bluuebunny/crossref_metadata_2025 huggingface dataset:
Migrant enclaves: disempowering economic ghettos or sanctuaries of opportunities for migrants?
Authors: Hack-Polay Dieu
Published: July 2019

Purpose

This paper aims to examine the migrant dilemma about operating extensively in migrant enclaves vs integration in host communities.

Design/methodology/approach

The paper is a critical literature review contrasting views and perspectives of the role of migrant enclaves in migrant integration and contribution in new societies. Research in the area of ethnic enclaves has been polarised: on the one hand, the optimists argue the critical benefits of migrant and ethnic community networks, thus downplaying potential drawbacks of such networks and the disadvantage externally imposed on migrants; on the other hand, the pessimists overemphasise the disadvantages of ethnic enclaves, portraying them as ghettos of alienation.

Findings

Based on the social solidarity integration model and immigrant-host and social interaction theory, the paper posits that migrant community networks could intentionally or unintentionally engender cultural alienation, worsening an already precarious educational, cultural and economic exclusion. Thus, migrants could remain in lower societal roles and experience limited upward social mobility if they operate exclusively within migrant and ethnic networks. However, ethnic enclaves, at the same time, offer the initial psychological nurturing on which future successful socialisation work with migrant communities can be built.

Research limitations/implications

From a research angle, the theorisation of migrant enclave requires a new approach, which identifies dynamism and contextualisation as central to the debate.

Practical implications

From a policy perspective, the research suggests the rethinking of the role of community support systems (and the wider enclave debate). The organisational implications the research suggests a shift of the organisational paradigm in the way migrant organisations manage themselves and support members in the enclave.

Originality/value

This paper’s contribution is to take a duality approach to studying the ethnic enclave and posits that this will engender effective social policy that helps reduce economic inequality.
Diffusion of blockchain technology
Authors: Grover Purva , Kar Arpan Kumar , Janssen Marijn
Published: July 2019

Purpose

Although blockchain is often discussed, its actual diffusion seems to be varying for different industries. The purpose of this paper is to explore the blockchain technology diffusion in different industries through a combination of academic literature and social media (Twitter).

Design/methodology/approach

The insights derived from the academic literature and social media have been used to classify industries into five stages of the innovation-decision process, namely, knowledge, persuasion, decision, implementation and confirmation (Rogers, 1995).

Findings

Blockchain is found to be diffused in almost all industries, but the level of diffusion varies. The analysis highlights that manufacturing industry is at the knowledge stage. Further public administration is at persuasion stage. Subsequently, transportation, communications, electric, gas and sanitary services and trading industry had reached to the decision stage. Then, services industries have reached to implementation stage while finance, insurance and real estate industries are the innovators of blockchain technologies and have reached the confirmation stage of innovation-decision process.

Practical implications

Actual implementations of blockchain technology are still in its infancy stage for most of the industries. The findings suggest that specific industries are developing specific blockchain applications.

Originality/value

To the best of the authors’ knowledge this is the first study which is using social media data for investigating the diffusion of blockchain in industries. The results show that the combination of Twitter and academic literature analysis gives better insights into diffusion than a single data source.
It ain’t my business: a coping perspective on employee effortful security behavior
Authors: Xu Zhengchuan , Guo Ken
Published: July 2019

Purpose

Human factor is often cited as one of the biggest challenges for organizational information security management. The purpose of this paper is to investigate how and why employees fail to carry out required security tasks.

Design/methodology/approach

On the basis of coping theory, this paper develops a theoretical model to examine employee effortful security behavior (ESB). The model is tested with the data collected through a survey of computer users.

Findings

The results suggest that employee procrastination of security tasks and psychological detachment from security issues are two antecedents of ESB. Psychological detachment and procrastination are in turn influenced by perceived externalities of security risk and triage of business tasks over security issues by employees.

Originality/value

This paper contributes to the information systems security literature by providing a nuanced understanding of the antecedents and process of how employees cope with security task demands. It also offers some insights for practitioners in terms of the importance of designing and implementing security measures that are viewed as relevant to employees.
Towards a unified model of human development
Authors: Haigh Rex , Benefield Nick
Published: July 2019

Purpose

The purpose of this paper is to collaborate across disciplines to agree a better map of human development.

Design/methodology/approach

This paper used an iterative process of consultation with professionals and specialists in relevant disciplines, and service users, continually refining the diagram and text until a “good enough” consensus was reached to produce a diagrammatic form and explanatory text.

Findings

The process revealed a strong commitment across many disciplines to find a common contextual framework within which specialist understandings could be accommodated. The consultation process and iterative development of the diagram and text was marked by widespread interest and many detailed discussions. The substance of this paper is the result of that process.

Research limitations/implications

The model places research in different specialist fields onto a single “map of the territory”. It can encourage collaboration across disciplines when they are studying similar areas from different perspectives. It indicates the value of collaborative rather than competitive research enterprises.

Practical implications

Too often, professionals involved in fields concerning human development become focussed within narrow frameworks of specialisation. The model supports better understanding of how different elements relating to developmental life interrelate. This can facilitate the basis upon which a wide range of training, education and research programmes can be formulated.

Social implications

The model proposes greater use of a “whole-person/whole-life” perspective, which should allow greater integration between disparate approaches, and less experience of fragmentation. For a wide range of public sector activities, the quality of relational activity should be central to effective organisational and human outcomes. Without a unifying context, the understanding required to support relational work is weak: this model ad-dresses that deficit.

Originality/value

This work is entirely original. It should be of value to all those interested in working in holistic ways; to policy makers wishing to avoid duplication, waste and ineffective interventions; and to researchers interested in working across disciplinary boundaries. Most importantly, it is for staff involved in health, justice, social care and education services at all levels. Their effectiveness relies on relational, as well as procedural working, and this model will support confidence in the primacy of these activities.
Risk assessment of attitudes and practices of students and practitioners toward studio dyeing in Ghana
Authors: Howard Ebenezer Kofi , Frimpong Charles , Seidu Raphael Kanyire
Published: July 2019

Purpose

The purpose of this study is to assess the attitudes and practices of students and practitioners in the dyeing studio. Empirical evidence shows that synthetic dyes are the most commonly used dyestuff because of their colour fastness as compared with natural dyes. However, it is proven scientifically that synthetic dyes and their auxiliaries are carcinogenic and allergenic, which pose as health risks to users.

Design/methodology/approach

The study used analytical observational study design, where observation, questionnaire and interview were the instruments for data collection.

Findings

A survey conducted at selected dyeing studios in Ghana revealed the excessive use of vat dyes by students and practitioners because of its availability and accessibility on the local market. Adversely, the study found non-use of personal protective equipment by students and practitioners for protection against hazardous effects of dye chemicals. Again, poor studio set up with limited space and lack of proper waste drainage systems at the various dyeing studios results in inappropriate disposal of dyes, leading to environmental pollution.

Originality/value

Dyeing throughout history has been practiced to colour a fabric or yarn for specific use in the environment, which brings in some revenue. This practice however employs the use of dyes coupled with its auxiliaries, which poses some health problems in the short, medium and long term because of certain attitudes and practices exhibited by students and practitioners in the studio. It is therefore imperative for effective compliance to safety rules and practices by students and practitioners to ensure their safety. It is also critical that educational institutions and practitioners build modern dyeing studios which are spacious, well ventilated and efficient in limiting environmental pollution in compliance with eco-friendly practices. The study further recommends collaboration between Academia, local dyers’ association , Ghana Health Service and the Environmental Protection Agency to organize workshops to ensure best safety practices to save lives and the environment.
Cerebrovascular autoregulation following cardiac arrest: Protocol for a post hoc analysis of the randomised COMACARE pilot trial
Authors: Aneman Anders , Laurikalla Johanna , Pham Paul , Wilkman Erika , Jakkula Pekka , Reinikainen Matti , Toppila Jussi , Skrifvars Markus B
Published: July 2019

Background

Approximately two‐thirds of the mortality following out of hospital cardiac arrest is related to devastating neurological injury. Previous small cohort studies have reported an impaired cerebrovascular autoregulation following cardiac arrest, but no studies have assessed the impact of differences in oxygen and carbon dioxide tensions in addition to mean arterial pressure management.

Methods

This is a protocol and statistical analysis plan to assess the correlation between changes in cerebral tissue oxygenation and arterial pressure as measure of cerebrovascular autoregulation, the tissue oxygenation index, in patients following out of hospital cardiac arrest and in healthy volunteers. The COMACARE study included 120 comatose survivors of out of hospital cardiac arrest admitted to ICU and managed with low‐normal or high‐normal targets for mean arterial pressure, arterial oxygen and carbon dioxide partial pressures. In addition, 102 healthy volunteers have been investigated as a reference group for the tissue oxygenation index. In both cohorts, the cerebral tissue oxygenation was measured by near infrared spectroscopy.

Conclusions

Cerebrovascular autoregulation is critical to maintain homoeostatic brain perfusion. This study of changes in autoregulation following out of hospital cardiac arrest over the first 48 hours, as compared to data from healthy volunteers, will generate important physiological information that may guide the rationale and design of interventional studies.
Australian general practice registrars and their experience with postpartum consultations: A cross‐sectional analysis of prevalence and associations
Authors: Hill Sophia , Tapley Amanda , van Driel Mieke L. , Holliday Elizabeth G. , Ball Jean , Davey Andrew , Patsan Irena , Spike Neil , Fitzgerald Kristen , Morgan Simon , Magin Parker
Published: July 2019

Background

In Australia, general practitioners (GPs) are recognised as an essential source of postpartum care. However, there remains a paucity of research pertaining to this, and in particular, to that of GP trainees (in Australia, termed ‘registrars’). Previous post‐graduate experience in obstetrics and gynaecology (O&G) is not a prerequisite for GP training, and thus, it is imperative that vocational training provides adequate exposure to postpartum consultations.

Aim

To investigate the prevalence and associations of Australian GP registrars’ (trainees’) experience in postpartum care.

Materials and Methods

A cross‐sectional study employing data from the Registrar Clinical Encounters in Training (ReCEnT) project. ReCEnT is an ongoing cohort study where GP registrars record 60 consecutive consultations mid‐way through each training term. The outcome variable was postpartum problem/diagnosis (compared to all other problems/diagnoses). The independent variables included registrar, practice, patient, consultation, clinical and educational factors. Analyses employed univariate and multivariable regression.

Results

Analysis included 2234 registrars (response rate 96.1%), 289 594 consultations, and 453 786 problems/diagnoses. Postpartum care (897) comprised 0.2% (95% CI: 0.19–0.21) of all problems/diagnoses in 0.3% (95% CI: 0.27–0.31) of all consultations. Significant multivariable associations included registrar's gender (female) and obtainment of post‐graduate O&G qualifications. Postpartum consultations were longer and resulted in more learning goals being generated.

Discussion

An overall low prevalence was established. Both male registrars, and those without pre‐existing O&G qualifications, may have particularly limited experience. These findings should inform educational policy and practice regarding postpartum care experience in general practice training.
The effect of tributyrin supplementation to milk replacer on plasma glucagon‐like peptide 2 concentrations in pre‐weaning calves
Authors: Inabu Yudai , Murayama Kyotaro , Inouchi Katsutoshi , Sugino Toshihisa
Published: July 2019

The objective of this study was to evaluate the effect of tributyrin (TB) supplementation to milk replacer (MR) on performance, health, and blood concentrations of metabolite and glucagon‐like peptide (GLP‐2) in pre‐weaning calves. Twenty Holstein heifer calves were raised on an intensified nursing program using MR supplemented with either palm oil (CON) or TB (TB) at 0.3% (as fed basis) for 7 weeks starting 1 week after birth. Calves were fed a calf starter and kleingrass from the beginning of the study. Blood samples were obtained weekly to measure blood glucose, serum β‐hydroxybutyric acid (BHBA), insulin‐like growth factor 1 (IGF‐1), and plasma GLP‐2 concentrations. Starter DMI and metabolizable energy (ME) intake were lower in TB calves at 46, 47, from 49 to 55 days after birth compared with the CON calves. However, any growth parameters were not affected by TB treatment. Blood glucose, serum BHBA, and IGF‐1 concentrations were not affected by TB supplementation. On the other hand, mean plasma GLP‐2 concentration among whole experimental period was higher for TB (0.60 ng/ml) compared with CON (0.41 ng/ml). In conclusion, feeding MR supplemented with TB increases plasma GLP‐2 concentration, which might counterbalance the growth performance of TB calves despite the decreased ME intake.
Effects of mediator competence and mediation process on user satisfaction with child custody, finances, and property outcomes
Authors: Wong Mooly Mei‐ching , Ma Joyce Lai‐Chong , Yuan Rhea Rui
Published: July 2019

This study draws on survey data from 205 family mediation service users concerning their satisfaction with the outcomes of mediation to address two research questions: (a) how satisfied are service users? and (b) what factors account for users' satisfaction with the outcome of child custody arrangements and the allocation of finances and property? Overall, users' level of satisfaction with outcomes was high. While the mediation process explained a significant variance in satisfaction with the outcomes for child custody and for finances and property, the mediator's perceived professional competence did not predict user satisfaction with the outcomes for either issue. This study contributes to our knowledge on the significance of mediators' process skill, specifically their calm and clear responses to the socioemotional needs of the mediated parties, on the service outcomes for both types of dispute. The implications for mediation training are discussed.
Estimation of covariance matrix of multivariate longitudinal data using modified Choleksky and hypersphere decompositions
Authors: Lee Keunbaik , Cho Hyunsoon , Kwak Min‐Sun , Jang Eun Jin
Published: July 2019

Linear models are typically used to analyze multivariate longitudinal data. With these models, estimating the covariance matrix is not easy because the covariance matrix should account for complex correlated structures: the correlation between responses at each time point, the correlation within separate responses over time, and the cross‐correlation between different responses at different times. In addition, the estimated covariance matrix should satisfy the positive definiteness condition, and it may be heteroscedastic. However, in practice, the structure of the covariance matrix is assumed to be homoscedastic and highly parsimonious, such as exchangeable or autoregressive with order one. These assumptions are too strong and result in inefficient estimates of the effects of covariates. Several studies have been conducted to solve these restrictions using modified Cholesky decomposition (MCD) and linear covariance models. However, modeling the correlation between responses at each time point is not easy because there is no natural ordering of the responses. In this paper, we use MCD and hypersphere decomposition to model the complex correlation structures for multivariate longitudinal data. We observe that the estimated covariance matrix using the decompositions is positive‐definite and can be heteroscedastic and that it is also interpretable. The proposed methods are illustrated using data from a nonalcoholic fatty liver disease study.
Adaptive treatment allocation for comparative clinical studies with recurrent events data
Authors: Gao Jingya , Su Pei‐Fang , Hu Feifang , Cheung Siu Hung
Published: July 2019

In long‐term clinical studies, recurrent event data are sometimes collected and used to contrast the efficacies of two different treatments. The event reoccurrence rates can be compared using the popular negative binomial model, which incorporates information related to patient heterogeneity into a data analysis. For treatment allocation, a balanced approach in which equal sample sizes are obtained for both treatments is predominately adopted. However, if one treatment is superior, then it may be desirable to allocate fewer subjects to the less‐effective treatment. To accommodate this objective, a sequential response‐adaptive treatment allocation procedure is derived based on the doubly adaptive biased coin design. Our proposed treatment allocation schemes have been shown to be capable of reducing the number of subjects receiving the inferior treatment while simultaneously retaining a test power level that is comparable to that of a balanced design. The redesign of a clinical study illustrates the advantages of using our procedure.
Fast Approximation of Laplace‐Beltrami Eigenproblems
Authors: Nasikun Ahmad , Brandt Christopher , Hildebrandt Klaus
Published: July 2019

The spectrum and eigenfunctions of the Laplace‐Beltrami operator are at the heart of effective schemes for a variety of problems in geometry processing. A burden attached to these spectral methods is that they need to numerically solve a large‐scale eigenvalue problem, which results in costly precomputation. In this paper, we address this problem by proposing a fast approximation algorithm for the lowest part of the spectrum of the Laplace‐Beltrami operator. Our experiments indicate that the resulting spectra well‐approximate reference spectra, which are computed with state‐of‐the‐art eigensolvers. Moreover, we demonstrate that for different applications that comparable results are produced with the approximate and the reference spectra and eigenfunctions. The benefits of the proposed algorithm are that the cost for computing the approximate spectra is just a fraction of the cost required for numerically solving the eigenvalue problems, the storage requirements are reduced and evaluation times are lower. Our approach can help to substantially reduce the computational burden attached to spectral methods for geometry processing.
Experiences of patient‐centred care in alcohol and other drug treatment settings: A qualitative study to inform design of a patient‐reported experience measure
Authors: Hinsley Kathryn , Kelly Peter J. , Davis Esther
Published: July 2019

Introduction and Aims

A growing body of literature supports the use of patient‐reported experience measures (PREMs) to monitor the provision of patient‐centred care to people accessing health services. However, there is an absence of research into PREMs in the alcohol and other drugs (AOD) field. The aim of this study was to explore patient experiences of AOD care and to develop a PREM for AOD treatment settings.

Design and Methods

Five focus groups were conducted with people accessing AOD treatment services in New South Wales, Australia (N = 39). Data were analysed using iterative categorisation. A draft PREM was developed based on focus group findings and was modified following a subsequent review by consumers and service providers.

Results

Participants emphasised the importance of timely access to integrated care delivered in a structured program by staff members who genuinely care. Furthermore, participants described positive experiences when services addressed the problems that maintain addiction, held them responsible for themselves and facilitated self‐reflection. The PREM for Addiction Treatment (PREMAT) is a 33‐item measure that captures what participants said regarding their experience of patient‐centred care in AOD treatment.

Discussion and Conclusions

The experiences of people accessing AOD treatment provided useful feedback that can be translated into service improvements and that informed the design of a PREM for AOD treatment settings. Future research is necessary to further investigate the validity of the PREMAT.
Long‐term efficacy and safety of combined insulin and glucagon‐like peptide‐1 therapy: Evidence from the LEADER trial
Authors: Tack Cees J. , Jacob Stephan , Desouza Cyrus , Bain Stephen C. , Buse John B. , Nauck Michael A. , Petrie John R. , Poulter Neil R. , Pratley Richard E. , Stegmann Helen Vanya B. K. , Bosch‐Traberg Heidrun , Startseva Elena , Zinman Bernard ,   the LEADER Publication Committee on behalf of the LEADER Trial Investigators
Published: July 2019

Aim

Glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) and insulin combination therapy is an effective treatment option for type 2 diabetes, but long‐term data are lacking. The aim was to assess the long‐term efficacy of the GLP‐1RA liraglutide in subgroups by insulin use in the LEADER trial.

Materials and Methods

LEADER assessed cardiovascular (CV) safety and efficacy of liraglutide (1.8 mg) versus placebo (plus standard of care therapy) in 9340 patients with type 2 diabetes and high risk of CV disease, for up to 5 years. We analyzed CV events, metabolic parameters and hypoglycaemia post hoc in three subgroups by baseline insulin use (basal‐only insulin, other insulin or no insulin). Insulin was a non‐random treatment allocation as part of standard of care therapy.

Results

At baseline, 5171 (55%) patients were not receiving insulin, 3159 (34%) were receiving basal‐only insulin and 1010 (11%) other insulins. Insulin users had a longer diabetes duration and slightly worse glycaemic control (HbA1c) than the no‐insulin subgroup. Liraglutide reduced HbA1c and weight versus placebo in all three subgroups (P < .001), and severe hypoglycaemia rate in the basal‐only insulin subgroup. The need for insulin was less with liraglutide. CV risk reduction with liraglutide was similar to the main trial results in the basal‐only and no‐insulin subgroups.

Conclusions

In patients on insulin, liraglutide improved glycaemic control, weight and need for insulin versus placebo, for at least 36 months with no increased risk of severe hypoglycaemia, while maintaining CV safety/efficacy, supporting the combination of liraglutide and insulin for management of type 2 diabetes.
Dieback and decline of wild almond (Amygdalus scopariaSpach) in the Harat protected forest of Yazd Province, Iran
Authors: Mirabdollahi Shamsi Morteza , Akbarinia Moslem , Mirabolfathy Mansoureh , Manzari Shahab , Ahmadikhah Asadollah
Published: July 2019

Wild almond (Amygdalus scoparia) is a dominant shrub species in mountain forests of the Irano‐Turanian region. Dieback and decline symptoms of wild almond shrubs were first observed in Harat protected forest (Yazd, Iran) in the autumn of 2014. Since then, the incidence and severity of the disease have increased. To study the aetiology and estimate losses from the disease, field studies were conducted in 2016 and 2017. For this purpose, eight stands were selected, in which 24%–99% of the trees were wild almond in their species composition. In total, 50 cankers and 50 infected twigs of wild almond shrubs were collected. Fungal isolates were identified based on morphological and cultural characteristics, as well as sequence data of ITS1 + 5.8S + ITS2 rDNA. Pathogenicity of fungi was checked on detached shoots and evaluated after 40 days by measuring the discoloured lesion length at the inoculation site. Among 681 wild almond shrubs checked, 84.44% showed decline symptoms with different severities; only 15.56% did not show observable disease symptoms. The most frequent colonizers of infected tissues taken from cankers wereWilsonomyces carpophilus(56%),Thyrostroma cornicola(40%) andCollophorina paarla(30%). Infected twigs were extensively colonized byW. carpophilus(36%),Th. cornicola(24%) andUlocladium consortiale(24%). Other species, such asEndoconidioma populi, Microsphaeropsis olivacea,Trichoderma asperellum, Paecilomyces formosus, Saccothecium rubi, Preussiasp.andChaetomium globosum,had lower isolation frequencies.W. carpophilus, Th. cornicola,C. paarlaandU. consortialewere found as pathogens on detached wild almond shoots. Based on the frequency of the isolates and the pathogenicity tests, four fungi, such asW. carpophilus,Th. cornicola,C. paarlaandU. consortiale, are considered serious contributing agents playing a significant role in the dieback and decline of wild almond. All isolated species are reported for the first time on the wild almond shrubs of the world.
Seizure specificities in patients with antibody‐mediated autoimmune encephalitis
Authors: Vogrig Alberto , Joubert Bastien , André‐Obadia Nathalie , Gigli Gian Luigi , Rheims Sylvain , Honnorat Jérome
Published: July 2019

Accumulating data on patients with autoimmune encephalitis have shed light on specificities concerning clinical presentation and outcomes, which are dependent on the antigen targeted by the autoantibodies found in the patients’ cerebrospinal fluid or sera. Such specificities include seizure‐related clinical manifestations as well as the responsiveness to antiepileptic drugs. Although increased enthusiasm accompanies the discovery of novel antibodies and their associated clinical syndromes, several issues remain unsettled. First, it appears that therapy needs to be personalized in the view of the severity of each antibody‐mediated syndrome, patient‐related characteristics, and timing of treatment. Second, the lack of randomized controlled trials is a major drawback in the formulation of an appropriate immunotherapeutic strategy. In this review, we discuss the novel developments and challenges for the diagnosis and treatment of epilepsy in patients with well‐characterized autoimmune encephalitis, and delineate the principles for a rational approach toward precision medicine in this emerging field.
Melatonin as a potential modulator of Nrf2
Authors: Ahmadi Zahra , Ashrafizadeh Milad
Published: July 2019

Nuclear factor erythroid 2‐related factor 2 (Nrf2) is considered as the sensor of oxidative stress, and the main aim of this signaling pathway is to maintain physiological condition by induction of redox balance. Also, this pathway exerts anti‐inflammatory effects via antioxidant response element. Oxidative stress is a key factor in a variety of pathological conditions and high level of oxidative stress is associated with damages in lipids, proteins, genetic material, and cell membrane. Multiple drugs have been developed in order to diminish oxidative stress. However, synthetic drugs suffer from various drawbacks such as high cost and side effects. On the other hand, naturally occurring compounds are of interest due to their minimal side effects and valuable biological activities. Melatonin is a hormone of pineal gland which is found in different plants. This compound has a variety of favorable biological and therapeutic activities such as antioxidant, anti‐inflammatory, anti‐tumor, anti‐diabetic, and cardioprotection. At the present review, we demonstrate that Nrf2 signaling pathway explains some of the therapeutic and biological effects of melatonin.
Heterozygous loss of epilepsy geneKCNQ2alters social, repetitive and exploratory behaviors
Authors: Kim Eung Chang , Patel Jaimin , Zhang Jiaren , Soh Heun , Rhodes Justin S. , Tzingounis Anastasios V. , Chung Hee Jung
Published: July 2019

KCNQ/Kv7 channels conduct voltage‐dependent outward potassium currents that potently decrease neuronal excitability. Heterozygous inherited mutations in their principle subunits Kv7.2/KCNQ2 and Kv7.3/KCNQ3 cause benign familial neonatal epilepsy whereas patients with de novo heterozygous Kv7.2 mutations are associated with early‐onset epileptic encephalopathy and neurodevelopmental disorders characterized by intellectual disability, developmental delay and autism. However, the role of Kv7.2‐containing Kv7 channels in behaviors especially autism‐associated behaviors has not been described. Because pathogenic Kv7.2 mutations in patients are typically heterozygous loss‐of‐function mutations, we investigated the contributions of Kv7.2 to exploratory, social, repetitive and compulsive‐like behaviors by behavioral phenotyping of both male and femaleKCNQ2+/−mice that were heterozygous null for theKCNQ2gene. Compared with their wild‐type littermates, male and femaleKCNQ2+/−mice displayed increased locomotor activity in their home cage during the light phase but not the dark phase and showed no difference in motor coordination, suggesting hyperactivity during the inactive light phase. In the dark phase,KCNQ2+/−group showed enhanced exploratory behaviors, and repetitive grooming but decreased sociability with sex differences in the degree of these behaviors. While maleKCNQ2+/−mice displayed enhanced compulsive‐like behavior and social dominance, femaleKCNQ2+/−mice did not. In addition to elevated seizure susceptibility, our findings together indicate that heterozygous loss of Kv7.2 induces behavioral abnormalities including autism‐associated behaviors such as reduced sociability and enhanced repetitive behaviors. Therefore, our study is the first to provide a tangible link between loss‐of‐function Kv7.2 mutations and the behavioral comorbidities of Kv7.2‐associated epilepsy.
Clinical advances in gene therapy updates on clinical trials of gene therapy in haemophilia
Authors: Peyvandi Flora , Garagiola Isabella
Published: July 2019

Gene therapy is rapidly becoming a new therapeutic strategy for haemophilia A and B treatment. In the 1990s, studies in animal models showed that adeno‐associated vectors (AAV) exhibited an efficient expression of factor IX (FIX). In the first clinical trial in patients with haemophilia B, therapeutic levels of FIX were documented but the expression remained only for few weeks. Subsequently, improvements in vector design, such as the use of different AAV serotypes, the development of the self‐complementary vector, the engineering of the transgene with codon optimization and liver‐specific expression cassette resulted in circulating FIX level between 2% and 5% for long‐lasting period. Recently, a natural gain of function FIX variant (Padua) inserted in the F9 cDNA improved the expression of FIX achieving a level of more than 30% resulting in cessation of infusions and in a greatly reduction of bleeding events. Encouraging clinical progresses have been also obtained from trials of gene therapy for haemophilia A. Transgene expression persisted for three years with circulating FVIII activity levels of 52.3% in patients treated with AAV vector containing a codon‐optimized F8 cDNA. A complication, reported in both clinical trials for haemophilia A and B, was the elevation of liver enzymes, which resolved with steroid treatment in a large group of patients. However, to date, the pathophysiological mechanism for the liver toxicity remains still unclear. Clinical trials with adeno‐associated vectors have documented a significant success for haemophilia gene therapy demonstrating potential to transform haemophilia treatment offering hope for a long‐term expression.
Investigation of nutraceutical potential of the microalgae Chlorella vulgaris and Arthrospira platensis
Authors: Matos Joana , Cardoso Carlos L. , Falé Pedro , Afonso Cláudia M. , Bandarra Narcisa M.
Published: July 2019

The microalgae Chlorella vulgaris and Arthrospira platensis were evaluated as nutraceuticals. It was observed that Arthrospira platensis is richer in saturated fatty acids (FA) and Chlorella vulgaris richer in monounsaturated FA. Within polyunsaturated FA (PUFA), n3 PUFA content was below 1% in Arthrospira sp and over 10% in Chlorella vulgaris. This microalga had the lowest polyphenolic content. The highest value was found in the aqueous extract of Arthrospira platensis, 334 ± 32 mg GAE per 100 g dw. Regarding DPPH, only aqueous extracts of Chlorella vulgaris yielded antioxidant activity with an inhibitory activity of 80 ± 1%. ABTS results showed stronger inhibition through the aqueous extracts than through the ethanolic extracts, 89%–93% vs. 24%–32%. Concerning cytotoxicity, ethanolic extracts of Chlorella vulgaris induced a cell viability decrease of approximately 80%. The biochemical characterisation and bioactivity assessment of Chlorella vulgaris and Arthrospira platensis showed that these microalgae have potential for nutraceutical applications.
Long‐term outcome of hypertensive patients with heart failure with mid‐range ejection fraction: The significance of blood pressure control
Authors: Marketou Maria E. , Maragkoudakis Spyros , Fragiadakis Kostantinos , Konstantinou John , Patrianakos Alexandros , Kassotakis Spyridon , Anastasiou Ioannis , Alevizaki Afroditi , Kostaki Artemis , Chlouverakis Gregory , Vardas Panos E. , Parthenakis Fragiskos I.
Published: July 2019

Heart failure (HF) with mid‐range ejection fraction (HFmrEF) is a newly suggested entity in HF. Since it has been inadequately addressed, there is an urgent need to determine the profile of HFmrEF patients and the optimal approach to their management. The present study aimed to assess the long‐term clinical outcomes of hypertensive patients with HFmrEF and the impact of blood pressure (BP) on their mortality and cardiovascular outcome. We performed a retrospective observational study that included 121 hypertensive patients with HFmrEF and 149 hypertensives with heart failure and preserved ejection fraction (HFpEF). The median follow‐up was 84 months (22‐122). Our analysis did not reveal any statistically significant difference between the two groups in total mortality (P = 0.34) or cardiovascular mortality (P = 0.54). The total mean survival time was 102.9 months (100.5‐110.1), while the mean survival time was 105.3 months (80.4‐90.2) in HFpEF and 97.6 months (92.7‐102.6) in HFmrEF. An office systolic BP > 139 mm Hg and diastolic BP > 89 mm Hg were significantly associated with both all‐cause mortality (P = 0.02 and P = 0.013, respectively) and cardiovascular mortality (P = 0.02 for both). In HFpEF patients, no significant association was found between outcome and office BP. HFpEF and HFmrEF have similar long‐term outcomes. Suboptimal BP levels are a significant risk factor for an adverse outcome in HFmrEF. Our results emphasize the importance of good BP control in order to achieve better outcomes in hypertensives with impaired EF and HF symptomatology.
HBx combined with AFB1 triggers hepatic steatosis via COX‐2‐mediated necrosome formation and mitochondrial dynamics disorder
Authors: Chen Yuan‐Yuan , Lin Yi , Han Pei‐Yu , Jiang Shan , Che Lin , He Cheng‐Yong , Lin Yu‐Chun , Lin Zhong‐Ning
Published: July 2019

Hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure have been recognized as independent risk factors for the occurrence and exacerbation of hepatic steatosis but their combined impacts and the potential mechanisms remain to be further elucidated. Here, we showed that exposure to AFB1 impaired mitochondrial dynamics and increased intracellular lipid droplets (LDs) in the liver of HBV‐transgenic mice in vivo and the hepatitis B virus X protein (HBx)‐expressing human hepatocytes both ex vivo and in vitro. HBx combined with AFB1 exposure also up‐regulated receptor interaction protein 1 (RIP1), receptor interaction protein 3 (RIP3) and activated mixed lineage kinase domain like protein (MLKL), providing evidence of necrosome formation in the hepatocytes. The shift of the mitochondrial dynamics towards imbalance of fission and fusion was rescued when MLKL was inhibited in the HBx and AFB1 co‐treated hepatocytes. Most importantly, based on siRNA or CRISPR/Cas9 system, we found that the combination of HBx and AFB1 exposure increased cyclooxygenase‐2 (COX‐2) to mediate up‐regulation of RIP3 and dynamin‐related protein 1 (Drp1), which in turn promoted location of RIP3‐MLKL necrosome on mitochondria, subsequently exacerbated steatosis in hepatocytes. Taken together, these findings advance the understanding of mechanism associated with HBx and AFB1‐induced hepatic necrosome formation, mitochondrial dysfunction and steatosis and make COX‐2 a good candidate for treatment.
Linoleic acid‐derived metabolites constitute the majority of oxylipins in the rat pup brain and stimulate axonal growth in primary rat cortical neuron‐glia co‐cultures in a sex‐dependent manner
Authors: Hennebelle Marie , Morgan Rhianna K. , Sethi Sunjay , Zhang Zhichao , Chen Hao , Grodzki Ana Cristina , Lein Pamela J. , Taha Ameer Y.
Published: July 2019

In adult rats, omega‐6 linoleic acid (LA, 18:2n‐6) serves as a precursor to oxidized LA metabolites (OXLAMs) known to regulate multiple signaling processes in the brain. However, little is known regarding the levels or role(s) of LA and its metabolites during brain development. To address this gap, fatty acids within various brain lipid pools, and their oxidized metabolites (oxylipins) were quantified in brains from 1‐day‐old male and female pups using gas chromatography and liquid chromatography coupled to tandem mass spectrometry, respectively. Primary neuron‐glia co‐cultures derived from postnatal day 0–1 male and female rat neocortex were exposed to vehicle (0.1% ethanol), LA, the OXLAM 13‐hydroxyoctadecadienoic acid (13‐HODE), or prostaglandin E2 at 10–1000 nM for 48 h to test their effects on neuronal morphology. In both male and female pups, LA accounted for 1–3% of fatty acids detected in brain phospholipids and cholesteryl esters. It was not detected in triacylglycerols, and free fatty acids. Unesterified OXLAMs constituted 47–53% of measured unesterified oxylipins in males and females (vs. ~5–7% reported in adult rat brain). Of these, 13‐HODE was the most abundant, accounting for 30–33% of measured OXLAMs. Brain fatty acid and OXLAM concentrations did not differ between sexes. LA and 13‐HODE significantly increased axonal outgrowth. Separate analyses of cultures derived from male versus female pups revealed that LA at 1, 50, and 1000 nM, significantly increased axonal outgrowth in female but not male cortical neurons, whereas 13‐HODE at 100 nM significantly increased axonal outgrowth in male but not female cortical neurons. prostaglandin E2 did not alter neuronal outgrowth in either sex. This study demonstrates that OXLAMs constitute the majority of unesterified oxylipins in the developing rat brain despite low relative abundance of their LA precursor, and highlights a novel role of LA and 13‐HODE in differentially influencing neuronal morphogenesis in the developing male and female brain.

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Effect of a collaborative transdisciplinary team approach on oral health status in acute stroke patients
Authors: Obana Michiyo , Furuya Junichi , Matsubara Chiaki , Tohara Haruka , Inaji Motoki , Miki Kazunori , Numasawa Yoshiyuki , Minakuchi Shunsuke , Maehara Taketoshi
Published: July 2019

Background

Oral function deteriorates easily during the acute phase of cerebral stroke. Therefore, oral health care involving a transdisciplinary approach consisting of dental and medical professionals might be important, but has not been studied in detail.

Objective

This study assessed the oral health status of patients with cerebral stroke in the acute phase, with the aim of elucidating the efficacy of collaborative, transdisciplinary oral health care involving dentists, dental hygienists, nurses and speech therapists.

Methods

The participants were 115 consecutive acute cerebral stroke patients, who received oral health care while hospitalised at the university hospital. Their oral health status was assessed using the oral health assessment tool (OHAT) on admission and discharge.

Results

Patients with acute cerebral stroke had high OHAT scores on admission, meaning poor oral health status. The collaborative oral health care resulted in significant decrease of OHAT scores at discharge, indicative of the improvement of oral health status. Multivariate analysis identified OHAT score for tongue, dentures and oral cleanliness on admission as the significant variables associated with poor oral health status at discharge.

Conclusions

Thus, the oral health of cerebral stroke patients in the acute phase can be improved by implementing transdisciplinary collaboration of medical and dental professionals. Particularly, patients with problems pertaining to the tongue, dentures and oral cleanliness as revealed through OHAT on admission may require more intensive intervention.
Long‐Term Survival and Peri‐Implant Health of Titanium Implants with Zirconia Abutments: A Systematic Review and Meta‐Analysis
Authors: Cao Yubin , Yu Changhao , Wu Yingyi , Li Longjiang , Li Chunjie
Published: July 2019

Purpose

To evaluate the long‐term implant survival rate of titanium implants with zirconia abutments, and the effects of implants with zirconia abutments on marginal bone loss (MBL) and pocket probing depth (PPD) compared with all‐titanium implants.

Materials and Methods

The searched electronic database included the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and the Chinese Biomedical Literature Database. Two types of studies were included: clinical studies reporting the survival rate of titanium implants with zirconia abutments with at least a mean/median 5‐year follow‐up, and clinical trials reporting the effects of implants with zirconia abutments on MBL and PPD compared with all‐titanium implants. Two reviewers screened and selected the records, assessed quality, and extracted data of included studies independently.

Results

This review included 16 studies from 18 publications. None of the comparative studies was assessed at a low risk of bias. The overall implant survival rate of implants with zirconia abutments was estimated to be 96% (confidence intervals [CIs] [94%, 98%], I2 = 0%). For the comparison between implants with zirconia abutments and all‐titanium implants, the results significantly favored implants with zirconia abutments (for MBL, mean difference [MD] = –0.09, CIs [–0.17, 0.00], p = 0.05, I2 = 40%; for PPD, MD = –0.18, CIs [–0.32, –0.05], p = 0.008, I2 = 0%). Zirconia abutments were favored more when the prosthesis was an implant‐supported overdenture rather than a single crown.

Conclusions

Implants with zirconia abutments may have an acceptable performance on peri‐implant health compared with all‐titanium implants; however, the implant survival rate of implants with zirconia abutments is slightly lower than all‐titanium implants in the long‐term follow‐up. Additional studies are needed to explain this dichotomy.
Bottom‐up or top‐down? Examining global and domain‐specific evaluations of how one's life is unfolding over time
Authors: Busseri Michael A. , Mise Taysa‐Rhea
Published: July 2019

Objective

We employed bottom‐up and top‐down perspectives to evaluate the link between how individuals view their lives as unfolding over time overall and in multiple life domains.

Method

Participants from an American adult lifespan sample (n = 1,003, mean age = 54.39 years, 49% female, 94% Caucasian) evaluated their recollected past, current, and anticipated future satisfaction in seven life domains (health, work, finances, contribution to others, relationships with one's children, close relationships, sex life) and for their lives overall (life satisfaction) at two time points separated by 9 years.

Results

Mean‐level trends varied by life domain and age. In cross‐sectional and longitudinal analyses, domain‐specific beliefs about changes in one's life explained substantial amounts of variance in perceived changes in overall life satisfaction, and multiple domains had unique predictive effects. Domain‐specific beliefs also substantially mediated the predictive effect of age on perceived change in life satisfaction.

Conclusions

Findings provide consistent support for the bottom‐up perspective and limited support for the top‐down model. Accordingly, individuals seem to derive beliefs concerning how their lives overall are unfolding over time based on perceived changes across multiple life domains.