bluuebunny/crossref_metadata_2025 huggingface dataset:
Collaborative learning methods and multimedia tools for the education and training of instructors
Authors: Armenteros Manuel , Benítez Anto J. , Fernández Marta , De la Vega Ricardo , Sillero-Quintana Manuel , Sánchez Cid Manuel
Published: March 2019

Purpose

The purpose of this paper is to analyze the new collaborative learning methods and tools used by elite FIFA referee technical instructors, referees and assistant referees to master the Laws of the Game. These tools allow instructors to learn through practical exercises off the field of play, while they carry out activities in a participative context in which they can share and improve their knowledge regarding the Laws of the Game and consequently the interpretations and the considerations soccer referees throughout the world use to make decisions on the field of play.

Design/methodology/approach

In this work, we assess a collaborative learning experience that took place during the annual FIFA FUTURO III courses that FIFA provided to FIFA referee technical instructors from its six confederations between 2013 and 2015, where 48 referee technical instructors selected from 211 national associations participated. These instructors constitute the elite of FIFA’s professional training and development chain. They teach other referee technical instructors who will then instruct international referees and assistant referees all over the world with the aim of achieving uniformity when applying the Laws of the Game.

Findings

The course participants showed a high degree of satisfaction with respect to these materials and methods, especially regarding the possibilities they offer for organizing group discussions and for “learning by doing,” and a lack of skills in ICT management has been detected for some participants, who have shown a willingness and interest to improve their skills in this field.

Research limitations/implications

The training and education of soccer referees is one of the most heterogeneous training processes in the world. This complex task is even more difficult because of the growing demand for video technology in referee decision making where successful teamwork requires a high level of communication and agreement among its members.

Practical implications

With 211 associations, FIFA is one of the largest organizations in the world. In international competitions such as the FIFA World Cup, the referees’ decisions are analyzed by media, thousands of fans and millions of viewers. Preparing new professionals for match analysis, interpretation of Laws of the Game and working in a team is a priority for FIFA and the world of soccer.

Originality/value

It is the first time that collaborative learning methods are used with interactive multimedia tools that facilitate collaborative work in the training environment of soccer referee instructors, international soccer referees and assistant referees. This paper establishes a basis and a reference for future research on the effectiveness of the new collaborative technologies used by FIFA for the training of international referees and assistant referees in general.
On the relationship between computer simulation training and the development of practical knowing in police education
Authors: Söderström Tor , Lindgren Carina , Neely Gregory
Published: March 2019

Purpose

The purpose of this paper is to focus on the practical knowing that is central in police education. Drawing on perspectives about tacit knowledge and embodied learning (e.g. Merleau-Ponty, 1945/1997; Polanyi, 1966; Argyris and Schön, 1974) as well as empirical examples, this paper discusses the design of and what can be expected from computer simulation training for the development of police students’ professional knowing.

Design/methodology/approach

The discussion is based on lessons learned from working with two different computer simulation training situations designed to prepare the students for an upcoming practical training by facilitating the understanding of complex situations as they should be handled in the physical training situation.

Findings

The experiences from the training sessions showed that the different characteristics of the simulations mediate how the training session was performed, e.g., unplanned trial and error vs focused and attentive, but also group discussions about how to act and appropriate actions in relation to the situation to be solved in the simulation.

Originality/value

Based on the lessons learned from working with the two different computer simulations, it is posited that the use of computer simulations for practical scenario training is a complex endeavor that needs, in various degrees, to be supported by pedagogical steering. The design of computer simulation training (both the simulation and how the training is designed and performed) need to consider the specific aspects that surround tacit knowledge and embodied learning in the “real sense” (anchored to the practical training) to be of relevance for police students development of professional knowing.
A two-wheel load balance control strategy for an HVTL inspection robot based on second-order sliding-mode
Authors: He Zhihang , Wang Wei , Ruan Huaping , Yao Yanzhang , Li Xuelong , Zou Dehua , Yan Yu , Jia Shaochun
Published: March 2019

Purpose

Overhead high-voltage transmission line (HVTL) inspection robots are used to inspect the transmission lines and/or maintain the infrastructures of a power transmission grid. One of the most serious problems is that the load on the front wheel is much larger than that on the back one when the robot travels along a sloping earth wire. Thus, ongoing operation of the inspection robot mainly depends on the front wheel motor’s ability. This paper aims to extend continuous operation time of the HVTL inspection robots.

Design/methodology/approach

By introducing a traction force model, the authors have established a dynamic model of the robot with slip. The total load is evenly distributed to both wheels. According to the traction force model, the desired wheel slip is calculated to achieve the goal of load balance. A wheel slip controller was designed based on second-order sliding-mode control methodology.

Findings

This controller accomplishes the control objective, such that the actual wheel slip tracks the desired wheel slip. A simulation and experiment verify the feasibility of the load balance control system. These results indicate that the loads on both wheels are generally equal.

Originality/value

By balancing the loads on both wheels, the inspection robot can travel along the earth wire longer, improving its efficiency.
Knowledge stock and absorptive capacity of small firms: the moderating role of formalization
Authors: Chaudhary Sanjay
Published: March 2019

Purpose

Despite the established significance of absorptive capacity, there is a worrying lack of research that empirically examines its antecedents. With a call for investigation guided by the knowledge-based theory, the purpose of this paper is to bridge any probable gap by exploring the effect that an organization’s knowledge stock and its knowledge integrating mechanisms have on the development of its absorptive capacity.

Design/methodology/approach

On the basis of a survey administered to a sample comprising owners of small Indian automotive firms, this paper empirically examines the direct effect of an organization’s knowledge stock (including knowledge breadth and depth) and the moderating role of its structure-related mechanisms (e.g., formalization) on its potential and realized absorptive capacities. The study uses survey data from 226 small business owners and multiple linear regression analysis to examine the significance of its hypotheses.

Findings

The results show that knowledge stock has a statistically notable influence on a small firm’s absorptive capacity. The enabling role of formalization in the relationship between knowledge stock and absorptive capacity is also evident.

Practical implications

Given the handicap of small firmsvis-à-vislarge firms to deploy internal R&D capabilities, business owners must ensure not to confuse absorptive capacity with the pre-existence of R&D capabilities.

Originality/value

The unbundling of knowledge stock into breadth and depth of knowledge enables business owners and researchers to understand how any particular knowledge stock can relate to an organization’s absorptive capacity.
Targeting the reduction of shipping emissions to air
Authors: Christodoulou Anastasia , Gonzalez-Aregall Marta , Linde Tobias , Vierth Inge , Cullinane Kevin
Published: March 2019

Purpose

The purpose of this paper is to identify and classify the various initiatives developed and implemented across the globe for the abatement of maritime air emissions.

Design/methodology/approach

In this paper, an extensive survey of various sources was conducted, including the official reports of international and regional institutions, government policy documents, port authority websites, classification society pages, private firms’ sites and the academic literature. The initiatives were then categorized in accordance with the classification of the Swedish Environmental Protection Agency and analyzed using the SPSS Statistics software to give some insight into their frequencies and the interrelationships between them.

Findings

This exploratory review resulted in the establishment of a comprehensive global database of initiatives encouraged by the whole range of shipping stakeholders and decision-makers for the reduction of shipping air emissions. According to the findings, economic incentives that provide motivation for the adoption of less environmentally damaging practices are the most commonly used initiative, followed by infrastructure investments and informative policies.

Research limitations/implications

The results provide implications for further research that include an in-depth analysis of ports’ policies, as well as an evaluation of initiatives applied on a large scale to map their emissions reduction potential for shipping.

Originality/value

The main contribution of this paper is the identification and analysis of all the diverse initiatives implemented globally in a comprehensive way and its dealing with air pollution from shipping as a whole.
The coaching process seen from the daily (and controversial) perspective of experts and coaches
Authors: Sarsur Amyra Moyzes , Parente Cristina
Published: March 2019

Purpose

The purpose of this paper is to analyze the coaching process as perceived by experts and coaches, addressing its routine aspects and areas that are object of dissent in the organizational field.

Design/methodology/approach

Qualitative research conducted through interviews with 20 experts and coaches who work in Portugal.

Findings

Lack of consensus on conceptual approaches, few demands from organizations for concrete results, and elitism due to its selective use for high-level professionals. There is an expectation of companies that adopt a “coaching culture,” which includes participative actions, dialogue and humanization of relationships. There are benefits for organizations and professionals that result from its application, which raises care in considering it just another management fad.

Originality/value

Professionals and organizations are increasingly adopting coaching processes, but there are few academic studies, with a scientific view, and more rarely from the perspective of practitioners (coaches). Hence, this topic lacks a more accurate approach, to better understand its application and extend the debate on controversial aspects, in order to make the discussion on its value more consistent.
Improving storytelling and vocabulary in secondary school students with language disorder: a randomized controlled trial
Authors: Joffe Victoria L. , Rixon Lorna , Hulme Charles
Published: March 2019

Background

Although language and communication difficulties are common in secondary school students, there has been limited research into the efficacy of interventions for adolescents with language and communication difficulties.

Aims

To investigate the efficacy of teaching assistant (TA)‐delivered narrative and vocabulary interventions to mainstream secondary school‐aged students with language disorder.

Methods & Procedures

A randomized controlled trial (RCT) of a language and communication intervention was used to evaluate the efficacy of vocabulary and narrative interventions to improve the vocabulary and narrative performance of adolescents (mean age = 12.8 years) with language disorder. The language and communication programmes (narrative, vocabulary and combined narrative and vocabulary) were delivered by TAs in the classroom, three times per week, for 45–60 min each, over 6 weeks, totalling 18 sessions. Standardized and intervention‐specific measures were used as outcomes.

Outcomes & Results

Twenty‐one schools with 358 eligible participants were recruited. The three intervention groups showed significant improvements (d = .296) on a narrative latent variable defined by a standardized narrative assessment (the Expression, Reception and Recall of Narrative Instrument—ERRNI), but there were no significant improvements on an overall vocabulary latent variable compared with the waiting control group. Differential effects were found on some non‐standardized intervention‐specific measures with the narrative group making significantly more progress on narrative tasks compared with the waiting control group, the vocabulary group showing the same pattern on specific vocabulary tasks, and the combined narrative and vocabulary group making significantly more progress on some of the intervention‐specific narrative, and all the intervention‐specific vocabulary outcomes compared with the waiting control group.

Conclusions & Implications

It is possible to improve narrative but not vocabulary skills, as assessed by standardized measures, in secondary school students with a relatively brief group TA‐delivered intervention. There were differential effects for both narrative and vocabulary with intervention‐specific measures. Future work is required to explore whether more intensive and longer lasting interventions would be more effective and to identify which students in this age group are most likely to benefit from such interventions.
Closely related viruses of the marine picoeukaryotic alga Ostreococcus lucimarinus exhibit different ecological strategies
Authors: Zimmerman Amy E. , Bachy Charles , Ma Xiufeng , Roux Simon , Jang Ho Bin , Sullivan Matthew B. , Waldbauer Jacob R. , Worden Alexandra Z.
Published: March 2019

In marine ecosystems, viruses are major disrupters of the direct flow of carbon and nutrients to higher trophic levels. Although the genetic diversity of several eukaryotic phytoplankton virus groups has been characterized, their infection dynamics are less understood, such that the physiological and ecological implications of their diversity remain unclear. We compared genomes and infection phenotypes of the two most closely related cultured phycodnaviruses infecting the widespread picoprasinophyte Ostreococcus lucimarinus under standard‐ (1.3 divisions per day) and limited‐light (0.41 divisions per day) nutrient replete conditions. OlV7 infection caused early arrest of the host cell cycle, coinciding with a significantly higher proportion of infected cells than OlV1‐amended treatments, regardless of host growth rate. OlV7 treatments showed a near‐50‐fold increase of progeny virions at the higher host growth rate, contrasting with OlV1's 16‐fold increase. However, production of OlV7 virions was more sensitive than OlV1 production to reduced host growth rate, suggesting fitness trade‐offs between infection efficiency and resilience to host physiology. Moreover, although organic matter released from OlV1‐ and OlV7‐infected hosts had broadly similar chemical composition, some distinct molecular signatures were observed. Collectively, these results suggest that current views on viral relatedness through marker and core gene analyses underplay operational divergence and consequences for host ecology.
Genomic adaptation to eutrophication of ammonia‐oxidizing archaea in the Pearl River estuary
Authors: Zou Dayu , Li Yingdong , Kao Shuh‐Ji , Liu Hongbin , Li Meng
Published: March 2019

Ammonia‐oxidizing archaea (AOA) are ubiquitous in natural ecosystems, and they are responsible for a significant fraction of ammonia oxidation globally. Since the first AOA isolate was established a decade ago, molecular surveys of their environmental distribution [based primarily on amplicon sequencing of the amoA, which codes for the alpha subunit of ammonia monooxygenase (AMO)], show that their habitats are believed to range from marine to terrestrial environments. However, the mechanisms of adaptation underpinning to their habitat expansion remain poorly understood. Here, we report that AOA accounts for almost all of the ammonia oxidizers in the shelf water adjacent to the Pearl River estuary (PRE), with the Nitrosopumilus maritimus SCM1‐like (SCM1‐like) being the main amoA genotype. Using a metagenomic approach, seven high‐quality AOA genomes were reconstructed from the PRE. Phylogenetic analysis indicated that four of these genomes with high completeness were closely affiliated with the Nitrosomatrinus catalina strain SPOT01, which was originally isolated off the coast of California. Genomic comparison revealed that the PRE AOA genomes encoded genes functioning in amino acid synthesis, xenobiotic biodegradation metabolism and transportation of inorganic phosphate and heavy metals. This illustrates the different adaptations of AOA in one of the largest estuaries in China, which is strongly influenced by anthropogenic input. Overall, this study provides additional genomic information about estuarine AOA and highlights the importance of their contribution to nitrification in eutrophic coastal environments.
Before and beyond Brexit: political dimensions of UK lifestyle migration
Authors: MacClancy Jeremy
Published: March 2019

Lifestyle migration is a now‐established subfield within the anthropology of migration, and interdisciplinary migration studies, usually justified by its extensive and increasing spread, globally. Yet, bar a few exceptions, the political behaviour of lifestyle migrants has been relatively neglected. I redress this imbalance by critically comparing two overlapping processes where British migrants to Spain act politically: elected councillors in town halls; and campaigning anti‐Brexit activists. This pair is as comparable as it is contrastive. In theoretical terms, I argue that modern versions of practice theory are a useful mode for analysing municipal activity by foreign agents, while the Brexit process, because novel, fast‐paced, and open‐ended, is better understood via Isin's ‘enactment of citizenship’ approach. Both explanatory modes are powerful, have perspectival slants, and are best applied to different contexts and styles of contest: practice theorists research how people work with change; Isinians research how they produce it. The article also furthers the anthropology of citizenship by investigating a case where citizenship of a country is no longer a prerequisite for legitimate political activity in it.
Interventional radiology‐operated percutaneous cholecystoscopy with ultrasonic lithotripsy and stone basket retrieval: A treatment for symptomatic cholelithiasis in non‐operative candidates
Authors: Roberts Dustin G , Plotnik Adam N , Chick Jeffrey FB , Srinivasa Ravi N
Published: March 2019

Interventional radiology‐operated percutaneous endoscopy has seen a recent resurgence with potential to return to the scope of Interventional Radiology practice. Endoscopy adds a new dimension to the Interventional Radiology armamentarium by offering a unique opportunity to diagnose and treat conditions under direct visualization with improved maneuverability. Cholecystoscopy (gallbladder endoscopy), as a method for percutaneous removal of gallstones, is an effective treatment option in patients with symptomatic cholelithiasis who are poor candidates for surgical cholecystectomy. This article presents a case of Interventional Radiology‐operated cholecystoscopy using ultrasonic lithotripsy and stone basket retrieval with an emphasis on the equipment, technique, and peri‐procedural management essential to the procedure, as well as a review of the literature.
Habitat species pools shape algal and bacterial communities and their correlations
Authors: Zhang Weizhen , Wang Huan , Zhang Jia , Chen Jun , Shen Hong , Xie Ping
Published: March 2019

Understanding of community ecology is scale dependent. When the scale definition changes from subjectively defined “regional species pools” to “habitat species pools”, heterogeneity differences occur for microbial communities. However, given the environmental gradients differences among habitats, responses of other organisms and interspecific correlations to habitat species pools may also be heterogeneous. This hypothesis is supported by our research about algal and bacterial communities among four different habitats in littoral zones. In our results, both the algal and bacterial community compositions varied along habitat species pools. Furthermore, at community level, significant correlation was only found between bacterioplankton and phytoplankton in pelagic habitat. And at individual level, the covariant trends between habitat generalists in algal and bacterial communities varied among habitats. Our results indicated that habitat‐specific patterns can not only influence the habitat species pools, but also shape the interspecies interaction, and this should be considered in the further study of algae‐bacterial correlation.
Cost‐effectiveness of real‐world administration of tobacco pharmacotherapy in the United States Veterans Health Administration
Authors: Barnett Paul G. , Ignacio Rosalinda V. , Kim Hyungjin Myra , Geraci Mark C. , Essenmacher Carol A. , Hall Stephanie V. , Sherman Scott E. , Duffy Sonia A.
Published: March 2019

Background and aims

Cost‐effectiveness studies in randomized clinical trials have shown that tobacco cessation pharmacotherapy is among the most cost‐effective of health‐care interventions. Clinical trial eligibility criteria and treatment protocols may not be followed in actual practice. This study aimed to determine whether tobacco cessation pharmacotherapy is cost‐effective in real‐world settings.

Design

A retrospective analysis of costs and outcomes.

Setting

Hospitals and clinics of the US Veterans Health Administration, USA.

Participants

A total of 589 862 US veterans who screened positive for tobacco use in 2011.

Intervention and comparator

Tobacco users who initiated smoking cessation pharmacotherapy in the 6 months after screening were compared with those who did not use pharmacotherapy in this period. Pharmacotherapy included nicotine replacement therapy, bupropion (if prescribed at 300 mg per day or specifically for tobacco cessation) or varenicline.

Measures

Effectiveness was determined from responses to a subsequent tobacco screening conducted between 7 and 18 months after the treatment observation period. Cost of medications and prescribing health‐care encounters was determined for the period between initial and follow‐up tobacco use screening. Multivariate fixed‐effects regression was used to assess the effect of initial treatment status on cost and outcome while controlling for differences in case‐mix with propensity weighting to adjust for confounding by indication.

Findings

Thirteen per cent of participants received tobacco cessation pharmacotherapy within 6 months of initial screening. After an average of an additional 218.1 days’ follow‐up, those who initially received pharmacotherapy incurred $143.79 in additional treatment cost and had a 3.1% absolute increase in tobacco quit rates compared with those who were not initially treated. This represents an incremental cost‐effectiveness ratio of $4705 per quit. The upper limit of the 99.9% confidence region was $5600 per quit. Without propensity adjustment, the cost‐effectiveness ratio was $7144 per quit, with the upper limit of the 99.9% confidence region $9500/quit.

Conclusions

Tobacco cessation pharmacotherapy provided by the US Veterans Health Administration in 2011/12 was cost‐effective in this real‐world setting, with an incremental cost‐effectiveness ratio of $4705 per quit.
A quantitative global proteomics approach to understanding the functional pathways dysregulated in the spermatozoa of asthenozoospermic testicular cancer patients
Authors: Panner Selvam M. K. , Agarwal A. , Pushparaj P. N.
Published: March 2019

Background

Testicular cancer (TC) is the most common cancer diagnosed in men of reproductive age group. Sperm banking is recommended in these patients prior to cancer treatment. There is no literature describing the proteins dysregulated in the spermatozoa of TC patients with poor motility.

Objective

The primary objective of this study was to compare the differences in the sperm proteome of normozoospermic (motility > 40%) and asthenozoospermic (motility < 40%) TC patients who had cryopreserved semen samples before initiating cancer therapy.

Materials and methods

Pooled sperm samples from healthy fertile men (n = 8), normozoospermic (n = 20), and asthenozoospermic (n = 11) TC patients were used for quantitative global proteomic profiling by liquid chromatography–tandem mass spectrometry (LC‐MS). The functional bioinformatic analysis was done by ingenuity pathway analysis software. Key differentially expressed proteins (DEPs) associated with binding of zona pellucida (CCT3), mitochondrial dysfunction (ATP5A1 and UQCRC2), sperm motility (ATP1A4), and an exosomal protein involved in the metabolic process of the spermatozoa (MMP9) were validated using Western blot analysis by comparing normozoospermic (n = 10) with asthenozoospermic (n = 10) TC patients. Statistical analysis was conducted using Mann–Whitney test.

Results

A total of 813 and 957 proteins were detected in spermatozoa of normozoospermic and asthenozoospermic TC patients, respectively. On the other hand, 1139 proteins were detected in the spermatozoa of healthy fertile men. 198 proteins were identified as DEPs between TC patients with normal and abnormal semen parameters. Validation of DEPs revealed downregulation of key proteins (CCT3, ATP1A4, ATP5A1, and UQCRC2) implicated in the reproductive function in asthenozoospermic TC patients.

Discussion

DEPs involved in the reproductive function pathways suggest defective spermatogenesis and maturation process in asthenozoospermic TC patients. Furthermore, dysfunctional exosomal pathway may be a possible cause of infertility in TC patients.

Conclusion

The proteins associated with sperm function and fertilization process are compromised in TC patients irrespective of their semen parameters.
Continuous positive airway pressure in children with severe pneumonia and hypoxaemia in Papua New Guinea: an evaluation of implementation
Authors: Pulsan Francis , Sobi Kone , Duke Trevor
Published: March 2019

Aim

To prospectively evaluate the use of bubble continuous positive airway pressure (CPAP) in children with very severe pneumonia and other acute lower respiratory infections, during its trial introduction in a low resource hospital in Papua New Guinea.

Methods

Prospective observational study of children treated with CPAP who had severe pneumonia and severe respiratory distress with hypoxaemia (SpO2 <90%). CPAP was driven by oxygen concentrators in which the fraction of inspired oxygen could be adjusted, and using low‐resistance tubing and nasal oxygen prongs.

Results

A total of 64 children were commenced on CPAP: 29 (45.3%) survived and were discharged well, 35 (54.7%) died. Prior to commencing CPAP, the median SpO2 was 78% (IQR 53.3–86.8%), at one hour SpO2 was 92% (IQR 80–97.75%, n = 64), and at 84 hours (3½ days) 98% (IQR 93–98%, n = 29), in survivors at each of these time points. A higher SpO2 at one hour after commencement of CPAP predicted survival (p = 0.013), and human immunodeficiency virus infection was an independent predictors of death (p = 0.017). Technical and clinical problems encountered are described.

Conclusion

Bubble CPAP improved oxygenation and reduced the severity of respiratory distress in some children with severe pneumonia; however, mortality was high reflecting high severity of illness and comorbidities. CPAP requires a quality system to be safe and effective.
Parent satisfaction before and after implementing of a developmental screening tool in nine well‐baby clinics in Norway
Authors: Valla Lisbeth , Slinning Kari , Wentzel‐Larsen Tore
Published: March 2019

Aim

The aim of the study was to compare parental satisfaction items before and after the implementation of The Ages & Stages Questionnaires (ASQ) as part of the health check‐up.

Methods

ASQ was implemented in regular health check‐ups of infants up to two years of age in 9 Norwegian well‐baby clinics. After the infant's two years' health check‐ups, a questionnaire‐based survey among 652 families before and 562 families after intervention was conducted. Descriptive analyses and ordinal logistic regression were used to report and compare parental satisfaction items before and after the project.

Results

Parents reported high satisfaction with well‐baby services both before and after the implementation of ASQ, and ninety‐six per cent recommended other well‐baby clinics to use ASQ. Some significant differences appeared, before the implementation of ASQ, parents were more satisfied with the support they received regarding parenting and child development in general and information about the child's physical health. After ASQ was implemented, parents were significantly more satisfied with the information they received about ‘the child's mental health’.

Conclusion

Developmental screening in well‐baby clinics in Norway is acceptable among parents with young children. The use of standardised instruments must not come at the expense of listening to parents’ concerns.
Disulfide engineering on temporin‐SHf: Stabilizing the bioactive conformation of an ultra‐short antimicrobial peptide
Authors: Dolle Ashwini , Nagati Veera Babu , Hunashal Yamanappa , Krishnamurthy Kiran , Pasupulati Anil Kumar , Raghothama Srinivasarao , Gowd Konkallu Hanumae
Published: March 2019

In Silico searching for short antimicrobial peptides has revealed temporin‐SHf as the short (8AA), hydrophobic, broad spectrum, and natural antimicrobial peptide. Important drawback associated with temporin‐SHf is the susceptibility of its bioactive conformation for denaturation and proteolytic degradation. In the current report, disulfide engineering strategy has been adopted to improve the stability of bioactive conformation of temporin‐SHf. The functionally non‐critical Leu4 and Ile7 residues at i and i + 3 position of helical conformation of temporin‐SHf were mutated with cysteine disulfide. Designed [L4C, I7C]temporin‐SHf was synthesized, characterized using NMR spectroscopy, and accessed for antimicrobial activity. [L4C, I7C]Temporin‐SHf adopts helical conformation from Phe3 to Phe8 in the absence of membrane‐mimetic environment and retains broad spectrum antimicrobial activity. The reduction potential of cysteine disulfide of [L4C, I7C]temporin‐SHf is −289 mV. Trypsin‐induced digestion and serum‐induced digestion have confirmed the advantage of cysteine disulfide in imparting proteolytic stability to temporin‐SHf. Disulfide‐stabilized temporin‐SHf may serve as a good model for the rational design of temporin‐SHf based antibiotics for treatment of infectious diseases.
Approaches for the discovery of metallo‐β‐lactamase inhibitors: A review
Authors: Shi Cheng , Chen Jiaxing , Kang Xinyue , Shen Xutong , Lao Xingzhen , Zheng Heng
Published: March 2019

After more than 80 years of development, β‐lactam drugs have become the most widely used high‐efficiency, low‐toxic broad‐spectrum antibacterial drugs. However, with the widespread use and even abuse of those drugs, the resistance of major pathogens to β‐lactam drugs has increased over years, which has become a thorny problem to the public health. A common mechanism of the resistance to β‐lactams is the producing of β‐lactamases, which can hydrolyze the β‐lactam ring and inactivate these drugs. Metallo‐β‐lactamases (MBLs) are one kind of β‐lactamases that require metal ions for their catalytic activities. Although it is a well‐known strategy to recover the efficacy of β‐lactams by the combination of β‐lactamase inhibitors, there are still no MBL inhibitors that can be used in clinical practice. Therefore, it is urgent to develop MBL inhibitors. This review outlines the currently discovered MBL inhibitors with an emphasis on various strategies and approaches taken to discover MBL inhibitors, which may lead to diverse classes of inhibitors. Recent progress, particularly new screening methods, and the rational design of potent MBL inhibitors are discussed.
Regulatory T cell features in chronic granulomatous disease
Authors: van de Geer A , Cuadrado E , Slot MC , van Bruggen R , Amsen D , Kuijpers TW
Published: March 2019

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations in any of the genes encoding the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system, responsible for the production of reactive oxygen species (ROS). CGD is marked by invasive bacterial and fungal infections and by autoinflammation/autoimmunity, of which the exact pathophysiology remains elusive. Contributing factors include decreased neutrophil apoptosis, impaired apoptotic neutrophil clearance, increased proinflammatory protein expression and reduced ROS-mediated inflammasome dampening. We have explored a fundamentally different potential mechanism: it has been reported that macrophage-mediated induction of regulatory T cells (Tregs) depends on ROS production. We have investigated whether numerical or functional deficiencies exist in Tregs of CGD patients. As the prevalence of autoinflammation/autoimmunity differs between CGD subtypes, we have also investigated Tregs from gp91phox-, p47phox- and p40phox-deficient CGD patients separately. Results show that Treg numbers and suppressive capacities are not different in CGD patients compared to healthy controls, with the exception that in gp91phox-deficiency effector Treg (eTreg) numbers are decreased. Expression of Treg markers CD25, inducible T cell co-stimulator (ICOS), Helios, cytotoxic T lymphocyte antigen 4 (CTLA-4) and glucocorticoid-induced tumor necrosis factor receptor (GITR) did not provide any clue for differences in Treg functionality or activation state. No correlation was seen between eTreg numbers and patients' clinical phenotype. To conclude, the only difference between Tregs from CGD patients and healthy controls is a decrease in circulating eTregs in gp91phox-deficiency. In terms of autoinflammation/autoimmunity, this group is the most affected. However, upon culture, patient-derived Tregs showed a normal phenotype and normal functional suppressor activity. No other findings pointed towards a role for Tregs in CGD-related autoinflammation/autoimmunity.
The All‐on‐4 treatment concept for the rehabilitation of the completely edentulous mandible: A longitudinal study with 10 to 18 years of follow‐up
Authors: Maló Paulo , de Araújo Nobre Miguel , Lopes Armando , Ferro Ana , Botto João
Published: March 2019

Background

There is a need for studies evaluating the long term outcomes of the All‐on‐4 treatment concept.

Purpose

To evaluate the long term clinical and radiographic outcomes of the All‐on‐4 treatment concept in the mandible.

Materials and Methods

This retrospective longitudinal case series study included 471 patients (women: 286, men: 185, average age = 57.7 years) rehabilitated with 1884 implants in immediate function supporting 471 fixed full‐arch mandibular prostheses and followed for 10 to 18 years. Primary outcome measures were prosthetic survival and implant success and survival (estimated using life tables). Secondary outcome measures were marginal bone loss (MBL) at 10 and 15 years, biological and mechanical complications. Multivariable analysis was used to estimate potential risk indicators for implant failure (Cox regression to estimate hazard ratios and 95% confidence intervals (95%CI)), MBL > 3 mm at 10 and 15 years, biological and mechanical complications (binary logistic regression to estimate odds ratios [ORs] with 95%CI).

Results

Twenty‐seven patients deceased (5.7%) and 149 patients (31.6%) were lost to follow‐up. The cumulative prosthetic survival rate was 98.8%; the implant cumulative survival and success rate was 93% and 91.7%, respectively up to 18 years of follow‐up. Previous biological complications (HR = 4.43) were significantly associated with implant failure. Average (95% CI) MBL at 10‐ and 15‐years were 1.72 mm (95%CI: 1.59, 1.85) and 2.32 mm (95% CI: 1.98, 2.66). Smoking (OR = 2.72), previous failure of a contiguous implant (OR = 3.89) and biological complication (OR = 8.11) were associated with MBL > 3 mm. The incidence of biological complications was 11.8% at implant level, with previous failure of a contiguous implant (OR = 5.56), smoking (OR = 1.75), and systemic condition (OR = 1.65) were significantly associated. The incidence of mechanical complications was 36.7% with male gender (OR = 1.67) and type of prosthetic material used in the restoration significantly associated (metal‐acrylic OR = 0.30; metal‐ceramic OR = 0.22)).

Conclusions

Considering the implant, prosthetic and MBL outcomes it is concluded that the All‐on‐4 is a viable treatment option validated in the long term. Nevertheless, biological and mechanical complications can occur.
Endemic fungal infections in solid organ transplant recipients—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice
Authors: Miller Rachel , Assi Maha ,   the AST Infectious Diseases Community of Practice
Published: March 2019

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention and management of blastomycosis, histoplasmosis, and coccidioidomycosis in the pre‐ and post‐transplant period. Though each of these endemic fungal infections has unique epidemiology and clinical manifestations, they all share a predilection for primary pulmonary infection and may cause disseminated infection, particularly in immunocompromised hosts. Culture remains the gold standard for definitive diagnosis, but more rapid diagnosis may be achieved with direct visualization of organisms from clinical specimens and antigen‐based enzyme immunoassay assays. Serology is of limited utility in transplant recipients. The mainstay of treatment for severe infections remains liposomal amphotericin followed by a step‐down azole therapy. Cases of mild to moderate severity with no CNS involvement may be treated with azole therapy alone. The newer generation azoles provide additional treatment options, but supported currently with limited clinical efficacy data. Azole therapy in transplant recipients presents a unique challenge owing to the drug‐drug interactions with immunosuppressant agents. Therapeutic drug monitoring of azole levels is an essential component of effective and safe therapy. Infection prevention centers around minimizing epidemiological exposures, early clinical recognition, and azole prophylaxis in selected individuals.
Low versus high carbohydrate diet in type 1 diabetes: A 12‐week randomized open‐label crossover study
Authors: Schmidt Signe , Christensen Merete B. , Serifovski Nermin , Damm‐Frydenberg Camilla , Jensen Jens‐Erik B. , Fløyel Tina , Størling Joachim , Ranjan Ajenthen , Nørgaard Kirsten
Published: March 2019

Aims

To compare the effects of a low carbohydrate diet (LCD < 100 g carbohydrate/d) and a high carbohydrate diet (HCD > 250 g carbohydrate/d) on glycaemic control and cardiovascular risk factors in adults with type 1 diabetes.

Materials and methods

In a randomized crossover study with two 12‐week intervention arms separated by a 12‐week washout, 14 participants using sensor‐augmented insulin pumps were included. Individual meal plans meeting the carbohydrate criteria were made for each study participant. Actual carbohydrate intake was entered into the insulin pumps throughout the study.

Results

Ten participants completed the study. Daily carbohydrate intake during the two intervention periods was (mean ± standard deviation) 98 ± 11 g and 246 ± 34 g, respectively. Time spent in the range 3.9‐10.0 mmol/L (primary outcome) did not differ between groups (LCD 68.6 ± 8.9% vs. HCD 65.3 ± 6.5%, P = 0.316). However, time spent <3.9 mmol/L was less (1.9 vs. 3.6%, P < 0.001) and glycaemic variability (assessed by coefficient of variation) was lower (32.7 vs. 37.5%, P = 0.013) during LCD. No events of severe hypoglycaemia were reported. Participants lost 2.0 ± 2.1 kg during LCD and gained 2.6 ± 1.8 kg during HCD (P = 0.001). No other cardiovascular risk factors, including fasting levels of lipids and inflammatory markers, were significantly affected.

Conclusions

Compared with an intake of 250 g of carbohydrate per day, restriction of carbohydrate intake to 100 g per day in adults with type 1 diabetes reduced time spent in hypoglycaemia, glycaemic variability and weight with no effect on cardiovascular risk factors.
Short‐term cost‐utility of degludec versus glargine U100 for patients with type 2 diabetes at high risk of hypoglycaemia and cardiovascular events: A Canadian setting (DEVOTE 9)
Authors: Pollock Richard F. , Heller Simon , Pieber Thomas R. , Woo Vincent , Gundgaard Jens , Hallén Nino , Luckevich Maria , Tutkunkardas Deniz , Zinman Bernard ,   On Behalf of the DEVOTE Study Group
Published: March 2019

Aims

To evaluate the short‐term cost‐effectiveness of insulin degludec (degludec) vs insulin glargine 100 units/mL (glargine U100) from a Canadian public healthcare payer perspective in patients with type 2 diabetes (T2D) who are at high risk of cardiovascular events and hypoglycaemia.

Materials and methods

A decision analytic model was developed to estimate costs (2017 Canadian dollars [CAD]) and clinical outcomes (quality‐adjusted life years [QALYs]) with degludec vs glargine U100 over a 2‐year time horizon. The model captured first major adverse cardiovascular event, death, severe hypoglycaemia and insulin dosing. Clinical outcomes were informed by a post hoc subgroup analysis of the DEVOTE trial (NCT01959529), which compared the cardiovascular safety of degludec and glargine U100 in patients with T2D who are at high cardiovascular risk. High hypoglycaemia risk was defined as the top quartile of patients (n = 1887) based on an index of baseline hypoglycaemia risk factors.

Results

In patients at high hypoglycaemia risk, degludec was associated with mean cost savings (CAD 129 per patient) relative to glargine U100, driven by a lower incidence of non‐fatal myocardial infarction, non‐fatal stroke and severe hypoglycaemia, which offset the slightly higher cost of treatment with degludec. A reduced risk of cardiovascular death and severe hypoglycaemia resulted in improved effectiveness (+0.0132 QALYs) with degludec relative to glargine U100. In sensitivity analyses, changes to the vast majority of model parameters did not materially affect model outcomes.

Conclusion

Over a 2‐year period, degludec improved clinical outcomes at a lower cost as compared to glargine U100 in patients with T2D at high risk of cardiovascular events and hypoglycaemia.
Proceeding report of the third symposium on Hidradenitis Suppurativa advances (SHSA) 2018
Authors: Posso‐De Los Rios Claudia J. , Sarfo Akua , Ghias Mondana , Alhusayen Raed , Hamzavi Iltefat , Lowes Michelle A. , Alavi Afsaneh
Published: March 2019

The 3rd Annual Symposium on Hidradenitis Suppurativa Advances (SHSA) took place on 12‐14 October 2018 at the Women's College Hospital in Toronto, Ontario, Canada. This symposium was a joint meeting of the Hidradenitis Suppurativa Foundation (HSF) founded in the USA and the Canadian Hidradenitis Suppurativa Foundation (CHSF). This cross‐disciplinary meeting with experts from around the world was an opportunity to discuss the most recent advances in the study of hidradenitis suppurativa pathogenesis, epidemiology, classification, scoring systems, radiologic diagnosis, treatment approaches and psychologic assessment. Two special sessions this year were HS as a systemic disease and HS management guidelines. There were focused workshops on wound healing and ultrasound. There were two sessions primarily for patients and their families in the HS School programme: One workshop focused on mindfulness, and the second involved discussion among clinicians and patients about various disease aspects and the latest management. To facilitate networking between clinical and research experts and those early in their career, a mentoring breakfast was held.
Sweetcane (Erianthus arundinaceus) as a native bioenergy crop with environmental remediation potential in southern China: A review
Authors: Wang Wenguo , Li Rui , Wang Hong , Qi Bufan , Jiang Xiaomei , Zhu Qili , Cai Denggao , Tang Xiaoyu , Zhao Qi
Published: March 2019

Sweetcane (Erianthus arundinaceus [Retzius] Jeswiet) is an ecologically dominant warm‐season perennial grass native to southern China. It traditionally plays an important role in sugarcane breeding due to its excellent biological traits and genetic relatedness to sugarcane. Recent studies have shown that sweetcane has a great potential in bioenergy and environmental remediation. The objective of this paper is to review the current research on sweetcane biology, phenology, biogeography, agronomy, and conversion technology, in order to explore its development as a bioenergy crop with environmental remediation potential. Sweetcane is resistant to a variety of stressors and can adapt to different growth environments. It can be used for ecological restoration, soil and water conservation, contaminated land repairing, nonpoint source pollutants barriers in buffer strips along surface waters, and as an ornamental and remediation plant on roadsides and in wetlands. Sweetcane exhibits higher biomass yield, calorific value and cellulose content than other bioenergy crops under the same growth conditions, thereby indicating its superior potential in second‐generation biofuel production. However, research on sweetcane as a bioenergy plant is still in its infancy. More works need be conducted on breeding, cultivation, genetic transformation, and energy conversion technologies.
The burden of bleeds and other clinical determinants on caregivers of children with haemophilia (the BBC Study)
Authors: Khair Kate , Klukowska Anna , Myrin Westesson Linda , Kavakli Kaan , Escuriola Carmen , Uitslager Nanda , Santoro Cristina , Holland Mike , von Mackensen Sylvia
Published: March 2019

Introduction

Treatment burden for the people with haemophilia has been documented, as has the burden of caring for a child with a common chronic disease such as asthma or diabetes. However, there remains a paucity of data about caregiver burden in haemophilia.

Aims

The aim of this study was to evaluate the impact of bleeding on caregivers of children with haemophilia. Caregiver burden was stratified by the clinical status of their child.

Methods

A multinational, non‐interventional study of caregivers of children with severe or moderate haemophilia, using the HEMOCABquestionnaire to evaluate caregiver burden.

Results

A total of 144 caregivers from seven EU countries participated in the study. Differences in caregiver burden were identified based on the clinical situation of the child. Greater burden was seen in caregivers of children who experienced joint bleeding in the preceding 12 months, or had target joints or reduced range of motion in most domains of the HEMOCAB. Caring for a child with a current inhibitor also caused significantly higher burden for caregivers when compared to caring for a child with tolerized inhibitor or without inhibitor. Caregivers of children with chronic pain reported significantly higher burden in all domains of the HEMOCAB except for “interaction with the father.”

Conclusion

Caregiver burden can be affected by the child's haemophilia status, particularly if joint health is impacted (eg bleeds, decreased mobility) or if the child suffers from chronic pain which was moderately correlated with joint bleeds.