bluuebunny/crossref_metadata_2025 huggingface dataset:
The quality of reporting RCT abstracts in four major orthodontics journals for the period 2012–2017
Authors: Alharbi Fahad , Almuzian Mohammed
Published: July 2019

Introduction:

Clear reporting of the abstracts of randomised controlled trials (RCTs) facilitates the assessment and identification of such trials.

Aim:

To assess whether authors in the orthodontic field of research currently report RCT abstracts adequately, as defined by the Consolidated Standards of Reporting Trials (CONSORT) statement.

Design:

An observational retrospective study.

Methods:

Electronic searches with supplementary hand searching were undertaken to identify RCTs published in (1) American Journal of Orthodontics and Dentofacial Orthopedics ( AJO-DO), (2) Angle Orthodontist ( AO), (3) European Journal of Orthodontics ( EJO) and (4) Journal of Orthodontics ( JO) for the period from January 2012 to December 2017. The completeness of the abstract reporting was evaluated using a modified CONSORT for abstract statement checklist.

Results:

A total of 3678 articles were retrieved, but only 224 RCT abstracts were identified and assessed. A high volume of RCTs were published with either the AO (39%) or AJO-DO (32%); the majority of the RCT abstracts (93.6%) were structured. The mean overall abstract reporting quality score was 69.1% (95% confidence interval = 67.5–70.7). In relation to individual quality items, the majority of the RCT abstracts (range = 96–100%) demonstrated clear reporting of the author/contact details, trial design, participants, interventions, objectives, outcomes, number of participants randomised to each group, recruitment, results and conclusions. However, reporting of the title, trial registration, funding and number of analysed participants were only moderately adequate and reporting of the assessment of blinding and adverse events were the least-reported items in the identified abstracts.

Conclusions:

As several CONSORT reporting items were poorly reported, it is the responsibility of authors, referees and editors alike to ensure that the CONSORT guidelines are followed.
Assessing financial capability among people with disabilities
Authors: McGarity Stephen V , Okech David O , Risler Edwin , Clees Thomas J
Published: July 2019

People with disabilities are five times more likely to experience poverty than the general population, yet very little is known about how financial capability can help increase their financial well-being. Using secondary data from the 2015 National Financial Capabilities Study, this study used path analysis to test Sherraden’s theoretical model of building financial capability on a nationally representative sample of people with disabilities. This included assessing how variables of ability (i.e., financial literacy) and variables of opportunity (i.e., financial inclusion) combine to improve one’s financial well-being and stability.

Findings

Multiple fit indices suggested that the data fit the path model well: χ2 = 37.73 (14), p = .001, RMSEA = 0.04 (90% CI: 0.03–0.05), TLI = 0.97, CFI = 0.99. Findings indicate that financial literacy and financial access both impact the financial well-being in this sample of people with disabilities ( N = 1232). Also, access to financial products moderated financial literacy to increase its impact. This study empirically substantiated the selected financial capability framework.

Applications

Implications of this study are targeted toward social work researchers and practitioners. There have been very few empirical studies on building financial capability among people with disabilities, so this article serves as a foundation for much needed research in this area while also filling a gap in the extant literature. Additionally, disability case managers will find this research useful, as it provides evidence for practical steps they can take to help their clients work toward achieving financial well-being.
Embodied Social Work Practice Within Risk Society
Authors: Smeeton Joe , O’Connor Patrick
Published: July 2019

This paper critically discusses the limitations of theorising social work from psychological and sociological perspectives and argues that phenomenology offers more opportunity to understand the embodied experiences of service users and social workers themselves. The paper argues that psychology and sociology have a limited analysis of being-in-the-world, which ought to be social work’s primary consideration. The paper offers an overview of the sociology of risk before embarking on an extensive description and discussion of Heidegger’s and Merleau-Ponty’s phenomenology applied to the lived experience of child protection social workers working within risk society. The argument is put that phenomenology is a useful tool for understanding the lived experience of social work practitioners.

Findings:

The authors conclude that embodied social work practice containing fear and anxiety can be thought of as akin to taking part in extreme risk sports and that this is an unhealthy experience that is likely to skew decision-making and adversely affect the lives of social workers and service users.

Applications:

The authors argue that phenomenology can enhance understanding of practice and decision-making and offers insights into the lived experience of social workers. Phenomenology is useful for helping social workers negotiate risk-saturated environments, through a focus on meaning.
On-board knock probability map learning–based spark advance control for combustion engines
Authors: Zhang Yahui , Shen Xun , Wu Yuhu , Shen Tielong
Published: July 2019

This article presents an on-board map learning–based spark advance control framework for combustion engines. The proposed control framework addresses the knock probabilistic constrained thermal efficiency optimization problem with three layers. First, in the upper layer, maps of knock event distribution and thermal efficiency are learned with manifold pressure and combustion phase as inputs. Second, the middle layer generates the knock probability constrained optimal combustion phase reference that is subsequently tracked by a hypothesis test-based feedback controller. Third, the lower layer employs a partial likelihood-based knock controller that retards the spark advance in case of the frequent knock events. The key contributions of this work are the three-layer control framework and the knock event distribution map learning in the upper layer. The knock event is supposed to obey binomial distribution, and the distribution is modeled by beta distribution and learned in the perspective of Bayesian learning. Moreover, the normalization algorithm is proposed for online feedfoward map update. The proposed map learning–based spark advance control framework is experimentally validated in a test bench equipped with a spark-ignition engine.
Understanding the training and education needs of homecare workers supporting people with dementia and cancer: A systematic review of reviews
Authors: Cunningham Nicola , Cowie Julie , Watchman Karen , Methven Karen
Published: July 2019

Many people with dementia, supported by family carers, prefer to live at home and may rely on homecare support services. People with dementia are also often living with multimorbidities, including cancer. The main risk factor for both cancer and dementia is age and the number of people living with dementia and cancer likely to rise. Upskilling the social care workforce to facilitate more complex care is central to national workforce strategies and challenges. Training and education development must also respond to the key requirements of a homecare workforce experiencing financial, recruitment and retention difficulties. This systematic review of reviews provides an overview of dementia and cancer training and education accessible to the homecare workforce. Findings reveal there is a diverse range of training and education available, with mixed evidence of effectiveness. Key barriers and facilitators to effective training and education are identified in order to inform future training, education and learning development for the homecare workforce supporting people with dementia and cancer.
Localism and police governance in England & Wales: Exploring continuity and change
Authors: Jones Trevor , Lister Stuart
Published: July 2019

This article develops further criminological understandings of ‘localism’ in police governance and contributes to broader theoretical discussions about ‘governance’ in contemporary policing, via a critical analysis of major recent law and policy reforms in England & Wales. Recent legislation has brought important changes to the balance of constitutional-legal powers and the institutional architecture of police governance. However, we argue that for several reasons it is problematic to interpret these developments in straightforward terms of greater ‘localization’. First, in so far as there has been a decentralization of control, this represents a growth of ‘regional’ rather than ‘local’ auspices of power. Second, there is widespread evidence of continuing interventionism by ‘the centre’, asserting strong influences on local policing via a range of national bodies. Third, important developments in the wider context of police policy-making – most importantly the conditions of austerity – have circumscribed the capacity of Commissioners to set their own policy agendas and resulted in a retrenchment of policing provision at the most ‘localized’ geographical units of neighbourhoods. Indeed, the combination of decentralizing formal responsibility for policing policy and restrictive central financial controls amounts in practice to a ‘devolution of blame’ by the centre for falling service standards. Finally, we argue that the growing complexity and fragmentation of police governance cannot be captured adequately by ‘vertical’ analysis of central–local relations. Although central influences remain predominant, policing policy networks have become more diverse, with important developments at ‘horizontal’ levels locally, regionally and nationally. Within this more fragmented governance framework, central influences continue to drive local policing, but primarily via a range of ‘arm’s length’ institutions and techniques.
City of Refuge or Digital Order? Refugee Recognition and the Digital Governmentality of Migration in the City
Authors: Georgiou Myria
Published: July 2019

This article analyses the digital governmentality of the city of refuge. It shows how digital infrastructures support refugees’ new life in the European city, while also normalizing the conditionality of their recognition as humans and as citizens-in-the-making. Research in Athens, Berlin, and London revealed the city as a vital but fierce space for refugees to claim, and sometimes find recognition that the nation often denies. A multimethod qualitative study with refugees and civil society actors at the aftermath of Europe’s “migration crisis” recorded urban cultures of hope for cities that are hospitable and open. Yet, it also recorded conditional welcoming that sets strict requirements for newcomers’ recognition as more than a category of external Others that need to prove their “right to have rights.” As shown, a digital order requires a performed refugeeness as precondition for recognition: that is, a swift move from abject vulnerability to resilient individualism.
Research on the flexible multibody dynamics of lifting mechanism of neutron spectrometer sample table
Authors: Li Yang , Wu Yun-xin , Gong Hai , Peng Fu-xia
Published: July 2019

First, the lifting mechanism of neutron spectrometer sample table was designed. Then, every single part flexible multibody models and all parts flexible multibody model were built using ANSYS and ADAMS. Finally, the single part flexible multibody models and all parts flexible multibody model were analyzed when lifting mechanism reached the highest position and sliding table was moving along the X- or Y-axis with 1 ton load. The results indicate that the average deformation along Z direction is maximum among all directions of sliding table center, which is 30.1 μm. Outer cylinder takes up the largest proportion of the deformation in X direction, which is 75.8%, middle cylinder takes up the largest proportion of the deformation in Y direction, which is 91.32%, and inner cylinder takes up the largest proportion of the deformation in Z direction, which is 89.36%. Among the eight guide rails of lifting mechanism, four guide rails between the inner and middle cylinders are under uniform load, and the other four guide rails between middle and outer cylinder are under non-uniform load. The findings of the research could guide the optimal design of the neutron spectrometer sample table.
Determination of the conductivity and thickness of conductive layers on conductive base materials
Authors: Burkhardt John
Published: July 2019

An eddy current technique for the simultaneous determination of the layer thickness and conductivity of a uniform conductive layer on a known conductive base material is presented. Layer thickness and conductivity are determined by fitting apparent conductivity measurements taken on the surface of the part at a discrete set of frequencies to a calibration volume. The calibration volume is constructed from apparent conductivity measurements taken on a set of known layer materials, of various known thicknesses, as a function of frequency. Experimental results that support the technique are presented.
Baicalin modulates apoptosis via RAGE, MAPK, and AP-1 in vascular endothelial cells during Haemophilus parasuis invasion
Authors: Fu Shulin , Zhao Wenhua , Xiong Chunhong , Guo Ling , Guo Jing , Qiu Yinsheng , Hu Chien-An Andy , Ye Chun , Liu Yu , Wu Zhongyuan , Hou Yongqing
Published: July 2019

Glässer’s disease, caused by Haemophilus parasuis, is a chronic disease related to an inflammatory immune response. Baicalin exerts important biological functions. In this study, we explored the protective efficacy of treatment with baicalin and the potential mechanism of activation of the MAPK signaling pathway in porcine aortic vascular endothelial cells (PAVECs) induced by H. parasuis. H. parasuis stimulated expression of receptor for advanced glycation end products, induced a significant increase in the level of protein kinase-α and protein kinase-δ phosphorylation, and significantly up-regulated ERK, c-Jun N-terminal kinase, and p38 phosphorylation in PAVECs. H. parasuis also up-regulated the levels of apoptotic genes ( Bax, C-myc, and Fasl) and the expression levels of c-Jun and c-Fos, and induced S-phase arrest in PAVECs. However, treatment with baicalin inhibited expression of RAGE, suppressed H. parasuis-induced protein kinase-α and protein kinase-δ phosphorylation, reduced ERK, c-Jun N-terminal kinase, and p38 phosphorylation, down-regulated apoptotic genes ( Bax, C-myc, and Fasl), attenuated phospho-c-Jun production from the extracellular to the nuclei, and reversed S-phase arrest in PAVECs. In conclusion, baicalin treatment inhibited the MAPK signaling pathway, thereby achieving its anti-inflammatory responses, which provides a new strategy to control H. parasuis infection.
Parkinson’s-adapted cognitive stimulation therapy: a pilot randomized controlled clinical trial
Authors: Leroi Iracema , Vatter Sabina , Carter Lesley-Anne , Smith Sarah J. , Orgeta Vasiliki , Poliakoff Ellen , Silverdale Monty A. , Raw Jason , Ahearn David J. , Taylor Christine , Rodda Joanne , Abdel-Ghany Tarek , McCormick Sheree A.
Published: July 2019

Cognitive stimulation therapy (CST) is widely used with people with dementia, but there is no evidence of its efficacy in mild cognitive impairment or dementia in Parkinson’s disease (PD-MCI; PDD) or dementia with Lewy bodies (DLB). We aimed to explore the impact of ‘CST-PD’, which is home-based, individualized CST adapted for this population. In a single-blind, randomized controlled exploratory pilot trial (RCT), we randomized 76 participant–dyads [PD-MCI ( n = 15), PDD ( n = 40), DLB ( n = 21) and their care partners] to CST-PD or treatment as usual (TAU). CST-PD involves home-based cognitively stimulating and engaging activities delivered by a trained care partner. Exploratory outcomes at 12 weeks included cognition (Addenbrooke’s Cognitive Evaluation; ACE-III), neuropsychiatric symptoms and function. In care partners, we assessed burden, stress and general health status. Relationship quality and quality of life were assessed in both dyad members. At 12 weeks, the ACE-III showed a nonstatistically significant improvement in the CST-PD group compared with the TAU group, although neuropsychiatric symptoms increased significantly in the former. In contrast, care partners’ quality of life ( d = 0.16) and relationship quality (‘satisfaction’, d = 0.01; ‘positive interaction’, d = 0.55) improved significantly in the CST-PD group, and care burden ( d = 0.16) and stress ( d = 0.05) were significantly lower. Qualitative findings in the CST-PD recipients revealed positive ‘in the moment’ responses to the intervention, supporting the quantitative results. In conclusion, care-partner-delivered CST-PD may improve a range of care-partner outcomes that are important in supporting home-based care. A full-scale follow-up RCT to evaluate clinical and cost effectiveness is warranted.
The decision to drop the case in the new EPPO’s regulation: Res Iudicata or transfer of competence?
Authors: Caianiello Michele
Published: July 2019

This article discusses one of the most important decisions the European Public Prosecutor’s Office (EPPO) can take: the decision to drop a case. When this happens, the case will either be referred to national prosecutors or to the European Anti-Fraud Office (OLAF) or dismissed entirely. Why is this an important decision? Because it means the EPPO declines to prosecute, prosecution being (along with investigation) its very raison d’être. This is why it is important to understand how and when the EPPO may drop a case. In this respect, the EPPO Regulation (adopted on 12 October 2017) pursues two goals: first, it seeks to leave the EPPO a certain margin of discretion when deciding whether to drop a case; secondly, however, it seeks to limit that discretion in order to reduce the risk of decisions that are arbitrary or based on irrelevant considerations. This article argues that this strikes an acceptable balance between two different legal traditions: the ones inspired by the strict legality principle, such as Italy and Germany, and those inspired by the principle of opportunity, such as France or England and Wales. The article further explores how this balance is consistent with the emerging principles of international criminal law, where international tribunals try the most serious crimes only.
Exploring the Extent in the Visual Field of the Honeycomb and Extinction Illusions
Authors: Bertamini Marco , Cretenoud Aline F. , Herzog Michael H.
Published: July 2019

There are situations in which what is perceived in central vision is different to what is perceived in the periphery, even though the stimulus display is uniform. Here, we studied two cases, known as the Extinction illusion and the Honeycomb illusion, involving small disks and lines, respectively, presented over a large extent of the visual field. Disks and lines are visible in the periphery on their own, but they become invisible when they are presented as part of a pattern (grid). Observers ( N = 56) adjusted a circular probe to report the size of the region in which they had seen the lines or the disks. Different images had black or white lines/disks, and we included control stimuli in which these features were spatially separated from the regular grid of squares. We confirmed that the illusion was experienced by the majority of observers and is dependent on the interaction between the elements (i.e., the lines/disks have to be near the squares). We found a dissociation between the two illusions in the dependence on contrast polarity suggesting different mechanisms. We analysed the variability between individuals with respect to schizotypical and autistic-spectrum traits (short version of the Oxford-Liverpool Inventory of Feelings and Experiences [O-LIFE] questionnaire and the Autistic Quotient, respectively) but found no significant relationships. We discuss how illusions relative to what observers are aware of in the periphery may offer a unique tool to study visual awareness.
Efficacy and safety of Gelsectan for diarrhoea‐predominant irritable bowel syndrome: A randomised, crossover clinical trial
Authors: Trifan Anca , Burta Ovidiu , Tiuca Nicoleta , Petrisor Diana Corina , Lenghel Augustin , Santos Javier
Published: July 2019

Background

Irritable bowel syndrome (IBS) is highly prevalent and presents a clinical challenge. Gelsectan is a medical device containing xyloglucan (XG), pea protein and tannins (PPT) from grape seed extract, and xylo‐oligosaccharides (XOS), which act together to protect and reinforce the intestinal barrier.

Objective

The objective of this study is to evaluate the efficacy and safety of XG + PPT + XOS in patients with diarrhoea‐predominant IBS (IBS‐D).

Methods

In this double‐blind study, 60 patients were randomly assigned to receive XG + PPT + XOS or placebo for 28 days, then crossed over to the alternative treatment. Patients were followed for 60 days.

Results

At Day 28, a significantly higher proportion of patients starting treatment with XG + PPT + XOS than placebo (87 vs 0%; p = 0.0019) presented normal stools (Bristol Stool Form Scale type 3−4). At Day 56, a significantly higher proportion of patients who crossed over to XG + PPT + XOS than placebo (93% vs 23%; p = 0.0001) presented normal stools. In the group allocated to receive XG + PPT + XOS after placebo, benefits of XG + PPT + XOS were maintained during follow‐up. Subjective assessments of abdominal pain, bloating, quality of life and general health indicated significant improvement with XG + PPT + XOS over placebo. There were no related adverse events.

Conclusion

XG + PPT + XOS effectively controlled diarrhoea and alleviated clinical symptoms in patients with IBS‐D, and was well tolerated.
Sexual and Reproductive Health Needs of Adolescent Girls and Young Women in Sub-Saharan Africa: Research, Policy, and Practice
Authors: Naidoo Kammila , Adeagbo Oluwafemi , Pleaner Melanie
Published: July 2019

Seventeen articles make up this special collection, covering a range of different, but cross-cutting themes. These highlight contemporary concerns in African research and scholarship about the factors configuring the sexual and reproductive health needs of adolescent girls and young women (AGYW). The articles interrogate contextual and cultural impediments, problematic representations, perceptions of vulnerabilities and rights, experiences of gender-based violence, coercive sex, unplanned motherhood—and agency, resistance and strategic interventions. While a diverse range of issues, theories, and methodologies are evident, all the articles reflect on how the circumstances of young women in Africa can be effectively improved to engender empowerment, good health, and personal and sexual autonomy.
The Management of Reputational Risks in Banks: Findings From Germany and Switzerland
Authors: Zaby Simon , Pohl Michael
Published: July 2019

This article identifies reputation-risk-relevant factors for banks, and the focus will be placed on the development of an indicator-based model for the assessment of reputation. Requirements and insights are based on a survey of credit institutions in Germany and Switzerland, which have been predominantly affected during the financial crisis by aptly nascent risks and which are thereby also partially affected even today. Reputation level can be considered as a temporally dynamical phenomenon which predominantly develops depending on the changes in the reputation drivers and expectations of the groups of stakeholders. This control parameter can be determined with the aid of Reputation Index Points (RIP). Efficient reputation risk management can, in the future, help prevent negative spillover effects from banks which face difficulties from the society or the taxpayers.
Bubbles in the Box: Recurrent Pneumothorax From Bronchopleural Fistula in Rheumatoid Arthritis
Authors: Taha Ahmed , Hazam Randa , Tseng Jim , Nahapetyan Lusine , Alzeerah Masoud , Islam Asm
Published: July 2019

When considering rheumatoid arthritis (RA)-associated pulmonary diseases, interstitial lung disease and pleural disease are the most common RA-associated pulmonary manifestations while spontaneous pneumothorax and bronchopleural fistula (BPF) are among the extremely rare ones. To the best of our knowledge, all the previous reports of RA-associated BPFs were attributed to peripherally located pulmonary nodules that necrotized, burst into the pleural cavity, and eventually lead to the fistula formation. However, we hereby present the first case of BPF in an RA patient that formed in the absence of any underlying rheumatic pulmonary nodules. Additionally, our patient was on chronic methotrexate therapy, and there are no data in the literature that suggest methotrexate-induced parenchymal lung disease can predispose to BPF formation. Our report is the first to introduce a probe to further investigate this association.
Safety assessment of Gossence™ (galactooligosaccharides): Genotoxicity and general toxicity studies in Sprague Dawley rats
Authors: Jain Manish , Narayanan S , Tiwari Deepika Pandey , Ranjan Bibhuti , Jadhav Avinash , Venkataramulu Deepa , Chandrayan Govind , Jayarao Chaitra , Bhoite Prabhakar , Krishnappa Mohan , Dubey Ashok Kumar
Published: July 2019

Galactooligosaccharides (GOS) used as prebiotics are one of the major constituents of the infant milk formulas. GOS (Gossence™) is produced by a patented process of biotransformation of lactose; hence toxicology studies were carried out to assess its safety. The objective of the present study was to evaluate the general and genetic toxicity of Gossence™. In 14-day and subchronic (90-day) oral toxicity studies in Sprague Dawley rats, daily administration of GOS at dose levels of 1000, 2000, or 5000 mg/kg (equivalent to 1347, 2694, and 6735 mg/kg/day of Gossence™, respectively) did not cause any mortality, or clinical signs, and changes in body weights, feed consumption, hematology, clinical chemistry, and urinalysis. In 90-day study, no changes in ophthalmological and neurological findings were observed. Significant increases in the cecum weights (with and/or without content) at dose levels of ≥2000 mg/kg were observed in both 14-day and 90-day studies. Based on the results of 90-day study, the no-observed-adverse-effect-level for GOS is 5000 mg/kg/day which is equivalent to 6735 mg Gossence™/kg/day. In the bacterial reverse mutation test, there was no significant increase in the mean numbers of revertants at the tested concentrations. Gossence™ was not mutagenic up to 5000 µg/plate. In chromosomal aberration test, there was no statistically significant increase in the number of percent aberrant metaphase for the Gossence™. Gossence™ is non-clastogenic (negative) in the in vitro chromosomal aberration test using human peripheral blood lymphocyte during short and prolonged treatment.
Regional Lymph Node Enlargement in Clinically Severe Cherubism
Authors: Chen Wongworawat Yan , Jack Daniel , Inman Jared C , Abdelhalim Fouad , Cobb Camilla , Zuppan Craig William , Raza Anwar
Published: July 2019

Cherubism is a rare benign autosomal dominant disorder characterized by progressive, painless, bilateral enlargement of the mandible and/or maxilla because of bone replacement by fibrotic stromal cells and osteoclast-like cells forming multilocular cysts. The lesions typically stabilize and regress after puberty. We present a 14-year-old male with severe familial cherubism. Bilateral mandibular enlargement began around age 4 and progressed until puberty, affecting his speech and mastication without subsequent involution. Composite mandibulectomy and mandible reconstruction with fibula free flap technique improved functionality and cosmesis. Histology was consistent with the diagnosis of cherubism, showing large areas of bland spindle-cell fibrous tissue and moderately abundant collagen and multiple nodules of giant cell-rich tissue resembling central giant cell granuloma. Regional lymph nodes were sampled due to enlargement, demonstrating hemosiderin-laden macrophages and basophilic laminated concretions localized to the cortical interfollicular space and along the peripheral follicular marginal zone, findings which have not been previously reported.
PRDM16s transforms megakaryocyte-erythroid progenitors into myeloid leukemia–initiating cells
Authors: Hu Tianyuan , Morita Kiyomi , Hill Matthew C. , Jiang Yajian , Kitano Ayumi , Saito Yusuke , Wang Feng , Mao Xizeng , Hoegenauer Kevin A. , Morishita Kazuhiro , Martin James F. , Futreal P. Andrew , Takahashi Koichi , Nakada Daisuke
Published: July 2019

Oncogenic mutations confer on cells the ability to propagate indefinitely, but whether oncogenes alter the cell fate of these cells is unknown. Here, we show that the transcriptional regulator PRDM16s causes oncogenic fate conversion by transforming cells fated to form platelets and erythrocytes into myeloid leukemia stem cells (LSCs). Prdm16s expression in megakaryocyte-erythroid progenitors (MEPs), which normally lack the potential to generate granulomonocytic cells, caused AML by converting MEPs into LSCs. Prdm16s blocked megakaryocytic/erythroid potential by interacting with super enhancers and activating myeloid master regulators, including PU.1. A CRISPR dropout screen confirmed that PU.1 is required for Prdm16s-induced leukemia. Ablating PU.1 attenuated leukemogenesis and reinstated the megakaryocytic/erythroid potential of leukemic MEPs in mouse models and human AML with PRDM16 rearrangement. Thus, oncogenic PRDM16s expression gives MEPs an LSC fate by activating myeloid gene regulatory networks.
Epigenome-wide association study of lung function level and its change
Authors: Imboden Medea , Wielscher Matthias , Rezwan Faisal I. , Amaral André F.S. , Schaffner Emmanuel , Jeong Ayoung , Beckmeyer-Borowko Anna , Harris Sarah E. , Starr John M. , Deary Ian J. , Flexeder Claudia , Waldenberger Melanie , Peters Annette , Schulz Holger , Chen Su , Sunny Shadia Khan , Karmaus Wilfried J.J. , Jiang Yu , Erhart Gertraud , Kronenberg Florian , Arathimos Ryan , Sharp Gemma C. , Henderson Alexander John , Fu Yu , Piirilä Päivi , Pietiläinen Kirsi H. , Ollikainen Miina , Johansson Asa , Gyllensten Ulf , de Vries Maaike , van der Plaat Diana A. , de Jong Kim , Boezen H. Marike , Hall Ian P. , Tobin Martin D. , Jarvelin Marjo-Riitta , Holloway John W. , Jarvis Deborah , Probst-Hensch Nicole M.
Published: July 2019

Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.

In a discovery–replication EWAS design, DNAme in blood and spirometry were measured twice, 6–15 years apart, in the same participants of three adult population-based discovery cohorts (n=2043). Associated DNAme markers (p<5×10−7) were tested in seven replication cohorts (adult: n=3327; childhood: n=420). Technical bias-adjusted residuals of a regression of the normalised absolute β-values on control probe-derived principle components were regressed on level and change of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and their ratio (FEV1/FVC) in the covariate-adjusted discovery EWAS. Inverse-variance-weighted meta-analyses were performed on results from discovery and replication samples in all participants and never-smokers.

EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme markers in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 (AHRR(aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV1/FVC: pdiscovery=3.96×10−21and pcombined=7.22×10−50). A score combining 10 DNAme markers previously reported to mediate the effect of smoking on lung function was associated with lung function (FEV1/FVC: p=2.65×10−20).

Our results reveal that lung function-associated methylation signals in adults are predominantly smoking related, and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time-points are needed to identify lung function DNAme in never-smokers and in children.
The Global Initiative for Asthma (GINA): 25 years later
Authors: Boulet Louis-Philippe , Reddel Helen K. , Bateman Eric , Pedersen Søren , FitzGerald J. Mark , O'Byrne Paul M.
Published: July 2019

The Global Initiative for Asthma (GINA) was launched in 1993 under the auspices of the National Heart, Lung, and Blood Institute, National Institutes of Health, USA, and the World Health Organization to produce a global strategy on asthma management and prevention. Now constituted as a non-profit entity, it continues to produce, on an annual basis, the most widely cited evidence-based report on the optimal management of asthma in both adults and children intended for global use. Although the GINA Report is often viewed and used as an asthma treatment guideline, it is designed to be a clinically oriented strategy document that supports the development of practice guidelines in different countries and regions.

Other GINA products, including the report's pocket guides, teaching slide kits and implementation tools, are also offered free of charge for public use. The GINA Scientific Committee comprises recognised international experts from primary, secondary and tertiary centres of care who are actively involved in both the care of patients and research in asthma. The GINA Assembly is a forum for exchange of scientific information and discussions on initiatives to improve asthma care in various countries, focusing on implementation strategies. GINA plays a role in shaping research on the diagnosis and treatment of asthma and informs the development of point of care practice guides and decision support tools. GINA supports the objectives of raising awareness of asthma and improving access to therapy and quality of care for asthmatic patients, in addition to presenting and promoting continuously updated evidence-based treatment approaches for global use.
Cerebellar transcranial direct current stimulation in spinocerebellar ataxia type 3 (SCA3-tDCS): rationale and protocol of a randomized, double-blind, sham-controlled study
Authors: Maas Roderick P. P. W. M. , Toni Ivan , Doorduin Jonne , Klockgether Thomas , Schutter Dennis J. L. G. , van de Warrenburg Bart P. C.
Published: July 2019

Background

Spinocerebellar ataxia type 3 (SCA3) is the most common subtype among the autosomal dominant cerebellar ataxias, a group of neurodegenerative disorders for which currently no disease-specific therapy is available. Evidence-based options for symptomatic treatment of ataxia are also limited. Recent investigations in a heterogeneous group of hereditary and acquired ataxias showed promising, prolonged effects of a two-week course with daily sessions of cerebellar anodal transcranial direct current stimulation (tDCS) on ataxia severity, gait speed, and upper limb dexterity. The aim of the SCA3-tDCS study is to further examine whether tDCS improves ataxia severity and various (cerebellar) non-motor symptoms in a homogeneous cohort of SCA3 patients and to explore the time course of these effects.

Methods/design

An investigator-initiated, double-blind, randomized, sham-controlled, single-center trial will be conducted. Twenty mildly to moderately affected SCA3 patients (Scale for the Assessment and Rating of Ataxia score between 3 and 20) will be included and randomly assigned in a 1:1 ratio to either cerebellar anodal tDCS or sham cerebellar tDCS. Patients, investigators, and outcome assessors are unaware of treatment allocation. Cerebellar tDCS (20 min, 2 mA, ramp-up and down periods of 30 s each) will be delivered over ten sessions, distributed in two groups of five consecutive days with a two-day break in between. Outcomes are assessed after a single session of tDCS, after the tenth stimulation (T1), and after three, six, and twelve months. The primary outcome measure is the absolute change of the SARA score between baseline and T1. In addition, effects on a variety of other motor and neuropsychological functions in which the cerebellum is known to be involved will be evaluated using quantitative motor tests, static posturography, neurophysiological measurements, cognitive assessment, and questionnaires.

Discussion

The results of this study will inform us whether repeated sessions of cerebellar anodal tDCS benefit SCA3 patients and whether this form of non-invasive stimulation might be a novel therapeutic approach to consider in a neurorehabilitation setting. Combined with two earlier controlled trials, a positive effect of the SCA3-tDCS study will encourage implementation of this intervention and stimulate further research in other SCAs and heredodegenerative ataxias.

Trial registration

NL7321, registered October 8, 2018.
A trust-aware task allocation method using deep q-learning for uncertain mobile crowdsourcing
Authors: Sun Yong , Tan Wenan
Published: July 2019

Mobile crowdsourcing has emerged as a promising collaboration paradigm in which each spatial task requires a set of mobile workers in near vicinity to the target location. Considering the desired privacy of the participating mobile devices, trust is considered to be an important factor to enable effective collaboration in mobile crowdsourcing. The main impediment to the success of mobile crowdsourcing is the allocation of trustworthy mobile workers to nearby spatial tasks for collaboration. This process becomes substantially more challenging for large-scale online spatial task allocations in uncertain mobile crowdsourcing systems. The uncertainty can mislead the task allocation, resulting in performance degradation. Moreover, the large-scale nature of real-world crowdsourcing poses a considerable challenge to spatial task allocation in uncertain environments. To address the aforementioned challenges, first, an optimization problem of mobile crowdsourcing task allocation is formulated to maximize the trustworthiness of workers and minimize movement distance costs. Second, for the uncertain crowdsourcing scenario, a Markov decision process-based mobile crowdsourcing model (MCMDP) is formulated to illustrate the dynamic trust-aware task allocation problem. Third, to solve large-scale MCMDP problems in a stable manner, this study proposes an improved deep Q-learning-based trust-aware task allocation (ImprovedDQL-TTA) algorithm that combines trust-aware task allocation and deep Q-learning as an improvement over the uncertain mobile crowdsourcing systems. Finally, experimental results illustrate that the ImprovedDQL-TTA algorithm can stably converge in a number of training iterations. Compared with the reference algorithm, our proposed algorithm achieves effective solutions on the experimental data sets.
Induced polarization response of porous media with metallic particles — Part 10: Influence of desiccation
Authors: Tartrat Timothé , Revil André , Abdulsamad Feras , Ghorbani Ahmad , Jougnot Damien , Coperey Antoine , Yven Béatrice , de la Vaissière Rémi
Published: July 2019

Desiccation influences the complex conductivity of porous media with disseminated metallic particles. We expand the mechanistic model developed in the previous papers of this series to include the effect of saturation upon the complex conductivity of mixtures of mineral grains, pyrite, and pore water. During desiccation, the salt is assumed to be segregated in the liquid pore water; therefore, the conductivity of the pore water increases when saturation decreases. We have performed 14 experiments corresponding to 91 complex conductivity spectra. In these experiments, the saturation of the water phase is changed over time by desiccation. The resulting spectra are fitted by a double Cole-Cole model used as the fitting model. We also developed a mechanistic model in which the chargeability and the relaxation time of the low-frequency polarization are expected to change with saturation in a predictable way. We first characterized the properties of the background material made by an illitic clay material. We determine how the Cole-Cole parameters depend on saturation. The Cole-Cole exponent is essentially independent on saturation. When the chargeability of the mixture is dominated by the presence of pyrite, it becomes independent of the saturation but a small effect on the chargeability is observed at low pyrite contents. The instantaneous conductivity of the background decreases with the saturation in a predictable way. The relaxation time depends on the inverse of the instantaneous conductivity and therefore on saturation. This dependence is well-explained through numerical simulations made with the finite-element method. Finally, we analyze the complex conductivity spectra of two clay-rock core samples from the Callovo-Oxfordian formation in the Paris Basin (France). The spectra are shown as a function of their desiccation and explained thanks to the newly developed model.
Ketosis and bipolar disorder: controlled analytic study of online reports
Authors: Campbell Iain H. , Campbell Harry
Published: July 2019

Background

Members of online bipolar disorder forums often report experiences of mood-stabilisation on the ketogenic diet, which has traditionally been used in the treatment of epilepsy. We examined the nature and extent of such reports.

Aims

To investigate associations between a ketogenic diet and mood stabilisation among individuals with bipolar disorder.

Method

We undertook an observational analytic study of free-text comments in online forums about mood effects of dietary interventions (ketogenic, omega-3 enriched or vegetarian) classified by a priori categories of change in mood stabilisation in 274 people with bipolar disorder.

Results

There were 141 (85.5%) free-text comments on ketogenic diets that reported a positive impact on mood stabilisation. Reports of significant mood stabilisation or remission of symptoms over a period were substantially higher for a ketogenic diet than for other diets (93/165, 56.4%, 95% CI 48.4–64.1) v. 14/94, 14.9%, 95% CI 8.4–23.7), odds ratio 7.4, 95% CI 3.8–14.1, P < 0.0001), many with detailed reports of the improvements experienced and several lasting for extended periods (months to years). Other reported associations included fewer episodes of depression (in 41.2%, 95% CI 30.6–52.4 of individuals); improved clarity of thought and speech (28.2%, 95% CI 19.0–39.0); increased energy (25.9, 95% CI 17.0–36.5); and weight loss (25.9%, 95% CI 17.0–36.5).

Conclusions

Despite the inherent limitations of the observational data based on self-reports posted online, the association strength and reports of sustained benefit support a hypothesis of a ketogenic diet being associated with beneficial effects on mood stabilisation. Caution should be exercised in interpreting this data until a controlled trial can be carried out to examine this hypothesis. These preliminary observations are generally consistent with a mitochondrial dysfunction component to bipolar disorder aetiology with ketones bypassing a block between glycolysis and the tricarboxylic acid cycle.

Declaration of interest

None.
HSD3B1 Genotypes Conferring Adrenal-Restrictive and Adrenal-Permissive Phenotypes in Prostate Cancer and Beyond
Authors: Sabharwal Navin , Sharifi Nima
Published: July 2019

Castration-resistant prostate cancer (PCa) almost invariably occurs after androgen deprivation therapy for metastatic disease and is driven in part by androgen synthesis within the tumor. 3β-hydroxysteroid dehydrogenase isoenzyme-1 catalyzes the conversion of adrenal precursor steroids into potent androgens essential for PCa progression. A common 1245 A→C missense-encoding single nucleotide polymorphism in HSD3B1 (rs1047303), the gene that encodes this enzyme, leads to a more stable protein that is resistant to degradation and thus increased production of potent androgens from adrenal precursors, facilitating castration-resistant PCa development. Consistent with this mechanism, this adrenal-permissive HSD3B1(1245C) genotype is associated with inferior outcomes after androgen deprivation therapy for advanced PCa, and increased sensitivity to pharmacologic blockade of adrenal precursors in metastatic disease. Herein, we review current knowledge of the mechanisms conferred by HSD3B1 genotype to alter androgen physiology and accelerate development of castration-resistant disease and its associations with clinical PCa outcomes. In light of its effect on steroid physiology, we also discuss its potential associations with non-PCa phenotypes.
Cord Blood Metabolomics: Association With Newborn Anthropometrics and C-Peptide Across Ancestries
Authors: Kadakia Rachel , Talbot Octavious , Kuang Alan , Bain James R , Muehlbauer Michael J , Stevens Robert D , Ilkayeva Olga R , Lowe Lynn P , Metzger Boyd E , Newgard Christopher B , Scholtens Denise M , Lowe William L ,   HAPO Study Cooperative Research Group
Published: July 2019

Context

Newborn adiposity is associated with childhood obesity. Cord blood metabolomics is one approach that can be used to understand early-life contributors to adiposity and insulin resistance.

Objective

To determine the association of cord blood metabolites with newborn adiposity and hyperinsulinemia in a multiethnic cohort of newborns.

Design

Cross-sectional, observational study.

Setting

Hyperglycemia and Adverse Pregnancy Outcome study.

Participants

One thousand six hundred multiethnic mother–newborn pairs.

Main Outcome Measure

Cord blood C-peptide, birthweight, and newborn sum of skinfolds.

Results

Meta-analyses across four ancestry groups (Afro-Caribbean, Northern European, Thai, and Mexican American) demonstrated significant associations of cord blood metabolites with cord blood C-peptide, birthweight, and newborn sum of skinfolds. Several metabolites, including branched-chain amino acids (BCAAs), medium- and long-chain acylcarnitines, nonesterified fatty acids, and triglycerides were negatively associated with cord C-peptide but positively associated with birthweight and/or sum of skinfolds. 1,5-Anhydroglucitol, an inverse marker of recent maternal glycemia, was significantly inversely associated with birthweight and sum of skinfolds. Network analyses revealed groups of interrelated amino acid, acylcarnitine, and fatty acid metabolites associated with all three newborn outcomes.

Conclusions

Cord blood metabolites are associated with newborn size and cord blood C-peptide levels after adjustment for maternal body mass index and glucose during pregnancy. Negative associations of metabolites with C-peptide at birth were observed. 1,5-Anhydroglucitol appears to be a marker of adiposity in newborns. BCAAs were individually associated with birthweight and demonstrated possible associations with newborn adiposity in network analyses.