bluuebunny/crossref_metadata_2025 huggingface dataset:
Behaviours and Beliefs Related to Whistleblowing Against Doping in Sport: A Cross-National Study
Authors: Bondarev Dmitriy , Barkoukis Vassilis , Lazuras Lambros , Bochaver Konstantin , Oudra Despoina , Theodorou Nikolaos
Published: May 2022

Background

Whistleblowing has been recognized as an important deterrent of doping in elite competitive sport. The present study examined athletes’ knowledge of external whistleblowing channels and on how and where to report doping misconduct, perceived trust in different whistleblowing reporting channels, whistleblowing behaviour and athletes’ reasons for reporting (or not) doping misconduct.

Methods

Athletes from Greece (n = 480), the Russian Federation (n = 512) and the United Kingdom (n = 171) completed a structured questionnaire on demographics, knowledge of different whistleblowing channels, perceived trust in internal and external whistleblowing channels, past whistleblowing behaviour and reasons for reporting (or not) doping misconduct.

Results

The British athletes reported greater awareness of whistleblowing reporting channels (e.g., WADA’s Speak Up and IOC’s reporting platform) than did athletes from Greece (all p < 0.001) and Russia (p = 0.07, and p = 0.012) respectively. However, British athletes reported the lowest scores on knowledge of how and where to report doping misconduct, as compared to athletes from Greece and Russia. The majority of respondents reported greater trust to their coach or a club manager than to other whistleblowing channels, however, responses regarding other channels varied by country. Among athletes who detected doping misconduct 62% of athletes did not report it, while 38% reported it. Reasons for and against reporting doping misconduct reflected in eight themes that were identified using thematic analysis.

Conclusion

Athletes showed low awareness of external whistleblowing channels and they predominantly trusted internal whistleblowing channels. Sportspersonship, confidence in resources and personal benefits were among the reasons that facilitate reporting doping misconduct. The present findings indicate that cultural context may play a role in the ways athletes perceive whistleblowing, and this should be taken into account by future interventions to promote the reporting of doping misconduct.
Burden or Blessing? CEO Early-Life Adversity Experience and Firm Internationalization Performance
Authors: Zhou Ping , Zhao Yujie , Zhao Kangsheng
Published: May 2022

Firm internationalization is a great challenge that needs a strong leader because of the uncertainty involved. Previous research has examined the antecedents of firm internationalization from the perspective of upper echelons theory, including chief executive officer (CEO) or top management team (TMT) characteristics, yet little research has examined the role of CEO early-life adversity experiences. Based on the imprinting theory and upper echelons theory, this study explores the relationship between CEO early-life adversity experience and firm internationalization. Using data from Chinese listed companies during the period 2007–2017, we demonstrate that CEO early-life adversity experiences have a significantly positive effect on firm internationalization; the effect is stronger when the CEO with early-life adversity has a higher level of organization discretion and institutional discretion. The findings are robust to a battery of alternative variable definitions and estimation methods. We contribute to upper echelons theory and the research on internationalization antecedents by showing that CEO early-life adversity has a positive effect on firm internationalization. The findings suggest boards aspiring to expand internationally place weight on candidates’ early-life experiences while selecting and hiring CEOs and confer them managerial discretion to better play their strength after CEO’s appointment decision is made.
Preventive Medication Patterns in Bipolar Disorder and Their Relationship With Comorbid Substance Use Disorders in a Cross-National Observational Study
Authors: Icick Romain , Melle Ingrid , Etain Bruno , Høegh Margrethe Collier , Gard Sébastien , Aminoff Sofie R. , Leboyer Marion , Andreassen Ole A. , Belzeaux Raoul , Henry Chantal , Bjella Thomas D. , Kahn Jean-Pierre , Steen Nils Eiel , Bellivier Frank , Lagerberg Trine Vik
Published: May 2022

Objective

The potential role of sub-optimal pharmacological treatment in the poorer outcomes observed in bipolar disorder (BD) with vs. without comorbid substance use disorders (SUDs) is not known. Thus, we investigated whether patients with BD and comorbid SUD had different medication regimens than those with BD alone, in samples from France and Norway, focusing on compliance to international guidelines.

Methods

Seven hundred and seventy patients from France and Norway with reliably ascertained BD I or II (68% BD-I) were included. Medication information was obtained from patients and hospital records, and preventive treatment was categorized according to compliance to guidelines. We used Bayesian and regression analyses to investigate associations between SUD comorbidity and medication. In the Norwegian subsample, we also investigated association with lack of medication.

Results

Comorbid SUDs were as follows: current tobacco smoking, 26%, alcohol use disorder (AUD), 16%; cannabis use disorder (CUD), 10%; other SUDs, 5%. Compliance to guidelines for preventive medication was lacking in 8%, partial in 44%, and complete in 48% of the sample. Compliance to guidelines was not different in BD with and without SUD comorbidity, as was supported by Bayesian analyses (highest Bayes Factor = 0.16). Cross national differences in treatment regimens led us to conduct country-specific adjusted regression analyses, showing that (1) CUD was associated with increased antipsychotics use in France (OR = 2.4, 95% CI = 1.4–3.9, p = 0.001), (2) current tobacco smoking was associated with increased anti-epileptics use in Norway (OR = 4.4, 95% CI = 1.9–11, p < 0.001), and (3) AUD was associated with decreased likelihood of being medicated in Norway (OR = 1.2, 95% CI = 1.04–1.3, p = 0.038).

Conclusion

SUD comorbidity in BD was overall not associated with different pharmacological treatment in our sample, and not related to the level of compliance to guidelines. We found country-specific associations between comorbid SUDs and specific medications that warrant further studies.
Evaluating the Implementation of a Mental Health App for Overseas Filipino Workers in Macao China: A Mixed-Methods Study of Stakeholders’ Perspectives
Authors: Liem Andrian , Pakingan Karmia A. , Garabiles Melissa R. , Sit Hao Fong , Burchert Sebastian , Lam Agnes I. F. , Hall Brian J.
Published: May 2022

Background

Overseas Filipino workers (OFWs) is one of the largest communities of international migrant workers. They face systemic barriers to fulfilling their health needs. The COVID-19 pandemic worsened this condition and provided a context to evaluate the utility of a digital mental health intervention delivered within a stepped-care model to address OFW mental health. Using an implementation science framework, this study aimed to evaluate stakeholders’ perspectives on the implementation of Kumusta Kabayan, a mobile phone-based mental health app, for OFWs in Macao.

Methods

A mixed-methods convergent design was used by conducting two parallel steps, including quantitative and qualitative measures. The quantitative data was collected from Filipino team members and local non-governmental organization (NGO) staff members (N = 12). The qualitative data were gathered from interviews with OFWs in Macao who used the app (N = 25; 80% females, 76% domestic workers).

Results

From the online survey, the staff members of the local partner NGO and the Filipino team members strongly perceived that their organization could adapt Kumusta Kabayan to their program and generally evaluated that Kumusta Kabayan achieved its goal and was received well by OFWs. In the interviews, the OFW app users shared their experiences in using Kumusta Kabayan, which was thematically organized into six aspects of the participants’ experience: (1) promotional channel and expectation; (2) when to use the app and in what language; (3) lessons learnt; (4) memorable aspects; (5) key facilitators and barriers; and (6) suggestions.

Conclusion

Kumusta Kabayan was well accepted and shows potential to be integrated into the existing support services for OFWs in Macao. This app has the promise of being scaled-up for OFWs in other countries by collaborating with local and overseas stakeholders. Lessons learnt from this evaluation could also be implemented in wider digital mental health services in different settings.
The Interaction Between POMC rs2071345 Polymorphism and Alcohol Dependence in Anxiety Symptoms Among Chinese Male Problem Drinkers
Authors: Hong Liuzhi , Wen Lutong , Niculescu Michelle , Zhou Fan , Zou Yang , Shen Guanghui , Wang Wei , Liu Yanlong , Chen Yu-Hsin , Wang Fan , Chen Li
Published: May 2022

Objective

Alcohol dependence can increase the level of anxiety. A growing body of research has identified a link between anxiety symptoms of problem drinkers and their genetic or environment factors, respectively. However, to date few studies have directly examined gene-environment (G × E) interaction on their anxiety symptoms during the acute alcohol withdrawal. The present study aims to examine the interaction between the proopiomelanocortin (POMC) rs2071345 polymorphism and alcohol dependence on anxiety symptoms of male problem drinkers, and further test the exact form of interaction on two competing models: the diathesis-stress model vs. the differential susceptibility model.

Methods

A total of 440 male problem drinkers (Mage = 44.5 years, SD = 9.45) were recruited from nine main psychiatric hospitals of northern China during acute alcohol withdrawal. Blood samples were collected for genotyping, self-reported anxiety symptoms, and levels of alcohol dependence were assessed.

Results

Results indicated that the POMC rs2071345 polymorphism significantly moderated anxiety symptoms associated with alcohol dependence. A region of significance (RoS) test showed that male problem drinkers with T allele were more likely to experience more anxiety symptoms than those with CC homozygote when the standardized score of concurrent alcohol dependence was above 0.31. Confirmatory model evaluation indicated that the interaction effect involving POMC gene polymorphism conformed to the diathesis-stress model rather than differential-susceptibility model of person × environment interaction.

Conclusions

This study suggested that the SNP in POMC rs2071345 was associated with alcohol dependence in anxiety symptoms of male problem drinkers and further provided evidence in support of the diathesis-stress hypothesis of alcohol dependence in terms of anxiety symptoms.
Operationalizing “One Health” as “One Digital Health” Through a Global Framework That Emphasizes Fair and Equitable Sharing of Benefits From the Use of Artificial Intelligence and Related Digital Technologies
Authors: Ho Calvin Wai-Loon
Published: May 2022

The operationalization of One Health (OH) through digitalization is a means to deploy digital technologies (including Artificial Intelligence (AI), big data and related digital technologies) to better capacitate us to deal with growing climate exigency and related threats to human, animal and plant health. With reference to the concept of One Digital Health (ODH), this paper considers how digital capabilities can help to overcome ‘operational brakes’ in OH through new and deeper insights, better predictions, and more targeted or precise preventive strategies and public health countermeasures. However, the data landscape is fragmented and access to certain types of data is increasingly restrictive as individuals, communities and countries seek to assert greater control over data taken from them. This paper proposes for a dedicated global ODH framework—centered on fairness and equity—to be established to promote data-sharing across all the key knowledge domains of OH and to devise data-driven solutions to challenges in the human-animal-ecosystems interface. It first considers the data landscape in relation to: (1) Human and population health; (2) Pathogens; (3) Animal and plant health; and (4) Ecosystems and biodiversity. The complexification from the application of advance genetic sequencing technology is then considered, with focus on current debates over whether certain types of data like digital (genetic) sequencing information (DSI) should remain openly and freely accessible. The proposed ODH framework must augment the existing access and benefit sharing (ABS) framework currently prescribed under the Nagoya Protocol to the Convention on Biological Diversity (CBD) in at least three different ways. First, the ODH framework should apply to all genetic resources and data, including DSI, whether from humans or non-humans. Second, the FAIRER principles should be implemented, with focus on fair and equitable benefit-sharing. Third, the ODH framework should adopt multilateral approaches to data sharing (such as through federated data systems) and to ABS. By operationalizing OH as ODH, we are more likely to be able to protect and restore natural habitats, secure the health and well-being of all living things, and thereby realize the goals set out in the post-2020 Global Biodiversity Framework under the CBD.
Determining Whether Tai Chi Chuan Is Related to the Updating Function in Older Adults: Differences Between Practitioners and Controls
Authors: Yang Yuan , Chen Tingting , Wang Chen , Zhang Ji , Yuan Xiaoxia , Zhong Xiaoke , Yan Shoufu , Jiang Changhao
Published: May 2022

Background

Tai Chi Chuan (TCC) is an effective method for delaying cognitive decline in older adults. However, in older adults, the association between long-term TCC practice and working memory updating has not been extensively studied.

Objective

This cross-sectional study investigated how updating function operationalized via Reaction Times (RTs) and Accuracy Rates (ARs) of N-Back tasks being measured in a laboratory setting is related to long term practice of TCC.

Methods

Twenty-six healthy elderly people participated in this experiment. According to the duration of time TCC was practiced, 13 subjects in the TCC group had more than 5 years of experience with TCC exercise, and 13 elderly subjects who had not been systematically exposed to mind-body exercise were assigned to the control group. The N-back task was administered to every participant to evaluate the updating function.

Results

The TCC group had faster RTs than the control group (p < 0.05). For the 1-back task, the TCC group showed faster RTs than the control group; for the 2-back task, the TCC group exhibited faster RTs than the control group. The TCC group had higher ARs than the control group (p < 0.05). For the 1-back task, the TCC group showed higher ARs than the control group; for the 2-back task, the TCC group exhibited higher ARs than the control group.

Conclusions

Long-term TCC practitioners exhibit a better updating function as compared to controls who did not practice TCC. Thus, our findings suggest that long-term TCC positively influences the updating function of older adults, making it, in turn, an effective mind-body exercise to maintain specific aspects of cognitive functioning.
Development of a Clinical Practice Guideline for Lower Limb Amputees. A Knowledge Translation Process in a Middle Income Country
Authors: Posada-Borrero Ana Maria , Patiño-Lugo Daniel Felipe , Plata-Contreras Jesus Alberto , Velasquez-Correa Juan Carlos , Lugo-Agudelo Luz Helena
Published: May 2022

Background and Aim

Knowledge translation processes are necessary for improving patients' and communities' health outcomes. The aim of this study was to systematically develop evidence-based recommendations for people over 16 years of age who are in risk for or have suffered a lower limb amputation for medical reasons (vascular, diabetes mellitus) or trauma (civilian or military trauma) in order to improve function, quality of life, decrease complications and morbidity.

Methods

Following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach we developed a Clinical Practice Guideline (CPG) for lower limb amputees with funding from the Ministry of Health in Colombia and participation of a multidisciplinary group. We included patients' preferences. Based on the scope, purposes and objectives the questions were elaborated with the PECOT strategy. The evidence search was performed for each question in the main databases: Cochrane Library, Embase and PubMed, without time limit or language restriction. Teams were formed with thematic experts and clinical epidemiologists to review the clinical studies, describe the evidence, and evaluate the quality of the body of evidence with the GRADE methodology. The recommendations were made according to the judgments proposed by the GRADE working group. We conducted a stakeholder's dialogue as a mechanism for the external validation of the guideline implementation.

Results

The CPG included 43 recommendations related to the diagnosis, surgical treatment, rehabilitation, prescription and adaptation of the prosthesis. They were strong in favor 37.2, weak in favor 53.5, strong against 2.3, Weak against 7.0%. Quality of evidence was high in 0, moderate in 11.6, low in 58.1, and very low 30.2%.

Discussion

In 93% of the recommendations, the quality of the evidence was between low and very low. This is why it was so important to validate and discuss each recommendation with an expanded multidisciplinary group. The research group identified 25 interventions and five milestones to be prioritized in the implementation and in the stakeholder's dialogue participants identified opportunities and barriers for implementation of recommendations.

Conclusion

It is necessary to develop a national policy for implementation strategies of CPG recommendations that promotes the necessary arrangements for the provision of services for diagnosis, treatment, and rehabilitation of individuals with amputations.
A Study on the Effects of Cognitive Overloading and Distractions on Human Movement During Robot-Assisted Dressing
Authors: Camilleri Antonella , Dogramadzi Sanja , Caleb-Solly Praminda
Published: May 2022

For robots that can provide physical assistance, maintaining synchronicity of the robot and human movement is a precursor for interaction safety. Existing research on collaborative HRI does not consider how synchronicity can be affected if humans are subjected to cognitive overloading and distractions during close physical interaction. Cognitive neuroscience has shown that unexpected events during interactions not only affect action cognition but also human motor control Gentsch et al. (Cognition, 2016, 146, 81–89). If the robot is to safely adapt its trajectory to distracted human motion, quantitative changes in the human movement should be evaluated. The main contribution of this study is the analysis and quantification of disrupted human movement during a physical collaborative task that involves robot-assisted dressing. Quantifying disrupted movement is the first step in maintaining the synchronicity of the human-robot interaction. The human movement data collected from a series of experiments where participants are subjected to cognitive loading and distractions during the human-robot interaction, are projected in a 2-D latent space that efficiently represents the high-dimensionality and non-linearity of the data. The quantitative data analysis is supported by a qualitative study of user experience, using the NASA Task Load Index to measure perceived workload, and the PeRDITA questionnaire to represent the human psychological state during these interactions. In addition, we present an experimental methodology to collect interaction data in this type of human-robot collaboration that provides realism, experimental rigour and high fidelity of the human-robot interaction in the scenarios.
Curvilinear Kirigami Skins Let Soft Bending Actuators Slither Faster
Authors: Branyan Callie , Rafsanjani Ahmad , Bertoldi Katia , Hatton Ross L. , Mengüç Yiğit
Published: May 2022

The locomotion of soft snake robots is dependent on frictional interactions with the environment. Frictional anisotropy is a morphological characteristic of snakeskin that allows snakes to engage selectively with surfaces and generate propulsive forces. The prototypical slithering gait of most snakes is lateral undulation, which requires a significant lateral resistance that is lacking in artificial skins of existing soft snake robots. We designed a set of kirigami lattices with curvilinearly-arranged cuts to take advantage of in-plane rotations of the 3D structures when wrapped around a soft bending actuator. By changing the initial orientation of the scales, the kirigami skin produces high lateral friction upon engagement with surface asperities, with lateral to cranial anisotropic friction ratios above 4. The proposed design increased the overall velocity of the soft snake robot more than fivefold compared to robots without skin.
Designing a District Energy Infrastructure - a Case-Study in Lisbon
Authors: Jewell Alexandre , Schüler Nils , Cajot Sébastien , Gomes Ricardo , Silva Carlos Santos , Marechal Francois M. A.
Published: May 2022

The paper describes a case study on the design of district energy infrastructure for the green-field project of the Vale de Santo António (Lisbon, Portugal). The methodology is based on a novel framework built on the sequential integration of three software tools: QGIS, City Energy Analyst (CEA) and Urbio. QGIS is used to define the building database (construction solutions, uses and schedules); CEA is used to model the neighborhood energy services (heating, cooling, domestic hot water and electricity, including for EVs); and Urbio is used to design the energy infrastructure to supply the neighborhood in an optimal manner. The study illustrates the high impact of building renovation on heat demand and the existing potential for a two-layout network to minimize pumping demand and heat distribution loss. Moreover, a sensitivity analysis with regard to future carbon tax changes and electricity greening concludes that an electricity-based heating mix is optimal.
A New Dressing System Reduces the Number of Dressing Changes in the Primary Total Knee Arthroplasty: A Randomized Controlled Trial
Authors: Su Shilong , He Juan , Wang Chenggong , Gao Fawei , Zhong Da , Lei Pengfei
Published: May 2022

Purpose

We devised a novel dressing system to accelerate the recovery after total knee arthroplasty (TKA). The purpose of this study was to assess the clinical outcomes and economic expenses of the new dressing system.

Methods

In this randomized and controlled trial, we enrolled 98 patients who underwent the first unilateral TKA between September 2020 and June 2021. The patients were randomly assigned to one of two groups: the intervention (the new dressing system group) or the control (the traditional gauze dressing) group. We gathered and evaluated patient data including age, gender, body mass index, surgical side, number of dressing changes, post-operative hospital stay, dressing-related expense, satisfaction, pain and function scores, wound scores and wound-related complications.

Results

The number of dressing changes and post-operative hospital stay in the intervention group were significantly less than in the control group (p = 0.000, p = 0.002). Satisfaction in the intervention group was significantly higher than in the control group's (p = 0.000). There were no significant differences between the two groups in dressing-related expense, pain and function scores. During the one month follow-up, the intervention group's Stony Brook Scar Evaluation Scale (SBSES) was considerably higher than the control group's (p = 0.012).

Conclusion

The new dressing system can reduce the number of dressing changes and post-operative hospital stays while increasing patient satisfaction with no difference in medical costs in TKA. This wound dressing system has potential for application in TKA

Clinical Trial Registration

https://clinicaltrials.gov, identifier ChiCTR2000033814.
Management and Treatment of External Hemorrhoidal Thrombosis
Authors: Picciariello Arcangelo , Rinaldi Marcella , Grossi Ugo , Verre Luigi , De Fazio Michele , Dezi Agnese , Tomasicchio Giovanni , Altomare Donato F , Gallo Gaetano
Published: May 2022

Background

External hemorrhoidal thrombosis (EHT) is a common complication of hemorrhoidal disease. This condition causes extreme pain, likely resulting from internal anal sphincter hypertonicity, which traps the hemorrhoids below the dentate line thus leading to congestion and swelling. The choice of treatment remains controversial and both conservative and surgical options have been proposed in the last decades.

Methods

This mini-review focuses on the most relevant studies found in literature evaluating conservative and surgical management of EHT. Special conditions such as pregnancy and EHT in elderly patients have been considered.

Results

Traditionally, symptoms duration represents the discriminant in the choice between medical and surgical treatment. Several Coloproctological Societies considered conservative treatment as the first-line approach to EHT and a variety of options have been proposed: wait and see, mixture of flavonoids, mix of lidocaine and nifedipine, botulinum toxin injection and topical application of 0.2% glyceryl trinitrate. Meanwhile, different surgical treatments are recommended when EHT fails to respond to conservative management or when symptoms onset falls within the last 48–72 h: drainage with radial incision, conventional excision, excision under local anesthesia and stapled technique.

Conclusion

The management and treatment of EHT is still controversial since no specific guidelines have been published. Both medical and surgical treatment have been proven effective but randomized clinical trials and structured consensus-based guidelines are warranted.
Efficacy of Xuebijing Combined with Ulinastatin in the Treatment of Traumatic Sepsis and Effects on Inflammatory Factors and Immune Function in Patients
Authors: Su Yuanchao , Zhang Yunliang , Yuan Hongsheng , Shen Chuan
Published: May 2022

Objective

To investigate the efficacy of xuebijing combined with ulinastatin in the treatment of traumatic sepsis and analyze the effects on inflammatory factors and immune function of patients.

Methods

182 patients with traumatic sepsis were selected from June 2017 to September 2021 in our hospital. The patients were divided into the control group and the observation group. Patients in both groups were given routine treatments such as initial resuscitation, blood transfusion, monitoring of lactic acid to guide fluid replacement, early control of infection source, selection of appropriate antibiotics, correction of acidosis, treatment of primary disease, prevention of hypothermia and stress ulcer, application of vasoactive drugs, application of glucocorticoid and nutritional support. The control group was treated with Xuebijing injection on the basis of routine treatment, and the observation group was given Xuebijing injection combined with ulinastatin treatment on the basis of routine treatment. The APACHE II score was applied to evaluate the patients before and after treatment, and the routine blood indicators, inflammatory factor indicators, immune function indicators and liver function indicators were tested.

Results

After the treatment, the APACHE II score of the observation group was (10.35 ± 3.04) lower than that of the control group (15.93 ± 4.52) (P < 0.05). After treatment, the WBC and neutrophils in the observation group (15.19 ± 2.91) and (0.65 ± 0.04) were lower than those in the control group (16.42 ± 3.44) and (0.79 ± 0.05), and the PLT(162.85 ± 43.92) was higher than that in the control group (122.68 ± 36.89) (P < 0.05). After treatment, the levels of serum PCT, IL-6, TNF-α in the observation group were (11.38 ± 3.05), (10.74 ± 3.82) and (9.82 ± 2.35) lower than those in the control groups (17.34 ± 3.29), (15.28 ± 4.05) and (13.24 ± 3.06) (P < 0.05). After treatment, the levels of CD3+, CD4+, CD8+, CD4+/CD8+ in the observation group were (50.64 ± 4.98), (40.56 ± 4.82), (27.22 ± 3.29), (1.49 ± 0.24) higher than those in the control groups (46.08 ± 4.75), (34.69 ± 4.08), (25.14 ± 3.18), (1.38 ± 0.19) (P < 0.05). After treatment, the levels of TBIL and AST in the observation group were (12.35 ± 3.82), (25.66 ± 4.49) lower than those in the control group (18.43 ± 4.06), (34.58 ± 5.06) (P < 0.05).

Conclusion

Xubijing combined with ulinastatin has a good effect in the treatment of patients with traumatic sepsis, which can effectively improve the condition, reduce the body’s inflammatory response, and promote the recovery of patients’ immune function and liver function.
Video Endoscopy-Guided Intrabronchial Spray Inoculation of Mycobacterium bovis in Goats and Comparative Assessment of Lung Lesions With Various Imaging Methods
Authors: Wedlich Nadine , Figl Julia , Liebler-Tenorio Elisabeth M. , Köhler Heike , von Pückler Kerstin , Rissmann Melanie , Petow Stefanie , Barth Stefanie A. , Reinhold Petra , Ulrich Reiner , Grode Leander , Kaufmann Stefan H. E. , Menge Christian
Published: May 2022

Bovine tuberculosis (bTB) not only poses a zoonotic threat to humans but also has a significant economic impact on livestock production in many areas of the world. Effective vaccines for humans, livestock, and wildlife are highly desirable to control tuberculosis. Suitable large animal models are indispensable for meaningful assessment of vaccine candidates. Here, we describe the refinement of an animal model for bTB in goats. Intrabronchial inoculation procedure via video-guided endoscopy in anesthetized animals, collection of lungs after intratracheal fixation in situ, and imaging of lungs by computed tomography (CT) were established in three goats using barium sulfate as surrogate inoculum. For subsequent infection experiments, four goats were infected with 4.7 × 102 colony-forming units of M. bovis by intrabronchial inoculation using video-guided endoscopy with spray catheters. Defined amounts of inoculum were deposited at five sites per lung. Four age-matched goats were mock-inoculated. None of the goats developed clinical signs until they were euthanized 5 months post infection, but simultaneous skin testing confirmed bTB infection in all goats inoculated with M. bovis. In tissues collected at necropsy, M. bovis was consistently re-isolated from granulomas in lymph nodes, draining the lungs of all the goats infected with M. bovis. Further dissemination was observed in one goat only. Pulmonary lesions were quantified by CT and digital 2D radiography (DR). CT revealed mineralized lesions in all the infected goats ranging from <5 mm to >10 mm in diameter. Small lesions <5 mm predominated. The DR failed to detect small lesions and to determine the exact location of lesions because of overlapping of pulmonary lobes. Relative volume of pulmonary lesions was low in three but high in one goat that also had extensive cavitation. CT lesions could be correlated to gross pathologic findings and histologic granuloma types in representative pulmonary lobes. In conclusion, video-guided intrabronchial inoculation with spray catheters, mimicking the natural way of infection, resulted in pulmonary infection of goats with M. bovis. CT, but not DR, presented as a highly sensitive method to quantify the extent of pulmonary lesions. This goat model of TB may serve as a model for testing TB vaccine efficacy.
Ex vivo Platforms to Study the Primary and Recall Immune Responses to Intracellular Mycobacterial Pathogens and Peptide-Based Vaccines
Authors: Davis William C. , Mahmoud Asmaa H. , Abdellrazeq Gaber S. , Elnaggar Mahmoud M. , Dahl John L. , Hulubei Victoria , Fry Lindsay M.
Published: May 2022

Progress in the study of the immune response to pathogens and candidate vaccines has been impeded by limitations in the methods to study the functional activity of T-cell subsets proliferating in response to antigens processed and presented by antigen presenting cells (APC). As described in this review, during our studies of the bovine immune response to a candidate peptide-based vaccine and candidate rel deletion mutants in Mycobacterium avium paratuberculosis (Map) and Mycbacterium bovis (BCG), we developed methods to study the primary and recall CD4 and CD8 T-cell responses using an ex vivo platform. An assay was developed to study intracellular killing of bacteria mediated by CD8 T cells using quantitative PCR to distinguish live bacteria from dead bacteria in a mixed population of live and dead bacteria. Through use of these assays, we were able to demonstrate vaccination with live rel Map and BCG deletion mutants and a Map peptide-based vaccine elicit development of CD8 cytotoxic T cells with the ability to kill intracellular bacteria using the perforin-granzyme B pathway. We also demonstrated tri-directional signaling between CD4 and CD8 T cells and antigen-primed APC is essential for eliciting CD8 cytotoxic T cells. Herein, we describe development of the assays and review progress made through their use in the study of the immune response to mycobacterial pathogens and candidate vaccines. The methods obviate some of the major difficulties encountered in characterizing the cell-mediated immune response to pathogens and development of attenuated and peptide-based vaccines.
Demonstrating Benefit-Risk Profiles of Novel Therapeutic Strategies in Kidney Transplantation: Opportunities and Challenges of Real-World Evidence
Authors: Helanterä Ilkka , Snyder Jon , Åsberg Anders , Cruzado Josep Maria , Bell Samira , Legendre Christophe , Tedesco-Silva Hélio , Barcelos Giovanna Tedesco , Geissbühler Yvonne , Prieto Luis , Christian Jennifer B. , Scalfaro Erik , Dreyer Nancy A.
Published: May 2022

While great progress has been made in transplantation medicine, long-term graft failure and serious side effects still pose a challenge in kidney transplantation. Effective and safe long-term treatments are needed. Therefore, evidence of the lasting benefit-risk of novel therapies is required. Demonstrating superiority of novel therapies is unlikely via conventional randomized controlled trials, as long-term follow-up in large sample sizes pose statistical and operational challenges. Furthermore, endpoints generally accepted in short-term clinical trials need to be translated to real-world (RW) care settings, enabling robust assessments of novel treatments. Hence, there is an evidence gap that calls for innovative clinical trial designs, with RW evidence (RWE) providing an opportunity to facilitate longitudinal transplant research with timely translation to clinical practice. Nonetheless, the current RWE landscape shows considerable heterogeneity, with few registries capturing detailed data to support the establishment of new endpoints. The main recommendations by leading scientists in the field are increased collaboration between registries for data harmonization and leveraging the development of technology innovations for data sharing under high privacy standards. This will aid the development of clinically meaningful endpoints and data models, enabling future long-term research and ultimately establish optimal long-term outcomes for transplant patients.
Postoperative Trapped Lung After Orthotopic Liver Transplantation is a Predictor of Increased Mortality
Authors: Cuk Natasha , Melamed Kathryn H. , Vangala Sitaram , Salah Ramy , Miller W. Dwight , Swanson Sarah , Dai David , Antongiorgi Zarah , Wang Tisha , Agopian Vatche G. , Dinorcia Joseph , Farmer Douglas G. , Yanagawa Jane , Kaldas Fady M. , Barjaktarevic Igor
Published: May 2022

Pleural effusions are a common complication of orthotopic liver transplantation (OLT), and chronic post-OLT pleural effusions have been associated with worse outcomes. Furthermore, “trapped lung” (TL), defined as a restrictive fibrous visceral pleural peel preventing lung re-expansion, may have prognostic significance. We performed a retrospective analysis of adult OLT recipients over a 9-year period at UCLA Medical Center. Post-OLT patients with persistent pleural effusions, defined by the presence of pleural fluid requiring drainage one to 12 months after OLT, were included for analysis. Outcomes for patients with and without TL were compared using univariate and multivariate analysis. Of the 1722 patients who underwent OLT, 117 (7%) patients met our criteria for persistent postoperative pleural effusion, and the incidence of TL was 21.4% (25/117). Compared to patients without TL, those with TL required more surgical pleural procedures (OR 59.8, 95%CI 19.7–181.4, p < 0.001), spent more days in the hospital (IRR 1.56, 95%CI 1.09–2.23, p = 0.015), and had a higher risk of mortality (HR 2.47, 95%CI 1.59–3.82, p < 0.001) following transplant. In sum, we found that post-OLT TL was associated with higher morbidity, mortality, and healthcare utilization. Future prospective investigation is warranted to further clarify the risk factors for developing postoperative pleural effusions and TL.
A Novel Resolution Scheme of Time-Energy Optimal Trajectory for Precise Acceleration Controlled Industrial Robot Using Neural Networks
Authors: Hou Renluan , Niu Jianwei , Guo Yuliang , Ren Tao , Yu Xiaolong , Han Bing , Ma Qun
Published: May 2022

The surging popularity of adopting industrial robots in smart manufacturing has led to an increasing trend in the simultaneous improvement of the energy costs and operational efficiency of motion trajectory. Motivated by this, multi-objective trajectory planning subject to kinematic and dynamic constraints at multiple levels has been considered as a promising paradigm to achieve the improvement. However, most existing model-based multi-objective optimization algorithms tend to come out with infeasible solutions, which results in non-zero initial and final acceleration. Popular commercial software toolkits applied to solve multi-objective optimization problems in actual situations are mostly based on the fussy conversion of the original objective and constraints into strict convex functions or linear functions, which could induce a failure of duality and obtain results exceeding limits. To address the problem, this paper proposes a time-energy optimization model in a phase plane based on the Riemann approximation method and a solution scheme using an iterative learning algorithm with neural networks. We present forward-substitution interpolation functions as basic functions to calculate indirect kinematic and dynamic expressions introduced in a discrete optimization model with coupled constraints. Moreover, we develop a solution scheme of the complex trajectory optimization problem based on artificial neural networks to generate candidate solutions for each iteration without any conversion into a strict convex function, until minimum optimization objectives are achieved. Experiments were carried out to verify the effectiveness of the proposed optimization solution scheme by comparing it with state-of-the-art trajectory optimization methods using Yalmip software. The proposed method was observed to improve the acceleration control performance of the solved robot trajectory by reducing accelerations exceeding values of joints 2, 3 and 5 by 3.277 rad/s2, 26.674 rad/s2, and 7.620 rad/s2, respectively.
On the Extrapolation of Stability Derivatives to Combined Changes in Airspeed and Angles of Attack and Sideslip
Authors: Campos Luís M. B. C. , Marques Joaquim M. G.
Published: May 2022

The variation in stability derivatives with airspeed and angles of attack and sideslip is determined using only the dependence of the aerodynamic forces and moments on the modulus and direction of the velocity. Analytic extrapolation factors are obtained for all 12 longitudinal plus 12 lateral stability derivatives of linear decoupled motion. The extrapolation factors relate the stability derivatives for two flight conditions with different airspeeds, angles of attack (AoA), and angles of sideslip (AoS). The extrapolation formulas were validated by comparison with results of computational fluid dynamics (CFD) using Reynolds-averaged Navier–Stokes (RANS) equations. The comparison concerns the extrapolated full longitudinal–lateral stability matrix from one landing and one takeoff condition of a V-tailed aircraft, to 10 other landing and takeoff flight cases with different airspeeds, AoAs, and AoSs. Thus, 420 comparisons were made between extrapolated stability derivatives and CFD–RANS results demonstrating the achievable levels of accuracy.
Utilization of Intra-Cultivar Variation for Grain Yield and Protein Content within Durum Wheat Cultivars
Authors: Ninou Elissavet , Mylonas Ioannis , Karagianni Ioulia , Michailidou Sonia , Tsivelikas Athanasios , Sistanis Iosif , Avdikos Ilias , Korpetis Evangelos , Papathanasiou Fokion
Published: May 2022

This study assessed the variations in grain yield (GY) and protein content (PC) within two commercial durum wheat cultivars (Svevo and Maestrale) and evaluated their responses to intra-cultivar selection for both traits. We investigated whether the variations are exploitable and could result in concurrent GY and PC upgrading. The experiments were conducted in the IPBGR, Thessaloniki, Greece (2018–2020). The first year included two identical honeycomb design trials under ultra-low plant density (ULD) where the divergent selection was applied based on single plant yield and protein content. In the second year, progeny evaluation under typical crop density (TCD) for GY and PC occurred in a randomized complete block (RCB) and with three replications for each cultivar selected line. This revealed considerable variation within already improved commercial cultivars. Single-plant selection for GY and PC simultaneously resulted in: (a) one high-yielding line that significantly outperformed the original cultivar Svevo while maintaining high PC, and (b) two high-grain PC lines that outperformed the original cultivar Maestrale significantly while maintaining high GY. ULD allowed efficient selection for GY and PC simultaneously within narrow gene pools by maximizing phenotypic expression and differentiation among individual plants.
Spatiotemporal Changes in the Geographic Imbalances between Crop Production and Farmland-Water Resources in China
Authors: Li Dajing , Zhang Hongqi , Xu Erqi
Published: May 2022

Agricultural production is constrained by farmland and water resources, especially in China with limited per capita resources. Understanding of the geographic changes between national crop production and resource availability with the spatial shift of crop production has been limited in recent decades. To solve this issue, we quantified the changes in geographic relationships between crop production and farmland-water resources in China from 1990 to 2015 by a spatial imbalance measurement model. Results found a clear spatial concentration trend of crop production in China, which increased the pressure on the limited farmland and water resources in the main production areas. The geographic imbalances between the total production of crops and farmland resources (∑SMI_PF) alleviated slightly, whereas that of water resources (∑SMI_PW) increased by 9.12%. The rice production moved toward the north of the country with less water but abundant farmland resources, which led to a decrease of 1.34% in ∑SMI_PF and an increase of 14.20% in ∑SMI_PW. The shift of wheat production to the south was conducive to alleviating the pressure on water resources, but the production concentration still increased the demand for farmland and water resources, resulting in an increase in ∑SMI_PF and ∑SMI_PW by 39.96% and 10.01%, respectively. Of the five crops, adjustments to the spatial distribution of corn production had the most significant effect on reducing pressure on farmland and water resources and ∑SMI_PF and ∑SMI_PW decreased by 11.23% and 1.43%, respectively. Our results provided a reference for adjustments in crop production distribution and for policy formulation to sustainably utilize farmland and water resources.
Open Questions and Research Needs in the Adoption of Conservation Agriculture in the Mediterranean Area
Authors: Rinaldi Michele , Almeida Ana Sofia , Álvaro Fuentes Jorge , Annabi Mohamed , Annicchiarico Paolo , Castellini Mirko , Cantero Martinez Carlos , Cruz Maria Gabriela , D’Alessandro Giuseppe , Gitsopoulos Thomas , Marandola Danilo , Marguerie Mathieu , Lamouchi Salah , Latati Mourad , Lopez Francos Antonio , Moussadek Rachid , Pecetti Luciano
Published: May 2022

This article aims to provide a review of major challenges and research needs for the diffusion of conservation agriculture (CA) and the improvement of crop–soil–water conditions in Southern Europe and Northern Africa. A multidisciplinary study and a participatory approach are at the basis of an international project of research and innovation action, “Research-based participatory approaches for adopting conservation agriculture in the Mediterranean Area-CAMA”. It aims to understand the reasons and the research needs that limit a large CA diffusion in the Mediterranean countries. CAMA aims to provide significant advances to CA through multidisciplinary research at the field and farm scales (with main emphasis on smallholder), encompassing a socio-economic analysis of the reasons that obstacle the CA diffusion, legume crop improvement as a component of improved CA cropping systems, and a network of long-term experiments on CA and soil characteristic modification. Its results will be available to scientific and farming communities.
Evaluating the Effectiveness of Hospital Antiseptics on Multidrug-Resistant Acinetobacter baumannii: Understanding the Relationship between Microbicide and Antibiotic Resistance
Authors: Betchen Melanie , Giovinco Holly M. , Curry Michael , Luu Jackson , Fraimow Henry , Carabetta Valerie J. , Nahra Raquel
Published: May 2022

Acinetobacter baumannii hospital infections are difficult to treat due to the rapid emergence of multidrug-resistant (MDR) strains. In addition, A. baumannii can survive in numerous adverse environments, including in the presence of common hospital antiseptics. We hypothesized that in addition to accumulating drug resistance determinants, MDR A. baumannii strains also accumulate mutations that allow for greater microbicide tolerance when compared to pan-susceptible (PS) strains. To test this hypothesis, we compared the survival of five MDR and five PS patient isolates when exposed to bleach, ethanol, quaternary ammonium compounds, chlorhexidine gluconate, and povidone. We evaluated bacteria in a free-living planktonic state and under biofilm conditions. Each disinfectant eliminated 99.9% of planktonic bacteria, but this was not the case for bacterial biofilms. Next, we characterized strains for the presence of the known microbicide-resistance genes cepA, qacEΔ1, qacE, and qacA. MDR strains did not survive more than PS strains in the presence of microbicides, but microbicide-resistant strains had higher survival rates under some conditions. Interestingly, the PS strains were more likely to possess microbicide-resistance genes. Microbicide resistance remains an important topic in healthcare and may be independent of antimicrobial resistance. Hospitals should consider stricter isolation precautions that take pan-susceptible strains into account.