bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic Sequencing from Sputum for Tuberculosis Disease Diagnosis, Lineage Determination and Drug Susceptibility Prediction
Authors: Nilgiriwala Kayzad , Rabodoarivelo Marie-Sylvianne , Hall Michael B. , Patel Grishma , Mandal Ayan , Mishra Shefali , Andrianomanana Fanantenana Randria , Dingle Kate , Rodger Gillian , George Sophie , Crook Derrick W. , Hoosdally Sarah , Mistry Nerges , Rakotosamimanana Niaina , Iqbal Zamin , Lapierre Simon Grandjean , Walker Timothy M.
Published: October 2022

Background

Universal access to drug susceptibility testing for newly diagnosed tuberculosis patients is recommended. Access to culture-based diagnostics remains limited and targeted molecular assays are vulnerable to emerging resistance conferring mutations. Improved sample preparation protocols for direct-from-sputum sequencing ofMycobacterium tuberculosiswould accelerate access to comprehensive drug susceptibility testing and molecular typing.

Methods

We assessed a thermo-protection buffer-based direct-from-sampleM. tuberculosiswhole-genome sequencing protocol. We prospectively processed and analyzed 60 acid-fast bacilli smear-positive sputum samples from tuberculosis patients in India and Madagascar. A diversity of semi-quantitative smear positivity level samples were included. Sequencing was performed using Illumina and MinION (monoplex and multiplex) technologies. We measured the impact of bacterial inoculum and sequencing platforms onM. tuberculosisgenomic mean read depth, drug susceptibility prediction performance and typing accuracy.

Results

M. tuberculosiswas identified from 88% (Illumina), 89% (MinION-monoplex) and 83% (MinION-multiplex) of samples for which sufficient DNA could be extracted. The fraction ofM. tuberculosisreads from MinION sequencing was lower than from Illumina, but monoplexing grade 3+ sputum samples on MinION produced higher read depth than Illumina (p<0.05) and MinION multiplex (p<0.01). No significant difference in overall sensitivity and specificity of drug susceptibility predictions was seen across these sequencing modalities or within each sequencing technology when stratified by smear grade. Lineage typing agreement percentages between direct and culture-based sequencing were 85% (MinION-monoplex), 88% (Illumina) and 100% (MinION-multiplex)

Conclusions

M. tuberculosisdirect-from-sample whole-genome sequencing remains challenging. Improved and affordable sample treatment protocols are needed prior to clinical deployment.
Direct detection of natural selection in Bronze Age Britain
Authors: Mathieson Iain , Terhorst Jonathan
Published: October 2022

We developed a novel method for efficiently estimating time-varying selection coefficients from genome-wide ancient DNA data. In simulations, our method accurately recovers selective trajectories and is robust to misspecification of population size. We applied it to a large data set of ancient and present-day human genomes from Britain and identified seven loci with genome-wide significant evidence of selection in the past 4500 yr. Almost all of them can be related to increased vitamin D or calcium levels, suggesting strong selective pressure on these or related phenotypes. However, the strength of selection on individual loci varied substantially over time, suggesting that cultural or environmental factors moderated the genetic response. Of 28 complex anthropometric and metabolic traits, skin pigmentation was the only one with significant evidence of polygenic selection, further underscoring the importance of phenotypes related to vitamin D. Our approach illustrates the power of ancient DNA to characterize selection in human populations and illuminates the recent evolutionary history of Britain.
A novel biallelic loss-of-function variant inDAND5causes heterotaxy syndrome
Authors: Ganapathi Mythily , Buchovecky Christie M. , Cristo Fernando , Ahimaz Priyanka , Ruzal-Shapiro Carrie , Wou Karen , Inácio José M. , Iglesias Alejandro , Belo José A. , Jobanputra Vaidehi
Published: October 2022

The majority of heterotaxy cases do not obtain a molecular diagnosis, although pathogenic variants in more than 50 genes are known to cause heterotaxy. A heterozygous missense variant inDAND5, a nodal inhibitor, which functions in early development for establishment of right–left patterning, has been implicated in heterotaxy. Recently, the first case was reported of aDAND5biallelic loss-of-function (LoF) variant in an individual with heterotaxy. Here, we describe a second unrelated individual with heterotaxy syndrome and a homozygous frameshift variant inDAND5(NM_152654.2:c.197del [p.Leu66ArgfsTer22]). Using an in vitro assay, we demonstrate that theDAND5c.197del variant is unable to inhibit nodal signaling when compared with the wild-type expression construct. This work strengthens the genetic and functional evidence for biallelic LoF variants inDAND5causing an autosomal recessive heterotaxy syndrome.
Recruiting volunteers: the roles of fear, hope and courage
Authors: Chowdhury Rafi M.M.I. , Septianto Felix
Published: October 2022

Purpose

Nonprofit organizations face challenges recruiting volunteers for morally important activities that may generate fear, such as firefighting, aid work and delinquent counseling. The purpose of this study is to examine how voluntary organizations can instill the virtue of courage among potential volunteers and motivate them to participate in such activities.

Design/methodology/approach

Three experimental studies examined how fear, hope and courage relate to the likelihood of volunteering. Study 1 investigated how integral hope (hope related to the context, i.e. hope emanating from volunteering activities) and incidental hope (hope unrelated to the context, i.e. a general hopeful feeling) affect volunteering intentions when there is low vs high fear. Study 2 examined whether courage mediated the effects of hope on volunteering intentions when there is low vs high fear. Study 3 replicated the findings in a different volunteering context.

Findings

Integral hope (but not incidental hope) in the face of high fear generates courage leading to intentions to volunteer. Both integral hope and incidental hope motivate volunteering intentions through positive affect (but not through courage) in low fear contexts.

Research limitations/implications

The hypothetical volunteering scenarios and the gender distribution in the samples restrict the external validity of the findings. Family background in volunteering was not controlled for. Moral courage, physical courage and psychological courage were not separately measured.

Practical implications

Nonprofit organizations recruiting volunteers for risky voluntary activities that induce high fear should use integral hope in their marketing communications to instill courage among potential volunteers. For voluntary activities that are not very risky and generate low levels of fear among potential volunteers, nonprofit organizations can recruit volunteers through communications that use either integral hope or incidental hope.

Originality/value

This research shows that hope and fear are critical emotions in relation to courage – an essential virtue for volunteers. Courage is manifested when there is high fear and integral hope. Findings contribute to the research literatures on the marketing of volunteering and the moral psychology of courage.
Dividend and investment decisions in asymmetric information environments: evidence from the restaurant industry
Authors: Gim Jaehee , Jang SooCheong (Shawn)
Published: October 2022

Purpose

This study aims to examine how information asymmetry, which refers to an information gap between a firm’s management and its investors regarding the firm’s true value, influences firms’ dividend and investment decisions in the restaurant industry. This study also investigated the moderating role of a firm’s level of franchising in the relationship between information asymmetry and these behaviors of restaurant firms.

Design/methodology/approach

This study used generalized method of moments panel regression analyses. Principal component analysis was also used to create a composite index of information symmetry.

Findings

This study demonstrated that in asymmetric information environments, restaurant managers tend to reduce dividend payments. In addition, this study showed that information asymmetry leads to restaurant managers’ investment inefficiency. However, the investment inefficiency of the restaurant industry was found to decrease as restaurant firms’ level of franchising increases.

Practical implications

Firms’ dividends and investment decisions are of great interest to investors because these decisions heavily influence investors’ wealth-maximization goals. By shedding light on the previously unrecognized determinants of dividend and investment behaviors in the restaurant industry, this study helps individual investors to make informed investing decisions.

Originality/value

Conflicting arguments can be made regarding the impact of asymmetric information environments on the dividend and investment behaviors of restaurant firms. This study aimed to verify these as-yet unclear relationships in the restaurant industry.
Developing structural modelling of inter-partner factors of international joint ventures performance
Authors: Batra Ishita , Dhir Sanjay
Published: October 2022

Purpose

The study aims to identify, analyse and develop a model for measuring the inter-relationship and interaction among the inter-partner factors. International joint ventures (IJVs) literature has scantly studied the interactions and inter-relationships among the inter-partner factors of IJVs performance. To address this gap, this research creates a hierarchical relationship framework among the inter-partner factors of IJVs performance.

Design/methodology/approach

The comprehensive literature review is used to identify the factors and possible relationships between the factors and IJVs performance. M-TISM (modified total interpretive structural modelling) methodology is used to examine the relationship among the factors of IJVs performance.

Findings

This study highlights 12 inter-partner factors that affect IJVs performance. The results suggest that size asymmetry, commitment, goal incongruency, competitive overlap, trust, control, the interdependency of resources, cooperation, economic distance, cultural distance, geographical distance and administrative distance significantly impact IJVs performance. Commitment is found to be a linkage variable as it has high dependence and driving power. Goal incongruency and competitive overlap have high driving power.

Research limitations/implications

This study gives a proposed list of critical inter-partner factors for policymakers and practitioners to consider when developing rules or recommendations to improve IJVs performance. The focus of policymakers should be on economic and geographical distance, followed by cultural distance, competitive overlap, goal incongruency, size asymmetry and administrative distance to improve inter-relationship among the partners in IJVs. The work contributes to the academician by presenting a modified TISM model that highlights the significance of ambidexterity in driving the performance of IJVs.

Originality/value

This study fills a gap in the literature by analysing the interactions among the inter-partner parameters that influence the performance of IJVs. It offers insights into the variables, such as driver dependence and the relationships between the variables.
Firm characteristics and forward-looking disclosure: the moderating role of gender diversity
Authors: Abdelazim Samir Ibrahim , Metwally Abdelmoneim Bahyeldin Mohamed , Aly Saleh Aly Saleh
Published: October 2022

Purpose

The purpose of this study is to examine the impact of firm financial and operational characteristics on the level of forward-looking information disclosure (FLID) by Egyptian-listed non-financial companies. The present research also aims to investigate the moderating role of gender diversity on the board of directors.

Design/methodology/approach

The sample incorporates the non-financial companies included in the EGX 100 of the Egyptian Stock Exchange (ESE), whose reports were available during the study period from 2013 to 2018. The final sample comprises 49 companies with 294 observations. Statistical analysis is performed using multiple regression analysis.

Findings

This study found a significant positive impact of return on assets, leverage, company size and age on the level FLID, while external audit firm type and industry were found to impact the level of FLID negatively. Further, the board gender diversity (BGD) is found to have a moderating impact as it strengthens the effect of financial and operational characteristics on the level of FLID.

Practical implications

The present study has some implications for Egyptian companies, investors in the Egyptian market and regulators in emerging economies, which include paying more attention to BGD when selecting the board members by companies as well as following up the female representation in all the listed companies by regulators.

Originality/value

To the best of the authors’ knowledge, this is the first study to investigate the moderating role of BGD and its impact on the level of FLID in emerging markets. This extends the disclosure literature as the present study brings new evidence from an emerging market regarding BGD moderating role as early research concentrated on the direct impact of BGD on the level of FLID.
Risk-taking and WOM as moderators in the relationship between status consumption, brand image and purchase intention of counterfeit brand shoes
Authors: Patel Ashok Kumar , Singh Anurag , Parayitam Satyanarayana
Published: October 2022

Purpose

The study's objective is to examine the consumers' intention to buy counterfeit brand shoes. A conceptual model is developed to test the risk-taking and word-of-mouth (WOM) as a moderator in the relationship between status consumption, brand image, and consumer intention to buy counterfeit shoes.

Design/methodology/approach

Based on the theory of reasoned action (TRA) and signaling theory (ST), this research was conducted in the Indian National Capital Region. Using a structured instrument, the data was collected from 240 respondents. After checking the psychometric properties of the survey instrument using the Lisrel package of structural equation modeling, Hayes's PROCESS macros were used for testing the hypotheses.

Findings

The findings from the study indicate that (1) status consumption and brand image are positively associated with purchase intention of counterfeit brand shoes, and (2) risk-taking moderates the relationship between (1) status consumption and purchase intention, and (2) brand image and purchase intension, (3) significant three-way interaction between WOM, risk-taking and status consumption on purchase intention, and (4) significant three-way interaction between brand image, WOM, and risk-taking on purchase intention of counterfeit brand shoes.

Research limitations/implications

As with any survey research, this study has common method variance as a potential problem. However, through the latent variable method and Harman's single-factor analysis, the common method variance was checked. The study has several implications for managers, e-marketers, and consumers.

Practical implications

The study has several implications for marketers selling counterfeit products and managers intending to protect their branded products.

Originality/value

A conceptual model showing two-way and three-way interactions between status consumption, risk-taking, and WOM influencing the consumer purchase intention of counterfeit products was discussed. This is the first of its kind in India to explore such relationships.
Impact of the time limits for the receipt of tenders on the number of bidders: evidence from public procurement in Greece
Authors: Pliatsidis Andreas Christos
Published: October 2022

Purpose

The purpose of this paper is to examine how the period for which a public procurement notice remains open for bidding (Δt) affects the number of bids.

Design/methodology/approach

The authors investigated data for 2.404 open procurement tenders in Greece for the years 2018–2021. Using Δtas the grouping factor, the authors defined two samples based on the European Union time limits for the receipt of tenders. Group 1 (Δt≤ 35) contains all tenders for which the contracting authorities (CAs) have chosen to limit themselves to the minimum number of days allowed by law. Group 2 (Δt>35) includes the remaining tenders where CAs have chosen to keep their notices open for periods beyond the existing minimum time limits, as they are encouraged to do by law.

Findings

A Mann–WhitneyUtest, in combination with graphical analysis, revealed that CAs from Group 2 tend to enjoy more bids per tender, that is, more intense competition.

Social implications

The paper allows decision-makers and legislators to understand the relationship between the time CAs choose to keep their notices open for bidding and the number of bidders in each tender, that is, competition, which according to other authors, affects the outcomes of public procurement procedures.

Originality/value

The paper fills the research gap regarding the relationship between time for preparation and the number of bids in each tender.
The nexus of servant leadership and project success: the mediation of emotional intelligence and job stress and moderation of team effectiveness
Authors: Malik Aizaz Ahmad , Muneeb Dilnaz , Khan Noman , Usman Muhammad , Latif Khawaja Fawad
Published: October 2022

Purpose

This study investigated the impact of servant leadership on project success in nongovernment organizations (NGOs) working in a developing country like Pakistan. A moderated mediation design was employed, and the mediating role of employees' emotional intelligence (EI) and job stress (JS) was tested between servant leadership on project success. Moreover, the study also examined the moderating role of team effectiveness.

Design/methodology/approach

Data were collected from 441 project team members working on different developed projects. Data were analyzed using partial least square-structural equation modeling (PLS-SEM) technique.

Findings

Results revealed that servant leadership exerts a significant positive impact on project success. Also, it is noted that servant leadership significantly increases the employee's emotional intelligence that contributes to project success although it does not reduce JS. However, JS was found to be a significant mediator in the association between servant leadership on project success. The findings also revealed that team effect plays an imperative moderating role in ensuring project success.

Originality/value

The study is one of the very few studies conducted to assess the impact of servant leadership on project success in not-for-profit organizations. The study contributes to the literature and methodology by adopting a holistic approach to investigate the mediation of EI and JS along with the moderation of team effectiveness in the nexus of servant leadership and project success.
Exploring the living experience of shame; protector or persecutor?
Authors: Lilley Kirsty
Published: October 2022

Purpose

The purpose of this opinion piece is to give voice to the living experience of shame within myself as the author, both psychologically and physically. This is in the hope to increase awareness among others who experience shame and mental health professionals tasked with supporting people in emotional distress.

Design/methodology/approach

The author has written a biographical piece outlining her experiences of living with shame and used rich, provocative and metaphorical language in describing the events which led to this and the impact this has had on my quality of life. The author has positioned shame as a character playing a role in her life.

Findings

This piece reveals the inner turmoil experienced when living alongside shame and the resilience and fortitude needed to understand the role of shame and how it developed. With this knowledge and awareness, the author has found it is possible to move forward in life.

Research limitations/implications

The author has lived through adverse and challenging early life experiences within a difficult family environment. The author has shown that it is possible to undertake a healing journey and to come to an acceptance of shame within my own life and still move forward to create supportive relationships with others and a life worth living. These are often the stories of those people who survive great difficulty and still go on to help and support other people.

Practical implications

The author has found and experienced that loving and supportive relationships give the best chance of healing from early life adversities. The author has also found that shame plays an interesting role as both necessary and painful. Moving forward from the distress often associated with shame is a long journey but one that is possible.

Social implications

The author has aimed to make clear that exploration and education about the lived experience of shame is both helpful for those who suffer and those who intend to help within the mental health professions. Listening to the stories of people with living experiences is vital and plays as important a role as academic theory and learning.

Originality/value

This is a subjective living experience of shame and, in that way, adds to the helpful canon of stories that can inform our understanding of distress and the ability to help. The author has described shame as a character playing a role in her life and belief that this is an interesting way to view this. This piece also contains stories regarding the genesis of shame which are unique to her. The author understands and makes clear that his experience does not necessarily translate or relate to anyone else but stands on its own merit. The author hopes to have much more to contribute in terms of others’ understanding of emotional distress and shame, especially considering its transdiagnostic nature.
Growing inequities in mental health crisis services offered to indigent patients in Puerto Rico versus the US states before and after Hurricanes Maria and Irma
Authors: Purtle Jonathan , Rivera‐González Alexandra C. , Mercado Damaris Lopez , Barajas Clara B. , Chavez Ligia , Canino Glorisa , Ortega Alexander N.
Published: October 2022

Objective

To assess changes in the availability of mental health crisis services in Puerto Rico relative to US states before and after Hurricanes Maria and Irma.

Data Sources/Study Setting

National Mental Health Services Surveys conducted in 2016 and 2020.

Study design

Repeated cross‐sectional design. The independent variable was mental health facility location in Puerto Rico or a US state. Dependent variables were the availability of three mental health crisis services (psychiatric emergency walk‐in services, suicide prevention services, and crisis intervention team services).

Data Collection/Extraction Methods

The proportion and per 100,000 population rate of facilities offering crisis services were calculated.

Principal Findings

The availability of crisis services at mental health facilities in Puerto Rico remained stable between 2016 and 2020. These services were offered less at indigent care facilities in Puerto Rico than US states (e.g., 38.2% vs. 49.5% for suicide prevention, p = 0.06) and the magnitude of difference increased following Hurricane Maria.

Conclusions

There are disparities between Puerto Rico and US states in the availability of mental health crisis services for indigent patients.
“Important for you to be there”: Employee activism and the dialectics of researcher–practitioner collaborations
Authors: Ramirez Manuel F. , Islam Gazi
Published: October 2022

The current study examines researcher–practitioner collaborations in the context of employee activism, a context in which the role of reflexivity and theorisation relate in unique ways. Specifically, we examine the collaboration between researchers and a practitioner sustainability manager, in the context of an ongoing organisational sustainability campaign at a French business school. Within the context of an ethnographic, participant observer study, we examine how the roles of “theory” and “practice” are distributed in dynamic ways, and how, across the study, roles are challenged and inverted, oscillating in dialectical moments which we term “praxis encounters”. We contribute to growing debates around academic–practitioner collaborations by showing how the roles of researchers and practitioners evolve dialectically over the course of a project, how employee activism may be studied using collaborative approaches, and how human resource managers may support employee activism. We call for future research about the variety of such dynamics across diverse contexts.
Lifting Diversity and Inclusion in Economics: How the Australian Women in Economics Network Put the Evidence into Action*
Authors: Cassells Rebecca , Risse Leonora , Wood Danielle , Yengin Duygu
Published: October 2022

To support broader global efforts to improve diversity and inclusion in economics, this paper provides a statistical picture of the gender composition of the economics profession in Australia and the evidence‐based initiatives taken by the Women in Economics Network (WEN) to improve women's representation and recognition. WEN's impact is evaluated across a range of metrics. This includes a case study of WEN's mentorship programme for university students that was delivered as a behavioural intervention and evaluated as a randomised control trial. Drawing on practical experiences in combination with research insights, the paper identifies some of the challenges encountered and the lessons that can be shared with similar organisations globally that are pursuing diversity and inclusion goals.
Know what you don't know: Embracing state uncertainty in disease‐structured multistate models
Authors: Hollanders Matthijs , Royle J. Andrew
Published: October 2022

Hidden Markov models (HMMs) are broadly applicable hierarchical models that derive their utility from separating state processes from observation processes yielding the data. Multistate models such as mark–recapture and dynamic multistate occupancy models are HMMs frequently used in ecology. In their early formulations, states, such as pathogen infection status, were assumed to be perfectly observed without ambiguity. However, state uncertainty is a pervasive feature of many ecological studies, and multievent models were developed to explicitly account for it.

We developed a novel extended multievent mark–recapture model that incorporates state uncertainty at multiple levels of detection. Using a disease‐structured example, both false negative and false positive state assignment errors are modelled at two levels of state assignment—the pathogen sampling process and the diagnostic process that samples are subjected to. We additionally describe methods to jointly model infection intensity to integrate heterogeneity in ecological parameters, such as mortality and infection dynamics, and the pathogen detection processes. We provide code to simulate and analyse datasets with various underlying ecological processes and fit our model to a mark–recapture dataset of Mixophyes fleayi (Fleay's barred frog) infected with the amphibian chytrid fungus (Batrachochytrium dendrobatidis, Bd).

In our case study, we found evidence for various state assignment errors: the sampling protocol performed poorly in detecting Bd, pathogen detection was highly dependent on infection intensity and false positives were non‐negligible. Incorporating state uncertainty yielded significantly higher estimates of infection prevalence and 4–5 times lower rates of infection state transitions compared to those obtained from a traditional multistate model.

Our results highlight that incorporating state assignment errors improves inference on the ecological process, especially when sensitivity and specificity of the state assignment processes are low. The general model structure can be applied to other HMMs, providing a foundation for modelling state uncertainty in related models. For disease‐structured multistate models, we recommend conducting robust design surveys and collecting samples during each capture event to facilitate incorporating pathogen detection errors.
Fintech business and firm access to bank loans
Authors: Xu Lei , Liu Qian , Li Bin , Ma Chen
Published: October 2022

Firms have widely participated in financial technology (Fintech) in recent years. Through a proprietary dataset of listed firms on the Shanghai and Shenzhen Stock Exchanges, we find that Fintech positively contributes to firm access to bank loans, and such link is stronger among private firms, non‐manufacturing firms or those in regions of better marketisation. Further tests suggest that enhanced trust underlies our primary findings, and that Fintech also positively contributes to loans without collateral, longer maturity and lower costs. In addition, Fintech may effectively curb firm's overinvestment. Our findings may have policy implications for firm investment behaviour and financing activities.
Hemostatic alterations during extracorporeal membrane oxygenation in ovine veno‐venous and veno‐arterial models
Authors: Gao Sizhe , Zhang Yang , Peng Rui , Yan Shujie , Teng Yuan , Qi Jiachen , Cheng Gaowa , Yu Dongze , Liu Gang , Xu Qiang , Cai Xiaohui , Zhou Zhou , Ji Bingyang
Published: October 2022

Background

Extracorporeal membrane oxygenation (ECMO) has salvaged many people's life during global pandemics. However, ECMO is associated with a high incidence of hemostatic complications. This study aims to explore the effects of the ECMO system on the coagulation system in the healthy ovine ECMO model.

Methods

Ten healthy male sheep were included. Five received the veno‐arterial ECMO and five received the veno‐venous ECMO. Heparin was infused for systemic anticoagulation and was adjusted according to the activated clotting time. Blood routine tests, coagulation factors, anticoagulation proteins, and fibrinolysis markers were tested at the baseline and every 24 h. After weaning, the pump heads were dissected to explore thrombosis.

Results

Platelets decreased in the first 72 h and returned to the baseline at the 120th hour. The neutrophils increased in the first 24 h and returned to the baseline at the 48th hour. Factors II, VII, and X decreased in the first 24 h and gradually increased, while factors VIII, IX, XI, and XII decreased in the first 24 h and remained at a low level. The baseline antithrombin was 73.2 ± 14.4% and reduced to 42.6 ± 9.9% at the 168th hour. Pathology showed seven sheep developed thrombus, but no clinically relevant bleeding or thrombosis events occurred.

Conclusions

The study explored hemostatic alterations during ECMO in healthy animal models, which eliminated the confounding under critically ill conditions. The study may provide insights into ECMO hemostatic disorders and aid the design of optimal therapeutic strategies.
Randomised clinical trial: comparison of tegoprazan and lansoprazole as maintenance therapy for healed mild erosive oesophagitis
Authors: Cho Yu Kyung , Kim Jae Hak , Kim Hyun‐Soo , Kim Tae‐Oh , Oh Jung‐Hwan , Choi Suck Chei , Moon Jeong Seop , Lee Sang Kil , Jung Sung Woo , Kim Sung Soo , Jung Hye‐Kyung , Lee Sang Pyo , Cheon Gab‐Jin , Park Moo In , Jung Hwoon‐Yong , Ko Kwang Hyun , Sung In Kyung , Lee Si Hyung , Lee Ju Yup , Lee Soo Teik , Rhee Poong‐Lyul , Kim Nayoung , Hong Su Jin , Kim Hyun Jin , Kim Gwang Ha , Lee Kwang Jae , Kim Sung Kook , Shin Woon Geon , Lee Oh Young
Published: October 2022

Background

Tegoprazan is a novel potassium‐competitive acid blocker used to treat acid‐related disorders.

Aim

To compare tegoprazan 25 mg with lansoprazole 15 mg as maintenance therapy in healed erosive oesophagitis (EE)

Methods

In this phase 3, double‐blind, multi‐centre study, patients with endoscopically confirmed healed EE were randomised 1:1 to receive tegoprazan 25 mg or lansoprazole 15 mg once daily for up to 24 weeks. The primary efficacy endpoint was the endoscopic remission rate after 24 weeks. The secondary efficacy endpoint was the endoscopic remission rate after 12 weeks. Safety endpoints included adverse events, clinical laboratory results and serum gastrin and pepsinogen I/II levels.

Results

We randomised patients to tegoprazan 25 mg (n = 174) or lansoprazole 15 mg (n = 177). Most had mild EE (Los Angeles (LA) grade A: 57.3%, LA grade B: 37.3%). The endoscopic remission rate after 24 weeks was 90.6% with tegoprazan and 89.5% with lansoprazole. Tegoprazan was not inferior to lansoprazole for maintaining endoscopic remission at 24 weeks and 12 weeks. In subgroup analysis, tegoprazan 25 mg showed no significant difference in maintenance rate according to LA grade (p = 0.47). The maintenance effect of tegoprazan was consistent in CYP2C19 extensive metabolisers (p = 0.76). Increases in serum gastrin were not higher in tegoprazan‐treated than lansoprazole‐treated patients.

Conclusions

Tegoprazan 25 mg was non‐inferior to lansoprazole 15 mg in maintenance of healing of mild EE. In this study, tegoprazan had a similar safety profile to lansoprazole.
Static penetration assessment of stone weapon tip geometry metrics and comparison of static and dynamic penetration depths
Authors: Sitton Jase , Stenzel Christopher , Buchanan Briggs , Eren Metin I. , Story Brett
Published: October 2022

Many factors governed the penetration efficacy of prehistoric projectile weaponry. Archaeologists broadly focus their efforts on understanding the effect of stone weapon tips because these specimens are often the only part of the weapon system that survives in the archaeological record. The tip cross‐sectional area (TCSA) and perimeter (TCSP) of stone weapon tips have been shown to correlate with target penetration depth. Here, using results from both static and dynamic penetration testing, we compare TCSA and TCSP against other tip geometry metrics: lateral surface area (LSA) and volume (V). Our analyses broadly show that using a single‐point geometry metric evaluated at multiple locations along the length of the point, or using multiple geometry metrics evaluated at a single location, better predicts required energy than using a single‐point geometry metric evaluated at a single location. Our results also show that in the case where a single geometry metric evaluated at multiple locations is used LSA provided the most robust prediction models. Finally, our results show that for the case where all geometry metrics evaluated at a single location are used the location that provides the most robust prediction model is dependent on how far the point penetrated the target.
Rejoinder to “Instrumented Difference-in-Differences”
Authors: Ye Ting , Ertefaie Ashkan , Flory James , Hennessy Sean , Small Dylan S.
Published: October 2022

We thank all the discussants for the careful reading and insightful comments. In our rejoinder, we extend the discussion of how the assumptions of instrumented difference-in-differences (iDID) compare to the assumptions of the standard instrumental variable method. We also make additional comments on how iDID is related to the fuzzy DID. We highlight future research directions to enhance the utility of iDID, including extensions to adjust for covariate shift in two-sample iDID design, and generalization of iDID to multiple time points and a multi-valued instrumental variable for DID.
Marginal Proportional Hazards Models for Clustered Interval-Censored Data with Time-Dependent Covariates
Authors: Cook Kaitlyn , Lu Wenbin , Wang Rui
Published: October 2022

The Botswana Combination Prevention Project was a cluster-randomized HIV prevention trial whose follow-up period coincided with Botswana's national adoption of a universal test and treat strategy for HIV management. Of interest is whether, and to what extent, this change in policy modified the preventative effects of the study intervention. To address such questions, we adopt a stratified proportional hazards model for clustered interval-censored data with time-dependent covariates and develop a composite expectation maximization algorithm that facilitates estimation of model parameters without placing parametric assumptions on either the baseline hazard functions or the within-cluster dependence structure. We show that the resulting estimators for the regression parameters are consistent and asymptotically normal. We also propose and provide theoretical justification for the use of the profile composite likelihood function to construct a robust sandwich estimator for the variance. We characterize the finite-sample performance and robustness of these estimators through extensive simulation studies. Finally, we conclude by applying this stratified proportional hazards model to a re-analysis of the Botswana Combination Prevention Project, with the national adoption of a universal test and treat strategy now modeled as a time-dependent covariate.
Improved Semiparametric Estimation of the Proportional Rate Model with Recurrent Event Data
Authors: Huang Ming-Yueh , Huang Chiung-Yu
Published: October 2022

Owing to its robustness properties, marginal interpretations, and ease of implementation, the pseudo-partial likelihood method proposed in the seminal papers of Pepe and Cai and Lin et al. has become the default approach for analyzing recurrent event data with Cox-type proportional rate models. However, the construction of the pseudo-partial score function ignores the dependency among recurrent events and thus can be inefficient. An attempt to investigate the asymptotic efficiency of weighted pseudo-partial likelihood estimation found that the optimal weight function involves the unknown variance–covariance process of the recurrent event process and may not have closed-form expression. Thus, instead of deriving the optimal weights, we propose to combine a system of pre-specified weighted pseudo-partial score equations via the generalized method of moments and empirical likelihood estimation. We show that a substantial efficiency gain can be easily achieved without imposing additional model assumptions. More importantly, the proposed estimation procedures can be implemented with existing software. Theoretical and numerical analyses show that the empirical likelihood estimator is more appealing than the generalized method of moments estimator when the sample size is sufficiently large. An analysis of readmission risk in colorectal cancer patients is presented to illustrate the proposed methodology.
The geodynamic and limnological evolution of Balkan Lake Ohrid, possibly the oldest extant lake in Europe
Authors: Wagner Bernd , Tauber Paul , Francke Alexander , Leicher Niklas , Binnie Steven A. , Cvetkoska Aleksandra , Jovanovska Elena , Just Janna , Lacey Jack H. , Levkov Zlatko , Lindhorst Katja , Kouli Katerina , Krastel Sebastian , Panagiotopoulos Konstantinos , Ulfers Arne , Zaova Dušica , Donders Timme H. , Grazhdani Andon , Koutsodendris Andreas , Leng Melanie J. , Sadori Laura , Scheinert Mirko , Vogel Hendrik , Wonik Thomas , Zanchetta Giovanni , Wilke Thomas
Published: October 2022

Studies of the upper 447 m of the DEEP site sediment succession from central Lake Ohrid, Balkan Peninsula, North Macedonia and Albania provided important insights into the regional climate history and evolutionary dynamics since permanent lacustrine conditions established at 1.36 million years ago (Ma). This paper focuses on the entire 584‐m‐long DEEP sediment succession and a comparison to a 197‐m‐long sediment succession from the Pestani site ~5 km to the east in the lake, where drilling ended close to the bedrock, to unravel the earliest history of Lake Ohrid and its basin development. 26Al/10Be dating of clasts from the base of the DEEP sediment succession implies that the sedimentation in the modern basin started at c. 2 Ma. Geophysical, sedimentological and micropalaeontological data allow for chronological information to be transposed from the DEEP to the Pestani succession. Fluvial conditions, slack water conditions, peat formation and/or complete desiccation prevailed at the DEEP and Pestani sites until 1.36 and 1.21 Ma, respectively, before a larger lake extended over both sites. Activation of karst aquifers to the east probably by tectonic activity and a potential existence of neighbouring Lake Prespa supported filling of Lake Ohrid. The lake deepened gradually, with a relatively constant vertical displacement rate of ~0.2 mm a−1 between the central and the eastern lateral basin and with greater water depth presumably during interglacial periods. Although the dynamic environment characterized by local processes and the fragmentary chronology of the basal sediment successions from both sites hamper palaeoclimatic significance prior to the existence of a larger lake, the new data provide an unprecedented and detailed picture of the geodynamic evolution of the basin and lake that is Europe’s presumed oldest extant freshwater lake.
Disseminated papular variant of Dowling‐Degos disease: Histopathological features in POGLUT1 mutation
Authors: Papadopoulou Katharina , Karsai Syrus , Böer‐Auer Almut
Published: October 2022

Dowling‐Degos disease is a rare benign genodermatosis. It is characterized by lentiginous hyperpigmentation and reddish‐brown papules and plaques. The flexor sides and intertrigines are often affected, but the clinical appearance may vary. Mutations in different genes are responsible for the clinical manifestation. While mutations in the keratin 5 (KRT5) gene favor a reticular distribution pattern, mutations in the POGLUT1 gene lead to a disseminated, papular clinical picture. Acantholytic variants of Dowling‐Degos disease have historically been referred to as Galli‐Galli disease, but our case study shows that the histopathological changes can vary even within a single patient. To date, no standardized therapy concept exists. The main focus is on keratolytic measures, with varying response. New therapeutic approaches using laser technology appear to be a promising treatment option.
Children's associations between space and pitch are differentially shaped by language
Authors: Dolscheid Sarah , Çelik Simge , Erkan Hasan , Küntay Aylin , Majid Asifa
Published: October 2022

Musical properties, such as auditory pitch, are not expressed in the same way across cultures. In some languages, pitch is expressed in terms of spatial height (high vs. low), whereas others rely on thickness vocabulary (thick = low frequency vs. thin = high frequency). We investigated how children represent pitch in the face of this variable linguistic input by examining the developmental trajectory of linguistic and non‐linguistic space‐pitch associations in children who acquire Dutch (a height‐pitch language) or Turkish (a thickness‐pitch language). Five‐year‐olds, 7‐year‐olds, 9‐year‐olds, and 11‐year‐olds were tested for their understanding of pitch terminology and their associations of spatial dimensions with auditory pitch when no language was used. Across tasks, thickness‐pitch associations were more robust than height‐pitch associations. This was true for Turkish children, and also Dutch children not exposed to thickness‐pitch vocabulary. Height‐pitch associations, on the other hand, were not reliable—not even in Dutch‐speaking children until age 11—the age when they demonstrated full comprehension of height‐pitch terminology. Moreover, Turkish‐speaking children reversed height‐pitch associations. Taken together, these findings suggest thickness‐pitch associations are acquired in similar ways by children from different cultures, but the acquisition of height‐pitch associations is more susceptible to linguistic input. Overall, then, despite cross‐cultural stability in some components, there is variation in how children come to represent musical pitch, one of the building blocks of music.

Research Highlights

Children from diverse cultures differ in their understanding of music vocabulary and in their nonlinguistic associations between spatial dimensions and auditory pitch.

Height‐pitch mappings are acquired late and require additional scaffolding from language, whereas thickness‐pitch mappings are acquired early and are less susceptible to language input.

Space‐pitch mappings are not static from birth to adulthood, but change over development, suggesting music cognition is shaped by cross‐cultural experience.
Continuous glucose monitoring metrics (Mean Glucose, time above range and time in range) are superior to glycated haemoglobin for assessment of therapeutic efficacy
Authors: Rodbard David
Published: October 2022

Aim

To evaluate continuous glucose monitoring (CGM) metrics for use as alternatives to glycated haemoglobin (HbA1c) to evaluate therapeutic efficacy.

Methods

We re‐analysed correlations among CGM metrics from studies involving 545 people with type 1 diabetes (T1D), 5910 people with type 2 diabetes (T2D) and 98 people with T1D during pregnancy and the postpartum period.

Results

Three CGM metrics, interstitial fluid Mean Glucose level, proportion of time above range (%TAR) and proportion of time in range (%TIR), were correlated with HbA1c and provided metrics that can be used to evaluate therapeutic efficacy. Mean Glucose showed the highest correlation with %TAR (r = 0.98 in T1D, 0.97 in T2D) but weaker correlations with %TIR (r = −0.92 in T1D, −0.83 in T2D) or with HbA1c (r = 0.78 in T1D). %TAR and %TIR were highly correlated (r = −0.96 in T1D, −0.91 in T2D). After 6 months of use of real‐time CGM by people with T1D, changes in Mean Glucose level were more highly correlated with changes in %TAR (r = 0.95) than with changes in %TIR (r = −0.85) or with changes in HbA1c level (r = 0.52). These metrics can be combined with metrics of hypoglycaemia and/or glycaemic variability to provide a more comprehensive assessment of overall quality of glycaemic control.

Conclusion

The CGM metrics %TAR and %TIR show much higher correlations with Mean Glucose than with HbA1c and provide sensitive indicators of efficacy. Mean glucose may be the best metric and shows consistently higher correlations with %TAR than with %TIR.
Experimental viral spillover can harmBombus terrestrisworkers under field conditions
Authors: Streicher Tabea , Tehel Anja , Tragust Simon , Paxton Robert J.
Published: October 2022

Deformed wing virus (DWV), notorious for its virulence in the western honey bee (Apis mellifera)when vectored by the ectoparasitic miteVarroa destructor, is also widespread among wild bumble bee species, presumably through spillover from honey bees. Experimental studies on the virulence of DWV inBombusspp. have provided equivocal results and have until now been confined to bumble bees under laboratory conditions.

Here, we inoculated commercially rearedBombus terrestrisworkers with DWV‐A through feeding or injection and introduced them into experimental colonies placed in the field, thus exposing them to the environment and associated stressors. We monitored the survival of inoculated worker bumble bees and quantified their viral load at 10 days post inoculation.

Bombus terrestrisworkers injected with DWV‐A supported high viral loads and exhibited significantly reduced median survival compared to controls. Bumble bees inoculated by feeding had low or zero detectable viral loads while their mortality did not differ from the control group.

Our results demonstrate that, although DWV‐A is pathogenic for commercialB. terrestris, the risks for individual fitness from spillover of DWV‐A during foraging on shared flowers appear limited.

The findings of this experiment also highlight the necessity to address the potential context‐dependence of virulence when evaluating the impact of a pathogen in an alternative host.