bluuebunny/crossref_metadata_2025 huggingface dataset:
An empirical analysis of human trafficking in an era of globalization
Authors: Malah Yselle Flora Kuete , Asongu Simplice
Published: October 2021

Purpose

The paper explores the dark side of economic openness by examining empirically the nexus between the globalization process and human trafficking. Specifically, it is about showing in a global perspective how the growing process of free movement of people, goods, capital, services and information technology make the globe a connected web of activity for the sale and exploitation of human beings.

Design/methodology/approach

After discussing some transmission channels through which globalization could increase this practice based on the lessons from the literature, an empirical analysis is done by employing ordinary least squares (OLS) and Probit regressions on a cross-sectional model covering 130 countries worldwide.

Findings

Findings, robust to the consideration of the sub-regional specificities and controlling for social, cultural and historical factors, suggest that globalization, particularly financial and cultural, favors human trafficking. In the light of these results, some policy recommendations are discussed.

Originality/value

This study complements the extant literature by assessing dynamics of globalization in human trafficking.
Perspectives on the evolution of a fabrication laboratory in an emerging country: a comparative lexicometric study of European FabLabs
Authors: Ben Rejeb Helmi , Roussel Benoit
Published: October 2021

Purpose

The purpose of this paper is to help in the establishment of the first fabrication laboratory (FabLab) in Tunisia. The FabLab movement offers many interesting opportunities through value creation, innovation, training and access to digital manufacturing technologies. A newly created FabLab should be well-positioned in terms of business model, purpose and management. The aim of this paper is to conduct a comparative analysis of FabLabs in developed countries (mainly in France and Luxembourg) and to provide recommendations on the possible development of a FabLab in Tunisia (FabLabENIT).

Design/methodology/approach

Twelve FabLabs were visited and experts from the makers movement were interviewed. Data from the visits and interviews were analysed using lexicometric tools. This methodology is based on three main steps: first, the identification and selection of panel of studied FabLabs interviews; second transcribing and coding for IRaMuTeQ software; and third, correspondence analysis.

Findings

The correspondence analysis determined five main factors of analysis that were interpreted using the most correlated words. The analysis of the correlation of the FabLabs and these five factors showed that FabLabENIT was strongly correlated with the third factor (interpreted as the organisation and structure factor). Recommendations for the purpose, local impact and methods were derived using the position of FabLabENIT in relation to the other factors.

Practical implications

This study highlighted five main topics that characterise FabLabs in developing countries before and after their creation. A second practical contribution of this paper is that it provides a framework for FabLab managers and founders to anticipate possible trajectories of evolution for their organisations, especially in an emerging country. Another contribution, both practical and methodological, is the demonstration of the use of textual interview analysis tools (mainly correspondence analysis) to determine the main practices and characteristics of a creative organisation, such as a FabLab.

Originality/value

One original feature of this paper is the topic of the study, especially in the current context of the COVID-19 outbreak, in which the FabLab movement provided interesting solutions that were designed and manufactured using digital manufacturing technologies. A second originality resides in the use of lexicometric techniques to analyse the information that was discussed during the interviews.
The jury is out – Can the HR managers be the choice architects in a post-pandemic work setting?
Authors: Sinha Subhashis , Jain Nikunj Kumar
Published: October 2021

Purpose

The purpose of this paper is to explore the role of HR managers as choice architects to increase the communication efforts for vaccination drives, thereby making the workplace a safe place for all employees.

Design/methodology/approach

This study used qualitative research methodology and interviewed 10 HR managers.

Findings

The findings indicate that HR managers can use the nudge theory and choice architecture to encourage employees towards coronavirus disease 2019 (COVID-19) vaccination.

Practical implications

HR professionals will get an alternate perspective regarding how learnings from behavioural economics can be leveraged in a post-pandemic world which can help them create a safe working environment.

Originality/value

This paper is an attempt to explore how learnings from behavioural economics (that is, nudge theory and choice architecture) can be leveraged by HR managers to design default options while organizing COVID-19 vaccination camps to motivate employees to get fully vaccinated and hence creating a safe working environment.
Whistleblowing by accountants: an integration of the fraud pentagon and the extended theory of planned behavior
Authors: Sarikhani Mehdi , Ebrahimi Fahime
Published: October 2021

Purpose

The purpose of this study is to investigate the factors affecting the whistleblowing intentions (WBI) by Iranian accountants by integrating the fraud pentagon and the extended theory of planned behavior.

Design/methodology/approach

The population was made up of accountants from all of the 400 companies listed in the Tehran Stock Exchange and the authors used a quantitative survey-based method. Out of a total of 300 questionnaires administered, 171 valid responses were used for analysis. This research used the partial least squares structural equation modeling analysis using SmartPLS 3.3.3 to examine the proposed hypotheses and to analyze the research model.

Findings

The results indicated that the extended theory of planned behavior components (perceived behavioral control, perceived subjective norms (PSN), perceived moral obligation and attitudes toward whistleblowing) have positive effects on accountants’ internal WBI. The results of investigating the moderating effect of perceived moral intensity (PMI) on the relationship between components of the extended theory of planned behavior and WBI show that PMI moderates the effect of PSN on WBI.

Originality/value

This study develops the whistleblowing literature by bringing together the components of the fraud pentagon and the extended theory of planned behavior and providing an integrated model. This model, which incorporates many variables from previous research, seeks to provide a comprehensive model for whistleblowing with the expansion of the Brown et al. (2016) model.
Behavior of strengthened concrete slab under eccentric compressive load
Authors: Youcef Bouamra , Taouche-Kheloui Fatma , Ait Tahar Kamal
Published: October 2021

Purpose

The purpose of this study is experimental research of the mechanical behavior of slab reinforced by cork composite patch submitted to an eccentric progressive compressive load applied to on impact rectangle of dimensions 28 × 23 cm2. An analytical model and numerical modeling by finite elements are performed. This study is motivated by the evaluation of the effectiveness of this type of partial reinforcement to improve strength and ductility. The results are given by load-displacement curves, tensile damages cartography and ultimate strength histogram.

Design/methodology/approach

In experimental protocol, the following two parameters have been considered: the dimensions of the patch and the eccentricity of the load. The sections of the patches are calculated so that the ratio (XP/YP) patch is proportional to the ratio (LD/lD), with a step of 6 cm longitudinally and 4 cm transversely. Several dimensions patches are considered: (6 × 4) cm2, (12 × 8) cm2 and (18 × 12) cm2. The eccentric punching loading test was performed with an eccentricity of the load (1/3) L’ and (2/3) L’ compared to the center of gravity of the slab. Taking into account the eccentricity of the load in estimating the rupture strength, the equations are developed. Thus, numerical simulations are carried, to extract tensile damages cartography.

Findings

The results show that the rupture begins with the appearance of cracks in the unreinforced area. For an eccentricity of 1/3L’, the best strength/section ratio is obtained for patch (12 × 8) cm2, whereas for an eccentricity de 2/3L’, the patch (6 × 4) cm2 gives a better resistance. The results highlight the influence of the composite on the ultimate load. The force-displacement relations are little modified in the elastic phase. The experimental results have been compared with the theoretical models showing a good correlation.

Originality/value

The strength and ductility are depended on the dimensions of the patch and the eccentricity of the load. The use of a patch to cover the most stressed area, in the event of an eccentric axial load is a very economical solution compared to the total reinforcement. The damage field shows that the evolution of cracks depends on dimensions and the position of the patch. Indeed, the eccentricity of the vertical load induces an additional bending moment that will influence the fracture surface. The rupture load and ultimate displacement increase with the surface of the patch.
NAMPT reduction‐induced NAD+ insufficiency contributes to the compromised oocyte quality from obese mice
Authors: Wang Hengjie , Zhu Shuai , Wu Xinghan , Liu Yuan , Ge Juan , Wang Qiang , Gu Ling
Published: October 2021

Maternal obesity is associated with multiple adverse reproductive outcomes, whereas the underlying molecular mechanisms are still not fully understood. Here, we found the reduced nicotinamide phosphoribosyl transferase (NAMPT) expression and lowered nicotinamide adenine dinucleotide (NAD+) content in oocytes from obese mice. Next, by performing morpholino knockdown assay and pharmacological inhibition, we revealed that NAMPT deficiency not only severely disrupts maturational progression and meiotic apparatus, but also induces the metabolic dysfunction in oocytes. Furthermore, overexpression analysis demonstrated that NAMPT insufficiency induced NAD+ loss contributes to the compromised developmental potential of oocytes and early embryos from obese mice. Importantly, in vitro supplement and in vivo administration of nicotinic acid (NA) was able to ameliorate the obesity‐associated meiotic defects and oxidative stress in oocytes. Our results indicate a role of NAMPT in modulating oocyte meiosis and metabolism, and uncover the beneficial effects of NA treatment on oocyte quality from obese mice.
Protected areas enter a new era of uncertain challenges: extinction of a non‐exigent falcon in Doñana National Park
Authors: Sergio F. , Blas J. , Tanferna A. , Hiraldo F.
Published: October 2021

Protected areas are supposed to maintain viable populations of plant and animal taxa and shield them from anthropogenic threats, but this role is increasingly under scrutiny. Here, we document the alarming extinction of a small falcon, the Eurasian hobby Falco subbuteo, in Doñana National Park, an iconic protected area renowned for its rich predator community. Hobbies were originally abundant at 50–60 pairs and acted as unique specialist hunters of swifts and dragonflies. This diet implies a unique niche within the raptor assemblage and frequent ranging over agricultural areas surrounding the park. The high density of other raptors likely constrained habitat availability. Predation was the main cause of breeding failure, and hatching and breeding success were always low, especially in drought years, and declined progressively through time. The extinction occurred rapidly after 2000 with several clues suggesting the synergistic contribution of prey depletion, farmland intensification, chemical contamination, predation and climate warming. Lack of detailed monitoring prevented a clear assessment of the relative role of these factors, but most of them seemed traceable to farming practices and climate change, i.e. large‐scale drivers generated outside the Park. The documented extinction is alarming because this species is not particularly exigent, it may imply widespread declines of other species, and because this loss adds to the imminent local extinction of another raptor with profoundly different requirements, suggesting mounting, broad‐level pressures affecting the whole ecosystem. This unforseen, rapid extinction in a Park that dedicates much effort to raptor management offers broad‐scale reflections. Climate change and growing anthropogenic pressures will make unexpected species losses increasingly common in protected areas, which will face growing difficulties in identifying decline‐drivers and in performing their protective task. Increased knowledge, quality monitoring and rapid management action will be needed for protected areas to deliver their role, but this will require increased funding.
Online shopping and the healthfulness of grocery purchases
Authors: Harris‐Lagoudakis Katherine
Published: October 2021

This paper utilizes novel household panel data to analyze the effect of online grocery shopping on the healthfulness of grocery purchases. We utilize variation in the timing that an online shopping service was introduced as a source of exogenous variation in the decision to shop online. Relative to pre‐online service averages, our estimates indicate that online shopping baskets allocate 10.2 (21.7)% more of the total spending (calories) toward healthful product categories and are 10.1% more nutrient dense. We also evaluate the effect of online shopping on the monthly aggregate (in‐store and online) basket. Average treatment effects for the treated (ATT) indicate a 2.3% decline in the sugar/sweet/candy budget share upon the introduction of the online shopping service; however, summary measures of healthfulness do not illustrate robust changes at the monthly level.
The role of non‐invasive prenatal testing (NIPT) for fetal blood group typing in Australia
Authors: Ginige Shamila , Daly James , Hyland Catherine , Powley Tanya , O’Brien Helen , Moreno Ana M. , Gardener Glenn , Flower Robert
Published: October 2021

Maternal alloimmunisation against red blood cell antigens can cause haemolytic disease of the fetus and newborn (HDFN). Although most frequently caused by anti‐D, since the implementation of rhesus D (RhD) immunoglobulin prophylaxis, other alloantibodies have become more prevalent in HDFN. Recent advances in non‐invasive prenatal testing (NIPT) have allowed early prediction of HDFN risk in alloimmunised pregnancies and allow clinicians to focus health resources on those pregnancies that require intervention. This article aims to provide updates on the current status of NIPT in Australia as both a diagnostic and screening tool in pregnancy.
National analysis of the Modified Monash Model, population distribution and a socio‐economic index to inform rural health workforce planning
Authors: Versace Vincent L. , Skinner Timothy C. , Bourke Lisa , Harvey Pam , Barnett Tony
Published: October 2021

Aims

To describe the population distribution and socio‐economic position of residents across all states and territories of Australia, stratified using the 7 Modified Monash Model classifications. The numerical summary, and the methods described, can be applied by a variety of end users including workforce planners, researchers, policy‐makers and funding bodies for guiding future investment under different scenarios, and aid in evaluating geographically focused programs.

Context

The Commonwealth Department of Health is transitioning to the Modified Monash Model to objectively describe geographical access. This change applies to the Rural Health Multidisciplinary Training Program, one of the Australian Government's key policies to address the maldistribution of the rural health workforce. Unlike the previously applied Australian Statistical Geography Standard‐Remoteness Areas, a summary of the population in each Modified Monash Model classification is not available, nor is a socio‐economic overview of the communities within these areas.

Approach

Spatial analysis of Australian Bureau of Statistics data (Modified Monash Model, population data and the Index of Relative Socio‐economic Advantage and Disadvantage collected or derived from the 2016 census) at the Statistical Area 1—the smallest unit for the release of census data.

Conclusion

Linking the Modified Monash Model, a socio‐economic index and granular population data at the national level highlights the disadvantage of many residents in small rural towns (Modified Monash 5). The Modified Monash Model does not exhibit a continuum of the largest population residing in the most accessible classification and the smallest population residing in the least accessible classification that is seen in the Australian Statistical Geography Standard‐Remoteness Areas. Coupled with policy relevance, the advantage of using the Modified Monash Model as the basis for analysis is that it highlights areas that have both a critical mass of residents and differing levels of socio‐economic advantage and disadvantage. This will help end users to target funding to those regions where there is potential to improve access to services for the greatest number of rural residents.
Ecosystem duties, green infrastructure, and environmental injustice in Los Angeles
Authors: Randle Sayd
Published: October 2021

In Los Angeles, water managers and environmentalist NGOs champion green infrastructure retrofits, installations intended to maximize the water‐absorbing capacity of the urban landscape. In such arrangements, the work of water management is necessarily spread among a more‐than‐human community, including (but certainly not limited to) humans, plants, soils, and gravels. This article analyzes the human labor within these collaborations, tracking when and how this work gets enrolled in networks of water management and circuits of value. I develop the term ecosystem duties to characterize these exertions and as a useful analytic for assessing emergent dynamics of environmental justice.
Between privileges and precariousness: Remaking whiteness in China's teaching English as a second language industry
Authors: Lan Shanshan
Published: October 2021

This research examines the multiple and contradictory racialization of white identities in China's booming ESL (English as a second language) industry. China represents a new geography of whiteness studies beyond Euro‐America due to the transformation of corporeal whiteness into a minority identity as a result of international migration. This research makes distinctions between white privilege as a form of structural domination in Western societies and white‐skin privilege as a form of embodied racial capital in China, which can be easily transformed into white‐skin vulnerability. It interprets the tension between white‐skin privilege and precariousness as a concurrent and mutually constitutive process that foregrounds the open‐ended nature of white racial formation in China. By focusing on the intersections between global white supremacist ideologies and local Chinese constructions of self/Other relations, this project explores new forms of racialization beyond the Black/white, superiority/inferiority binaries in the Western context.
Use of contraceptives and risk of inflammatory bowel disease: a nested case–control study
Authors: Pasvol Thomas Joshua , Bloom Stuart , Segal Anthony Walter , Rait Greta , Horsfall Laura
Published: October 2021

Background

How contraceptive formulation, dose, duration of therapy and mode of delivery affects the risk of inflammatory bowel disease (IBD) is poorly described.

Aim

To examine associations between types of hormonal contraception and development of IBD.

Methods

This was a nested case–control study using IQVIA Medical Research Data. Women aged 15‐49 years with a new diagnosis of IBD were matched with up to six controls by age, practice and year. Odds ratios (OR) and 95% confidence intervals (95% CI) for incident IBD and use of contraception were calculated.

Results

4932 incident cases of IBD were matched to 29 340 controls. Use of combined oral contraceptive pills (COCPs) was associated with the development of Crohn's disease and ulcerative colitis (OR 1.60 [1.41‐1.82] and 1.30 [1.15‐1.45], respectively). Each additional month of COCP exposure per year of follow‐up increased risk of Crohn's disease by 6.4% (5.1%‐7.7%) and ulcerative colitis by 3.3% (2.1%‐4.4%). Progestogen‐only pills had no effect on Crohn's disease risk (OR 1.09 [0.84‐1.40]) but there was a modest association with ulcerative colitis (OR 1.35 [1.12‐1.64]). Parenteral contraception was not associated with the development of Crohn's disease or ulcerative colitis (OR 1.15 [0.99‐1.47] and 1.17 [0.98‐1.39], respectively).

Conclusions

We observed an increase in the risk of IBD with increasing duration of exposure to COCPs. Progestogen‐only pills were not associated with Crohn's disease but there was a modest association with ulcerative colitis. There was no association between parenteral progestogen‐only contraception and IBD. These findings are broadly consistent with a hypothesis that the oestrogen component of contraception may drive IBD pathogenesis.
Patient‐reported outcomes in relapsed/refractory multiple myeloma treated with melflufen plus dexamethasone: analyses from the Phase II HORIZON study
Authors: Larocca Alessandra , Leleu Xavier , Touzeau Cyrille , Bladé Joan , Paner Agne , Mateos María‐Victoria , Cavo Michele , Maisel Christopher , Alegre Adrían , Oriol Albert , Raptis Anastasios , Rodriguez‐Otero Paula , Mazumder Amitabha , Laubach Jacob , Nadeem Omar , Sandberg Anna , Orre Marie , Torrång Anna , Bakker Nicolaas A. , Richardson Paul G.
Published: October 2021

Relapsed/refractory multiple myeloma (RRMM) is known to have a high burden of disease and complications associated with refractoriness to prior lines of therapy. Severe pain and fatigue symptoms and impairments in physical and emotional functioning have been strongly linked to reduced health‐related quality of life (HRQoL) in patients with RRMM. Assessment of patient reported‐outcome measures from the pivotal, Phase II HORIZON study (OP‐106; NCT02963493) in patients with RRMM (n = 64) demonstrated that melphalan flufenamide (melflufen) plus dexamethasone treatment preserved HRQoL. Patients had clinically meaningful improvements, even after eight treatment cycles, in relevant scales such as global health status/QoL, physical functioning, emotional functioning, pain, and fatigue. Patients with triple‐class–refractory disease (n = 50) displayed similar improvements. Patient‐reported outcome deterioration was delayed for a substantial amount of time in patients who experienced a response to melflufen plus dexamethasone treatment relative to patients who did not experience a response. These findings support the notion that treatment with melflufen plus dexamethasone may sustain or improve HRQoL over time in patients with RRMM, including in patients with triple‐class–refractory disease for whom outcomes are generally worse. The clinical benefits observed in patients from the HORIZON trial are encouraging and supportive of translation into real‐world practice.
Tracking the evolution of untreated high‐intermediate/high‐risk diffuse large B‐cell lymphoma by circulating tumour DNA
Authors: Zhang Sicong , Zhang Tingting , Liu Hengqi , Zhao Jing , Zhou Haifei , Su Xiaoxing , Liu Xianming , Li Lanfang , Qiu Lihua , Qian Zhengzi , Zhou Shiyong , Gong Wenchen , Meng Bin , Ren Xiubao , He Jin , Wang Xianhuo , Zhang Huilai
Published: October 2021

Diffuse large B‐cell lymphoma (DLBCL) is a highly heterogenous malignancy, early identification of patients for relapse remains challenging. The potential to non‐invasively monitor tumour evolutionary dynamics of DLBCL needs to be further established. In the present study, 17 tumour biopsy and 38 plasma samples from 38 patients with high‐intermediate/high‐risk DLBCL were evaluated at baseline. Longitudinal blood samples were also collected during therapy. Circulating tumour DNA (ctDNA) was analysed using targeted sequencing based on a gene panel via a recently developed methodology, circulating single‐molecule amplification and re‐sequencing technology (cSMART). We found that the most frequently mutated genes were tumour protein p53 (TP53; 42·1%), histone‐lysine N‐methyltransferase 2D (KMT2D; 28·9%), caspase recruitment domain family member 11 (CARD11; 21·1%), cAMP response element‐binding protein binding protein (CREBBP; 15·8%), β2‐microglobulin (B2M; 15·8%), and tumour necrosis factor alpha‐induced protein 3 (TNFAIP3; 15·8%). The mutation profiles between ctDNA and matched tumour tissue showed good concordance; however, more mutation sites were detected in ctDNA samples. Either TP53 or B2M mutations before treatment predicted poor prognosis. Analysis of dynamic blood samples confirmed the utility of ctDNA for the real‐time assessment of treatment response and revealed that the increases in ctDNA levels and changes in KMT2D mutation status could be useful predictors of disease progression. Our present results suggest that ctDNA is a promising method for the detection of mutation spectrum and serves as a biomarker for disease monitoring and predicting clinical recurrence.
Use of medical exome sequencing for identification of underlying genetic defects in NICU: Experience in a cohort of 2303 neonates in China
Authors: Yang Lin , Wei Zejun , Chen Xiang , Hu Liyuan , Peng Xiaomin , Wang Jin , Lu Chunmei , Kong Yanting , Dong Xinran , Ni Qi , Lu Yulan , Wu Bingbing , Wang Huijun , Meirelles Katia , Tian Xia , Zhang Jing , Chang Fengqi , Liu Liu , Li Changhua , You Wesley , Cheng Guoqiang , Wang Laishuan , Cao Yun , Chen Chao , Fang Ping , Tang Sha , Zhou Wenhao
Published: October 2021

Emerging evidence demonstrates the clinical utility of genomic applications in newborn intensive care unit (NICU) patients with strong indications of Mendelian etiology. However, such applications' diagnostic yield and utility remain unclear for NICU cohorts with minimal phenotype selection. In this study, focused medical exome sequencing was used as a first‐tier, singleton‐focused diagnostic tool for 2303 unrelated sick neonates. Integrated analysis of single nucleotide variants (SNVs), small insertions and deletions (Indels), and large copy number variants (CNVs) was performed. The diagnostic rate in this NICU cohort is 12.3% (284/2303), with 190 probands with molecular diagnoses made from SNV/Indel analyses (66.9%), 93 patients with diagnostic aneuploidy/CNVs findings (32.8%), and 1 patient with both SNV and CNV (0.4%). In addition, 54 (2.3%) of patients had a reportable incidental finding. Multiple organ involvements, craniofacial abnormalities, and dermatologic abnormalities were the strongest positive predictors for a molecular diagnosis. Among the 190 cases with SNV/Indel defects, direct impacts on medical management were observed in 46.8% of patients after the results were reported. In this study, we demonstrate that focused medical exome sequencing is a powerful first‐line diagnostic tool for NICU patients. Significant number of diagnosed NICU patients can benefit from more focused medical management and long‐term care.
Inflammatory effects of individualized abutments bonded onto titanium base on peri‐implant tissue health: A randomized controlled clinical trial
Authors: Rathe Florian , Junker Rüdiger , Gröger Sabine , Meyle Jörg , Schlee Markus
Published: October 2021

Background

In implant prosthodontics, computer‐assisted design and computer‐assisted manufacturing (CAD/CAM) zirconia abutments bonded onto titanium bases are frequently used in prosthetic dentistry. Unpolymerized monomer of the bonding material or the adhesive gap itself may have a negative effect on peri‐implant tissue health. However, evidence addressing this problem is not available.

Purpose

The aim of the current trial was to study inflammatory effects of individualized abutments bonded onto titanium bases.

Material and Method

A total of 24 patients with one test abutment and one control abutment each participated in this prospective, double‐blind, randomized controlled clinical trial. Thereby, test abutments were CAD/CAM titanium abutments bonded onto titanium abutments (Ti‐Base). As control abutments individualized, one‐piece CAD/CAM titanium abutments were used. At abutment installation as well as 6 and 12 months thereafter bone level changes, clinical parameters as well as Il‐1β levels were assessed.

Results

Neither for bone level or clinical parameters nor for Il‐1β levels, significant differences between test and control abutments could be found. However, in both groups Il‐1β levels were significantly elevated at both the 6 and 12 months follow‐up compared to baseline.

Conclusion

Within the limits of this RCT, it can be concluded that effects on the inflammatory state of peri‐implant tissues do not differ between individualized abutments bonded onto Ti‐Bases and individualized one‐piece abutments.
Pharmacokinetics and safety of a novel influenza treatment (baloxavir marboxil) in Korean subjects compared with Japanese subjects
Authors: Kim Yun , Lee Sangwon , Kim Yohan , Jang In‐Jin , Lee SeungHwan
Published: October 2021

Baloxavir marboxil, a novel influenza therapeutic agent, is a prodrug rapidly metabolized into its active form, baloxavir acid, which inhibits cap‐dependent endonuclease. This study evaluated the pharmacokinetics (PKs) and safety of baloxavir acid in healthy Korean subjects and compared them with published data in Japanese subjects. This open‐label and single‐ascending dose study was conducted in 30 Korean male subjects, with a single oral dose of baloxavir marboxil (20, 40, or 80 mg) administered to eight subjects each; additionally, 80 mg was administered to six subjects (body weight >80 kg). Noncompartmental and population PK analyses were performed, and results were compared with those of Japanese subjects. Appropriateness of the body weight‐based dosing regimen was evaluated by simulation. PK profiles of baloxavir acid revealed multicompartment behavior with a long half‐life (80.8–98.3 h), demonstrating a dose‐proportional increase. Baloxavir acid reached peak plasma concentration from 3.5 to 4.0 h postdosing. Body weight was identified as a significant covariate of apparent oral clearance and apparent volume of distribution, which was similar to that observed in Japanese subjects. Body weight‐adjusted analysis revealed that exposure to baloxavir acid did not significantly differ between Korean and Japanese subjects. Simulated exposures to baloxavir acid demonstrated that the body weight‐based dosing regimen for baloxavir marboxil was appropriate. Based on a PK study, clinical data including dosing regimen developed in Japan were adequately extrapolated to Korea, supporting the approval of baloxavir marboxil in Korean as a new treatment option for influenza.
Using forecasting to evaluate the impact of COVID‐19 on passenger air transport demand
Authors: Li Xishu , de Groot Maurits , Bäck Thomas
Published: October 2021

The COVID‐19 pandemic caused a drastic drop in passenger air transport demand due to two forces: supply restriction and demand depression. In order for airlines to recover, the key is to identify which force they are fighting against. We propose a method for separating the two forces of COVID‐19 and evaluating the respective impact on demand. Our method involves dividing passengers into different segments based on passenger characteristics, simulating different scenarios, and predicting demand for each passenger segment in each scenario. Comparing the predictions with each other and with the real situation, we quantify the impact of COVID‐19 associated with the two forces, respectively. We apply our method to a dataset from Air France–KLM and show that from March 1st to May 31st 2020, the pandemic caused demand at the airline to drop 40.3% on average for passengers segmented based on age and purpose of travel. The 57.4% of this decline is due to demand depression, whereas the other 42.6% is due to supply restriction. In addition, we find that the impact of COVID‐19 associated with each force varies between passenger segments. The demand depression force impacted business passengers between age 41 and 60 the most, and it impacted leisure passengers between age 20 and 40 the least. The opposite result holds for the supply restriction force. We give suggestions on how airlines can plan their recovery using our results and how other industries can use our evaluation method.
Endoscopic features and clinical importance of autoimmune gastritis
Authors: Kamada Tomoari , Maruyama Yasuhiko , Monobe Yasumasa , Haruma Ken
Published: October 2021

Autoimmune gastritis (AIG) is a special type of chronic gastritis characterized by autoimmune disorders caused by cellular immunity, resulting in the destruction of parietal cells and production of antiparietal cell antibodies. Endoscopic findings of AIG are mainly characterized by corpus‐dominant advanced atrophy. The antral area is generally considered to have no or mild atrophy; however, there are cases wherein the gastric mucosa is red or faded due to past infection with Helicobacter pylori or bile reflux. Currently, there are no diagnostic criteria for AIG in Japan, and it is important to make a diagnosis based on the presence of gastric autoantibodies and characteristic endoscopic and histological findings. AIG is associated with gastric cancer, neuroendocrine tumors (NETs), and other autoimmune diseases, such as thyroid diseases, anemia, and neurological symptoms due to impaired absorption of iron and vitamin B12, and thus requires systemic treatment. The significance of diagnosing AIG is to include patients as a high‐risk group for the development of gastric cancer and gastric NETs, provide an opportunity to detect autoimmune endocrine diseases, and initiate therapeutic intervention before anemia and neurological symptoms develop. It is important to pay close attention to the occurrence of AIG comorbidities not only at the time of AIG diagnosis but also during follow‐up after detection.
Painful diabetic peripheral neuropathy: Role of oxidative stress and central sensitisation
Authors: Ye Di , Fairchild Timothy J. , Vo Lechi , Drummond Peter D.
Published: October 2021

Aims

Diabetic peripheral neuropathy (DPN) occurs in about half of people with diabetes, of whom a quarter may develop chronic pain. Pain may remain for years yet be difficult to treat because the underlying mechanisms remain unclear. There is consensus that processing excessive glucose leads to oxidative stress, interfering with normal metabolism. In this narrative review, we argue that oxidative stress may also contribute to pain.

Methods

We reviewed literature in PubMed published between January 2005 and August 2021.

Results and conclusions

In diabetes, hyperglycaemia and associated production of reactive species can directly increase pain signalling and activate sensory neurons; or the effects can be indirect, mediated by mitochondrial damage and enhanced inflammation. Furthermore, pain processing in the central nervous system is compromised in painful DPN. This is implicated in central sensitisation and dysfunctional pain modulation. However, central pain modulatory function is understudied in diabetes. Future research is required to clarify whether central sensitisation and/or disturbances in central pain modulation contribute to painful DPN. Positive results would facilitate early detection and future treatment.
megaSDM: integrating dispersal and time‐step analyses into species distribution models
Authors: Shipley Benjamin R. , Bach Renee , Do Younje , Strathearn Heather , McGuire Jenny L. , Dilkina Bistra
Published: October 2021

Understanding how species ranges shift as climates rapidly change informs us how to effectively conserve vulnerable species. Species distribution models (SDMs) are an important method for examining these range shifts. The tools for performing SDMs are ever improving. Here, we present the megaSDM R package. This package facilitates realistic spatiotemporal SDM analyses by incorporating dispersal probabilities, creating time‐step maps of range change dynamics and efficiently handling large datasets and computationally intensive environmental subsampling techniques. Provided a list of species and environmental data, megaSDM synthesizes GIS processing, subsampling methods, MaxEnt modelling, dispersal rate restrictions and additional statistical tools to create a variety of outputs for each species, time period and climate scenario requested. For each of these, megaSDM generates a series of distribution maps and outputs visual representations of statistical data. megaSDM offers several advantages over other commonly used SDM tools. First, many of the functions in megaSDM natively implement parallelization, enabling the package to handle large amounts of data efficiently without the need for additional coding. megaSDM also implements environmental subsampling of occurrences, making the technique broadly available in a way that was not possible before due to computational considerations. Uniquely, megaSDM generates maps showing the expansion and contraction of a species range across all considered time periods (time‐maps), and constrains both presence/absence and continuous suitability maps of species ranges according to species‐specific dispersal constraints. The user can then directly compare non‐dispersal and dispersal‐limited distribution predictions. This paper discusses the unique features and highlights of megaSDM, describes the structure of the package and demonstrates the package's features and the model flow through examples.
Phylogenetic niche conservatism and variations in species diversity–climate relationships
Authors: Wang Qinggang , Li Yaoqi , Zou Dongting , Su Xiangyan , Cai Hongyu , Luo Ao , Jiang Ke , Zhang Xiaoling , Xu Xiaoting , Shrestha Nawal , Wang Zhiheng
Published: October 2021

Although contemporary climate has been identified as one of the major determinants of large‐scale species diversity patterns, its effect on species diversity greatly varies among clades. Understanding the drivers of the variation in species diversity–climate relationships (DCRs) across clades, which is critical for developing general mechanisms underlying the effects of climate on species diversity patterns, remains a current challenge. Using newly compiled distribution data of 914 Rosaceae species in China and a dated genus‐level phylogeny, we first assessed the DCRs for the entire family, the two major growth forms (woody versus herbaceous), and each genus separately, and then explored the drivers underlying the variation in DCRs across different clades. We found that the DCRs significantly differed between woody and herbaceous plants and among different genera in this family. Closely related genera had more similar species diversity patterns and DCRs than expected. Both the ancestral climate niches of different genera and the discrepancy between contemporary and ancestral climate niches explained the variations in DCR slopes across genera with high explanatory power, indicating the effect of niche conservatism on DCRs. Our study suggests that niche conservatism is a major driver of DCR variations between clades, which enhances our understanding of the mechanisms underlying large‐scale species diversity patterns.
Experiential modulation of social dominance in a SYNGAP1 rat model of Autism Spectrum Disorders
Authors: Harris Emma , Myers Honor , Saxena Kapil , Mitchell‐Heggs Rufus , Kind Peter , Chattarji Shona , Morris Richard G. M.
Published: October 2021

Advances in the understanding of developmental brain disorders such as autism spectrum disorders (ASDs) are being achieved through human neurogenetics such as, for example, identifying de novo mutations in SYNGAP1 as one relatively common cause of ASD. A recently developed rat line lacking the calcium/lipid binding (C2) and GTPase activation protein (GAP) domain may further help uncover the neurobiological basis of deficits in children with ASD. This study focused on social dominance in the tube test using Syngap+/Δ‐GAP (rats heterozygous for the C2/GAP domain deletion) as alterations in social behaviour are a key facet of the human phenotype. Male animals of this line living together formed a stable intra‐cage hierarchy, but they were submissive when living with wild‐type (WT) cage‐mates, thereby modelling the social withdrawal seen in ASD. The study includes a detailed analysis of specific behaviours expressed in social interactions by WT and mutant animals, including the observation that when the Syngap+/Δ‐GAP mutants that had been living together had separate dominance encounters with WT animals from other cages, the two higher ranking Syngap+/Δ‐GAP rats remained dominant whereas the two lower ranking mutants were still submissive. Although only observed in a small subset of animals, these findings support earlier observations with a rat model of Fragile X, indicating that their experience of winning or losing dominance encounters has a lasting influence on subsequent encounters with others. Our results highlight and model that even with single‐gene mutations, dominance phenotypes reflect an interaction between genotypic and environmental factors.
Contrasting nutrient availability between marine and brackish waters in the late Mesoproterozoic: Evidence from the Paranoá Group, Brazil
Authors: Stüeken Eva E. , Viehmann Sebastian , Hohl Simon V.
Published: October 2021

Understanding the delayed rise of eukaryotic life on Earth is one of the most fundamental questions about biological evolution. Numerous studies have presented evidence for oxygen and nutrient limitations in seawater during the Mesoproterozoic era, indicating that open marine settings may not have been able to sustain a eukaryotic biosphere with complex, multicellular organisms. However, many of these data sets represent restricted marine basins, which may bias our view of habitability. Furthermore, it remains untested whether rivers could have supplied significant nutrient fluxes to coastal habitats. To better characterize the sources of the major nutrients nitrogen and phosphorus, we turned to the late Mesoproterozoic Paranoá Group in Brazil (~1.1 Ga), which was deposited on a passive margin of the São Francisco craton. We present carbon, nitrogen and sulphur isotope data from an open shelf setting (Fazenda Funil) and from a brackish‐water environment with significant riverine input (São Gabriel). Our results show that waters were well‐oxygenated and nitrate was bioavailable in the open ocean setting at Fazenda Funil; the redoxcline appears to have been deeper and further offshore compared to restricted marine basins elsewhere in the Mesoproterozoic. In contrast, the brackish site at São Gabriel received only limited input of marine nitrate and sulphate. Nevertheless, previous reports of acritarchs reveal that this brackish‐water setting was habitable to eukaryotic life. Paired with previously published cadmium isotope data, which can be used as a proxy for phosphorus cycling, our results suggest that complex organisms were perhaps not strictly dependent on marine nutrient supplies. Riverine influxes of P and possibly other nutrients likely rendered coastal waters perhaps equally habitable to the Mesoproterozoic open ocean. This conclusion supports the notion that eukaryotic organisms may have thrived in brackish or perhaps even freshwater environments.
Quantification of blue carbon pathways contributing to negative feedback on climate change following glacier retreat in West Antarctic fjords
Authors: Zwerschke Nadescha , Sands Chester J. , Roman‐Gonzalez Alejandro , Barnes David K. A. , Guzzi Alice , Jenkins Stuart , Muñoz‐Ramírez Carlos , Scourse James
Published: October 2021

Global warming is causing significant losses of marine ice around the polar regions. In Antarctica, the retreat of tidewater glaciers is opening up novel, low‐energy habitats (fjords) that have the potential to provide a negative feedback loop to climate change. These fjords are being colonized by organisms on and within the sediment and act as a sink for particulate matter. So far, blue carbon potential in Antarctic habitats has mainly been estimated using epifaunal megazoobenthos (although some studies have also considered macrozoobenthos). We investigated two further pathways of carbon storage and potential sequestration by measuring the concentration of carbon of infaunal macrozoobenthos and total organic carbon (TOC) deposited in the sediment. We took samples along a temporal gradient since time of last glacier ice cover (1–1000 years) at three fjords along the West Antarctic Peninsula. We tested the hypothesis that seabed carbon standing stock would be mainly driven by time since last glacier covered. However, results showed this to be much more complex. Infauna were highly variable over this temporal gradient and showed similar total mass of carbon standing stock per m2 as literature estimates of Antarctic epifauna. TOC mass in the sediment, however, was an order of magnitude greater than stocks of infaunal and epifaunal carbon and increased with time since last ice cover. Thus, blue carbon stocks and recent gains around Antarctica are likely much higher than previously estimated as is their negative feedback on climate change.
Clinical assessment and point of care ultrasonography: How to diagnose haemophilic synovitis
Authors: De la Corte‐Rodriguez Hortensia , Rodriguez‐Merchan E. Carlos , Alvarez‐Roman María Teresa , Martin‐Salces Monica , Jimenez‐Yuste Victor
Published: October 2021

Background

The ability of clinical tools to identify early joint changes is limited. Synovitis is a fundamental finding in understanding haemophilia activity and the response to its therapies; thus, there is a need for sensitive methods to better diagnose subclinical synovitis early.

Purpose

Our aim was to compare the frequency with which clinical assessment and ultrasound detected synovial hypertrophy in the most frequently affected joints in patients with haemophilia (elbows, knees and ankles).

Methods

We analysed patients with haemophilia older than 16 years who came to the haemophilia centre for routine follow‐up. From the clinical assessment carried out in the consultation, the swelling, pain and history of haemarthrosis were evaluated and compared with the findings of synovial hypertrophy detected by ultrasound. This comparison was also analysed independently for elbows, knees and ankles.

Results

A total of 203 joints of 66 patients with haemophilia (mean age 34 years), most of them on secondary, tertiary prophylaxis or on demand treatment, were included. In joints with swelling, pain and history of haemarthrosis, 78% of the joints showed synovial hypertrophy on ultrasound. However, in joints with no swelling, no pain and no history of haemarthrosis, 40% presented subclinical synovial hypertrophy on ultrasound. This percentage was higher in elbows than in knees and ankles.

Conclusion

In adults with haemophilia, physical examination and point‐of‐care ultrasound study provide complementary data on their joint disease. However, without ultrasound, the ability to detect subclinical synovitis is considerably reduced, especially in the elbows.