bluuebunny/crossref_metadata_2025 huggingface dataset:
On anisotropic mechanical properties of heterogeneous magnetic polymeric composites
Authors: Borin Dmitry , Stepanov Gennady , Dohmen Eike
Published: March 2019

This study is devoted to the magneto-mechanical characterization of heterogeneous magnetoactive elastomers based on an elastic polydimethylsiloxane matrix with embedded spherical magnetic soft microparticles and magnetic hard microparticles of irregular shape. An issue of the anisotropic mechanical properties of these smart composites is considered. Non-magnetized and pre-magnetized specimens are characterized using a planar shear and axial loading in an externally applied homogeneous magnetic field. The field direction differs relative to the direction of the field used for the specimens pre-magnetization. Results of the different methods allow comparison of the tensile shear moduli for the samples with an initially identical composition. Obtained results demonstrate a strong correlation between the composite behaviour and orientation of the magnetic field used for the pre-magnetization of the sample relative to the external field applied to a sample during the test. Composites pre-magnetized in the direction parallel to an applied mechanical force and external magnetic field show higher magnetorheological response than composites pre-magnetized transversally to the force and the field. Application of the external field directed opposite to the direction of the pre-magnetization reduces the observed stiffening. Moreover, in this situation a softening of the material can be observed, depending on the magnitude of the external field and the field used for pre-magnetization.

This article is part of the theme issue ‘Heterogeneous materials: metastable and non-ergodic internal structures’.
Phase transformations in metastable liquids combined with polymerization
Authors: Ivanov Alexander A. , Alexandrova Irina V. , Alexandrov Dmitri V.
Published: March 2019

This paper is concerned with the theory of nucleation and growth of crystals in a metastable polymer melt with allowance for the polymerization of a monomer. A mathematical model consisting of the heat balance equation, equations governing the particle-radius distribution function and the polymerization degree is formulated. The exact steady-state analytical solutions are found. In the case of unsteady-state crystallization with polymerization, the particle-size distribution function is determined analytically for different space–time regions by means of the Laplace transform. Two functional integro-differential equations governing the dimensionless temperature and polymerization degree are deduced. These equations are solved by means of the saddle-point technique for the evaluation of a Laplace-type integral. The time-dependent distribution function, temperature and polymerization degree at different polymerization rates and nucleation kinetics are derived with allowance for the main contribution to the Laplace-type integral. In addition, the general analytical solution by means of the saddle-point technique and an example showing how to construct the analytical solutions in particular cases are given in the appendices. The analytical method developed in the present paper can be used to describe the similar phase transition phenomena in the presence of chemical reactions.

This article is part of the theme issue ‘Heterogeneous materials: metastable and non-ergodic internal structures’.
Effect of interparticle interaction on magnetic hyperthermia: homogeneous spatial distribution of the particles
Authors: Abu-Bakr Ali Fathi , Zubarev Andrey
Published: March 2019

The paper deals with the theoretical study of the effect of magnetic interparticle interaction on magnetic hyperthermia, produced by the particles under the action of a linearly polarized oscillating field. The particles are homogeneously distributed and immobilized in a rigid medium. The supposed size of the magnetite particles is about 20–30 nm. For these particles, the characteristic time of the Neel remagnetization is much longer than the time of observation. This is why we concluded that the dissipation occurs as a result of the particle magnetic moment oscillation in the pit of energy of magnetic anisotropy.

This article is part of the theme issue ‘Heterogeneous materials: metastable and non-ergodic internal structures’.
Anisotropic magnetic hydrogels: design, structure and mechanical properties
Authors: Gila-Vilchez Cristina , Mañas-Torres Mari C. , Contreras-Montoya Rafael , Alaminos Miguel , Duran Juan D. G. , de Cienfuegos Luis Álvarez , Lopez-Lopez Modesto T.
Published: March 2019

Anisotropy is an intrinsic feature of most of the human tissues (e.g. muscle, skin or cartilage). Because of this, there has been an intense effort in the search of methods for the induction of permanent anisotropy in hydrogels intended for biomedical applications. The dispersion of magnetic particles or beads in the hydrogel precursor solution prior to cross-linking, in combination with applied magnetic fields, which gives rise to columnar structures, is one of the most recently proposed approaches for this goal. We have gone even further and, in this paper, we show that it is possible to use magnetic particles as actuators for the alignment of the polymer chains in order to obtain anisotropic hydrogels. Furthermore, we characterize the microstructural arrangement and mechanical properties of the resulting hydrogels.

This article is part of a theme issue ‘Heterogeneous materials: metastable and non-ergodic internal structures’.
A framework for predicting soft-fruit yields and phenology using embedded, networked microsensors, coupled weather models and machine-learning techniques
Authors: Lee Mark A. , Monteiro Angelo , Barclay Andrew , Marcar Jon , Miteva-Neagu Mirena , Parker Joe
Published: March 2019

Predicting harvest timing is a key challenge to sustainably develop soft fruit farming and reduce food waste. Soft fruits are perishable, high-value and seasonal, and sales prices are typically time-sensitive. In addition, fruit harvesting is labour-intensive and increasingly expensive making accurate phenological predictions valuable for growers. A novel approach for predicting soft fruit phenology and yields was developed and tested, using strawberries as the model crop. Seedlings were planted in polytunnels, and environmental and yield data were collected throughout the growing season. Over 1.2 million datapoints were collected by networked microsensors which measured spatial and temporal variability in air temperature, relative humidity (RH), soil moisture and photosynthetically active radiation (PAR). Fleeces were added to a subset of the plants to generate additional within-polytunnel variation. Cumulative fruit yields followed logistic growth curves and the coefficients of these curves were dependent on micro-climatic growing conditions. After 10,000 iterations, machine learning revealed that RH was the optimal factor informing the coefficients of these curves, perhaps because it is an integrative metric of air temperature and water status. Trigonometric models transformed weather forecasts, which showed a relatively low agreement with polytunnel air temperature (R2 = 0.6) and RH (R2 = 0.5) measurements, into more accurate polytunnel-specific predictions for temperature and RH (both R2 = 0.8). We present a framework for using machine-learning techniques to calculate curve coefficients and parametrise coupled weather models which can predict fruit yields and timing to a greater degree of accuracy that previously possible. Dataloggers measuring environmental and yield data could infer model parameters using iterative training for novel fruit varieties or crop types growing in different locations without a-priori phenological information. At this stage in the development of artificial intelligence and networked microsensors, this is a step forward in generating bespoke phenological prediction models to inform and support growers.
Programmable Modulation for Extracellular Vesicles
Authors: Wang Yihua , Melvin Richard , Bemis Lynne T. , Worrell Gregory A. , Wang Hai-Long
Published: March 2019

Every living cell releases extracellular vesicles (EVs) that are critical for cellular signaling and a wide range of biological functions. The potential diagnostic and therapeutic applications of EVs are well recognized, and rapidly expanding. While a complete understanding of the molecular mechanisms underpinning EVs release remains elusive, here we demonstrate a novel method for programmable control of the release of EVs and their cargo using external electric fields. As a proof of principle, we use cultured rat astrocytes to demonstrate how the frequency of external electrical stimulation selectively modulates EV release, their surface proteins, and microRNA profiles. This method could broadly impact biological science and medical applications. First, it raises an interesting question of how endogenous electrical activity could modulate EV production. Second, it provides a novel mechanism for tuning therapeutic electrical stimulation that may be useful for treating brain disorders. Third, it provides a new way to generate EVs carrying desired cargos by tuning electrical stimulation parameters. Unlike chemical methods for creating EVs, electrical stimulation is a clean physical method with adjustable parameters including stimulation frequency, field strength and waveform morphology.
Distinct RhoGEFs activate apical and junctional actomyosin contractility under control of G proteins during epithelial morphogenesis
Authors: De Las Bayonas Alain Garcia , Philippe Jean-Marc , Lellouch Annemarie C. , Lecuit Thomas
Published: March 2019

Small RhoGTPases and Myosin-II direct cell shape changes and movements during tissue morphogenesis. Their activities are tightly regulated in space and time to specify the desired pattern of contractility that supports tissue morphogenesis. This is expected to stem from polarized surface stimuli and from polarized signaling processing inside cells. We examined this general problem in the context of cell intercalation that drives extension of theDrosophilaectoderm. In the ectoderm, G protein coupled receptors (GPCRs) and their downstream heterotrimeric G proteins (Gα and Gβγ) activate Rho1 both medial-apically, where it exhibits pulsed dynamics, and at junctions, where its activity is planar polarized (Kerridge et al., 2016; Munjal et al., 2015). However, the mechanisms responsible for polarizing Rho1 activity are unclear. In particular, it is unknown how Rho1 activity is controlled at junctions. We report a division of labor in the mechanisms of Rho1 activation in that distinct guanine exchange factors (GEFs), that serve as activators of Rho1, operate in these distinct cellular compartments. RhoGEF2 acts uniquely to activate medial-apical Rho1. Although RhoGEF2 is recruited both medial-apically and at junctions by Gα12/13-GTP, also called Concertina (Cta) inDrosophila, its activity is restricted to the medial-apical compartment. Furthermore, we characterize a novel RhoGEF, p114RhoGEF/Wireless (Wrl), and report its requirement for cell intercalation in the extending ectoderm. p114RhoGEF/Wireless activates Rho1 specifically at junctions. Strikingly it is restricted to adherens junctions and is under Gβ13F/Gγ1 control. Gβ13F/Gγ1 activates junctional Rho1 and exerts quantitative control over planar polarization of Rho1. In particular, overexpression of Gβ13F/Gγ1 leads to hyper planar polarization of Rho1 and MyoII. Finally, we found that p114RhoGEF/Wireless is absent in the mesoderm, arguing for a tissue-specific control over junctional Rho1 activity. These results shed light on the mechanisms of polarization of Rho1 activity in different cellular compartments and reveal that distinct GEFs are sensitive tuning parameters of cell contractility in remodeling epithelia.
Exploiting evolutionary herding to control drug resistance in cancer
Authors: Acar Ahmet , Nichol Daniel , Fernandez-Mateos Javier , Cresswell George D. , Barozzi Iros , Hong Sung Pil , Spiteri Inmaculada , Stubbs Mark , Burke Rosemary , Stewart Adam , Vlachogiannis Georgios , Maley Carlo C. , Magnani Luca , Valeri Nicola , Banerji Udai , Sottoriva Andrea
Published: March 2019

Drug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at a cost of decreased growth rate or increased sensitivity to another drug due to evolutionary trade-offs. This weakness can be exploited in the clinic using an approach called ‘evolutionary herding’ that aims at controlling the tumour cell population to delay or prevent resistance. However, recapitulating cancer evolutionary dynamics experimentally remains challenging. Here we present a novel approach for evolutionary herding based on a combination of single-cell barcoding, very large populations of 108–109cells grown without re-plating, longitudinal non-destructive monitoring of cancer clones, and mathematical modelling of tumour evolution. We demonstrate evolutionary herding in non-small cell lung cancer, showing that herding allows shifting the clonal composition of a tumour in our favour, leading to collateral drug sensitivity and proliferative fitness costs. Through genomic analysis and single-cell sequencing, we were also able to determine the mechanisms that drive such evolved sensitivity. Our approach allows modelling evolutionary trade-offs experimentally to test patient-specific evolutionary herding strategies that can potentially be translated into the clinic to control treatment resistance.
Response to olaparib in a PALB2 germline mutated prostate cancer and genetic events associated with resistance
Authors: Horak Peter , Weischenfeldt Joachim , von Amsberg Gunhild , Beyer Burkhard , Schütte Andreas , Uhrig Sebastian , Gieldon Laura , Klink Barbara , Feuerbach Lars , Hübschmann Daniel , Kreutzfeldt Simon , Heining Christoph , Maier Sebastian , Hutter Barbara , Penzel Roland , Schlesner Matthias , Eils Roland , Sauter Guido , Stenzinger Albrecht , Brors Benedikt , Schröck Evelin , Glimm Hanno , Fröhling Stefan , Schlomm Thorsten
Published: March 2019

Prostate cancers harboring DNA repair gene alterations are particularly sensitive to PARP inhibitor treatment. We report a case of an advanced prostate cancer patient profiled within the NCT-MASTER (Molecularly Aided Stratification for Tumor Eradication Research) precision oncology program using next-generation sequencing. Comprehensive genomic and transcriptomic analysis identified a pathogenic germline PALB2 variant as well as a mutational signature associated with disturbed homologous recombination together with structural genomic rearrangements. A molecular tumor board identified a potential benefit of targeted therapy and recommended PARP inhibition and platinum-based chemotherapy. Single-agent treatment with the PARP inhibitor olaparib as well as subsequent combination with platinum-based chemotherapy resulted in disease stabilization and substantial improvement of clinical symptoms. Upon progression, we performed whole-exome and RNA sequencing of a liver metastasis, which demonstrated up-regulation of several genes characteristic for the neuroendocrine prostate cancer phenotype as well as a novel translocation resulting in an in-frame, loss-of-function fusion of RB1. We suggest that multidimensional genomic characterization of prostate cancer patients undergoing PARP inhibitor therapy will be necessary to capture and understand predictive biomarkers of PARP inhibitor sensitivity and resistance.
Concurrent-learning-based visual servo tracking and scene identification of mobile robots
Authors: Qiu Yu , Li Baoquan , Shi Wuxi , Chen Yimei
Published: March 2019

Purpose

The purpose of this paper is to present a visual servo tracking strategy for the wheeled mobile robot, where the unknown feature depth information can be identified simultaneously in the visual servoing process.

Design/methodology/approach

By using reference, desired and current images, system errors are constructed by measurable signals that are obtained by decomposing Euclidean homographies. Subsequently, by taking the advantage of the concurrent learning framework, both historical and current system data are used to construct an adaptive updating mechanism for recovering the unknown feature depth. Then, the kinematic controller is designed for the mobile robot to achieve the visual servo trajectory tracking task. Lyapunov techniques and LaSalle’s invariance principle are used to prove that system errors and the depth estimation error converge to zero synchronously.

Findings

The concurrent learning-based visual servo tracking and identification technology is found to be reliable, accurate and efficient with both simulation and comparative experimental results. Both trajectory tracking and depth estimation errors converge to zero successfully.

Originality/value

On the basis of the concurrent learning framework, an adaptive control strategy is developed for the mobile robot to successfully identify the unknown scene depth while accomplishing the visual servo trajectory tracking task.
Definition and representation of stiffened shell structures in the context of an integrated development process
Authors: Krieglsteiner Joscha , Horst Peter , Schmidt Carsten
Published: March 2019

Purpose

A novel development process aims at finding solutions for lightweight stiffened shell structures and their efficient production. To respect the strong interdependency of structural design and production planning, particularly observed for composite structures, it is of high interest to start considering production effects in early development phases. This integrated approach requires an integrated representation of structure and production. The purpose of this study is to investigate the scope of relevant data and to find a structure for its representation.

Design/methodology/approach

The development task is analyzed and a system of so-called solution dimensions is presented, which covers all important aspects of stiffened shell structures and their production. An integrated product data model is developed to cover all of the solution dimensions.

Findings

The product data model consists of five coherent partial models. It is explained how these models are defined and how they are connected to each other. An academic example of an aircraft fuselage panel is used to demonstrate the definition process. It is shown how even complex structural concepts are defined systematically.

Practical implications

It is explained how this integrated product data model is used in a software project for the development of aircraft fuselage structures.

Originality/value

The presented approach for the definition and representation of stiffened shell structures enables the developer, e.g. of aircraft fuselage, to respect the crucial criterion of manufacturability from early development phases on. Further, new design approaches, e.g. as inspired by topology optimization, can be considered.
Challenges to mothering while incarcerated: preliminary study of two women’s prisons in Java, Indonesia
Authors: Mustofa Muhammad , West Brooke S. , Sri Supadmi Mamik , Sari Herlina
Published: March 2019

Purpose

The purpose of this paper is to present the characteristics of incarcerated women in two prisons in Java, Indonesia and discuss the specific problems and needs incarcerated women with children face with regard to mothering.

Design/methodology/approach

A cross-sectional survey using a semi-structured questionnaire was administered to 399 incarcerated women in two prisons. Focus group discussions provided additional information on mother’s experiences in prison.

Findings

This research finds that children’s welfare was an important concern for mothers while in prison and that they faced various problems in maintaining family ties during their incarceration, including distance, costs and time for family to visit (49.3 percent), and challenges to being able to communicate with family and children (26.6 percent).

Originality/value

This study contributes to the limited research on incarcerated women in Indonesia, broadly, and on mothering and incarceration, in particular, and suggests that women’s needs as mothers have not been taken into consideration by prisons and the criminal justice system.
Identification of service development needs for incarcerated adults with autism spectrum disorders in an Australian prison system
Authors: Newman Claire , Cashin Andrew , Graham Iain
Published: March 2019

Purpose

The purpose of this paper is to identify and deliberate the service development needs required for the improvement of service provision for incarcerated adults with autism spectrum disorder (ASD) in NSW, Australia.

Design/methodology/approach

Consultation groups were conducted to bring togethern=5 key stakeholders from heath and correctional-based services in the prison system. A facilitated asynchronous e-mail-based discussion occurred amongst group members between consultation group meetings.

Findings

Two main themes were identified: detecting persons with ASD and providing appropriate care. Participants discussed current service gaps with regard to the identification of people with ASD at the point of contact with the prison service, and the difficulties associated with diagnosing prisoners with ASD. The need for effective alert systems to detect persons with ASD in custody was identified. The current absence of ASD-specific support services in prison was highlighted, and recommendations for improvement suggested.

Practical implications

Current health and correctional-based service provision failed to adequately support incarcerated adults with ASD. Improvements in prison-entry screening processes, alert systems and diagnostic practices are required. Multidisciplinary collaboration between prison-based and external service providers is required for the development of a model of care based on individualised case management to adequately support incarcerated adults with ASD in prison.

Originality/value

Given the lack of reported service provision for incarcerated adults with ASD internationally, other prison-based services are likely to experience similar service development needs and see the relevance of the recommendations made directly from the study findings.
High frequency of HBV in HIV-infected prisoners in Mozambique
Authors: Augusto Angelo , Augusto Orvalho , Taquibo Atija , Nhachigule Carina , Siyawadya Narcisa , Gudo Eduardo Samo
Published: March 2019

Purpose

The purpose of this paper is to determine the prevalence of hepatitis B virus (HBV) among 448 HIV-infected prisoners from 32 prisons in Mozambique.

Design/methodology/approach

All HIV seropositive prisoners were screened for HBV.

Findings

Of the 448 HIV seropositive prisoners, 51 (11.4 percent, 95%CI: 9.3–13.9 percent) were HBsAg-positive and was significantly higher in prisoners aged<25 years.

Originality/value

Data from this study show for the first time that the frequency of HBV among HIV-infected prisoners is high, suggesting that immediate interventions are needed during incarceration.
Factors associated with health care seeking behavior for musculoskeletal pain in Indonesia: A cross‐sectional study
Authors: Andarini Sri , Arif Achmad Zainudin , Al Rasyid Harun , Wahono Cesarius Singgih , Kalim Handono , Handono Kusworini
Published: March 2019

Aim

To assess the factors defining healthcare‐seeking behavior of people with musculoskeletal pain in the urban community of Malang City, East Java, Indonesia.

Methods

A cross‐sectional survey was performed in Malang City, East Java, Indonesia. In total, 2067 participants aged 16‐93 years were interviewed. The sociodemographic and socioeconomic factors of healthcare seeking behavior, musculoskeletal pain, disability, and adverse drug reactions were assessed using the validated Indonesian version of Community Oriented Program for the Control of Rheumatic Disease (COPCORD) protocol by International League of Associations for Rheumatology and the World Health Organization core questionnaire. Chi‐square test was applied to assess the determinants of health‐seeking behavior for musculoskeletal pain.

Results

Slightly more than one‐third of the respondents (36%) with musculoskeletal pain, described as osteoarthritis, low back pain, gouty arthritis, soft tissue rheumatism, and autoimmune arthritis, were assessed for their health‐seeking behavior. About 73% of all those participants sought treatment for their musculoskeletal symptoms. Treatment modality used was modern healthcare, traditional healthcare, self‐treatment using traditional medication, self‐treatment using modern medication with the proportions of 20.94%, 25.23%, 33.95%, 25.77%, respectively. Disability significantly affected health‐seeking behavior as the major determinant (prevalence ratio [PR] 1.087, 95% CI 1.031‐1.146, P = 0.002), followed by age (PR 1.043, 95% CI 1.000‐1.087, P = 0.049). Healthcare‐seeking behavior was associated with the presence of adverse drug reactions (P < 0.001).

Conclusion

Factors associated with musculoskeletal pain health‐seeking behavior were disability and age. Self and traditional healthcare treatment were further associated with an adverse drug reaction.
Risks Associated with Mid level Cannabis Use Among People Treated for Alcohol Use Disorder
Authors: Subbaraman Meenakshi S. , Barnett Sarah Beth , Karriker‐Jaffe Katherine J.
Published: March 2019

Background

The relationships between cannabis use frequency with alcohol use, alcohol‐related harms, and persistent alcohol use disorder (AUD) in a general population subsample of individuals previously treated for AUD were examined.

Methods

Secondary analyses of the 2005, 2010, and 2015 U.S. National Alcohol Surveys, a nationwide general population sample of individuals ages 18+, were performed. The analytic subsample (N = 772) reported 3+ lifetime DSM‐IV alcohol dependence criteria and prior AUD treatment. Primary exposure was past 12‐month frequency of cannabis use (weekly or more, or “heavy;” more than monthly/less than weekly or “midlevel;” less than monthly or “light;” none). Primary outcomes were past 12‐month total volume, average frequency of 5+ drinks/month, past 12‐month alcohol‐related harms, and past 12‐month DSM‐IV alcohol dependence.

Results

Multivariable negative binomial and logistic regressions showed that the only cannabis users who consistently differed significantly from cannabis abstainers were midlevel users; specifically, more than monthly/less than weekly cannabis users drank 2.83 times as many drinks (95% CI: 1.43, 5.60); had 2.83 as many 5+ occasions (95% CI: 1.38, 5.79); had 6.82 times the odds of experiencing any harms (95% CI: 2.29, 20.33); and had 6.53 times the odds of persistent AUD as cannabis abstainers (95% CI: 2.66, 16.02; all ps < 0.05). The relationship between midlevel cannabis use and harms remained significant after adjustment for volume and frequency of 5+ (OR = 6.18, 95% CI: 1.35, 28.37).

Conclusions

Among those with lifetime AUD who have been to treatment, only more than monthly/less than weekly cannabis use is related to more alcohol‐related harms and persistent AUD compared to cannabis abstinence. Heavier and lighter cannabis use is not related to worse alcohol outcomes compared to cannabis abstinence.
Are long‐term vapers interested in vaping cessation support?
Authors: Etter Jean‐François
Published: March 2019

Aims

We investigated whether long‐term vapers were interested in vaping cessation support.

Design, Setting and Participants

Online survey in 2017 of long‐term vapers (n = 347), mainly in France, Switzerland and Belgium, enrolled through e‐cigarette and smoking cessation websites.

Measurements

Opinions on potential vaping cessation services.

Findings

Participants had been vaping for 4 years on average (standard deviation 1 year), most were daily vapers (96%, n = 333), former smokers (88%, n = 303), vaped nicotine‐containing liquids (88%, n = 305), reported being dependent on e‐cigarettes (89%, n = 308) and had no intention to stop vaping (66%, n = 229). Few (10%, n = 34) had already tried to stop vaping. Among those (n = 118, 34% of 347) who intended to stop vaping, 27% (n = 32) thought that a health professional could help them stop vaping, 33% (n = 39) would visit a vaping cessation service if available in their neighbourhood, 23% (n = 27) would use nicotine medications to stop vaping, and if a vaping cessation website or smartphone app. were available, 46% (n = 54) would use them. In open‐ended comments (n = 94), participants reported that they did not see why they should stop vaping (n = 37), in particular because vaping helped them quit smoking (n = 17) and was less toxic than smoking (n = 9), that smoking cessation aids had not worked for them and neither would similar aids help them stop vaping (n = 6), and that they would stop vaping by gradually decreasing the nicotine content in their e‐liquids (n = 12).

Conclusions

Most long‐term vapers in this 2017 European online survey had no intention of stopping vaping, but one‐quarter to one‐half of those who intended to stop were interested in using vaping cessation support.
Prevalence of fetal alcohol spectrum disorder among special subpopulations: a systematic review and meta‐analysis
Authors: Popova Svetlana , Lange Shannon , Shield Kevin , Burd Larry , Rehm Jürgen
Published: March 2019

Aim

To collate prevalence estimates of fetal alcohol spectrum disorder (FASD) among special subpopulations (defined by service use).

Design

Systematic literature review and meta‐analysis of original, quantitative studies published between 1 November 1973 and 1 December 2018. The PRISMAGATHER were adhered to. The review protocol [includes FASD prevalence in (a) general and (b) special populations] is available on PROSPERO (registration number: CRD42016033837). Prevalence estimates were collated for all included studies with country‐, disorder‐ [FASD and fetal alcohol syndrome (FAS)] and population‐specific random‐effects meta‐analyses conducted.

Setting and Participants

A number of service‐defined subpopulations globally (see Findings).

Measurements

The main outcome was the prevalence of FASD among special subpopulations. The critical appraisal of each study was conducted using the Joanna Briggs Institute tool.

Findings

We identified 69 studies, comprising 6177 individuals diagnosed with FASD from 17 countries: Australia (n = 5), Brazil (n = 2), Canada (n = 15), Chile (n = 4), eastern Europe (Moldova, Romania and Ukraine; n = 1), Germany (n = 1), Israel (n = 1), Lithuania (n = 1), the Netherlands (n = 1), Poland (n = 1), Russia (n = 9), South Korea (n = 1), Spain (n = 1), Sweden (n = 1) and United States (n = 25). FAS and FASD prevalence rates were collated for the following five subpopulations: children in care, correctional, special education, specialized clinical and Aboriginal populations. The estimated prevalence of FASD in these special subpopulations was 10–40 times higher compared with the 7.7 per 1000 (95% confidence interval = 4.9–11.7) global FASD prevalence in the general population.

Conclusions

Global subpopulations of children in care, correctional, special education, specialized clinical and Aboriginal populations have a significantly higher prevalence of fetal alcohol spectrum disorder compared with the general population, which poses a substantial global health problem.
Transient epidermal barrier deficiency and lowered allergic threshold in filaggrin‐hornerin (FlgHrnr−/−) double‐deficient mice
Authors: Rahrig Sebastian , Dettmann Judith M. , Brauns Birka , Lorenz Verena N. , Buhl Timo , Kezic Sanja , Elias Peter M. , Weidinger Stephan , Mempel Martin , Schön Michael P. , Braun Andrea
Published: March 2019

Background

Filaggrin (Flg) and hornerin (Hrnr) share similar structural and functional features. Both proteins have been implicated as essential proteins for skin barrier maintenance. Loss‐of‐function mutations of these genes constitute a risk factor for atopic dermatitis and eczema‐related asthma. Furthermore, both FLG and HRNR protein levels are downregulated in patients with atopic dermatitis. Thus, mice deficient for Flg and Hrnr provide a novel model to study skin barrier impairment and the susceptibility for cutaneous inflammation.

Methods

By using appropriate targeting vectors and breeding strategies, we established a homozygous FlgHrnr double‐deficient (FlgHrnr−/−) mouse model lacking both genes including the intergenomic sequence.

Results

Neonates appeared normal, but developed a transient scaly phenotype with overall flaky appearance, but no overt skin phenotype in adulthood, thereby reflecting a subclinical barrier defect seen in humans. Structurally, FlgHrnr−/− mice displayed a markedly reduced granular layer and a condensed cornified layer. Functionally, FlgHrnr−/− mice showed permeability abnormalities and metabolic aberrations regarding the production of natural moisturizing factors (NMFs) in the stratum corneum. Surprisingly, although the immune system revealed no aberrations under steady‐state conditions, FlgHrnr−/− mice are predisposed to mount an allergic contact dermatitis, especially at hapten threshold levels eliciting allergic reactions.

Conclusions

Together, our FlgHrnr−/− mouse model nicely reflects the epicutaneous sensitization susceptibilities and inflammatory reactions to environmental insults in humans with impaired skin barrier functions.
IL‐4 receptor α blockade prevents sensitization and alters acute and long‐lasting effects of allergen‐specific immunotherapy of murine allergic asthma
Authors: Russkamp D. , Aguilar‐Pimentel A. , Alessandrini F. , Gailus‐Durner V. , Fuchs H. , Ohnmacht C. , Chaker A. , de Angelis M. H. , Ollert M. , Schmidt‐Weber C. B. , Blank S.
Published: March 2019

Background

Allergen‐specific immunotherapy (AIT) is the only causal treatment for allergy. However, success rates vary depending on the type of allergy and disease background of the patient. Hence, strategies targeting an increased therapeutic efficacy are urgently needed. Here, the effects of blockade of IL‐4 and IL‐13 signaling on different phases of AIT were addressed.

Methods

The impact of the recombinantly produced IL‐4 and IL‐13 antagonist IL‐4 mutein (IL‐4M) on allergic sensitization and AIT outcome in experimental allergic asthma were analyzed in a murine model. The effects of IL‐4M administration were assessed prior/during sensitization, immediately after AIT under allergen challenge, and two weeks post‐treatment.

Results

Intervention with IL‐4M prior/during sensitization led to strong induction of IgG1, IgG2a, IgG2b, and IgG3, decrease of specific and total IgE, as well as of IL‐5 in serum. Similar effects on the serum immunoglobulin levels were observed immediately after IL4M‐supplemented AIT during allergen challenge. Additionally, IL4M markedly suppressed type‐2 cytokine secretion of splenocytes beyond the effect of AIT alone. These effects were equaled to those of AIT alone two weeks post‐treatment. Intriguingly, here, IL‐4M induced a sustained decrease of Th2‐biased Tregs (ST2+FOXP3+GATA3intermediate).

Conclusions

IL‐4 and IL‐13 blockade during experimental AIT demonstrates beneficial effects on immunological key parameters such as immunoglobulin and cytokine secretion immediately after AIT. Although two weeks later these effects were dropped to those of AIT alone, the number of potentially disease‐triggering Th2‐biased Tregs was further significantly decreased by IL‐4M treatment. Hence, IL‐4/IL13‐targeting therapies prime the immune memory in therapy success‐favoring manner.
Identification of an antigenic determinant of clavulanic acid responsible for IgE‐mediated reactions
Authors: Barbero Nekane , Fernández‐Santamaría Rubén , Mayorga Cristobalina , Martin‐Serrano Ángela , Salas María , Bogas Gador , Nájera Francisco , Pérez‐Sala Dolores , Pérez‐Inestrosa Ezequiel , Fernandez Tahia D. , Montañez María I. , Torres María J.
Published: March 2019

Background

Selective reactions to clavulanic acid (CLV) account for around 30% of immediate reactions after administration of amoxicillin‐CLV. Currently, no immunoassay is available for detecting specific IgE to CLV, and its specific recognition in patients with immediate reactions has only been demonstrated by basophil activation testing, however with suboptimal sensitivity. The lack of knowledge regarding the structure of the drug that remains bound to proteins (antigenic determinant) is hampering the development of in vitro diagnostics. We aimed to identify the antigenic determinants of CLV as well as to evaluate their specific IgE recognition and potential role for diagnosis.

Methods

Based on complex CLV degradation mechanisms, we hypothesized the formation of two antigenic determinants for CLV, AD‐I (N‐protein, 3‐oxopropanamide) and AD‐II (N‐protein, 3‐aminopropanamide), and designed different synthetic analogs to each one. IgE recognition of these structures was evaluated in basophils from patients with selective reactions to CLV and tolerant subjects. In parallel, the CLV fragments bound to proteins were identified by proteomic approaches.

Results

Two synthetic analogs of AD‐I were found to activate basophils from allergic patients. This determinant was also detected bound to lysines 195 and 475 of CLV‐treated human serum albumin. One of these analogs was able to activate basophils in 59% of patients whereas CLV only in 41%. Combining both results led to an increase in basophil activation in 69% of patients, and only in 12% of controls.

Conclusion

We have identified AD‐I as one CLV antigenic determinant, which is the drug fragment that remains protein‐bound.
The antiviral effects of human microRNA miR‐302c‐3p against hepatitis B virus infection
Authors: Hamada‐Tsutsumi Susumu , Naito Yutaka , Sato Seiichi , Takaoka Akinori , Kawashima Keigo , Isogawa Masanori , Ochiya Takahiro , Tanaka Yasuhito
Published: March 2019

Background

Conventional treatments of chronic hepatitis B virus (HBV) infection rarely achieve a decline of serum hepatitis B surface antigen (HBsAg) levels and eradication of the virus.

Aim

To elucidate the antiviral mechanisms of a human microRNA, miR‐302c‐3p, against HBV replication.

Methods

The antiviral effect of miR‐302c‐3p was evaluated in vitro and in vivo by transfecting the miR‐302c‐3p mimic into HBV‐infected HepG2‐hNTCP‐C4 cells and HBV transgenic mice respectively.

Results

miR‐302c‐3p decreased not only HBV replication but also production of HBsAg. Pregenomic RNA and HBsAg mRNA concentrations decreased in the cells treated with miR‐302c‐3p. Interestingly, the amount of cccDNA was significantly reduced in the miR‐302c‐3p‐treated cells, in association with disappearance of the HBV core protein. An RNA immunoprecipitation assay showed that miR‐302c‐3p decreased the binding of the HBV polymerase to the pregenomic RNA by hybridising with the ε‐loop region. A number of host genes were downregulated in miR‐302c‐3p‐treated cells, including BMPR2 and HNF4A. Knockdown of these two genes by corresponding siRNAs also suppressed HBV replication and HBsAg secretion. The antiviral effect of miR‐302c‐3p was also observed in HBV transgenic mice.

Conclusion

miR‐302c‐3p had anti‐HBV activity, in vitro and in vivo, via several mechanisms.
Auto‐photographic study of everyday emotional geographies
Authors: Klingorová Kamila , Gökarıksel Banu
Published: March 2019

Recent developments in cultural geography have brought forth everyday life and emotions as critical categories for understanding place. Yet, the focus on everyday emotional geographies also presents methodological challenges. This paper argues that auto‐photography is a particularly well‐suited method to explore the intricate relations between everyday practices, emotions and the formation of places. Auto‐photography combines participant‐generated photographs and participants’ interpretative narrations of these photographs. Our argument is based on auto‐photographic research we conducted with 38 young women in Czechia in 2016. We asked participants to photograph everyday places that they associate with positive or negative emotions, or religious meanings, and to discuss their emotions in a following interview. We analysed participants’ photographs together with their narrations. This analysis reveals the emotions and meanings participants attached to photographed places. We argue that the method of auto‐photography helps understand the complexity of everyday emotional geographies that may not be possible through other geographical methods. The strength of auto‐photography is its combination of visual representations and narratives, which help identify how ordinary everyday places without any apparent significance, such as a door or a staircase, might be sites of strong emotional intensity. The insights gained by analysing photographs and narratives together and in relation to one another produce an understanding of emotional bordering practices, anxieties and desires of place‐making. Auto‐photography thus provides multiple layers of visual and textual data that help understand the complexity of emotional geographies in mundane everyday places.
Geographic space, relief, and soils predict plant community patterns of Asteraceae in rupestrian grasslands, Brazil
Authors: Chaves Daniel A. , Ribeiro‐Silva Suelma , Proença Carolyn E. B. , Oliveira Washington L. , Bringel João Bernardo A. , Medeiros Marcelo B.
Published: March 2019

We investigated the effects of geographic distance and environmental heterogeneity on Asteraceae communities in the rupestrian grasslands of the Espinhaço Range, southeastern Brazil. Asteraceae species composition and relative abundance were sampled in 21–1 ha plots distributed across park conservation units, comprising an environmental gradient in soils and relief (elevation and slope). We found high levels of heterogeneity overall in assemblages of herbaceous and woody Asteraceae species at the intermediate spatial scale of this study (10–100 km). We found that both relief and soil properties (texture and total exchangeable bases) explained significant proportions of variation in community composition, suggesting that definitions or expansions of conservation units should span the highest possible variability in observed relief and soil values. We also found that Asteraceae distribution exhibited strong spatial structure independent of environmental variation, reinforcing the need to consider conservation across larger areas. Considering the dystrophic character of the soils found in the Espinhaço Range and the few differences in the fertility observed between the sampling units, our results also support the hypothesis that plant distributions in the tropics are controlled by a hierarchy of environmental gradients, where variables such as altitude and exchangeable bases and Al texture are important predictors in low‐fertility soils. We suggest that Asteraceae could be a model family for conservation planning in other countries and regions because it is particularly well represented in open and montane areas of the Neotropics in general.

Abstract in Portuguese is available with online material.
Important report on cerebral palsy in Bangladesh: but different findings compared with other countries need further exploration
Authors: Andrews Carin , Kakooza‐Mwesige Angelina , Eliasson Ann‐Christin , Forssberg Hans
Published: March 2019

This commentary is on the original article by Khandaker et al. on pages 601–609 of this issue.
Safety and efficacy of ertugliflozin in Asian patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy: VERTIS Asia
Authors: Ji Linong , Liu Yanmei , Miao Heng , Xie Yongli , Yang Ming , Wang Wei , Mu Yuting , Yan Ping , Pan Sharon , Lauring Brett , Liu Shu , Huyck Susan , Qiu Yanping , Terra Steven G.
Published: March 2019

Aim

Phase III, randomized, double‐blind study evaluating the efficacy and safety of ertugliflozin in Asian patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin, including evaluation in the China subpopulation.

Materials and methods

A 26‐week, double‐blind study of 506 Asian patients (80.2% from mainland China), randomized 1:1:1 to placebo, ertugliflozin 5‐ or 15 mg, was performed. Primary endpoint was change from baseline in HbA1c at week 26. Secondary endpoints were change from baseline at week 26 in fasting plasma glucose (FPG), body weight (BW), systolic/diastolic blood pressure (SBP/DBP), and proportion of patients with HbA1c <7.0%. Hypotheses for the primary endpoint and FPG and BW secondary endpoints were tested in the China subpopulation.

Results

At week 26, least squares mean (95% CI) change from baseline HbA1c was significantly greater with ertugliflozin 5‐ and 15 mg versus placebo: −1.0% (−1.1, −0.9), −0.9% (−1.0, −0.8), −0.2% (−0.3, −0.1), respectively. Ertugliflozin significantly reduced FPG, BW and SBP. Reductions in DBP with ertugliflozin were not significant. At week 26, 16.2%, 38.2% and 40.8% of patients had HbA1c <7.0% with placebo, ertugliflozin 5‐ and 15 mg, respectively. 59.3%, 56.5% and 53.3% of patients experienced adverse events with placebo, ertugliflozin 5‐ and 15 mg, respectively. Incidence of symptomatic hypoglycaemia was higher for ertugliflozin 15 mg vs placebo. Results in the China subpopulation were consistent.

Conclusions

Ertugliflozin significantly improved glycaemic control and reduced BW and SBP in Asian patients with T2DM. Ertugliflozin was generally well‐tolerated. Results in the China subpopulation were consistent with the overall population.ClinicalTrials.gov: NCT02630706.
Better glycaemic control with BioChaperone glargine lispro co‐formulation than with insulin lispro Mix25 or separate glargine and lispro administrations after a test meal in people with type 2 diabetes
Authors: Meiffren Grégory , Herbrand Theresa , Anastassiadis Ernestos , Klein Oliver , DeVries J. Hans , Heise Tim , Alluis Bertrand , Mégret Claire , Gaudier Martin , Soula Olivier , Plum‐Mörschel Leona
Published: March 2019

Because of its physico‐chemical properties, insulin glargine is usually not mixable with rapid insulins. BioChaperone BC147 is a polyanionic amphiphilic polymer, solubilizing insulin glargine at neutral pH, and thus enabling stable glargine formulation with fast‐acting insulin lispro (BioChaperone glargine lispro co‐formulation [BC Combo]). We investigated pharmacokinetic (PK) endpoints and postprandial glucose (PPG) control after administration of BC Combo (75% insulin glargine, 25% insulin lispro), insulin lispro Mix25 (LMix) and separate injections of insulins glargine (75% total dose) and lispro (25% total dose [G + L]) immediately before ingestion of a mixed meal in people with type 2 diabetes mellitus (T2DM), using a randomized, double‐blind, double‐dummy crossover study design. Participants received individualized bolus doses (mean 0.62 U/kg) of BC Combo, LMix or G + L, together with a solid mixed meal (610 kcal, 50% carbohydrate, 30% fat, 20% protein). Insulin dosages were kept constant for each study day. Thirty‐nine participants with T2DM (mean ± SD age and glycated haemoglobin 60.8 ± 7.5 years and  64 ± 6 mmol/mol, respectively) were randomized. BC Combo improved the predefined primary endpoint, early PPG control, compared to LMix (incremental area under the blood glucose concentration–time curve from 0 to 2 hours after the meal [ΔAUCBG,0–2h] reduction of 18%; P = 0.0009) and G + L (ΔAUCBG,0–2h reduction of 10%; P = 0.0450). The number of mealtime hypoglycaemic episodes per participant was lower with BC Combo (22 episodes in 14 participants) compared to LMix (43 episodes in 20 participants; P = 0.0028), but not significantly different from G + L (28 episodes in 19 participants; P = 0.2523). BC Combo demonstrated superior early PPG control with fewer hypoglycaemic episodes compared to LMix and superior early PPG control compared to separate G + L administrations.