bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring the performance of strategy
Authors: Hoverstadt Patrick , Loh Lucy , Marguet Natalie
Published: July 2020

Purpose

This paper aims to look at the problems of measuring the performance of business strategy. The authors look at the problem using two classical performance management paradigms and suggest a third approach which treats strategy as a stochastic network of actors and manoeuvres between those actors.

Design/methodology/approach

This has been developed using action research in a number of strategy projects with a range of organisations in the private, public and third sectors.

Findings

The two normal paradigms in use for performance measurement and management both struggle when applied to strategy. The problems are not merely ones of execution, they are much more fundamental and sit at the level of conceptual design. Modelling strategy as a series of manoeuvres between different actor organisations is both a more useful way to develop strategy but also provides a simple way to develop measures of strategic performance that can tell us not merely whether the strategy is being executed but also whether it is working.

Originality/value

The paper describes a totally new approach to measuring strategy – both its execution and also its effectiveness which contrasts with both the two prevailing paradigms commonly used in the field of strategy.
Foregrounding the perspectives of mental health services users during the COVID-19 pandemic
Authors: Zeilig Hannah , Gee Brioney , Teague Bonnie , Wilson Jonathan , Hackmann Corinna
Published: July 2020

Purpose

This paper aims to highlight the critical importance of the perspectives of mental health service-users during the COVID-19 pandemic.

Design/methodology/approach

This viewpoint is based on a review of recent research and literature and draws on consultations with experts by experience, including the lead author.

Findings

The authors argue that expertise-by-experience is critical to policy, service development and research; but there is a risk it will be neglected at a time of rapid and reactive clinical development.

Research limitations/implications

Understanding and responding to the nuances of individual need can only be achieved through coproducing service strategy design, delivery and research with mental health service users. The consultation outlined in this viewpoint gives some indication of the type of valuable insights that can be gained through seeking and listening to the perspectives of experts by experience.

Originality/value

The discussions revealed that experience of managing severe and complex mental health conditions can actually be advantageous when facing a crisis such as COVID-19.
Sir Allen Stanford: inmate # 35017-183; a case study of a Ponzi scheme and its aftermath
Authors: Flynn Kevin , Belak Phyllis , Andre Sean
Published: July 2020

Research methodology

This case involves a real-life Ponzi scheme perpetrated by Sir Allen Stanford, a man who bribed Antiguan regulators and a certified public accountant firm to perpetuate his scam. The case includes the process of making victims whole, which involves a court-initiated clawback process: taking back payouts to investors or charities to redistribute the funds to other fraud victims who did not receive their fair payout. Students apply theory learned in an upper-level fraud or forensic accounting course. Finally, the case addresses the aftermath of a fraud scheme.

Case overview/synopsis

Ponzi schemes – one of the most common types of investment fraud – have caused investors to lose billions of dollars. Because of the prevalence of Ponzi schemes and the ramifications to investors, it is important for business students to understand the nature of these schemes and to learn how to recognize them. As future business professionals, students will be charged with recognizing a Ponzi scheme early and uncovering it before investors lose their investments.

Complexity academic level

This case is designed for upper-level undergraduate students or graduate students taking a fraud or forensic accounting course, which is best introduced after professors cover Ponzi schemes and also these concepts: fraud triangle, fraud diamond and fraud red flags.
Causes and consequences of liana infestation in southern Amazonia
Authors: Reis Simone Matias , Marimon Beatriz Schwantes , Morandi Paulo S. , Elias Fernando , Esquivel‐Muelbert Adriane , Marimon Junior Ben Hur , Fauset Sophie , de Oliveira Edmar Almeida , van der Heijden Geertje M. F. , Galbraith David , Feldpausch Ted R. , Phillips Oliver L.
Published: July 2020

Lianas, a key component of tropical forests, can limit growth of trees, impacting both the structure and functioning of forests, and are expected to benefit from fragmentation and potentially from global climatic changes. While it is critical to understand the impacts of liana infestation on contemporary tropical forests across large geographical areas, to date most liana studies have been focussed on single or few sites.

We measured and quantified liana infestation of 16,066 trees with diameter ≥10 cm in 27 plots distributed across southern Amazonia, a region characterized by substantial ecological and environmental variation and environmental change. We examined the influence of potential drivers of liana infestation at the plot, species and individual tree level. Additionally, we evaluated the effect of liana infestation on tree growth.

More than half of all trees had lianas in their crown. At the plot level, infestation by lianas was driven by forest structure but not by the studied climate or soil fertility variables, though low levels of liana infestation were found in seasonally flooded forests.

At the tree level, larger and stouter trees had a greater proportion of their crown infested with lianas. At the species level, trees belonging to intrinsically slow‐growing, dense‐wooded species were more susceptible to liana infestation.

Liana infestation had a negative impact on tree growth, with growth of heavily infested trees reduced by 33% compared to non‐infested. The impact of liana infestation on tree growth was strongest for the best‐lit tree crowns, indicating that lianas act to reduce the large competitive advantage that well‐lit trees otherwise hold over their neighbours.

Synthesis. Lianas are a pervasive and influential feature of the extensive forests at the southern edge of Amazonia. The degree of liana infestation in forests was closely linked to species‐level variables such as potential growth and wood density as well as the size of the individual tree. The growth of heavily infested trees was particularly restricted by lianas, and especially so for trees growing in otherwise favourable conditions, indicating the potential for lianas not only to reduce forest growth rates overall, but also to modify competitive hierarchies among trees within tropical forests.
Protective Arrangements Across Class: Understanding Social Segregation in La Plata, Argentina
Authors: Segura Ramiro
Published: July 2020

This essay develops the concept of protective arrangements (a socio‐material relationship between house architecture, objects and human practices) in order to develop a new understanding of urban social segregation. Drawing from ethnographic fieldwork in La Plata (Argentina) I compare the protective arrangements of lower and upper middle‐class residents against the background of the commonly sensed need to self‐organize protection. While in the gated communities of the upper‐middle class walls and fences enclose an ‘open interior space’, members of the upper‐middle class who live in or close to the city centre protect their homes with individual security systems. In contrast, people at the poorer end of society attune their repertoires of protection towards the constant threat of eviction and burglary with dogs and improvised fences and by guaranteeing the permanent presence in the home of at least one household member. The analysis of these strategies at the house scale shows an increasing process of socio‐spatial fragmentation in the city as a product of the materialization of discursive‐material practices deployed in search of protection.
Identifying Fatal Head Injuries on Postmortem Computed Tomography Using Convolutional Neural Network/Deep Learning: A Feasibility Study
Authors: Garland Jack , Ondruschka Benjamin , Stables Simon , Morrow Paul , Kesha Kilak , Glenn Charley , Tse Rexson
Published: July 2020

Postmortem computed tomography (PMCT) is a relatively recent advancement in forensic pathology practice that has been increasingly used as an ancillary investigation and screening tool. One area of clinical CT imaging that has garnered a lot of research interest recently is the area of “artificial intelligence” (AI), such as in screening and computer‐assisted diagnostics. This feasibility study investigated the application of convolutional neural network, a form of deep learning AI, to PMCT head imaging in differentiating fatal head injury from controls. PMCT images of a transverse section of the head at the level of the frontal sinus from 25 cases of fatal head injury were combined with 25 nonhead‐injury controls and divided into training and testing datasets. A convolutional neural network was constructed using Keras and was trained against the training data before being assessed against the testing dataset. The results of this study demonstrated an accuracy of between 70% and 92.5%, with difficulties in recognizing subarachnoid hemorrhage and in distinguishing congested vessels and prominent falx from head injury. These results are promising for potential applications as a screening tool or in computer‐assisted diagnostics in the future.
The impact of type 2 diabetes and its management on the prognosis of patients with severe COVID‐19
Authors: Xu Zihui , Wang Zhongjing , Wang Shuo , Ye Yingchun , Luo Deng , Wan Li , Yu Ailin , Sun Lifang , Tesfaye Solomon , Meng Qingtao , Gao Ling
Published: July 2020

Background

Although type 2 diabetes mellitus (T2DM) patients with coronavirus disease 2019 (COVID‐19) develop a more severe condition compared to those without diabetes, the mechanisms for this are unknown. Moreover, the impact of treatment with antihyperglycemic drugs and glucocorticoids is unclear.

Methods

From 1584 COVID‐19 patients, 364 severe/critical COVID‐19 patients with clinical outcome were enrolled for the final analysis, and patients without preexisting T2DM but elevated glucose levels were excluded. Epidemiological data were obtained and clinical status evaluation carried out to assess the impact of T2DM and its management on clinical outcomes.

Results

Of 364 enrolled severe COVID‐19 inpatients, 114 (31.3%) had a history of T2DM. Twenty‐seven (23.7%) T2DM patients died, who had more severe inflammation, coagulation activation, myocardia injury, hepatic injury, and kidney injury compared with non‐DM patients. In severe COVID‐19 patients with T2DM, we demonstrated a higher risk of all‐cause fatality with glucocorticoid treatment (adjusted hazard ratio [HR], 3.61; 95% CI, 1.14‐11.46; P = .029) and severe hyperglycemia (fasting plasma glucose ≥11.1 mmol/L; adjusted HR, 11.86; 95% CI, 1.21‐116.44; P = .034).

Conclusions

T2DM status aggravated the clinical condition of COVID‐19 patients and increased their critical illness risk. Poor fasting blood glucose (≥ 11.1 mmol/L) and glucocorticoid treatment are associated with poor prognosis for T2DM patients with severe COVID‐19.
Swift's Queer Camp
Authors: Klein Ula Lukszo
Published: July 2020

While many have read Swift's poems as displaying misogyny against women and against the tools women use for beautification, this article argues that Swift's dressing‐room poems offer a more nuanced reading of this process and the women involved. This article contends that ‘The Progress of Beauty’ (1719), ‘A Beautiful Young Nymph Going to Bed’ (1731) and ‘The Lady’s Dressing Room’ (1732) are poems of feminine decomposition which are ultimately about the embracing of abjection and disgust and questioning heteronormative ideals of purity. The language of hyperbole suggests a camp element to these women, queering the aesthetics of the abject.
Trade Negotiations in the Digital Era: The Case of OTT Video Streaming Services
Authors: Kwak Dongchul , Kim Minjung
Published: July 2020

This paper explores the dynamics of trade negotiations over over‐the‐top (OTT) video streaming services (VSS) in the multilateral trading system. Specifically, it compares specific commitments made under the General Agreement on Trade in Services (GATS) and offers submitted to the Doha Round negotiations by the European Union and the United States, and examines the two countries’ recent domestic media regulatory reforms in order to delineate major negotiation issues for OTT VSS. The findings of the analysis suggest that the EU continues to take an ‘all‐or‐nothing’ negotiating strategy while the US takes a ‘salami‐slice’ strategy on OTT VSS to pursue the utmost trade liberalization in the sector. The case study of OTT VSS highlights fundamental issues central to the ongoing services trade negotiations in the digital era. It may provide policymakers with significant implications regarding digital trade policy.
Boosting China’s Film Production: An Assessment of the Subsidies for China’s ‘Mainstream Films’
Authors: Zhou Xiaolan
Published: July 2020

Since 1991, the Chinese government has implemented a number of film policies which have sought to provide subsidies in order to promote this industry. Specifically, it is seeking to boost the so‐called ‘mainstream films’ which serve the purpose of distributing the state’s ideology and beliefs. However, these policies, such as tax relief and seat tax, have not helped to boost the production of this particular type of film. By drawing upon comparisons with subsidy policies in France and Korea, this paper provides explanations for why, after twenty years of market‐based reform in the film industry, China’s subsidies have not achieved the same results as these countries. In fact, they have deteriorated the quality and quantity of these mainstream films rather than helping them to become internationally more competitive. In this respect, this paper assesses the state of the mainstream film sector through the prism of Porter’s diamond model on competitiveness. This approach provides evidence of the real competitiveness of Chinese‐produced films, which could have crucial implications for the consistent application of ongoing subsidy policies.
Liver osteopontin is required to prevent the progression of age‐related nonalcoholic fatty liver disease
Authors: Gómez‐Santos Beatriz , Saenz de Urturi Diego , Nuñez‐García Maitane , Gonzalez‐Romero Francisco , Buque Xabier , Aurrekoetxea Igor , Gutiérrez de Juan Virginia , Gonzalez‐Rellan Maria J. , García‐Monzón Carmelo , González‐Rodríguez Águeda , Mosteiro Lorena , Errazti Gaizka , Mifsut Patricia , Gaztambide Sonia , Castaño Luis , Martin Cesar , Nogueiras Rubén , Martinez‐Chantar María L. , Syn Wing‐Kin , Aspichueta Patricia
Published: July 2020

Osteopontin (OPN), a senescence‐associated secretory phenotype factor, is increased in patients with nonalcoholic fatty liver disease (NAFLD). Cellular senescence has been associated with age‐dependent hepatosteatosis. Thus, we investigated the role of OPN in the age‐related hepatosteatosis. For this, human serum samples, animal models of aging, and cell lines in which senescence was induced were used. Metabolic fluxes, lipid, and protein concentration were determined. Among individuals with a normal liver, we observed a positive correlation between serum OPN levels and increasing age. This correlation with age, however, was absent in patients with NAFLD. In wild‐type (WT) mice, serum and liver OPN were increased at 10 months old (m) along with liver p53 levels and remained elevated at 20m. Markers of liver senescence increased in association with synthesis and concentration of triglycerides (TG) in 10m OPN‐deficient (KO) hepatocytes when compared to WT hepatocytes. These changes in senescence and lipid metabolism in 10m OPN‐KO mice liver were associated with the decrease of 78 kDa glucose‐regulated protein (GRP78), induction of ER stress, and the increase in fatty acid synthase and CD36 levels. OPN deficiency in senescent cells also diminished GRP78, the accumulation of intracellular TG, and the increase in CD36 levels. In 20m mice, OPN loss led to increased liver fibrosis. Finally, we showed that OPN expression in vitro and in vivo was regulated by p53. In conclusion, OPN deficiency leads to earlier cellular senescence, ER stress, and TG accumulation during aging. The p53‐OPN axis is required to inhibit the onset of age‐related hepatosteatosis.
Inbred Substrain Differences Influence Neuroimmune Response and Drinking Behavior
Authors: Warden Anna S. , DaCosta Adriana , Mason Sonia , Blednov Yuri A. , Mayfield Roy Dayne , Harris Robert Adron
Published: July 2020

Background

The inbred mouse strain C57BL/6 is widely used in both models of addiction and immunological disease. However, there are pronounced phenotypic differences in ethanol (EtOH) consumption and innate immune response between C57BL/6 substrains. The focus of this study was to examine the effects of substrain on innate immune response and neuroimmune‐induced escalation of voluntary EtOH consumption. The main goal was to identify whether substrain differences in immune response can account for differences in EtOH behavior.

Methods

We compared acute innate immune response with a viral dsRNA mimic, polyinosinic:polycytidylic acid (poly(I:C)), in brain using qRT‐PCR in both C57BL/6N and C57BL/6J mice. Next, we used a neuroimmune model of escalation using poly(I:C) to compare drinking behavior between substrains. Finally, we compared brain neuroimmune response with both EtOH and repeated poly(I:C) in both substrains as a way to account for differences in EtOH behavior.

Results

We found that C57BL/6 substrains have differing immune response and drinking behaviors. C57BL/6N mice have a shorter but more robust inflammatory response to acute poly(I:C). In contrast, C57BL/6J mice have a smaller but longer‐lasting acute immune response to poly(I:C). In our neuroimmune‐induced escalation model, C57BL/6J mice but not C57BL/6N mice escalate EtOH intake after poly(I:C). Finally, only C57BL/6J mice show enhanced proinflammatory transcript abundance after poly(I:C) and EtOH, suggesting that longer‐lasting immune responses are critical to neuroimmune drinking phenotypes.

Conclusions

Altogether, this work has elucidated additional influences that substrain has on both innate immune response and drinking phenotypes. Our observations highlight the importance of considering and reporting the source and background used for production of transgenic and knockout mice. These data provide further evidence that genetic background must be carefully considered when investigating the role of neuroimmune signaling in EtOH abuse.
Endothelial cells and angiogenesis in the horse in health and disease—A review
Authors: Rieger Juliane , Kaessmeyer Sabine , Al Masri Salah , Hünigen Hana , Plendl Johanna
Published: July 2020

The cardiovascular system is the first functional organ in the embryo, and its blood vessels form a widespread conductive network within the organism. Blood vessels develop de novo, by the differentiation of endothelial progenitor cells (vasculogenesis) or by angiogenesis, which is the formation of new blood vessels from existing ones. This review presents an overview of the current knowledge on physiological and pathological angiogenesis in the horse including studies on equine endothelial cells. Principal study fields in equine angiogenesis research were identified: equine endothelial progenitor cells; equine endothelial cells and angiogenesis (heterogeneity, markers and assessment); endothelial regulatory molecules in equine angiogenesis; angiogenesis research in equine reproduction (ovary, uterus, placenta and conceptus, testis); angiogenesis research in pathological conditions (tumours, ocular pathologies, equine wound healing, musculoskeletal system and laminitis). The review also includes a table that summarizesin vitrostudies on equine endothelial cells, either describing the isolation procedure or using previously isolated endothelial cells. A particular challenge of the review was that results published are fragmentary and sometimes even contradictory, raising more questions than they answer. In conclusion, angiogenesis is a major factor in several diseases frequently occurring in horses, but relatively few studies focus on angiogenesis in the horse. The challenge for the future is therefore to continue exploring new therapeutic angiogenesis strategies for horses to fill in the missing pieces of the puzzle.
Tape strips from early‐onset pediatric atopic dermatitis highlight disease abnormalities in nonlesional skin
Authors: Pavel Ana B. , Renert‐Yuval Yael , Wu Jianni , Del Duca Ester , Diaz Aisleen , Lefferdink Rachel , Fang Milie M. , Canter Talia , Rangel Stephanie M. , Zhang Ning , Krueger James G. , Paller Amy S. , Guttman‐Yassky Emma
Published: July 2020

Background

Skin biopsies promote our understanding of atopic dermatitis/AD pathomechanisms in infants/toddlers with early‐onset AD, but are not feasible in pediatric populations. Tape strips are an emerging, minimally invasive alternative, but global transcriptomic profiling in early pediatric AD is lacking. We aimed to provide global lesional and nonlesional skin profiles of infants/toddlers with recent‐onset, moderate‐to‐severe AD using tape strips.

Methods

Sixteen tape strips were collected for RNA‐seq profiling from 19 infants/toddlers (<5 years old; lesional and nonlesional) with early‐onset moderate‐to‐severe AD (≤6 months) and 17 healthy controls.

Results

We identified 1829 differentially expressed genes/DEGs in lesional AD and 662 DEGs in nonlesional AD, vs healthy skin (fold‐change ≥2, FDR <0.05), with 100% sample recovery. Both lesional and nonlesional skin showed significant dysregulations of Th2 (CCL17 and IL4R) and Th22/Th17 (IL36G, CCL20, and S100As)‐related genes, largely lacking significant Th1‐skewing. Significant down‐regulation of terminal differentiation (FLG and FLG2), lipid synthesis/metabolism (ELOVL3 and FA2H), and tight junction (CLDN8) genes were primarily seen in lesional AD. Significant negative correlations were identified between Th2 measures and epidermal barrier gene‐subsets and individual genes (FLG with IL‐4R and CCL17; r < −0.4, P < .05). Significant correlations were also identified between clinical measures (body surface area/BSA, pruritus ADQ, and transepidermal water loss/TEWL) with immune and barrier mRNAs in lesional and/or nonlesional AD (FLG/FLG2 with TEWL; r < −0.4, P < .05).

Conclusion

RNA‐seq profiling using tape strips in early‐onset pediatric AD captures immune and barrier alterations in both lesional and nonlesional skin. Tape strips provide insight into disease pathomechanisms and cutaneous disease activity.
A new pathophysiology in heart failure patients
Authors: Sciomer Susanna , Rellini Carlotta , Agostoni Piergiuseppe , Moscucci Federica
Published: July 2020

In the treatment of patients with severe heart failure, left ventricle assist device plays an important role, especially as a destination therapy. Nevertheless, even in successful cases, patients’ progressive weaning is rarely taken into consideration. The recovery of more physiological circulation conditions is not a main goal. This hypothesis is discussed in this article.
Review article: the impact of liver‐directed therapies on the atherogenic risk profile in non‐alcoholic steatohepatitis
Authors: Connelly Margery A. , Velez Rivera Jonathan , Guyton John R. , Siddiqui Mohammad Shadab , Sanyal Arun J.
Published: July 2020

Background

Patients with non‐alcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease, are at higher risk of cardiovascular disease (CVD) and associated mortality. Therefore, it is important to understand how new therapies for non‐alcoholic steatohepatitis (NASH) may impact CVD risk factors in these patients.

Aims

To summarise the effects of drug therapies on lipid and lipoprotein levels in patients with NASH and provide insight into the potential mechanisms for the observed changes.

Methods

PubMed searches of the literature were performed and results were compiled.

Results

Recent clinical trials have highlighted the safety and efficacy of drug candidates for the treatment of NASH. Several agents have shown improvements in the histological features of NASH and liver function. Pioglitazone, a drug that is currently available for type 2 diabetes and may be useful for NASH, exhibits beneficial effects on lipids. However, agents such as farnesoid X receptor agonists, which are in development for NASH, may adversely affect circulating lipids and lipoproteins.

Conclusions

NASH is a multi‐system disease with a disproportionate CVD burden. Current and future drugs for NASH have had variable impact on the atherogenic risk profile. Potential co‐administration of a statin may help mitigate the negative impact of some of these therapies on lipid and lipoprotein levels.
Appropriate traction can help identify the optimal dissectable layer for infrapyloric lymph node dissection in laparoscopic gastrectomy
Authors: Miura Susumu , Hosogi Hisahiro , Kawada Hironori , Ito Takeshi , Okada Toshihiro , Okumura Shintaro , Shimoike Norihiro , Akagawa Shin , Yamaura Tadayoshi , Yoshimura Fumihiro , Kanaya Seiichiro
Published: July 2020

Introduction

Appropriate dissection of the infrapyloric lymph nodes (no. 6 LNs) is important in gastric cancer surgery. In laparoscopic surgery, dissection of the no. 6 LNs along the inner dissectable layer from the left side of patient has been reported. However, it is difficult for surgeons to provide appropriate traction with their left hand from the left side. To resolve this difficulty, we dissected the no. 6 LNs from the patient’s right side to identify the optimal layer. We then evaluated the oncologic reliability of the layer and the safety of this procedure.

Methods

From the patient’s right side, the surgeon used their left hand to provide appropriate traction when pulling the adipose tissue, including the no. 6 LNs. This exposed the optimal layer between the adipose tissue and the pancreas. To assess this maneuver, the surgical outcomes of patients who underwent laparoscopic distal gastrectomy from April 2011 to March 2013 were retrospectively analyzed. The surgical outcomes included the number of the no. 6 LNs resected, time to dissect the no. 6 LNs, incidence of pancreatic complications, and recurrence in the no. 6 LNs.

Results

There were 112 patients identified. The median number of the no. 6 LNs resected was five. The median time to dissect the no. 6 LNs was 14 minutes. Four patients developed pancreatic fistula, and another four patients developed intra‐abdominal abscess. There was no recurrence in the no. 6 LNs.

Conclusion

The optimal layer was oncologically reliable, and these procedures were safe.
The phenotypic characteristics and relational database for Vietnamese native pig populations
Authors: Ishihara Shinya , Yamasaki Fukuhiro , Ninh Pham Hai , Dinh Nguyen Cong , Arakawa Aisaku , Taniguchi Masaaki , Cuc Ngo Thi Kim , Mikawa Satoshi , Takeya Masaru , Kikuchi Kazuhiro
Published: July 2020

Although there are a number of Vietnamese native pig (VnP) populations, some are on the verge of extinction, and therefore adequate management and conservation are necessary. In this study, we conducted a field survey of VnP populations and analyzed interrelationships among their characteristics. We also established a relational database for management of field data on these populations. For data collection, we conducted interviews with farmers and visual inspection of 32 VnP populations in 22 provinces of Vietnam, as well as taking photographs of individual animals. Data on the characteristics of VnP populations were subjected to multiple correspondence analysis (MCA). For establishment of the database, normalization and table partitioning were performed to eliminate redundancy and ensure consistency of the collected data items. Passport data, characteristics data, and image data were collected from a total of 1,918 VnPs and entered as a normalized table. Upon MCA, most of the populations were not separated from each other, but the Mong Cai, O Lam, and Chu Prong populations were separated from the other populations. Thus, we have constructed a relational database from comprehensive information on the characteristics of VnP populations.
Harmonizing and improving European education in prescribing: An overview of digital educational resources used in clinical pharmacology and therapeutics
Authors: Bakkum Michiel J. , Tichelaar Jelle , Papaioannidou Paraskevi , Likic Robert , Sanz Alvarez Emilio J. , Christiaens Thierry , Costa João N. , Mačiulaitis Romaldas , Dima Lorena , Coleman Jamie , Richir Milan C. , van Agtmael Michiel A. ,   for the Education Working Group of the European Association for Clinical Pharmacology and Therapeutics (EACPT) and its affiliated Network of Teachers in Pharmacotherapy (NOTIP)
Published: July 2020

Aim

Improvement and harmonization of European clinical pharmacology and therapeutics (CPT) education is urgently required. Because digital educational resources can be easily shared, adapted to local situations and re‐used widely across a variety of educational systems, they may be ideally suited for this purpose.

Methods

With a cross‐sectional survey among principal CPT teachers in 279 out of 304 European medical schools, an overview and classification of digital resources was compiled.

Results

Teachers from 95 (34%) medical schools in 26 of 28 EU countries responded, 66 (70%) of whom used digital educational resources in their CPT curriculum. A total of 89 of such resources were described in detail, including e‐learning (24%), simulators to teach pharmacokinetics and/or pharmacodynamics (10%), virtual patients (8%), and serious games (5%). Together, these resources covered 235 knowledge‐based learning objectives, 88 skills, and 13 attitudes. Only one third (27) of the resources were in‐part or totally free and only two were licensed open educational resources (free to use, distribute and adapt). A narrative overview of the largest, free and most novel resources is given.

Conclusion

Digital educational resources, ranging from e‐learning to virtual patients and games, are widely used for CPT education in EU medical schools. Learning objectives are based largely on knowledge rather than skills or attitudes. This may be improved by including more real‐life clinical case scenarios. Moreover, the majority of resources are neither free nor open. Therefore, with a view to harmonizing international CPT education, more needs to be learned about why CPT teachers are not currently sharing their educational materials.
Combination of pegylated interferon-alpha and nucleos(t)ide analogue treatment enhances the activity of natural killer cells in nucleos(t)ide analogue experienced chronic hepatitis B patients
Authors: Pang X , Zhang L , Liu N , Liu B , Chen Z , Li H , Chen M , Peng M , Ren H , Hu P
Published: July 2020

A combination of pegylated interferon-alpha (peg-IFN-α) and nucleos(t)ides analogue (NA) therapy can effectively reduce hepatitis B surface antigen (HBsAg), especially in NA-experienced chronic hepatitis B (CHB) patients. However, the immune mechanism of this therapy is unclear. Forty NA-experienced CHB patients were enrolled into this study. The frequencies of peripheral blood natural killer (NK) cells, dendritic cells (DCs), CD4+ T cells, CD8+ T cells, T helper (Th) cells, regulatory T cells (Treg), B cells and follicular T helper (Tfh) cells were evaluated by flow cytometry. Seven of the 40 patients converted to peg-IFN-α combined with NA treatment, while the other 33 continued to NA therapy. The decrease in HBsAg was more pronounced in the combination treatment group, and only patients receiving combination treatment achieved HBsAg loss. The frequency and absolute number of CD56bright NK cells in the combination treatment group increased significantly compared with the NA treatment group, whereas the CD56dim NK cells were decreased. In the NA treatment group, the proportions of CD4+ TN, CD8+ TN, CD19+ B and cytotoxic T lymphocyte antigen-4 (CTLA-4)+CD4+ T cells were increased, while the proportions of CD4+ TEM, CD8+ TEM, CD25+CD4+ Treg, CD25highCD4+ Treg, CD127lowCD25+ Treg, programmed cell death 1 (PD-1)+CD4+ T, PD-1+CD8+ T, CTLA-4+CD8+ T, CCR4+CD25+ Treg and CCR4+CD25high Treg cells were decreased after therapy. For NA-experienced CHB patients who achieved low HBsAg levels, combination treatment is more likely to result in HBsAg decline and HBsAg clearance by increasing the activity of CD56brightNK cells.
Epigenetic alterations in Sjögren's syndrome patient saliva
Authors: Karagianni P , Goules A V , Tzioufas A G
Published: July 2020

Epigenetic mechanisms have been implicated in the pathogenesis of Sjögren's syndrome (SS). Extensive alterations in DNA methylation have been described in minor salivary gland (MSG) epithelial cells and lymphocytes derived from SS patients compared to sicca controls. In an effort to identify novel potential epigenetic markers that could prove useful in diagnosis and disease monitoring, we explored whether DNA methylation differences can also be detected in saliva from SS patients compared to sicca controls. We performed DNA methylation analysis by methylation-sensitive restriction digestion followed by quantitative real-time polymerase chain reaction of selected genomic loci in saliva samples of 16 SS patients and 10 sicca controls with negative MSG biopsy. We identified reduced DNA methylation of the imprinting control region (ICR) of the H19 locus in SS patient saliva compared to sicca controls. Levels of saliva H19 ICR methylation were negatively correlated with C4 serum complement levels. Consistent with the reduced methylation of the ICR, H19 RNA levels were increased in SS patient peripheral blood mononuclear cells (PBMCs), while no significant change was observed in MSG H19 RNA levels compared to sicca controls. Our findings support that H19 ICR methylation could be a useful molecular epigenetic marker in monitoring patients with SS, highlighting saliva as a valuable biological sample in SS research and clinical practice. The role of H19 in SS pathogenesis remains to be addressed.
Female care leavers' journey to young adulthood from residential care in South Africa: Gender‐specific psychosocial processes of resilience
Authors: Hlungwani Joyce , van Breda Adrian D.
Published: July 2020

The journey from care to young adulthood is often accompanied by many challenges, making care leavers one of society's most vulnerable populations. Although research on young people leaving residential care is gaining increased attention globally, there is limited research that focuses on female care leavers. This article describes the psychosocial resilience processes that facilitate successful transitioning of young women as they journey out of residential care towards young adulthood. The methodology employed is a modified replication of a previous study with young men, with the aim of determining whether women utilize resilience processes in the journey out of care that are different from men. A sample of nine female care leavers was purposively selected and interviewed. Data were analysed using grounded theory methods. The findings indicate that although similar resilience processes are found in both male and female care leavers, there are also resilience processes that are specific to women, notably embracing motherhood and taking on responsibilities. It is concluded that resilience‐building programmes for young people leaving care should attend both to males and females together and also address issues specific to the care transition of women.
Retrospective study of the renal function using estimated glomerular filtration rate and congenital anomalies of the kidney‐urinary tract in pediatric Turner syndrome
Authors: Izumita Yukie , Nishigaki Satsuki , Satoh Mari , Takubo Noriyuki , Numakura Chikahiko , Takahashi Ikuko , Soneda Shun , Abe Yoshifusa , Kamasaki Hotaka , Ohtsu Yoshiaki , Igaki Junko , Hasegawa Yukihiro , Nagasaki Keisuke
Published: July 2020

Although Turner syndrome (TS) is frequently associated with congenital anomalies of the kidney‐urinary tract (CAKUT), which is a major cause of pediatric chronic kidney disease, renal function in TS is usually considered normal. The present study aimed to analyze the frequency of renal dysfunction and CAKUT in pediatric patients with TS. Our study included 122 patients with TS between the ages of 2 and 18 years from 30 hospitals across Japan. Clinical data related to renal function and CAKUT were retrospectively collected. The estimated glomerular filtration rate (eGFR) was calculated using the serum creatinine‐based formula recommended by the Japanese Society for Pediatric Nephrology. An eGFR <90 mL/min/1.73 m2 for two consecutive years was defined as renal dysfunction. Fifteen (13.5%) of 122 patients had CAKUT, and four patients had renal dysfunction (3.2%, 95% confidence interval: 0%‐6.7%). Three of the four did not have CAKUT. Of the CAKUT manifestations, horseshoe kidney, renal hypodysplasia, and multicystic dysplastic kidney were seen in nine, two, and one patient, respectively. Eight of the nine patients with horseshoe kidney had a normal renal function; however, the remaining patient with renal hypodysplasia had renal dysfunction. A small percentage of patients with pediatric TS may had an eGFR below 90 mL/min/1.73 m2 which was not necessarily associated with CAKUT.
Lithuanian version of nasolacrimal duct obstruction symptom scoring questionnaire. Cross‐cultural adaptation and validation. Short‐ and long‐term results
Authors: Jakštas Tomas , Balsevičius Tomas , Vaitkus Saulius , Padervinskis Evaldas
Published: July 2020

Objectives

The objective of this study was to perform translation, cross‐cultural adaptation and validation of the Lithuanian version of specific nasolacrimal duct obstruction symptom scoring (NLDO‐SS) questionnaire and to evaluate short‐ and long‐term results of endoscopic endonasal dacryocystorhinostomy (EN‐DCRS) procedure.

Design, Setting, Participants

Permission for questionnaire translation, cross‐cultural adaptation and validation was obtained from the authors of the original questionnaire. Translation, validation and cross‐cultural adaptation were carried out according to generally accepted methodology. Validation study of the Lithuanian version of NLDO‐SS (L‐NLDO‐SS) was performed, and short‐ and long‐term results of EN‐DCRS procedure were evaluated according to symptoms. In total, 44 patients were evaluated 2 weeks before the surgical intervention, a day before the surgery and 41 patients 2 months after the surgery, and again 10 months later.

Main outcome measures

We analysed the internal consistency and test‐retest reliability of the L‐NLDO‐SS questionnaire. Cronbach's alpha was used to represent and evaluate internal consistency for ordinal responses. Validity was assessed by comparing scores between a control group of volunteers without NLDO and the NLDO group using Mann‐Whitney test. To test the limiting score on which the sensitivity and specificity curves cross in identifying patients with NLDO, receiver operating characteristic (ROC) curve analysis was used. The pre‐ and post‐operative scores were compared using the paired t‐test.

Results

The results showed an acceptable internal consistency of L‐NLDO‐SS questionnaire, with Cronbach's alpha—.73 in the initial test group and .71 in the retest group. Pearson's correlation coefficient was .94 (P < .001), revealing good correlation between the initial scores and the retest scores. Our sample of healthy individuals had a mean L‐NLDO‐SS score of 11.42 (±12.69) points, and patients being scheduled for EN‐DCRS had a mean L‐NLDO‐SS score of 27.45 (±9.81) points. Post‐operatively mean L‐NLDO‐SS scores improved from 27.45 (±9.81) points to 4.45 (±6.29) points in the short term and to 5.83 (±4.17) in the long term, demonstrating the statistically significant responsiveness of the instrument over both timescales.

Conclusions

Lithuanian version of NLDO‐SS questionnaire is a valid instrument for assessing patients with NLDO in the Lithuanian population. It demonstrated good internal consistency, reproducibility, validity and responsiveness.
Combined strategies following surgical drainage for perianal fistulizing Crohn's disease: failure rates and prognostic factors
Authors: Herissay A. , Siproudhis L. , Le Balc’h E. , Merlini L’Heritier A. , Dewitte M. , Wallenhorst T. , Bouguen G. , Brochard C.
Published: July 2020

Aim

The medico‐surgical strategy for the treatment of perianal fistulizing Crohn's disease (CD) following surgical drainage remains challenging and debated. Our aims were to describe the failure rate of therapeutic interventions after drainage of the fistula tract and determine the factors associated with failure to optimize medico‐surgical strategies.

Method

All consecutive patients with perianal fistulizing CD who underwent surgical drainage with at least a 12‐week follow‐up were included. Failure was defined as the occurrence of at least one of the following items: abscess recurrence, purulent discharge from the tract, visible external opening and further drainage procedure(s).

Results

One hundred and sixty‐nine patients were included. The median follow‐up was 4.0 years. The cumulative failure rates were 20%, 30% and 36% at 1, 3 and 5 years, respectively. The cumulative failure rates in patients who had sphincter‐sparing surgeries or seton removal were significantly higher than in those who had a fistulotomy. Anterior fistula [hazard ratio (HR) = 2.52 (1.13–5.61), P = 0.024], supralevator extension [HR = 20.78 (3.38–127.80), P = 0.001] and the absence or discontinuation of immunosuppressants after anal drainage [HR = 3.74 (1.11–12.5), P = 0.032] were significantly associated with failure in the multivariate analysis model.

Conclusion

Combined strategies for perianal fistulizing CD lead to a failure rate of 36% at 5 years. Where advisable, fistulotomy may be preferred because it has a lower rate of recurrence. The benefits of immunosuppressants require a dedicated prospective randomized trial.
Symptom‐based scoring for haemorrhoidal disease: a systematic review
Authors: Jin J. , Xia W. , Connolly A. , Hill A.G.
Published: July 2020

Aim

Haemorrhoidal disease can severely affect a patient’s quality of life. Its classification is commonly based on morphology of the degree of prolapse; however, this does not take into account the symptoms and impact on the quality of life. The aim of this systematic review was to determine the most appropriate instruments that classify the severity of disease according to symptoms.

Method

A PRISMA‐compliant search was conducted in December 2019 to identify studies that described the validation of a haemorrhoidal symptom score. The measurement properties of the scoring systems were assessed based on the consensus‐based standards for the selection of health status measurement instruments (COSMIN) methodology for systematic reviews for patient‐reported outcome measures.

Results

A total of 5288 articles were identified, with five articles included. Three studies developed a scoring system based on a set of core symptoms for a cohort of patients and validated the score against treatment outcomes. One study developed a disease‐specific quality of life questionnaire based on symptoms to evaluate disease burden. One study combined both quality of life and symptom measures and tested measurement properties on two cohorts of patients. Only one study demonstrated satisfactory valid, reliable and responsive measurement criteria.

Conclusion

A single study demonstrated sufficient quality in measurement properties to be recommended for clinical use. Further studies in this area should utilize consensus‐based standards for designing and reporting validation research to ensure that the appropriate evidence base is acquired if any further patient‐reported outcome measures are to be recommended.
Patterns of emergency department utilization between transplant and non‐transplant centers and impact on clinical outcomes in kidney recipients
Authors: Perkins Haley , Taber David , Patel Neha , Rohan Vinayak , Su Zemin , Dubay Derek , McGillicuddy John
Published: July 2020

There is a high rate of Emergency Department (ED) utilization in kidney recipients post‐transplant; ED visits are associated with readmission rates and lower survival rates. However, utilization within and outside transplant centers may lead to different outcomes. The objective was to analyze ED utilization patterns at transplant and non‐transplant centers as well as common etiologies of ED visits and correlation with hospitalization, graft, and patient outcomes. This was a longitudinal, retrospective, single‐center cohort study in kidney transplant recipients evaluating ED utilization. Comparator groups were determined by ED location, time from transplant, and disposition/readmission from ED visit. 1,106 kidney recipients were included in the study. ED utilization dropped at the transplant center after the 1st year (P < .001), while remaining at a similar rate at non‐transplant centers (0.22 vs 1.06 VPPY). Infection and allograft complications were the most common causes of ED visits. In multivariable Cox modeling, an ED visit due to allograft complication at a non‐transplant center >1 year post‐transplant was associated with higher risk for graft loss and death (aHR 2.93 and aHR 1.75, P < .0001). The results of this study demonstrate an increased risk of graft loss among patients who utilize non‐transplant center emergency departments. Improved communication and coordination between transplant centers and non‐transplant centers may contribute to better long‐term outcomes.
Secondary cutaneous involvement by direct extension in high‐grade B‐cell lymphomas
Authors: Subtil Antonio , Gru Alejandro A.
Published: July 2020

Cutaneous involvement by a systemic lymphoma via direct extension is a very rare phenomenon, historically described in patients who had advanced‐stage disease with bulky lymphadenopathy. Since its original description, most cases of cutaneous lymphomatous spread via direct extension are attributable to Hodgkin disease. Here, we report the occurrence of direct cutaneous dissemination in the setting of nodal high‐grade B‐cell lymphomas, specifically diffuse large B‐cell lymphoma (DLBCL) and B‐cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma (also called gray‐zone lymphoma). Both cases are adequately documented with clinical, histopathologic, and immunophenotypic data, as well as additional cytogenetic analysis.