto , Nepomuceno-Silva José Luciano , Nunes-da-Fonseca Rodrigo
Published: October 2020

Chagas disease is estimated to affect 8 million people worldwide and is responsible for circa 10,000 deaths in Latin America every year. Vector control has been developed as the main strategy to control disease spreading. The identification of new targets is essential, and genes containing small open reading frames (smORFs - < 100 amino acids) are present as hundreds of putative new candidate targets in insect genomes. Here, we show that the prototypic smORF containing genemille-pattes/polished-rice/tarsalless(mlpt/pri/tal) is essential for post-embryonic development of the kissing bugRhodnius prolixusand for the metacyclogenesis of theTrypanosoma cruziparasite during nymphal stages. Injection of double-stranded RNA againstmlpt(Rp-dsmlpt) during nymphal stages leads to a plethora of phenotypes which impairs post-embryonic development. First, nymphs of fourth or fifth stage injected with Rp-dsmlptdo not moult. Second, vector digestive physiology is largely modified, and haemozoin is significantly increased in the posterior midgut of Rp-dsmlptnymphs. Third, Rp-mlptknockdown inhibits the metacyclogenesis ofTrypanosoma cruzi, the etiologic agent of Chagas disease. Thus, our study provides the first evidence of a smORF-containing gene regulating vector physiology, parasitic cycle and disease transmission.
Edition of complex gene families in tobacco with GoldenBraid 4.0, a multipurpose web-based platform for plant genome engineering
Authors: Vazquez-Vilar Marta , Garcia-Carpintero Víctor , Selma Sara , Bernabé-Orts Joan M , Sanchez-Vicente Javier , Salazar-Sarasua Blanca , Ressa Arianna , de Paola Carmine , Ajenjo María , Fernández-del-Carmen Asun , Granell Antonio , Orzáez Diego
Published: October 2020

CRISPR/Cas ability to target several loci simultaneously (multiplexing) is a game-changer in plant breeding. Multiplexing not only accelerates trait pyramiding but also can unveil traits hidden by functional redundancy in polyploid crops. Furthermore, multiplexing enhances dCas-based programmable gene expression and enables cascade-like gene regulation. However, multiplex constructs comprising tandemly arrayed gRNAs are difficult to assemble, this hampering more widespread use. Here we present a comprehensive upgrade of the popular cloning platform GoldenBraid (GB), in which, on top of its classical multigene cloning software, we integrate new assembly tools for two-dimensions gRNA multiplexing with both Cas9 and Cas12a, using the gRNA-tRNA-spaced and the gRNA unspaced approaches, respectively. As functional validation, we show, among others, the assembly of up to 17 tandemly-arrayed gRNAs constructs against a subset of the Squamosa-Promoter Binding Protein-Like (SPL) gene family in tobacco. With these constructs we generated a collection of Cas9-free SPL mutants harboring up to 9 biallelic mutations in a single generation. The functionality of GB-assembled dCas9 and dCas12a-based CRISPR activators and repressors using single and multiplexing gRNAs is also validated. With the incorporation of the new CRISPR tools and part’s collection, GB4.0 turns an unprecedentedly comprehensive open platform for plant genetic engineering.
Proton wires mediate the optical signal for ArcLight-type Genetically Encoded Voltage Indicators
Authors: Kang B.E , Leong L. M. , Kim Y. , Miyazaki K. , Ross W. N. , Baker B. J.
Published: October 2020

The genetically encoded voltage indicators, ArcLight and its derivatives, mediate voltage dependent optical signals by intermolecular, electrostatic interactions between neighboring fluorescent proteins (FPs) via proton wires. A random mutagenesis event placed a negative charge on the exterior of the FP resulting in a greater than 10-fold improvement of the voltage-dependent optical signal. Repositioning this negative charge on the exterior of the FP reversed the polarity of voltage-dependent optical signals suggesting the presence of ‘hot spots’ capable of interacting with the negative charge on a neighboring FP thereby changing the fluorescent output. To explore the potential effect on the chromophore state, voltage-clamp fluorometry was performed with alternating excitation at 390 nm followed by excitation at 470 nm resulting in several mutants exhibiting voltage-dependent, ratiometric optical signals of opposing polarities. However, the kinetics, voltage ranges, and optimal FP fusion sites were different depending on the wavelength of excitation. These results suggest that the FP has external, electrostatic pathways capable of quenching fluorescence that are wavelength specific. ArcLight-derived GEVIs may therefore offer a novel way to map how conditions external to the β-can structure can affect the fluorescence of the chromophore and transiently manipulate those pathways via conformational changes mediated by whole cell voltage clamp.

Statement of Significance

ArcLight-type GEVIs utilize proton pathways that send charge information outside of the FP to the internal chromophore enabling voltage induced conformational changes to affect fluorescence. These pathways are excitation wavelength specific suggesting that different external positions affect the protonated and deprotonated states of the chromophore.
Oligomerisation of THAP9 transposase: role of DNA and amino-terminal domains
Authors: Sanghavi Hiral M. , Majumdar Sharmistha
Published: October 2020

Active DNA transposases like the Drosophila P element transposase (DmTNP) undergo oligomerisation as a prerequisite for transposition. Human THAP9 (hTHAP9) is a catalytically active but functionally uncharacterised homologue of DmTNP. Here we report (using co-IP, pull down, co-localization, PLA) that both the full length as well as truncated hTHAP9 and DmTNP (corresponding to amino-terminal DNA binding and Leucine-rich coiled coil domains) undergo homo-oligomerisation, predominantly in the nuclei of HEK293T cells. Interestingly, the oligomerisation is shown to be partially mediated by DNA. However, mutating the leucines (either individually or together) or deleting the predicted coiled coil region did not significantly affect oligomerisation. Thus, we highlight the importance of DNA as well as the amino-terminal regions of both hTHAP9 and DmTNP, for their ability to form higher order oligomeric states. We also report that Hcf-1, THAP1, THAP10 and THAP11 are possible protein interaction partners of hTHAP9. These studies lead to several questions about the different putative oligomeric states of hTHAP9 and how they may be related to its yet unknown physiological role as well as interaction partners.
APEX-Gold: A genetically-encoded particulate marker for robust 3D electron microscopy
Authors: Rae James , Ferguson Charles , Ariotti Nicholas , Webb Richard I. , Cheng Han-Hao , Mead James L. , Riches Jamie , Hunter Dominic J.B. , Martel Nick , Baltos Joanne , Christopoulos Arthur , Bryce Nicole S. , Cagigas Maria Lastra , Fonseka Sachini , Hardeman Edna C. , Gunning Peter W. , Gambin Yann , Hall Thomas , Parton Robert G.
Published: October 2020

Genetic tags allow rapid localization of tagged proteins in cells and tissues. APEX, an ascorbate peroxidase, has proven to be one of the most versatile and robust genetic tags for ultrastructural localization by electron microscopy. Here we describe a simple method, APEX-Gold, which converts the diffuse oxidized diaminobenzidine reaction product of APEX into a silver/gold particle akin to that used for immunogold labelling. The method increases the signal to noise ratio for EM detection, providing unambiguous detection of the tagged protein, and creates a readily quantifiable particulate signal. We demonstrate the wide applicability of this method for detection of membrane proteins, cytoplasmic proteins and cytoskeletal proteins. The method can be combined with different electron microscopic techniques including fast freezing and freeze substitution, focussed ion beam scanning electron microscopy, and electron tomography. The method allows detection of endogenously expressed proteins in genome-edited cells. We make use of a cell-free expression system to generate membrane particles with a defined quantum of an APEX-fusion protein. These particles can be added to cells to provide an internal standard for estimating absolute density of expressed APEX-fusion proteins.
Determinants of the annual rate of change of union membership in divergent national contexts after the nations survive through major economic crisis
Authors: Sarkar Santanu , Chakraborty Ranabir
Published: October 2020

Purpose

We were intrigued by the question of whether the convergence of businesses across nations in search of flexibility to survive economic crisis led to a convergence of the annual rate of change of union membership. The question emerged because the convergence theory was controverted, especially when the neo-capitalist idea failed to withstand the test of time during the economic crisis.

Design/methodology/approach

By adopting the model from Bain and Elsheik (1976) and using time-series data from 1990 to 2014 for Finland and India that survived economic crisis during this period, whereby union membership remained steady in Finland but declined in India, we assessed the empirical distinction between the changes in union membership.

Findings

We argued that when hit by an economic crisis, different nations had divergent responses and chose different means of economic recovery because of which the countries have not withstood the crisis in one specific way/direction that at all times, marginalises unions. Our main finding is that in both the countries, the annual rate of change of union membership during the years of economic recovery was determined by the policy response. And, policy responses were determined not only by the causes of economic crisis but also by the strength of unique national institutional configurations and history of the country.

Originality/value

The annual rate of change of union membership during the years of economic recovery was determined by the policy response. And, policy responses were determined not only by the causes of economic crisis but also by the strength of unique national institutional configurations and history of the country.
Goals of the national mathematics curriculum of Pakistan: educators’ perceptions and challenges toward achievement
Authors: Mughal Shahid Hussain , Asad Muhammad Mujtaba , Adams Donnie
Published: October 2020

Purpose

The national mathematics curriculum of Pakistan has emphasized on improving content knowledge, reasoning abilities and problem-solving skills of students about thinking, communicating and solving mathematics (national mathematics curriculum of Pakistan, 2006). Whereas, there is a need to understand the point of view of teachers about the challenges they face in achieving the goals of national mathematics curriculum. This will help leading teacher training institutions to revisit their math teacher continuous professional development (CPD) programs and facilitate school leadership in improving the quality of math education in rural schools of the province. However, the purpose of this research study is to figure out the challenges that teachers are facing while achieving the goals of the national curriculum by teaching mathematics at the primary level in educational institutes of Pakistan.

Design/methodology/approach

In this research study qualitative research approaches have been utilized, in which focus group discussions (FGDs) were used as data collection techniques. Furthermore, thematic analysis of the data led toward the development of four overarching themes such as teachers' knowledge about mathematics curriculum, challenges relating to mathematics content and pedagogy, difficulties in developing conceptual understanding and designing lesson plans to address students' diversity.

Findings

The overall findings of this research study suggested that the majority of teachers are facing difficulties in mathematics content teaching such as decimal fraction, unitary method, measurement principles, practical geometry and data handling. Moreover, teachers are also facing challenges and difficulties in developing hands-on and minds-on activities in the teaching of mathematical concepts to the students of primary level in educational institutes of Pakistan.

Practical implications

This research study will facilitate the teachers and stakeholders to address the problematic issues in the domain of content delivery of mathematics. Whereas, this study recommends educating teachers about national mathematics curriculum and to develop a CPD framework for mathematics teachers for the enhancement of their pedagogical content knowledge. The study also recommends orientating school heads about the different aspects of math curriculum so that they can mentor math teachers in achieving math curriculum goals.

Originality/value

This is the first research study of its nature, which targets and highlights the teacher's perceptions toward the achieving the goals of national mathematics curriculum of Pakistan and addressing the pedagogical challenges faced in mathematics teachers. There is a dearth of studies in mathematics education in Sindh province. The issue is of immense importance, the findings will help teachers to improve mathematics instructions at primary level.
Critical variables and constructs in the context of project management: importance-performance analysis
Authors: Haverila Matti , Haverila Kai Christian , Twyford Jenny Carita
Published: October 2020

Purpose

Relying on the importance-performance theory first established by Martilla and James (1977), this research paper utilizes a unique statistical analysis instrument embedded into the SmartPLS software. It explores the importance and performance of key project management constructs and indicators with a purpose to make practical and actionable recommendations for project managers to identify and improve project management practices.

Design/methodology/approach

The data used were derived from 3,130 system delivery projects in the facilities management industry. The data was analyzed with Partial Least Squares Modelling (PLS) software SmartPLS, using its embedded importance-performance functionality.

Findings

The findings indicate the importance and performance of the project management constructs and their respective indicator variables in an importance-performance (IPMA) map. All three project management phases (constructs); proposal, installation and commissioning, were significantly related to satisfaction. The installation phase (construct) showed the highest potential for performance improvement in project management. With regard to the specific indicator variables, the variable “Coordinating their work with other contractors (or the owner's staff)” received a strong “Do better” recommendation.

Originality/value

The approach and results provide an easy to use and visual tool for project managers to assess the importance and performance of the various elements of project management. The instrument provides a project management direction for the identification of strategic enhancement areas as it is essential to recognize what facets of project management contribute most to the improvement of project management performance over a longer period of time (Cronin and Taylor, 1992; Palmer, 1998).
Linking work, occupational identity and burnout: the case of managers
Authors: Hamouche Salima , Marchand Alain
Published: October 2020

Purpose

Based on identity theory, identity represents a set of meanings individuals hold for themselves based on their role in the society. Hence, they often engage in the process of verifying their role, seeking for the compatibility between these meanings and those perceived in a specific lived situation. If this compatibility is not perceived, this is likely to generate negative emotions. that could compromise their mental health. This paper examines the contribution of a weak verification of role identity in the explanation of managers ‘burnout. It aims at integrating identity theory into occupational stress research by analysing the proposition that a low level of verification of a salient role-identity will be associated with a high level of burnout. Hence, we consider identity salience as a moderating variable.

Design/methodology/approach

Cross-sectional data of 314 Canadian managers employed in 56 Quebec firms. Multilevel regression analyses were performed to analyse the data.

Findings

Low levels of verification of some standards of managers' role identity, mainly work demands and recognition which encompasses (monetary and non-monetary recognition, career prospects and job security) are significantly associated with managers' burnout. Furthermore, as predicted, results show that identity salience plays a moderating role on the relation between a weak verification of some standards of managers' role identity and burnout, mainly work demands, superior support and recognition.

Originality/value

This study proposes a relatively unexplored approach for the study of managers' burnout. It broadens the scope of research on workplace mental health issues, by the integration of the identity theory.
Nationalistic appeals and consumer boycotts in China, 1900-1949
Authors: Yan Tony , Hyman Michael R.
Published: October 2020

Purpose

The purpose of this study is to explore how nationalistic appeals may affect consumers’ perception and purchasing of targeted brands. Qualitative historical data from old China (1900–1949) reveal that social movement groups can adopt nationalistic appeals assisted by meaning framing – defined as a creative interpretation of symbols, designs, behaviors, social events and cultural identities to serve social and political goals – to shape consumers’ attitudes toward foreign brands. After examining the mechanisms and processes underlying consumer boycotts from 1900 to 1949, the responsive strategies of affected foreign companies are illustrated.

Design/methodology/approach

Critical historical research method is applied to historical data and historical “traces” from China’s corporate documents, memoirs, posters, advertisements, newspapers and secondhand sources documenting Chinese boycotts from 1900 to 1949.

Findings

Consumers may pursue interests beyond economic interests. Nationalistic appeals can mobilize consumer boycotts against foreign brands that were perceived to support or relate to targeted countries. Political framing of certain events shapes consumers’ perceptions and concomitant brand choices.

Research limitations/implications

Although differences between historical and current contexts may require tailoring past marketing strategies to current conditions, past strategies can inform current and future strategies.

Practical implications

Strategies adopted by foreign companies in old China (1900–1949) can help contemporary companies design effective marketing strategies for a hostile marketplace infused with nationalistic appeals and competing interests.

Social implications

Although local companies can adopt economic or political nationalism to realize their economic goals, it represents a double-edged sword that can harm national brands.

Originality/value

A historical analysis of nationalistic business appeals in pre-1949 China can inform the counterstrategies modern companies adopt to overcome consumer boycotts.
Identity leadership and well-being: team identification and trust as underlying mechanisms
Authors: Krug Henning , Geibel Hannah V. , Otto Kathleen
Published: October 2020

Purpose

The purpose of the present research was to examine the impact of identity leadership on employees' well-being mediated by team identification and trust in the leader.

Design/methodology/approach

In study 1, N = 192 employees participated in a cross-sectional online survey measuring identity leadership, team identification, trust in the leader and well-being (i.e., job satisfaction, work engagement, burnout). In study 2, N = 72 university students participated in a vignette study that manipulated high/low identity leadership and tested its effect on team identification and trust in the leader.

Findings

In study 1, identity leadership predicted higher team identification, trust in the leader and well-being of employees. Team identification mediated the positive relationship of identity leadership with both job satisfaction and work engagement, while trust in the leader mediated the negative relationship of identity leadership with burnout. In study 2, team identification and trust in the leader were significantly higher in the high identity leadership condition.

Research limitations/implications

The findings are consistent with the few existing studies on the positive effects of identity leadership. However, due to the correlational nature of the data in study 1, future longitudinal field research is needed to support the current findings and further establish causality for the model as a whole.

Practical implications

Identity leadership seems to be promising to increase well-being among employees. Thus, leadership development programs to foster identity leadership and collective identity should be implemented in organizations and further tested with respect to well-being.

Originality/value

This research contributes to an emerging body of research on the social identity approach to leadership and supports the recent claims that social identity might be one of the links between leader behavior and well-being of employees. Moreover, this study is among the first to investigate and experimentally test the underlying mechanisms of identity leadership.
The thermomechanical response of a poroelastic medium with two thermal relaxation times
Authors: Abbas Ibrahim , Hobiny Aatef
Published: October 2020

Purpose

The purpose of this paper is to study the wave propagation in a porous medium through the porothermoelastic process using the finite element method (FEM).

Design/methodology/approach

One-dimensional (1D) application for a poroelastic half-space is considered. Due to the complex governing equation, the finite element approach has been adopted to solve these problems.

Findings

The effect of porosity and thermal relaxation times in a porothermoelastic material was investigated.

Originality/value

The numerical results for stresses, displacements and temperatures for the solid and the fluid are represented graphically. This work will enable future investigators to have the insight of nonsimple porothermoelasticity with different phases in detail.
Personal and organizational level relationships in relational exchanges in supply chains – a bottom-up model
Authors: Qian Chen , Seuring Stefan , Wagner Ralf , Dion Paul A.
Published: October 2020

Purpose

This paper aims to examine how trust and communication at the personal level relationships conform to trust and communication at the organizational level relationships and which role do the two different level relationships play in influencing firms’ commitment, performance and propensity to stay in long-term relationships.

Design/methodology/approach

A face-to-face questionnaire study was conducted using a sample of 209 in Mainland China companies, which were surveyed in nine exhibitions. The data were analyzed using structural equation modeling.

Findings

The results support the bottom-up effect of interpersonal trust and communication on inter-organizational trust and communication. Interorganizational trust has a more powerful total effect on firm commitment. Interpersonal communication has a more powerful total effect on inter-organizational trust and communication and firms’ operational performance. Interpersonal communication, inter-organizational trust and communication have comparably high impacts on firms’ propensity to stay in long-term relationships.

Research limitations/implications

This paper selects Mainland China as the research context and targets a single boundary spanner in each respondent firm to evaluate both the interpersonal and inter-organizational relationships. A cross-sectional approach was used.

Practical implications

This paper suggests that business people should pay attention to the role of human factors in a firm’s relational exchanges with SC partners and effectively use the positive effects of these factors to create relationship-building benefits.

Originality/value

This paper conducts cross-level research, which has been called for in recently published inter-organizational literature. It develops and provides empirical evidence for a bottom-up model from interpersonal relationships to inter-organizational relationships and identifies their impacts on organizational outcomes simultaneously.
Using Musical Play with children with profound and multiple learning disabilities at school
Authors: Rushton Rosie , Kossyvaki Lila
Published: October 2020

We all ‘play’ music! Play experiences for children with profound and multiple learning disabilities (PMLD) are often compromised, lost in complex care routines, increasingly stretched timetables and a lack of suitable play interventions. This study investigates combining music with play, using a set of guidelines and principles developed by the researcher and staff participants: Musical Play. It evaluates the impact of Musical Play on the play experiences of both the learners and staff. This study included five primary‐aged children and four teaching staff, during a five‐week implementation period in a UK special school. The study collected multiple data sources to evaluate the impact of the intervention. Results reveal that Musical Play elicited engaged, playful and creative responses, encouraging peer‐awareness and interactions. The intervention allowed staff a sense of freedom from target‐driven work, providing a unique opportunity to immerse themselves fully in the play experience.
3D forensic facial approximation: Implementation protocol in a forensic activity
Authors: Baldasso Rosane Pérez , Moraes Cicero , Gallardo Elisa , Stumvoll Monica Bujes , Crespo Kleber Cardoso , Strapasson Raíssa Ananda Paim , de Oliveira Rogério Nogueira
Published: October 2020

The primary objective of this paper is to report on the successful implementation of forensic facial approximation in a real case in the forensic context. A three‐dimensional (3D) facial approximation protocol of the skull was performed with free software, applying techniques in a virtual environment that have already been consolidated in the literature. The skull was scanned with the photogrammetry technique, the digital replica was imported in the Blender software (Blender Foundation, Amsterdam) and individualized model sketches of the face were traced with the MakeHuman software (MakeHuman Org) according to the anthropological profile of the victim. The face created was imported in Blender, where it was adapted, modeled, and sculpted on the 3D skull and its soft tissue markers, using an American open‐source application of the technique in the digital environment. The face created in a virtual environment was recognized and legal identification procedures were started, resulting in the more agile delivery of the disappeared body to its next of kin. It is therefore concluded that facial approximation may not be a primary method of human identification, but it can be satisfactorily applied in the forensic field as an individual recognition resource. It has great value in narrowing the search, reducing the number of alleged victims, and leading to identification tests, therefore significantly reducing the number of genetic DNA (deoxyribonucleic acid) tests—which are considered costly for the State or Federation—and consequently reducing the waiting time before delivery of the body to its family.
Factors influencing duration of compensation following road traffic crash injury in older vs younger adults
Authors: Brown Katherine , Cameron Ian D. , Keay Lisa , Rogers Kris , Nguyen Ha , Vines Prue , Ivers Rebecca
Published: October 2020

Objective

To identify factors independently associated with late claim closure, a proxy for recovery, in older (65+ years) compared to younger (17‐64 years) adults following road traffic crash injury (RTI).

Methods

Multivariable analysis of statewide compensation data from New South Wales (NSW), Australia, for NSW residents aged ≥17 years injured in a non‐catastrophic RTI between July 2010 and June 2013 with finalised claims (n = 16 687).

Results

Legal representation was the dominant factor independently associated with late claim closure in both age groups. However, the odds were doubly high for the younger group (younger: AOR 8.46, 95% CI 7.7‐9.4; older: AOR 3.95, 95% CI 3.1‐5.0). Median time to claim closure was shorter for older people.

Conclusion

Older (and younger) claimants with legal representation are at increased risk of late claim closure and can be readily identified within routinely collected compensation data, enabling delivery of targeted strategies or supports early in the claims process.
The effect of advanced recovery room care on postoperative outcomes in moderate‐risk surgical patients: a multicentre feasibility study
Authors: Ludbrook G. , Lloyd C. , Story D. , Maddern G. , Riedel B. , Richardson I. , Scott D. , Louise J. , Edwards S.
Published: October 2020

Postoperative complications are common and may be under‐recognised. It has been suggested that enhanced postoperative care in the recovery room may reduce in‐hospital complications in moderate‐ and high‐risk surgical patients. We investigated the feasibility of providing advanced recovery room care for 12–18 h postoperatively in the post‐anaesthesia care unit. The primary hypothesis was that a clinical trial of advanced recovery room care was feasible. The secondary hypothesis was that this model may have a sustained impact on postoperative in‐hospital and post‐discharge events. This was a multicentre, prospective, feasibility before‐and‐after trial of moderate‐risk patients (predicted 30‐day mortality of 1–4%) undergoing non‐cardiac surgery and who were scheduled for postoperative ward care. Patients were managed using defined assessment checklists and goals of care in an advanced recovery room care setting in the immediate postoperative period. This utilised existing post‐anaesthesia care unit infrastructure and staffing, but extended care until the morning of the first postoperative day. The advanced recovery room care trial was deemed feasible, as defined by the recruitment and per protocol management of > 120 patients. However, in a specialised cancer centre, recruitment was slow due to low rates of eligibility according to narrow inclusion criteria. At a rural site, advanced recovery room care could not be commenced due to logistical issues in establishing a new model of care. A definitive randomised controlled trial of advanced recovery room care appears feasible and, based on the indicative data on outcomes, we believe this is warranted.
Using genetics to understand the role of antihypertensive drugs modulating angiotensin‐converting enzyme in immune function and inflammation
Authors: Zhao Jie V. , Schooling C. Mary , Leung Gabriel M.
Published: October 2020

Aim

Angiotensin‐converting enzyme 2 (ACE 2) is the binding domain for severe acute respiratory syndrome coronavirus (SARS‐CoV) and SARSCoV‐2. Some antihypertensive drugs affect ACE2 expression or activity (ACE inhibitors and angiotensin II receptor blockers [ARBs]), suggesting use of other hypertensives might be preferable, such as calcium channel blockers (CCBs). Given the limited evidence, the International Society of Hypertension does not support such a policy.

Methods

We used a Mendelian randomization study to obtain unconfounded associations of antihypertensives, instrumented by published genetic variants in genes regulating target proteins of these drugs, with immune (lymphocyte and neutrophil percentage) and inflammatory (tumour necrosis factor alpha [TNF‐α]) markers in the largest available genome‐wide association studies.

Results

Genetically predicted effects of ACE inhibitors increased lymphocyte percentage (0.78, 95% confidence interval [CI] 0.35, 1.22), decreased neutrophil percentage (−0.64, 95% CI −1.09, −0.20) and possibly lowered TNF‐α (−4.92, 95% CI −8.50, −1.33). CCBs showed a similar pattern for immune function (lymphocyte percentage 0.21, 95% CI 0.05 to 0.36; neutrophil percentage −0.23, 95% CI −0.39 to −0.08) but had no effect on TNF‐α, as did potassium‐sparing diuretics and aldosterone antagonists, and vasodilator antihypertensives. ARBs and other classes of hypertensives had no effect on immune function or TNF‐α.

Conclusion

Varying effects of different classes of antihypertensives on immune and inflammatory markers do not suggest antihypertensive use based on their role in ACE2 expression, but instead suggest investigation of the role of antihypertensives in immune function and inflammation might reveal important information that could optimize their use in SARSCoV‐2.
Monitoring the tacrolimus concentration in peripheral blood mononuclear cells of kidney transplant recipients
Authors: Francke Marith I. , Hesselink Dennis A. , Li Yi , Koch Birgit C.P. , de Wit Lucia E.A. , van Schaik Ron H.N. , Yang Lin , Baan Carla C. , van Gelder Teun , de Winter Brenda C.M.
Published: October 2020

Aims

Tacrolimus is a critical dose drug and to avoid under‐ and overexposure, therapeutic drug monitoring is standard practice. However, rejection and drug‐related toxicity occur despite whole‐blood tacrolimus pre‐dose concentrations ([Tac]blood) being on target. Monitoring tacrolimus concentrations at the target site (within peripheral blood mononuclear cells; [Tac]cells) may better correlate with drug‐efficacy. The aim of this study was to (1) investigate the relationship between [Tac]blood and [Tac]cells, (2) identify factors affecting the tacrolimus distribution in cells and whole‐blood, and (3) study the relationship between [Tac]cells and clinical outcomes after kidney transplantation.

Methods

A total of 175 renal transplant recipients were prospectively followed. [Tac]blood and [Tac]cells were determined at Months 3, 6 and 12 post‐transplantation. Patients were genotyped for ABCB1 1199G>A and 3435C>T, CYP3A4 15389C>T, and CYP3A5 6986G>A. Data on rejection and tacrolimus‐related nephrotoxicity and post‐transplant diabetes mellitus were collected.

Results

Correlations between [Tac]blood and [Tac]cells were moderate to poor (Spearman's r = 0.31; r = 0.41; r = 0.61 at Months 3, 6 and 12, respectively). The [Tac]cells/[Tac]blood ratio was stable over time in most patients (median intra‐patient variability 39.0%; range 3.5%–173.2%). Age, albumin and haematocrit correlated with the [Tac]cells/[Tac]blood ratio. CYP3A5 and CYP3A4 genotype combined affected both dose‐corrected [Tac]blood and [Tac]cells. ABCB1 was not significantly related to tacrolimus distribution. Neither [Tac]blood nor [Tac]cells correlated with clinical outcomes.

Conclusions

The correlation between [Tac]blood and [Tac]cells is poor. Age, albumin and haematocrit correlate with the [Tac]cells/[Tac]blood ratio, whereas genetic variation in ABCB1, CYP3A4 and CYP3A5 do not. Neither [Tac]blood nor [Tac]cells correlated with clinical outcomes.
Continent diversion: five decades of developments and evolution
Authors: Stangl Fabian P. , Thalmann George N.
Published: October 2020

Objective

To provide a chronological overview of the evolution of continent urinary diversion (CUD) over the last 50 years and to highlight important milestones.

Methods

We performed an extensive literature review and analysed different forms of urinary diversion worldwide. After the evaluation of surgical techniques, we assessed the advantages and disadvantages of assorted CUD approaches based on published long‐term follow‐up data.

Results

A wide variety of surgical options for CUD is available and feasible to date, although consensus among urologists regarding the 'gold standard' is still lacking. Several forms of orthotopic bladder substitutes and continent cutaneous urinary reservoirs have been shown to provide excellent long‐term results.

Conclusion

The last 50 years of CUD have seen constant evolution and refinement of techniques, but the best surgical approach remains unclear and there is no ‘one‐size‐fits‐all’ option, but rather tailor‐made approaches are necessary to ensure patient satisfaction.
Multi‐institutional validation of a perfused robot‐assisted partial nephrectomy procedural simulation platform utilizing clinically relevant objective metrics of simulators (CROMS)
Authors: Ghazi Ahmed , Melnyk Rachel , Hung Andrew J. , Collins Justin , Ertefaie Ashkan , Saba Patrick , Gurung Pratik , Frye Thomas , Rashid Hani , Wu Guan , Mottrie Alex , Costello Tony , Dasgupta Prokar , Joseph Jean
Published: October 2020

Objective

To conduct a multi‐institutional validation of a high‐fidelity, perfused, inanimate, simulation platform for robot‐assisted partial nephrectomy (RAPN) using incorporated clinically relevant objective metrics of simulation (CROMS), applying modern validity standards.

Materials and Methods

Using a combination of three‐dimensional (3D) printing and hydrogel casting, a RAPN model was developed from the computed tomography scan of a patient with a 4.2‐cm, upper‐pole renal tumour (RENAL nephrometry score 7×). 3D‐printed casts designed from the patient’s imaging were used to fabricate and register hydrogel (polyvinyl alcohol) components of the kidney, including the vascular and pelvicalyceal systems. After mechanical and anatomical verification of the kidney phantom, it was surrounded by other relevant hydrogel organs and placed in a laparoscopic trainer. Twenty‐seven novice and 16 expert urologists, categorized according to caseload, from five academic institutions completed the simulation.

Results

Clinically relevant objective metrics of simulators, operative complications, and objective performance ratings (Global Evaluative Assessment of Robotic Skills [GEARS]) were compared between groups using Wilcoxon rank‐sum (continuous variables) and parametric chi‐squared (categorical variables) tests. Pearson and point‐biserial correlation coefficients were used to correlate GEARS scores to each CROMS variable. Post‐simulation questionnaires were used to obtain subjective supplementation of realism ratings and training effectiveness.

Results

Expert ratings demonstrated the model’s superiority to other procedural simulations in replicating procedural steps, bleeding, tissue texture and appearance. A significant difference between groups was demonstrated in CROMS [console time (P < 0.001), warm ischaemia time (P < 0.001), estimated blood loss (P < 0.001)] and GEARS (P < 0.001). Six major intra‐operative complications occurred only in novice simulations. GEARS scores highly correlated with the CROMS.

Conclusions

This perfused, procedural model offers an unprecedented realistic simulation platform, which incorporates objective, clinically relevant and procedure‐specific performance metrics.
Inclusive approaches to developing content valid patient‐reported outcome measure response scales for youth with intellectual/developmental disabilities
Authors: Schwartz Ariel E. , Kramer Jessica M. ,   PEDI‐PRO Youth Team
Published: October 2020

Accessible Summary

People with disabilities have the right to use patient‐reported outcome measures (PROMs) to tell their doctors and therapists what they think and feel. Therefore, PROMs need to be accessible for people with disabilities. This means that the questions and the response choices for the questions need to be easy to understand. Response choices can be words like, “yes” and “no,” or “agree” and “disagree,” or “easy” and “hard.”

To make sure that the response choices are easy to understand, it is a good idea to collaborate with people with disabilities when designing PROM response choices, or response scales.

We describe how we worked with 8 young people with disabilities to make an easy‐to‐use response scale for a PROM.

After our data collection and work together, we decided the best response scale was “very easy,” “a little easy,” “a little hard.”

This research is important, because other researchers and people making PROMs can use our process to help make their response scales easy to use.

Background

Patient‐reported outcome measures (PROMs) are increasingly used in health care to evaluate service quality and client progress. Response scales are a critical component of PROM content validity and must be designed to be relevant and comprehensible by users.

Methods

In collaboration with eight youth co‐researchers with intellectual/developmental disabilities ages 14–21, we used an iterative, three‐stage approach to develop and select a response scale for the PEDI‐PRO. Stages: 1) inclusive development of response scale options; 2) Collecting data about response scale options during focus groups with youth with intellectual/ developmental disabilities (n = 62); and 3) Analysing data to refine response options.

Results

Through two cycles of the three‐stage process, the inclusive research approach led to the development of a content valid response scale that describes functional performance of everyday activities (“very easy,” “a little easy,” “a little hard”).

Conclusion

An inclusive research approach can support the development of content valid PROM scales. We identified four broad strategies that supported youth co‐researchers to engage in this response scale development process: universal design for learning, use of lived experiences, breaking down tasks, and peer support. Researchers may adopt and/or adapt the accessible inclusive research approaches described in this manuscript for measurement development and other research projects.
Forest biomass stocks and dynamics across the subtropical Andes
Authors: Blundo Cecilia , Malizia Agustina , Malizia Lucio R. , Lichstein Jeremy W.
Published: October 2020

Forest biomass plays an important role in the global carbon cycle. Therefore, understanding the factors that control forest biomass stocks and dynamics is a key challenge in the context of global change. We analyzed data from 60 forest plots in the subtropical Andes (22–27.5° S and 300–2300 m asl) to describe patterns and identify drivers of aboveground biomass (AGB) stocks and dynamics. We found that AGB stocks remained roughly constant with elevation due to compensating changes in basal area (which increased with elevation) and plot‐mean wood specific gravity (which decreased with elevation). AGB gain and loss rates both decreased with elevation and were explained mainly by temperature and rainfall (positive effects on both AGB gains and losses). AGB gain was also correlated with forest‐use history and weakly correlated with forest structure. Mean annual temperature and rainfall showed minor effects on AGB stocks and AGB change (gains minus losses) over recent decades. Although AGB change was only weakly correlated with climate variables, increases in AGB gains and losses with increasing rainfall—together with observed increases in rainfall in the subtropical Andes—suggest that these forests may become increasingly dynamic in the future.

Abstract in Spanish is available with online material