bluuebunny/crossref_metadata_2025 huggingface dataset:
Mobile telephone‐delivered contingency management interventions promoting behaviour change in individuals with substance use disorders: a meta‐analysis
Authors: Getty Carol‐Ann , Morande Ana , Lynskey Michael , Weaver Tim , Metrebian Nicola
Published: July 2019

Background/aims

Contingency management (CM) interventions have gained considerable interest due to their success in the treatment of addiction. However, their implementation can be resource‐intensive for clinical staff. Mobile telephone‐based systems might offer a low‐cost alternative. This approach could facilitate remote monitoring of behaviour and delivery of the reinforcer and minimize issues of staffing and resources. This systematic review and meta‐analysis assessed the evidence for the effectiveness of mobile telephone‐delivered CM interventions to promote abstinence (from drugs, alcohol and tobacco), medication adherence and treatment engagement among individuals with substance use disorders.

Design

A systematic search of databases (PsychINFO, CINAHL, MEDLINE PubMed, CENTRAL, Embase) for randomized controlled trials and within‐subject design studies (1995–2019). The review was conducted in accordance with the PRISMA statement. The protocol was registered on PROSPERO.

Setting

All included studies originated in the United states.

Participants

Seven studies were found, including 222 participants; two targeted alcohol abstinence among frequent drinkers and four targeted smoking cessation (in homeless veterans and those with post‐traumatic stress disorder). One targeted medication adherence.

Measures

The efficacy of CM to increase alcohol and nicotine abstinence was compared with control using several outcomes; percentage of negative samples (PNS), quit rate (QR) and longest duration abstinent (LDA) at the end of the intervention.

Findings

The random‐effects meta‐analyses produced pooled effect sizes of; PNS [d = 0.94, 95% confidence interval (CI) = 0.63–1.25], LDA (d = 1.08, 95% CI = 0.69–1.46) and QR (d = 0.46, 95% CI = 0.27–0.66), demonstrating better outcomes across the CM conditions. Most of the studies were rated as of moderate quality. ‘Fail‐safe N' computations for PNS indicated that 50 studies would be needed to produce a non‐significant overall effect size. None could be calculated for QR and LDA due to insufficient number of studies.

Conclusion

Mobile telephone‐delivered contingency management performs significantly better than control conditions in reducing tobacco and alcohol use among adults not in treatment for substance use disorders.
Implant education patterns and clinical practice of general dentists in Australia
Authors: Cheung MC , Hopcraft MS , Darby IB
Published: July 2019

Background

This study aimed to understand trends in dentists' implant training attendance and correlation to treatment provision. Implant‐specific oral hygiene instruction coverage in training programs was investigated.

Methods

A cross‐sectional web‐survey of dentists registered in Australia was conducted. Respondents were asked about their background, implant training history and treatment provision. Results were analysed by implant provision characteristics and graduation decade.

Results

Three hundred and three responses from general dental practitioners (GDPs) were received and analysed. The highest implant training levels attained post‐graduation were postgraduate non‐specialist qualification (7.9% of respondents), continuing professional development (CPD) (73.6%) versus none (18.5%), with differences between implant providers and non‐providers (P < 0.001), different graduation decades (P < 0.001) and those restoring implants or performing surgery as well (P < 0.001). University‐based CPD was attended less than dental association/society or implant company CPD. Non‐providers were significantly less likely to recall implant oral hygiene instruction sources (P < 0.001). Most GDPs (74.9%) provided implant services, with younger GDPs beginning earlier after graduation. About 16% of respondents did not provide implants once established career‐wise.

Conclusions

Dentists might be providing implant treatments increasingly earlier in their careers. Respondents with more training were significantly more likely to perform more complex procedures, while implant training attendance trends varied by graduation decade.
Patterns of care for orbital marginal zone B‐cell lymphoma of mucosa‐associated lymphoid tissue in Korea throughout 2016: Results from a multicenter cross‐sectional cohort study (KROG 16–19)
Authors: Lee Jeongshim , Oh Dongryul , Choi Byung Ock , Eom Keun‐Yong , Lee Jong Hoon , Kim Jung Hoon , Lee Sang Wook , Suh Yang Kwon , Suh Chang‐Ok
Published: July 2019

Aim

Primary orbital mucosa‐associated lymphoid tissue (MALT) lymphomas are generally sensitive to radiotherapy (RT), but a “wait and see” strategy has also been used in asymptomatic patients. Recently, orbital MALT lymphoma has been reported to be associated with Chlamydia psittaci infection. This study aimed to assess the current patterns of care in clinical practice for orbital MALT lymphoma in South Korea.

Methods

We performed a multicenter, cross‐sectional cohort study of patterns of care for orbital MALT lymphoma in South Korea throughout 2016. All patients were pathologically confirmed to have orbital MALT lymphoma.

Results

Overall, eight institutions with 90 patients participated. The survey showed that the most frequent upfront treatment for orbital MALT lymphoma was RT (80/90, 90%). Other treatment modalities were given to a limited number of orbital MALT lymphoma patients as follows: watch and wait, 6/90 (7%); antibiotics, 3/90 (3%) and chemotherapy, 1/90 (1%). Generally, RT was administered to the entire involved site such as the entire conjunctiva/eyelid or entire orbit (96%), with a median total dose of 25.2 Gy. Lens shielding was performed for most patients with conjunctival and eyelid tumors (93%).

Conclusions

RT was the conventional treatment modality for orbital MALT lymphoma. Currently, RT is performed for the entire involved subsites at a lower dose than that previously used, and lens shielding was applied to minimize the orbital complication.
The c‐Myc‐regulated miR‐17‐92 cluster mediates ATRA‐induced APL cell differentiation
Authors: Yu Xibao , Hu Yanyun , Wu Yifan , Fang Chunsheng , Lai Jing , Chen Shaohua , Li Yangqiu , Zeng Chengwu , Zeng Yixin
Published: July 2019

Background

Despite advances in the treatment of acute promyelocytic leukemia (APL) with all‐trans‐retinoic acid (ATRA), its underlying mechanism has not been fully elucidated. The oncogenic microRNA cluster miR‐17‐92 modulates multiple cellular processes, including survival, proliferation, and apoptosis. However, the role of miR‐17‐92 and its regulation has not yet been documented for APL.

Methods

We analyzed miR‐17‐92 expression in APL samples and cell lines by qRT‐PCR. The expression of c‐Myc was measured by western blot. Cell differentiation was assessed by measuring the surface CD11b antigen expression by flow cytometry analysis.

Results

We observed that miR‐17‐92 was upregulated in APL compared with healthy donors. Furthermore, we demonstrated that expressions of c‐Myc and miR‐17‐92 are markedly suppressed during ATRA‐induced NB4 cell differentiation. Importantly, we also demonstrated that miR‐17‐92 is directly regulated by c‐Myc during the granulocytic differentiation of APL cells. Finally, the overexpression of miR‐17‐5p blocks ATRA‐induced differentiation.

Conclusions

We report abnormal expression of the miR‐17‐92 cluster in APL cells, which is responsible for the differentiation block in blast cells in APL. In addition, we identified miR‐17‐92 as a target gene of c‐Myc during ATRA‐induced granulocytic differentiation.
Incidence rate and clinicopathological features of 62 atypical fibroxanthomas in a North‐Western Spanish population
Authors: Iglesias‐Pena Nicolás , López‐Solache Laura , Martínez‐Campayo Nieves , Meilán‐Sánchez Iago , Yebra‐Pimentel María Teresa , Balboa‐Barreiro Vanesa , Paradela Sabela , Fonseca Eduardo
Published: July 2019

Background/Objectives

Atypical fibroxanthoma (AFX) is a mesenchymal neoplasm of unknown incidence. It has been determined that AFX is a tumour with low aggressiveness as long as it is properly diagnosed. Our objectives were to exclude pleomorphic dermal sarcomas or other skin tumours incorrectly diagnosed as AFX in our centre after applying strict diagnostic criteria and to assess the behaviour of appropriately diagnosed AFX.

Methods

We conducted an observational retrospective analysis of 73 patients diagnosed with AFX in our centre between 1998 and 2018. After selecting cases fulfilling AFX criteria, we made an analysis of predictive factors for local recurrence. Crude and sex‐adjusted incidence rates were calculated.

Results

Out of 73 cases, 62 were eventually diagnosed as AFX. We examined for absence of tumour necrosis, lymphovascular or perineural invasion and infiltration of deep structures. Cytokeratin AE1‐AE3, desmin and CD34 were negative in all cases. The remaining tumours were reclassified. The incidence of AFX in our health‐care area was estimated at 0.59 cases every 100 000 inhabitants per year. In our series, 72.6% of the patients were men with mean age at diagnosis of 81 years. Average tumour diameter was 12 mm. The most common location was head and neck (96.8%). Only four local recurrences were detected over a mean of 47‐month follow‐up.

Conclusions

We report a series of AFX in our health‐care area. We verify its indolent course when it is properly diagnosed.
Prevalence and histopathological signatures of optic disc drusen based on microscopy of 1713 enucleated eyes
Authors: Skougaard Marie , Heegaard Steffen , Malmqvist Lasse , Hamann Steffen
Published: July 2019

Purpose

Optic disc drusen (ODD) are calcified optic nerve head deposits. Objectives of this study were to examine the prevalence of ODD in eyes removed by enucleation and to describe related histopathological signatures of ODD and surrounding tissues.

Methods

The study was a retrospective observational case series study assessing and re‐evaluating enucleated eyes in Denmark from 1980 to 2015 by microscopy. Individual ODD were described based on size, number and location (superficial and/or deep) within the optic nerve. Optic nerve heads with ODD were assessed for elevated discs, retinal nerve fibre layer (RNFL) thickness, oedematous axons and presence of localized peripapillary axonal distension (LPAD) equivalent to the peripapillary hyperreflective ovoid mass‐like structures seen on optical coherence tomography.

Results

Microscopy of 1713 eyes revealed ODD in 31 eyes equivalent to a prevalence of 1.8%. Optic disc drusen (ODD) were seen as circular shapes of different sizes and varying number. Elevated discs were present in 15 (54%) of the cases. Thickening of the superficial RNFL was present in eyes with large deeply located ODD. For more superficial ODD of approximately same size, the RNFL was thinner. Oedematous axons were present in three eyes. Localized peripapillary axonal distension (LPAD) was seen in five eyes.

Conclusions

Prevalence of ODD in this study of histopathological signatures was higher than the prevalence found in clinical studies. Our results suggest that large, deep ODD might cause crowding and herniation of axons in the optic nerve head leading to a thickened superficial nerve fibre layer, pseudopapilledema and LPAD.
Making sense of models: How teachers use agent‐based modeling to advance mechanistic reasoning
Authors: Hsiao Ling , Lee Irene , Klopfer Eric
Published: July 2019

Computer modeling promotes mechanistic reasoning when learners build and analyze models of complex systems to explore causal mechanisms and use models to generate patterns. StarLogo Nova (SLN), an agent‐based modeling (ABM) environment, enables novice programmers to model a system's individual components and investigate its emergent, collective behavior. Through case analysis of teachers using SLN, we demonstrate how ABM advances thinking about mechanisms generating phenomenon. Teachers who used simulation combined with the decoding of SLN models utilized mechanistic reasoning to make sense of how and why complex phenomenon emerged.

Practitioner Notes

What is already known about this topic

Mechanisms, or causal explanatory processes, are critical in science. Mechanistic reasoning is concerned with why a phenomenon occurs.

Traditionally in science classrooms, teachers incorporate pre‐packaged simulations that limit the ability to understand mechanisms within the simulations.

Agent‐based modeling empowers learners to model at the micro‐level to understand how macro‐level phenomenon emerge in complex systems.

What this paper adds

StarLogo Nova, an agent‐based modeling environment, has features that support mechanistic reasoning.

Using simulation combined with decoding of models in StarLogo Nova promotes mechanistic explanations of why phenomenon occurs.

Teachers are able to scaffold student interactions in StarLogo Nova to support students' mechanistic reasoning.

Implications for practice and/or policy

When using computer simulations in instruction, incorporate decoding of models to engage students in uncovering why a phenomenon occurs.

In professional development programs on scientific modeling, it is important for educators to learn how decoding contributes to students' understanding of mechanisms in models and experience modeling as a scientific practice.
Distinct functions of endogenous cannabinoid system in alcohol abuse disorders
Authors: Basavarajappa Balapal S. , Joshi Vikram , Shivakumar Madhu , Subbanna Shivakumar
Published: July 2019

Δ9‐tetrahydrocannabinol, the principal active component in Cannabis sativa extracts such as marijuana, participates in cell signalling by binding to cannabinoid CB1 and CB2 receptors on the cell surface. The CB1 receptors are present in both inhibitory and excitatory presynaptic terminals and the CB2 receptors are found in neuronal subpopulations in addition to microglial cells and astrocytes and are present in both presynaptic and postsynaptic terminals. Subsequent to the discovery of the endocannabinoid (eCB) system, studies have suggested that alcohol alters the eCB system and that this system plays a major role in the motivation to abuse alcohol. Preclinical studies have provided evidence that chronic alcohol consumption modulates eCBs and expression of CB1 receptors in brain addiction circuits. In addition, studies have further established the distinct function of the eCB system in the development of fetal alcohol spectrum disorders. This review provides a recent and comprehensive assessment of the literature related to the function of the eCB system in alcohol abuse disorders.
Can't see the colony for the bees: behavioural perspectives of biological individuality
Authors: Smith‐Ferguson Jules , Beekman Madeleine
Published: July 2019

The question ‘what is an individual’ does not often arise in studies within the field of behavioural ecology. Generally behavioural ecologists do not think about what makes an individual because they tend to use intuitive working concepts of individuality. Rarely do they explicitly mention how individuality affects their experimental design and interpretation of results. By contrast, the concept of individuality continues to intrigue philosophers of biology. It is interesting that while philosophers of biology debate definitions of individuality, biologists generally use the concept of individuality every day without much thought. Here we review the philosophical approaches to defining biological individuality, and illustrate how the biological individuality concepts used by biologists are affected by their study question and choice of organism. We clarify the behavioural perspective of biological individuality by introducing the concept of the behavioural individual. The notion of the behavioural individual is particularly interesting when explored in less‐conventional study organisms. By including less‐conventional organisms, it becomes clear why the concept of biological individuality is usually intuitive in behavioural ecology.
Does time heal all wounds? Restoring place attachment in Halifax's Point Pleasant Park after Hurricane Juan
Authors: Larter Patrick , Grek‐Martin Jason , Silver Amber
Published: July 2019

On September 29, 2003, Hurricane Juan profoundly altered Halifax's Point Pleasant Park, resulting in feelings of solastalgia (the distress caused by perceived negative changes to a beloved place) as park users mourned the loss of a place that held great significance for the city. Starting in 2008, over 100,000 trees have been planted in order to restore the original Acadian mixed forest to this landscape. Drawing on scholarly literature focused on place attachment and disaster recovery, this paper utilizes interviews (n = 11) and online surveys (n = 79) to determine whether long‐term park users have re‐established positive place attachments in conjunction with the park's restoration. Our results indicate that participants have largely overcome their solastalgic outlook and restored meaningful place attachments to the park. Unexpectedly, our results also suggest that long‐term participants have current place attachments that appear stronger than the place attachments expressed by participating short‐term users, who never experienced the traumatic impact of Hurricane Juan on Point Pleasant Park.
Short‐term high‐fat diet feeding protects from the development of experimental allergic asthma in mice
Authors: Schröder Torsten , Wiese Anna V. , Ender Fanny , Quell Katharina M. , Vollbrandt Tillman , Duhn Jannis , Sünderhauf Annika , Künstner Axel , Moreno‐Fernandez Maria E. , Derer Stefanie , Aherrahrou Zouhair , Lewkowich Ian , Divanovic Senad , Sina Christian , Köhl Jörg , Laumonnier Yves
Published: July 2019

Background

A close association between obesity and asthma has been described. The nature of this association remains elusive, especially with respect to allergic asthma. Controversial findings exist regarding the impact of short‐term high‐fat diet (HFD) feeding on the development of allergic asthma.

Objective

To delineate the impact of short‐term HFD feeding on the development of experimental allergic asthma.

Methods

Female C57BL/6JRJ mice were fed with a short‐term HFD or chow diet (CD) for 12 weeks. Allergic asthma was induced by intraperitoneal OVA/alum sensitization followed by repeated OVA airway challenges. We determined airway hyperresponsiveness (AHR) and pulmonary inflammation by histologic and flow cytometric analysis of immune cells. Furthermore, we assessed the impact of HFD on dendritic cell (DC)‐mediated activation of T cells.

Results

Female mice showed a mild increase in body weight accompanied by mild metabolic alterations. Upon OVA challenge, CD‐fed mice developed strong AHR and airway inflammation, which were markedly reduced in HFD‐fed mice. Mucus production was similar in both treatment groups. OVA‐induced increases in DC and CD4+ T‐cell recruitment to the lungs were significantly attenuated in HFD‐fed mice. MHC‐II expression and CD40 expression in pulmonary CD11b+ DCs were markedly lower in HFD‐fed compared to CD‐fed mice, which was associated in vivo with a decreased T helper (Th) 1/17 differentiation and Treg formation without impacting Th2 differentiation.

Conclusions/clinical relevance

These findings suggest that short‐term HFD feeding attenuates the development of AHR, airway inflammation, pulmonary DC recruitment and MHC‐II/CD40 expression leading to diminished Th1/17 but unchanged Th2 differentiation. Thus, short‐term HFD feeding and associated metabolic alterations may have protective effects in allergic asthma development.
Group cognitive behavioural therapy can reduce stigma and improve treatment compliance in major depressive disorder patients
Authors: Tong Ping , Bu Ping , Yang Yang , Dong Liping , Sun Ting , Shi Yuanhong
Published: July 2019

Aim

The stigma of mental disorders and poor treatment compliance can deprive patients with major depressive disorder (MDD) of receiving standard treatment. This study aimed to clarify whether MDD patients' stigma and treatment non‐compliance issues can be mitigated using group cognitive behavioural therapy (GCBT).

Methods

Eighty‐eight participants with first‐episode MDD were randomly divided into GCBT groups (GCBTs) and control groups (Cs). The Hamilton Rating Scale for Depression (HRSD‐24), Morisky Medication Adherence Scale (MMAS‐8™) and Stigma Scale (SS) were used to evaluate the therapeutic effect on all participants before and after receiving GCBT. Data were assessed at baseline and post‐treatment.

Results

At the baseline, there were no significant differences (in terms of the demographic data of the participants and the scores on HRSD‐24, MMAS‐8™ and SS) between the two groups. After 8 weeks of GCBT, there were significant differences in HRSD‐24 (P < .01), MMAS‐8™ (P < .01), SS (P < .01), treatment compliance (P < .01) and therapeutic effect evaluation based on rate of deduction (P < .05) between the two groups.

Conclusion

GCBT can reduce patients' sense of stigma, improve treatment compliance, effectively alleviate depressive symptoms and promote the recovery of MDD patients.
Negative symptoms in the clinical high‐risk state for psychosis: Connection with cognition and primacy in impacting functioning
Authors: Gerritsen Cory , Maheandiran Margaret , Lepock Jenny , Ahmed Sarah , Kiang Michael , Bagby Robert Michael , Mizrahi Romina
Published: July 2019

Aim

In the clinical high‐risk (CHR) state for psychosis, both negative symptoms and lower cognitive function have been associated with poorer daily functioning. Recent evidence suggests that negative symptoms share overlapping variability with cognition and may partially mediate the relationship between cognition and functioning. However, the nature of this overlap is unknown, and the reverse mediation model remains untested leaving the precise nature of these associations unclear.

Methods

In order to clarify these relationships, a sample of community‐dwelling youth meeting CHR criteria was collected from a specialty CHR clinic (n = 91, mean age = 21, 63% male). Bootstrapping methods were then applied in a mediation analysis to test both negative symptoms and cognition as independent variables and mediating variables predicting social and role functioning in CHR individuals. Canonical correlation analysis was used to characterize the overlapping variability between negative symptoms and cognition.

Results

Support for a primary role of negative symptoms in predicting functioning and cognition was observed. Canonical correlation revealed a single dimension of overlap between the two symptom types (r = .62), represented by a strong correlation between negative symptoms in general and tasks involving verbal working memory, vigilance and social cognition specifically. A single cognitive factor composed primarily of these tasks was found to predict role functioning (adjusted R
2 = .04).

Conclusions

The results highlight the importance of considering specific cognitive mechanisms overlapping with negative symptoms in research and rehabilitative practice in CHR populations, as well as the primary importance of targeting negative symptoms.
Addressing mental health in elite athletes as a vehicle for early detection and intervention in the general community
Authors: Walton Courtney C. , Purcell Rosemary , Rice Simon
Published: July 2019

Recent scientific literature in addition to increased media attention has highlighted the important role of mental health in elite athletes. Often defined by terms such as “mental toughness”, athletes are now becoming more open to discussing the role of anxiety, depression and other psychologically distressing processes that are intertwined with their time both during and after elite sport. In line with this, recent international position statements regarding the mental health of athletes have been released. The current New Hypothesis article follows on from these statements and proposes that further work must be performed to better understand this aspect of elite sport in addition to developing sport‐specific interventions for athletes, their families, and support staff. Furthermore, we propose that by better understanding and treating the mental health of elite athletes a follow‐on effect may occur, whereby help‐seeking in the general community will increase. In particular, young adults who were previously hesitant to seek help may take strength from this shift, maximizing the success of early intervention occurring.
A Mixed Gamble Approach of the Impact of Family Management on Firm's Growth: A Longitudinal Analysis
Authors: Bauweraerts Jonathan , Diaz‐Moriana Vanessa , Arzubiaga Unai
Published: July 2019

We draw upon the socioemotional wealth perspective and the mixed gamble approach to employ a five‐year panel dataset of 223 Belgian private family firms to investigate the relationship between family management and growth, with family management ownership, generational involvement, and the CEO's family status moderating this link. We find an inverted U‐shaped relationship, with growth reaching its maximum at intermediate levels of family management. Additionally, we demonstrate that family management ownership, generational involvement, and the presence of a family CEO hamper the family management‐growth link: all these variables attenuate the positive effect of low to moderate family management, and accentuate the negative impact of high family management. Consequently, our research contributes to a deeper understanding of the relationship between family management and growth.
Improving privacy in health care with an ontology‐based provenance management system
Authors: Can Ozgu , Yilmazer Dilek
Published: July 2019

Provenanc refers to the origin of information. Therefore, provenance is the metadata that record the history of data. As provenance is the derivation history of an object starting from its original source, the provenance information is used to analyse processes that are performed on an object and to track by whom these processes are performed. Thus, provenance shows the trustworthiness and quality of data. In a provenance management system in order to verify the trustworthy of provenance information, security needs must be also fulfilled. In this work, an ontology‐based privacy‐aware provenance management model is proposed. The proposed model is based on the Open Provenance Model, which is a common model for provenance. The proposed model aims to detect privacy violations, to reduce privacy risks by using permissions and prohibitions, and also to query the provenance data. The proposed model is implemented with Semantic Web technologies and demonstrated for the health care domain in order to preserve patients' privacy. Also, an infectious disease ontology and a vaccination ontology are integrated to the system in order to track the patients' vaccination history, to improve the quality of medical processes, the reliability of medical data, and the decision making in the health care domain.
A scheduling algorithm based on the singular value decomposition heuristic method in a distributed manufacturing system
Authors: Shao Xia , Xin Yu
Published: July 2019

Because distributed manufacturing technology is the foundation of modernized production and traditional heuristic methods exhibit problems of high complexity and low efficiency, this paper designs a scheduling algorithm based on the singular value decomposition heuristic (SVDH) method. The algorithm uses the device distribution and the transportation relationship between devices in a distributed manufacturing system. The algorithm takes the sequence relationship between tasks and the distance between devices as the implicit relationship between the task and the device. The algorithm makes use of the implicit relationship to amend the processing time matrix of the task and corrects the processing time matrix that contains the transportation relationship. Singular value decomposition principal component analysis is performed on the corrected processing time to find the most suitable processing device for each process, and an initial solution matrix is established. The heuristic solution is used to optimize the initial solution to find the optimal scheduling result based on the initial solution matrix. The establishment of the initial solution can effectively reduce the computational complexity of the heuristic solution, realize a parallelizing solution, and improve the efficiency of the heuristic solutions. In addition, the SVDH scheduling result has a lower transfer time between devices due to the consideration of the topology of tasks and devices, that is, the transit time. In this paper, the experiments are conducted on the heuristic performance, scheduling results, and transportation time. The experimental results show the advantages of SVDH over general heuristic algorithms in terms of efficiency and transit time.
Modelling hospital readmissions under frailty conditions for healthy aging
Authors: Graña Manuel , Lopez‐Guede Jose Manuel , Irazusta Jon , Labayen Idoia , Besga Ariadna
Published: July 2019

In the current context of an aging population in many developed countries, the issue of healthy aging is at the forefront of the political, scientific, and technological concerns. The frailty accompanying the late years of elderly people (>70 years old) deserves special consideration due to its great economical and personal costs and the workload imposed on the health care system. Hospital readmissions under a short time after hospital discharge are one of the sources of concern, and much effort is being devoted to their prediction for better care of the elder and optimized resource management. In this paper, we consider the prediction of readmissions for patients that are evaluated positively in the frailty scales. The computational experiments are carried out over a gender‐balanced cohort of 645 patients recruited at the University Hospital of Alava. We report machine‐learning prediction results of the readmission before the standard readmission limit of 30 days. We apply an upsampling technique to correct for class imbalance. Results are positive, encouraging further research and the creation of larger cohorts in international efforts.
Crack morphology models for fracture toughness and fatigue strength analysis
Authors: Carpinteri Andrea , Spagnoli Andrea , Terzano Michele
Published: July 2019

Planar cracks represent an approximation, largely adopted in fracture mechanics and fatigue problems, of the physical reality, where cracks feature complex geometric morphologies related to material microstructure, residual stresses, material properties dispersions and so on. In the present paper, firstly a model to describe the influence of roughness and friction of the crack surfaces is reviewed in relation to the resulting near‐tip stress field and the fracture resistance under monotonic loading. Such a model is based on the Distributed Dislocation Technique, and considers a periodic profile of the crack. Then, some approximate theoretical models describing periodically kinked cracks are reviewed in their application to the estimation of fatigue strength of materials. In particular, the influence of crack path meandering on fatigue propagation is analysed by modelling the crack profile as a piecewise linear periodic curve in two dimensions. The same type of model is discussed within the framework of self‐similar fractal geometries. In the paper, emphasis is given to the effect of crack size on the fracture resistance and fatigue strength, where such an effect depends on the ratio between the characteristic length of the crack morphology and the nominal length of the crack itself.
Monitoring of corrosion‐fatigue degradation of grade R4 steel using an electrochemical‐mechanical combined approach
Authors: Canut Felipe A. , Simões Alda M.P. , Reis Luis , Freitas Manuel , Bastos Ivan N. , Castro Fábio C. , Mamiya Edgar N.
Published: July 2019

The study deals with degradation and failure of mooring chains by the combined effect of corrosion and mechanical cyclic stresses on steel. Monitoring of the corrosion‐fatigue damage was carried out using electrochemical assessment during the application of the cyclic mechanical loading on grade R4 martensitic steel specimens, immersed in artificial seawater. The spontaneous potential of the steel specimens and Electrochemical Impedance Spectroscopy measurements were performed to assess the corrosion degradation. Tests conducted under fully reversed stress‐controlled loading have shown earlier failure caused by the corrosive environment when compared with the tests performed in ambient air. The corrosion potential response was used to identify the crack initiation and propagation stages.
Disrupted‐in‐schizophrenia 1 functional polymorphisms and D2/D3 receptor availability: A [11C]‐(+)‐PHNO imaging study
Authors: Dahoun Tarik , Nour Matthew M. , Adams Rick A. , Trossbach Svenja , Lee Sang H. , Patel Hamel , Curtis Charles , Korth Carsten , Howes Oliver D.
Published: July 2019

The disrupted‐in‐schizophrenia 1 (DISC1) protein has been implicated in a range of biological mechanisms underlying chronic mental disorders such as schizophrenia. Schizophrenia is associated with abnormal striatal dopamine signalling, and all antipsychotic drugs block striatal dopamine 2/3 receptors (D2/3Rs). Importantly, the DISC1 protein directly interacts and forms a protein complex with the dopamine D2 receptor (D2R) that inhibits agonist‐induced D2R internalisation. Moreover, animal studies have found large striatal increases in the proportion of D2R receptors in a high affinity state (D2highR) in DISC1 rodent models. Here, we investigated the relationship between the three most common polymorphisms altering the amino‐acid sequence of the DISC1 protein (Ser704Cys (rs821616), Leu607Phe (rs6675281) and Arg264Gln (rs3738401)) and striatal D2/3R availability in 41 healthy human volunteers, using [11C]‐(+)‐PHNO positron emission tomography. We found no association between DISC1 polymorphisms and D2/3R availability in the striatum and D2R availability in the caudate and putamen. Therefore, despite a direct interaction between DISC1 and the D2R, none of its main functional polymorphisms impact striatal D2/3R binding potential, suggesting DISC1 variants act through other mechanisms.
Case Report: Shortest Course of Pediatric Paroxysmal Hemicrania
Authors: Ishii Ryotaro , Fukazawa Ryosuke , Takezawa Hidesato , Fujii Akihiro
Published: July 2019

Paroxysmal hemicrania (PH) is a rare primary headache disorder, especially among children. We describe herein a case with the shortest course of pediatric PH among previously reported cases, and the first case report of Japanese pediatric PH. An 11‐year‐old boy was referred to our clinic by his primary care physician for a headache evaluation. He had been complaining of severe, sharp, pulsating headache for 5 days. Attacks were restricted to the left side with a duration ranging from 2 to 20 minutes, 20‐30 times a day. Attacks were associated with left autonomic symptoms (conjunctival injection, lacrimation, nasal congestion, eyelid edema, and ptosis). Two days after we prescribed indomethacin at 0.9 mg/kg/day, the patient was headache free. He stopped taking indomethacin 14 days after consultation because of drug eruptions. As of the time of writing, more than 1 year later, he has experienced no recurrence of headache. This case indicates the importance of improving awareness among general doctors regarding PH in children, and of conducting further investigations about low‐dose, short‐term indomethacin treatment.
CRISPR/dCas9‐mediated activation of multiple endogenous target genes directly converts human foreskin fibroblasts into Leydig‐like cells
Authors: Huang Hua , Zou Xiangyu , Zhong Liang , Hou Yanping , Zhou Jin , Zhang Zhiyuan , Xing Xiaoyu , Sun Jie
Published: July 2019

Recently, Leydig cell (LC) transplantation has been revealed as a promising strategy for treating male hypogonadism; however, the key problem restricting the application of LC transplantation is a severe lack of seed cells. It seems that targeted activation of endogenous genes may provide a potential alternative. Therefore, the aim of this study was to determine whether targeted activation of Nr5a1, Gata4 and Dmrt1 (NGD) via the CRISPR/dCas9 synergistic activation mediator system could convert human foreskin fibroblasts (HFFs) into functional Leydig‐like cells. We first constructed the stable Hsd3b‐dCas9‐MPH‐HFF cell line using the Hsd3b‐EGFP, dCas9‐VP64 and MS2‐P65‐HSF1 lentiviral vectors and then infected it with single guide RNAs. Next, we evaluated the reprogrammed cells for their reprogramming efficiency, testosterone production characteristics and expression levels of Leydig steroidogenic markers by quantitative real‐time polymerase chain reaction or Western blotting. Our results showed that the reprogramming efficiency was close to 10% and that the reprogrammed Leydig‐like cells secreted testosterone rapidly and, more importantly, responded effectively to stimulation with human chorionic gonadotropin and expressed Leydig steroidogenic markers. Our findings demonstrate that simultaneous targeted activation of the endogenous NGD genes directly reprograms HFFs into functional Leydig‐like cells, providing an innovative technology that may have promising potential for the treatment of male androgen deficiency diseases.
Patient‐assigned health utility values for controlled and uncontrolled pemphigus vulgaris and foliaceus
Authors: Hajdu K. , Brodszky V. , Stalmeier P.F.M. , Ruzsa G. , Tamási B. , Gulácsi L. , Péntek M. , Sárdy M. , Bata‐Csörgő Z. , Kinyó Á. , Szegedi A. , Rencz F.
Published: July 2019

Background

The assessment of health‐related quality of life (HRQoL) in patients with pemphigus is now of increasing interest due to the availability of highly effective new therapies. Preference‐based HRQoL values or health utilities required for medical and financial decision‐making are not yet available directly from pemphigus patients.

Objective

To obtain health utility values for current health and hypothetical health states from the perspective of pemphigus patients.

Methods

A cross‐sectional questionnaire survey was carried out with pemphigus patients. Disease severity was rated by Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). Patients were asked to evaluate their current health as well as three common hypothetical pemphigus health states [uncontrolled pemphigus vulgaris (PV), uncontrolled pemphigus foliaceus (PF) and controlled PV/PF] by using composite time trade‐off (cTTO). Multiple regression was applied to explore determinants of utility values.

Results

Responses of 108 patients (64.8% women, mean age 57.4 years) were analysed. Mean ABSIS score was 11.6. The mean utility values for the hypothetical uncontrolled PV, uncontrolled PF and controlled PV/PF health states were 0.41, 0.52 and 0.66 with cTTO. The mean cTTO scores for current health were higher compared with the hypothetical health states (0.76; P < 0.001). Patients with higher ABSIS, worse pain intensity scores and those having a caregiver reported lower utility values for current health (P < 0.05).

Conclusions

In pemphigus, HRQoL impairment expressed in utility values seems to be considerable, especially in comparison with other chronic dermatological conditions (e.g. psoriasis, atopic eczema, chronic hand eczema). These health utilities inform physicians, policymakers and funders about the overall extent of health loss in pemphigus and provide evidence to guide medical decisions and cost‐effectiveness analyses of treatment strategies. Future research is needed to evaluate the caregiver burden in pemphigus.
Lichen planus: a comprehensive evidence‐based analysis of medical treatment
Authors: Husein‐ElAhmed H. , Gieler U. , Steinhoff M.
Published: July 2019

Lichen planus (LP) is a chronic‐relapsing inflammatory skin disease. Although many drugs have been used for the management of LP, some of them lack the backup by strong therapeutic evidence, while others are not suitable for some patients due to safety profile issues. The aim of this study was to review the recent status of available medical therapies for LP to help physicians make better decisions upon best medical practice while facing patients with this condition. A review of published articles on management of LP was conducted with the MEDLINE and PubMed databases. The quality of the evidence was graded as high, moderate, low or very low. A total of 1366 articles were retrieved, and 219 (16%) were included in the final analysis. Twenty‐one different treatment modalities were analysed. The quality of evidence was high for topical steroid and calcineurin inhibitor, while it was moderate for oral steroids. All the other modalities reached low or very low quality of evidence. Topical steroids and calcineurin inhibitors are the current first‐line therapies, while for other therapies the strength of recommendation is not so evident. Unfortunately, larger randomized, controlled trials to support the efficacy, safety and tolerability of other therapies in LP are lacking, and many of them are recommended based on studies with small sample sizes, lack of standardized outcome measures or lack of controlled duration or even in anecdotal evidence. Thus, large‐scale randomized clinical trials are still warranted to establish the exact benefits of other topical treatments, phototherapy, immunosuppressant and new immunomodulators for an optimized treatment of LP.
Influence of experimental set‐up and methodology for measurements of metabolic rates and critical swimming speed in Atlantic salmon Salmo salar
Authors: Hvas Malthe , Oppedal Frode
Published: July 2019

In this study, swim‐tunnel respirometry was performed on Atlantic salmon Salmo salar post‐smolts in a 90 l respirometer on individuals and compared with groups or individuals of similar sizes tested in a 1905 l respirometer, to determine if differences between set‐ups and protocols exist. Standard metabolic rate (SMR) derived from the lowest oxygen uptake rate cycles over a 20 h period was statistically similar to SMR derived from back extrapolating to zero swim speed. However, maximum metabolic rate (MMR) estimates varied significantly between swimming at maximum speed, following an exhaustive chase protocol and during confinement stress. Most notably, the mean (±SE) MMR was 511 ± 15 mg O2 kg−1 h−1 in the swim test which was 52% higher compared with 337 ± 9 mg O2 kg−1 in the chase protocol, showing that the latter approach causes a substantial underestimation. Performing group respirometry in the larger swim tunnel provided statistically similar estimates of SMR and MMR as for individual fish tested in the smaller tunnel. While we hypothesised a larger swim section and swimming in groups would improve swimming performance, Ucrit was statistically similar between both set‐ups and statistically similar between swimming alone v. swimming in groups in the larger set‐up, suggesting that this species does not benefit hydrodynamically from swimming in a school in these conditions. Different methods and set‐ups have their own respective limitations and advantages depending on the questions being addressed, the time available, the number of replicates required and if supplementary samplings such as blood or gill tissues are needed. Hence, method choice should be carefully considered when planning experiments and when comparing previous studies.
The ARRIVE Trial: Interpretation from an Epidemiologic Perspective
Authors: Carmichael Suzan L. , Snowden Jonathan M.
Published: July 2019

The findings of the ARRIVE trial (A Randomized Trial of Induction Versus Expectant Management) were recently published. This multisite randomized trial was designed to provide evidence regarding whether labor induction or expectant management is associated with increased adverse perinatal outcomes and risk of cesarean birth among healthy nulliparous women at term. The trial reported that the primary outcome, a composite of adverse neonatal outcomes, was not significantly different between the 2 groups; the principal secondary outcome, cesarean birth, was significantly more common among women whose pregnancy was expectantly managed than among women whose labor was induced at 39 weeks. These results have the potential to change existing practice. Several aspects of the study design may influence its potential internal and external validity and should be considered in order to make sound causal inferences from this trial, which will in turn affect how its findings are translated to practice. Although chance and confounding are of minimal concern, given the sample size and randomization used in the study, selection bias may be a concern. Studies are vulnerable to selection bias when the sample population differs from eligible nonparticipants, including in randomized controlled trials. External validity is defined as the extent to which the study population and setting are representative of the larger source population the study intends to represent. External validity may be limited given the characteristics of the women enrolled in the ARRIVE trial and the practice settings where the study was conducted. This brief report provides concrete suggestions for further analyses that could help solidify conclusions from the trial, and for further research questions that will continue advancement toward answering this complex question of how best to manage labor and birth decisions at full term among low‐risk women.
Cellular models of alpha‐synuclein toxicity and aggregation
Authors: Delenclos Marion , Burgess Jeremy D. , Lamprokostopoulou Agaristi , Outeiro Tiago F. , Vekrellis Kostas , McLean Pamela J.
Published: July 2019

Misfolding and aggregation of alpha‐synuclein (α‐synuclein) with concomitant cytotoxicity is a hallmark of Lewy body related disorders such as Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Although it plays a pivotal role in pathogenesis and disease progression, the function of α‐synuclein and the molecular mechanisms underlying α‐synuclein‐induced neurotoxicity in these diseases are still elusive. Many in vitro and in vivo experimental models mimicking α‐synuclein pathology such as oligomerization, toxicity and more recently neuronal propagation have been generated over the years. In particular, cellular models have been crucial for our comprehension of the pathogenic process of the disease and are beneficial for screening of molecules capable of modulating α‐synuclein toxicity. Here, we review α‐synuclein based cell culture models that reproduce some features of the neuronal populations affected in patients, from basic unicellular organisms to mammalian cell lines and primary neurons, to the cutting edge models of patient‐specific cell lines. These reprogrammed cells known as induced pluripotent stem cells (iPSCs) have garnered attention because they closely reproduce the characteristics of neurons found in patients and provide a valuable tool for mechanistic studies. We also discuss how different cell models may constitute powerful tools for high‐throughput screening of molecules capable of modulating α‐synuclein toxicity and prevention of its propagation.

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This article is part of the Special Issue “Synuclein”.