bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of low‐molecular‐weight heparin on the outcomes of in vitro fertilization/intracytoplasmic sperm injection pregnancy in non‐thrombophilic women: a meta‐analysis
Authors: Yang Xiu‐Li , Chen Fei , Yang Xiu‐Ying , Du Guan‐Hua , Xu Yang
Published: April 2018

Introduction

The aim of our study was to evaluate the effect of low‐molecular‐weight heparin on pregnancy outcomes in women without thrombophilia during in vitro fertilization/intracytoplasmic sperm injection treatment.

Material and methods

We searched Pubmed, Web of Science, Embase, Cochrane and CNKI (from inception to 2 February 2018). Our study identified randomized controlled trials or quasi‐randomized controlled trials comparing low‐molecular‐weight heparin subcutaneous treatment with no treatment or only luteal support control. The outcomes included live birth rate, clinical pregnancy rate and miscarriage rate.

Results

Five trials, including 935 women receiving in vitro fertilization/intracytoplasmic sperm injection treatment, were included in meta‐analyses. There were 458 women receiving low‐molecular‐weight heparin and 477 in the control group. No significant differences for live birth rate, clinical pregnancy rate and miscarriage rate were found between the low‐molecular‐weight heparin and control groups. Of them, four trials reported live birth rate as an outcome and the risk ratio was 1.13 (95% confidence interval 0.88–1.43, p = 0.34). All five trials reported clinical pregnancy rate as an outcome, the risk ratio was 1.08 (95% confidence interval 0.87–1.32, p = 0.47). Three trials reported miscarriage rate and the risk ratio was 0.58 (95% confidence interval 0.30–1.10, p = 0.09). In women with two or more failed in vitro fertilization/intracytoplasmic sperm injection cycles, the risk ratio of live birth rate was 1.15 and the risk ratio of clinical pregnancy rate was 1.17. In women with three or more failed in vitro fertilization/intracytoplasmic sperm injection cycles, the risk ratios of live birth rate and clinical pregnancy rate were 1.36 and 1.35, respectively.

Conclusions

Our results suggested that low‐molecular‐weight heparin had no effect on pregnancy success rate in non‐thrombophilic women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. However, to justify the use of low‐molecular‐weight heparin in clinical practice, multicenter trials are still necessary.
Effects of UGT1A1, CYP3A5 and ABCB1 Genetic Variants on Pharmacokinetics of Antihistamine Drug Mizolastine in Chinese Healthy Volunteers
Authors: Li Pu , Wei Min‐Ji , Zhang Zhi‐Yuan , Yin Sheng‐Ju , Wang Xin , Lou Ya‐Qing , Kang Zi‐Sheng , Lu Yuan , Wei Xuan , Zhai Suo‐Di , Zhang Guo‐Liang
Published: April 2018

Mizolastine is a selective histamine H1 receptor antagonist for chronic urticaria or allergic rhinitis. We investigated whether the variant genotypes of metabolic enzymes UGT1A1, CYP3A5 and transporter ABCB1 influence pharmacokinetic phenotype of substrate mizolastine in Chinese volunteers. Genotyping of single nucleotide polymorphisms in UGT1A1*6 (G211A), CYP3A5*3 (A6986G) and ABCB1 (C3435T) was determined by the pyrosequencing method. After a single oral dose of 10 mg mizolastine, the plasma concentrations were measured using validated high‐performance liquid chromatography in 24 Chinese healthy volunteers. The results showed that the distributions of wild‐type homozygotes and variant allele carriers (the sum of variant heterozygotes and variant homozygotes) were as follows: 17 cases (70.8%) versus seven cases (29.2%) in UGT1A1*6 genotypes, five cases (20.8%) versus 19 cases (79.2%) in CYP3A5*3 genotypes and seven cases (29.2%) versus 17 cases (70.8%) in ABCB1 3435T genotypes, respectively. There were no significant differences in pharmacokinetic parameters of mizolastine between the variant allele UGT1A1*6, CYP3A5*3 and ABCB1 3435T carriers and the wild‐type homozygotes, and the ratios were as follows: Cmax was 101.03%, 86.02% and 105.78%; Tmax was 162.35%, 98.98% and 144.90%; AUC0–28 was 113.04%, 77.35% and 112.71%; and t1/2 was 95.77%, 72.40% and 100.97%, respectively. In conclusion, these results suggested that the UGT1A1, CYP3A5 and ABCB1 genetic polymorphisms might be not contributed to the interindividual variation of mizolastine pharmacokinetic phenotype in the Chinese population.
Estimation of the Optimal Surrogate Based on a Randomized Trial
Authors: Price Brenda L. , Gilbert Peter B. , van der Laan Mark J.
Published: April 2018

A common scientific problem is to determine a surrogate outcome for a long-term outcome so that future randomized studies can restrict themselves to only collecting the surrogate outcome. We consider the setting that we observe n independent and identically distributed observations of a random variable consisting of baseline covariates, a treatment, a vector of candidate surrogate outcomes at an intermediate time point, and the final outcome of interest at a final time point. We assume the treatment is randomized, conditional on the baseline covariates. The goal is to use these data to learn a most-promising surrogate for use in future trials for inference about a mean contrast treatment effect on the final outcome. We define an optimal surrogate for the current study as the function of the data generating distribution collected by the intermediate time point that satisfies the Prentice definition of a valid surrogate endpoint and that optimally predicts the final outcome: this optimal surrogate is an unknown parameter. We show that this optimal surrogate is a conditional mean and present super-learner and targeted super-learner based estimators, whose predicted outcomes are used as the surrogate in applications. We demonstrate a number of desirable properties of this optimal surrogate and its estimators, and study the methodology in simulations and an application to dengue vaccine efficacy trials.
Application of the microbial community coalescence concept to riverine networks
Authors: Mansour India , Heppell Catherine M. , Ryo Masahiro , Rillig Matthias C.
Published: April 2018

Flows of water, soil, litter, and anthropogenic materials in and around rivers lead to the mixing of their resident microbial communities and subsequently to a resultant community distinct from its precursors. Consideration of these events through a new conceptual lens, namely, community coalescence, could provide a means of integrating physical, environmental, and ecological mechanisms to predict microbial community assembly patterns better in these habitats. Here, we review field studies of microbial communities in riverine habitats where environmental mixing regularly occurs, interpret some of these studies within the community coalescence framework and posit novel hypotheses and insights that may be gained in riverine microbial ecology through the application of this concept. Particularly in the face of a changing climate and rivers under increasing anthropogenic pressures, knowledge about the factors governing microbial community assembly is essential to forecast and/or respond to changes in ecosystem function. Additionally, there is the potential for microbial ecology studies in rivers to become a driver of theory development: riverine systems are ideal for coalescence studies because regular and predictable environmental mixing occurs. Data appropriate for testing community coalescence theory could be collected with minimal alteration to existing study designs.
Refractive regression after laser in situ keratomileusis
Authors: Yan Mabel K , Chang John SM , Chan Tommy CY
Published: April 2018

Uncorrected refractive errors are a leading cause of visual impairment across the world. In today's society, laser in situ keratomileusis (LASIK) has become the most commonly performed surgical procedure to correct refractive errors. However, regression of the initially achieved refractive correction has been a widely observed phenomenon following LASIK since its inception more than two decades ago. Despite technological advances in laser refractive surgery and various proposed management strategies, post‐LASIK regression is still frequently observed and has significant implications for the long‐term visual performance and quality of life of patients. This review explores the mechanism of refractive regression after both myopic and hyperopic LASIK, predisposing risk factors and its clinical course. In addition, current preventative strategies and therapies are also reviewed.
Long‐term extrapulmonary comorbidities after lung transplantation in cystic fibrosis: Update of specificities
Authors: Jardel Sabine , Reynaud Quitterie , Durieu Isabelle
Published: April 2018

Lung transplantation (LT) is the standard therapeutic option for cystic fibrosis (CF) patients with end‐stage lung disease. Both conditions lead to extrarespiratory complications, such as diabetes, renal insufficiency, bone disease, and cancer. The purpose of this study was to provide an update of the nonrespiratory comorbidities following LT in adult patients with CF and their specificities regarding their multisystemic underlying condition despite their younger age compared to other patients undergoing LT. Diabetes, renal insufficiency, metabolic bone disease, hypertension, liver disease, and cancer are the comorbidities considered in this review. The increase in CF adults living with a lung transplant justifies an update of knowledge for this specific situation (the prevalence of these complications, underlying risk factors), to provide better medical care and establish early diagnosis strategies.
Sorafenib Dose Recommendation in Acute Myeloid Leukemia Based on Exposure‐FLT3 Relationship
Authors: Liu Tao , Ivaturi Vijay , Sabato Philip , Gobburu Jogarao V. S. , Greer Jacqueline M. , Wright John J. , Smith B. Douglas , Pratz Keith W. , Rudek Michelle A. ,   on behalf of the ETCTN‐6745 study team
Published: April 2018

Sorafenib administered at the approved dose continuously is not tolerated long‐term in patients with acute myeloid leukemia (AML). The purpose of this study was to optimize the dosing regimen by characterizing the sorafenib exposure‐response relationship in patients with AML. A one‐compartment model with a transit absorption compartment and enterohepatic recirculation described the exposure. The relationship between sorafenib exposure and target modulation of kinase targets (FMS‐like tyrosine kinase 3 (FLT3)‐ITD and extracellular signal‐regulated kinase (ERK)) were described by an inhibitory maximum effect (Emax) model. Sorafenib could inhibit FLT3‐ITD activity by 100% with an IC50 of 69.3 ng/mL and ERK activity by 84% with an IC50 of 85.7 ng/mL (both adjusted for metabolite potency). Different dosing regimens utilizing 200 or 400 mg at varying frequencies were simulated based on the exposure‐response relationship. Simulations demonstrate that a 200 mg twice daily (b.i.d.) dosing regimen showed similar FLT3‐ITD and ERK inhibitory activity compared with 400 mg b.i.d. and is recommended in further clinical trials in patients with AML.
Mountaintop removal mining alters stream salamander population dynamics
Authors: Price Steven J. , Freytag Sara Beth , Bonner Simon J. , Drayer Andrea N. , Muncy Brenee' L. , Hutton Jacob M. , Barton Christopher D.
Published: April 2018

Aim

Population dynamics are often tightly linked to the condition of the landscape. Focusing on a landscape impacted by mountaintop removal coal mining (MTR), we ask the following questions: (1) How does MTR influence vital rates including occupancy, colonization and persistence probabilities, and conditional abundance of stream salamander species and life stages? (2) Do species and life stages respond similar to MTR mining or is there significant variation among species and life stages?

Location

Freshwater and terrestrial habitats in Central Appalachia (South‐eastern Kentucky, USA).

Methods

We conducted salamander counts for three consecutive years in 23 headwater stream reaches in forested or previously mined landscapes. We used a hierarchical, N‐mixture model with dynamic occupancy to calculate species‐ and life stage‐specific occupancy, colonization and persistence rates, and abundance given occupancy. We examined the coefficients of the hierarchical priors to determine population variation among species and life stages.

Results

Over 3 years, reference sites had greater salamander abundances and were occupied at a much higher rate than streams impacted by MTR. At sites impacted by MTR mining, most salamander species and life stages exhibited reduced initial occupancy, colonization rates, persistence rates and conditional abundance relative to reference stream reaches. Furthermore, the rates in MTR sites showed low variance, reinforcing that species and life stages were responding similar to MTR.

Main conclusions

Salamander populations in landscapes modified by MTR mining exhibited significantly reduced vital rates compared to reference sites. Yet, similarity in responses across species suggests that management or restoration may benefit the entire salamander assemblage. For example, reforestation could reduce landscape resistance, repair altered hydrologic regimes and allow for higher rates of colonization and persistence in streams impacted by MTR.
Defining the Potential of Nanoscale Re‐Os Isotope Systematics Using Atom Probe Microscopy
Authors: Daly Luke , Bland Phil A. , Tessalina Svetlana , Saxey David W. , Reddy Steven M. , Fougerouse Denis , Rickard William D.A. , Forman Lucy V. , La Fontaine Alexandre , Cairney Julie M. , Ringer Simon P. , Schaefer Bruce F. , Schwander Daniel
Published: April 2018

Atom probe microscopy (APM) is a relatively new in situ tool for measuring isotope fractions from nanoscale volumes (< 0.01 μm3). We calculate the theoretical detectable difference of an isotope ratio measurement result from APM using counting statistics of a hypothetical data set to be ± 4δ or 0.4% (2s). However, challenges associated with APM measurements (e.g., peak ranging, hydride formation and isobaric interferences), result in larger uncertainties if not properly accounted for. We evaluate these factors for Re‐Os isotope ratio measurements by comparing APM and negative thermal ionisation mass spectrometry (N‐TIMS) measurement results of pure Os, pure Re, and two synthetic Re‐Os‐bearing alloys from Schwander et al. (2015, Meteoritics and Planetary Science, 50, 893) [the original metal alloy (HSE) and alloys produced by heating HSE within silicate liquid (SYN)]. From this, we propose a current best practice for APM Re‐Os isotope ratio measurements. Using this refined approach, mean APM and N‐TIMS 187Os/189Os measurement results agree within 0.05% and 2s (pure Os), 0.6–2% and 2s (SYN) and 5–10% (HSE). The good agreement of N‐TIMS and APM 187Os/189Os measurements confirms that APM can extract robust isotope ratios. Therefore, this approach permits nanoscale isotope measurements of Os‐bearing alloys using the Re‐Os geochronometer that could not be measured by conventional measurement principles.
The opposing roles of CD4+ T cells in anti‐tumour immunity
Authors: Ahrends Tomasz , Borst Jannie
Published: April 2018

Cancer immunotherapy focuses mainly on anti‐tumour activity of CD8+ cytotoxic T lymphocytes (CTLs). CTLs can directly kill all tumour cell types, provided they carry recognizable antigens. However, CD4+ T cells also play important roles in anti‐tumour immunity. CD4+ T cells can either suppress or promote the anti‐tumour CTL response, either in secondary lymphoid organs or in the tumour. In this review, we highlight opposing mechanisms of conventional and regulatory T cells at both sites. We outline how current cancer immunotherapy strategies affect both subsets and how selective modulation of each subset is important to maximize the clinical response of cancer patients.
Early programming and late‐acting checkpoints governing the development of CD4 T‐cell memory
Authors: Dhume Kunal , McKinstry Karl Kai
Published: April 2018

CD4 T cells contribute to protection against pathogens through numerous mechanisms. Incorporating the goal of memory CD4 T‐cell generation into vaccine strategies therefore offers a powerful approach to improve their efficacy, especially in situations where humoral responses alone cannot confer long‐term immunity. These threats include viruses such as influenza that mutate coat proteins to avoid neutralizing antibodies, but that are targeted by T cells that recognize more conserved protein epitopes shared by different strains. A major barrier in the design of such vaccines is that the mechanisms controlling the efficiency with which memory cells form remain incompletely understood. Here, we discuss recent insights into fate decisions controlling memory generation. We focus on the importance of three general cues: interleukin‐2, antigen and co‐stimulatory interactions. It is increasingly clear that these signals have a powerful influence on the capacity of CD4 T cells to form memory during two distinct phases of the immune response. First, through ‘programming’ that occurs during initial priming, and second, through ‘checkpoints’ that operate later during the effector stage. These findings indicate that novel vaccine strategies must seek to optimize cognate interactions, during which interleukin‐2‐, antigen‐ and co‐stimulation‐dependent signals are tightly linked, well beyond initial antigen encounter to induce robust memory CD4 T cells.
Detection of selection signatures for agonistic behaviour in cattle
Authors: Eusebi P.G. , Cortés O. , Carleos C. , Dunner S. , Cañon J.
Published: April 2018

The identification of genomic regions including signatures of selection produced by domestication and its subsequent artificial selection processes allows the understanding of the evolution of bovine breeds. Although several studies describe the genomic variability among meat or milk production cattle breeds, there are limited studies orientated towards bovine behavioural features. This study is focused on mapping genomic signatures of selection which may provide insights of differentiation between neutral and selected polymorphisms. Their effects are studied in the Lidia cattle traditionally selected for agonistic behaviour compared with Spanish breeds showing tamed behaviour. Two different approaches, BayeScan and SelEstim, were applied using genotypic 50K SNP BeadChip data. Both procedures detected two genomic regions bearing genes previously related to behavioural traits. The frequencies of the selected allele in these two regions in Lidia breed were opposite to those found in the tamed breeds. In these genomic regions, several putative genes associated with enriched metabolic pathways related to the behavioural development were identified, as neurochondrin gene (NCDN) or glutamate ionotropic receptor kainate type subunit 3 (GRIK3) both located at BTA3 or leucine‐rich repeat and Ig domain containing 2 (LINGO2) and phospholipase A2‐activating protein (PLAA) at BTA8.
Rates of woody encroachment in African savannas reflect water constraints and fire disturbance
Authors: Axelsson Christoffer R. , Hanan Niall P.
Published: April 2018

Aim

The aims of this study were to (1) estimate current rates of woody encroachment across African savannas; (2) identify relationships between change in woody cover and potential drivers, including water constraints, fire frequency and livestock density. The found relationships led us to pursue a third goal: (3) use temporal dynamics in woody cover to estimate potential woody cover.

Location

Sub‐Saharan African savannas.

Methods

The study used very high spatial resolution satellite imagery at sites with overlapping older (2002–2006) and newer (2011–2016) imagery to estimate change in woody cover. We sampled 596 sites in 38 separate areas across African savannas. Areas with high anthropogenic impact were avoided in order to more clearly identify the influence of environmental factors. Relationships between woody cover change and potential drivers were identified using linear regression and simultaneous autoregression, where the latter accounts for spatial autocorrelation.

Results

The mean annual change in woody cover across our study areas was 0.25% per year. Although we cannot explain the general trend of encroachment based on our data, we found that change rates were positively correlated with the difference between potential woody cover and actual woody cover (a proxy for water availability; p < .001), and negatively correlated with fire frequency (p < .01). Using the relationship between rates of encroachment and initial cover, we estimated potential woody cover at different rainfall levels.

Main conclusions

The results indicate that woody encroachment is ongoing and widespread across African savannas. The fact that the difference between potential and actual cover was the most significant predictor highlights the central role of water availability and tree–tree competition in controlling change in woody populations, both in water‐limited and mesic savannas. Our approach to derive potential woody cover from the woody cover change trajectories demonstrates that temporal dynamics in woody populations can be used to infer resource limitations.
Leaf age affects the efficacy of insecticides to control Asian citrus psyllid, Diaphorina citri (Hemiptera: Liviidae)
Authors: De Carli L. F. , Miranda M. P. , Volpe H. X. L. , Zanardi O. Z. , Vizoni M. C. , Martini F. M. , Lopes J. P. A.
Published: April 2018

Huanglongbing (HLB), the most destructive citrus disease worldwide, is associated with the bacteria transmitted by the psyllid Diaphorina citri Kuwayama (Hemiptera: Liviidae). One of the main tactics used to manage this disease is the chemical control of D. citri. In this study, the efficacy of four insecticides commonly used by the citrus growers against the D. citri adults was assessed in two vegetative growth stages of flush: young shoots (~ 10 cm in length) and mature leaves. The bioassays were carried out under the greenhouse and field conditions. The insecticides bifenthrin, dimethoate, imidacloprid and thiamethoxam were tested at the recommended rates of 15, 450, 40 and 25 mg/L of water, respectively. The insecticides were sprayed onto the leaves of each stage until runoff. Psyllid mortality was assessed at different periods after insecticide application (0, 1 and 2 weeks). In both greenhouse and field trees, the period of control was shorter in the young shoots than in the mature leaves. In addition, the efficacy of insecticides rapidly decreased in the young shoots over time, mainly for imidacloprid and bifenthrin (less than 1 week). Thus, these results suggest that the number of spray applications to control D. citri should be more frequent during the flushing period.
Marriage and Family Therapy Students’ Experience with Common Factors Training
Authors: Fife Stephen T. , D'Aniello Carissa , Scott Sarah , Sullivan Erin
Published: April 2018

With the increased empirical and theoretical support for common factors in the psychotherapy literature, marriage and family therapy (MFT) scholars have begun discussing the inclusion of common factors in MFT training. However, there is very little empirical research on common factors training or how to include common factors in MFT curricula. The purpose of this phenomenological study was to investigate MFT students’ experience with common factors training. Seventeen master's degree students who received training in common factors participated in the study. Data was comprised of participants’ journal reflections and focus group interviews on their experience learning about common factors and how this influenced their work with clients. Participants’ responses to the training were overwhelmingly positive and highlighted the ways in which studying common factors enhanced their confidence, understanding of MFT models, conceptual abilities, and clinical practice. Additional results and discussion about incorporating common factors in MFT training are presented
Adaptation of evidence‐based guideline recommendations to address urinary incontinence in nursing home residents according to the ADAPTE‐process
Authors: Hoedl Manuela , Schoberer Daniela , Halfens Ruud J. G. , Lohrmann Christa
Published: April 2018

Aims and objectives

To adapt international guideline recommendations for the conservative management of urinary incontinence (UI), defined as any involuntary loss of urine, in Austrian nursing home residents following the ADAPTE‐process.

Background

Many international guidelines for managing UI are available. Nevertheless, the international recommendations have not yet been adapted to address the Austrian nursing home context. This crucial adaptation process will enhance the acceptance and applicability of the recommendations as well as encourage adherence among Austrian nurses and nursing home residents.

Design

This study is a methodological study based on the ADAPTE‐process, including a systematic search, quality appraisal of the guidelines using the Appraisal of Clinical Guidelines for REsearch & Evaluation II (AGREE II) instrument as well as an external review by means of a Delphi technique. The guidelines had to be topic‐relevant, published within the last 3 years and achieve a rigor of development score of 80% using the AGREE II instrument.

Methods

We searched international guideline databases to identify adequate guidelines. Two raters assessed the quality of each guideline, ascertaining that it fulfilled the inclusion criteria using the AGREE II instrument. We translated the identified recommendations into German and externally reviewed for their applicability in the Austrian context.

Results

We identified 1,612 hits in 10 databases. After applying inclusion and exclusion criteria, we assessed five international clinical guidelines for quality using the AGREE II instrument. One clinical guideline fulfilled the inclusion criteria. This clinical guideline contains 116 recommendations, of which 29 were applicable in the Austrian nursing home setting.

Conclusion

We identified only one suitable guideline, possibly due to the stringent nature of the inclusion criteria. However, following low‐quality guidelines may result in the use of recommendations that are not based on evidence and, therefore, may lead to suboptimal nursing care and outcomes.
Phytomelatonin receptor PMTR1‐mediated signaling regulates stomatal closure in Arabidopsis thaliana
Authors: Wei Jian , Li Dong‐Xu , Zhang Jia‐Rong , Shan Chi , Rengel Zed , Song Zhong‐Bang , Chen Qi
Published: April 2018

Melatonin has been detected in plants in 1995; however, the function and signaling pathway of this putative phytohormone are largely undetermined due to a lack of knowledge about its receptor. Here, we discovered the first phytomelatonin receptor (CAND2/PMTR1) in Arabidopsis thaliana and found that melatonin governs the receptor‐dependent stomatal closure. The application of melatonin induced stomatal closure through the heterotrimeric G protein α subunit‐regulated H2O2 and Ca2+ signals. The Arabidopsis mutant lines lacking AtCand2 that encodes a candidate G protein‐coupled receptor were insensitive to melatonin‐induced stomatal closure. Accordingly, the melatonin‐induced H2O2 production and Ca2+ influx were completely abolished in cand2. CAND2 is a membrane protein that interacts with GPA1 and the expression of AtCand2 was tightly regulated by melatonin in various organs and guard cells. CAND2 showed saturable and specific 125I‐melatonin binding, with apparent Kd (dissociation constant) of 0.73 ± 0.10 nmol/L (r2 = .99), demonstrating this protein is a phytomelatonin receptor (PMTR1). Our results suggest that the phytomelatonin regulation of stomatal closure is dependent on its receptor CAND2/PMTR1‐mediated H2O2 and Ca2+signaling transduction cascade.
Melatonin and its derivatives counteract the ultraviolet B radiation‐induced damage in human and porcine skin ex vivo
Authors: Skobowiat Cezary , Brożyna Anna A. , Janjetovic Zorica , Jeayeng Saowanee , Oak Allen S. W. , Kim Tae‐Kang , Panich Uraiwan , Reiter Russel J. , Slominski Andrzej T.
Published: April 2018

Melatonin and its derivatives (N1‐acetyl‐N2‐formyl‐5‐methoxykynurenine [AFMK] and N‐acetyl serotonin [NAS]) have broad‐spectrum protective effects against photocarcinogenesis, including both direct and indirect antioxidative actions, regulation of apoptosis and DNA damage repair; these data were primarily derived from in vitro models. This study evaluates possible beneficial effects of melatonin and its active derivatives against ultraviolet B (UVB)‐induced harm to human and porcine skin ex vivo and to cultured HaCaT cells. The topical application of melatonin, AFMK, or NAS protected epidermal cells against UVB‐induced 8‐OHdG formation and apoptosis with a further increase in p53ser15 expression, especially after application of melatonin or AFMK but not after NAS use. The photoprotective action was observed in pre‐ and post‐UVB treatment in both human and porcine models. Melatonin along with its derivatives upregulated also the expression of antioxidative enzymes after UVB radiation of HaCaT cells. The exogenous application of melatonin or its derivatives represents a potent and promising tool for preventing UVB‐induced oxidative stress and DNA damage. This protection results in improved genomic, cellular, and tissue integrity against UVB‐induced carcinogenesis, especially when applied prior to UV exposure. In addition, our ex vivo experiments provide fundamental justification for further testing the clinical utility of melatonin and metabolites as protectors again UVB in human subjects. Our ex vivo data constitute the bridge between vitro to vivo translation and thus justifies the pursue for further clinical utility of melatonin in maintaining skin homeostasis.
Why Did God Make Me This Way? Religious Coping and Framing in the Virtuous Pedophile Community
Authors: Cranney Stephen
Published: April 2018

“Virtuous Pedophiles” (or VPs) have a sexual attraction to children but view child/adult sexual relations as wrong. Research on VPs is nascent but has theoretical importance for our understanding of sexuality, labeling, and extreme stigma. Their relevance is particularly acute in regard to religious coping and framing. As their primary stressor is a predisposition towards a highly stigmatized (or “sinful”) activity, religious VPs find themselves in a unique situation, and it is unknown to what extent they employ conventional religious coping mechanisms. I investigate how VPs use their religious frameworks to make sense of and react to their pedophilia with a survey of respondents recruited from an online VP forum, a content analysis of forum discussions, and several in‐depth, semistructured interviews. Religious VPs tend to employ the same basic religious coping mechanisms (both positive and negative) but customize their approaches to accommodate their unique situation. Positive and negative religious coping show the same relationships with mental health as found in other populations. Religiosity is associated with both lower mental distress as well as less cognitive distortions associated with sexual offending.
Airway persistence by the emerging multi‐azole‐resistant Rasamsonia argillacea complex in cystic fibrosis
Authors: Abdolrasouli Alireza , Bercusson Amelia C. , Rhodes Johanna L. , Hagen Ferry , Buil Jochem B. , Tang Alison Y. Y. , de Boer Leonard L. , Shah Anand , Milburn Andrew J. , Elborn J. Stuart , Jones Andrew L. , Meis Jacques F. , Fisher Matthew C. , Schelenz Silke , Simmonds Nicholas J. , Armstrong‐James Darius
Published: April 2018

Infections caused by Rasamsonia argillacea complex have been reported in various clinical settings. Cystic fibrosis (CF) is one of the main underlying conditions. An observational cohort study of CF patients with Rasamsonia in respiratory samples was conducted. Eight isolates from 6 patients were identified as R. argillacea complex and tested for antifungal susceptibility. All isolates had high MICs to voriconazole and posaconazole and low MECs to echinocandins. Four patients experienced lung function decline in the year preceding first Rasamsonia isolation. This continued in the year following first isolation in 3 out of 4 cases. Antifungal therapy was initiated in 2 patients, to which only one exhibited a clinical response. Three out of 6 patients died within 3 years of isolating Rasamsonia. Genotyping suggests that similar genotypes of Rasamsonia can persist in CF airways. Consistent with other fungi in CF, the clinical impact of airway colonisation by Rasamsonia is variable. In certain patients, Rasamsonia may be able to drive clinical decline. In others, though a clear impact on lung function may be difficult to determine, the appearance of Rasamsonia acts as a marker of disease severity. In others it does not appear to have an obvious clinical impact on disease progression.
How do arbuscular mycorrhizal fungi handle phosphate? New insight into fine‐tuning of phosphate metabolism
Authors: Ezawa Tatsuhiro , Saito Katsuharu
Published: April 2018

Contents

Summary
1116

I.
Introduction
1116

II.
Foraging for phosphate
1117

III.
Fine‐tuning of phosphate homeostasis
1117

IV.
The frontiers: phosphate translocation and export
1119

V.
Conclusions and outlook
1120

Acknowledgements
1120

References
1120

Arbuscular mycorrhizal fungi form symbiotic associations with most land plants and deliver mineral nutrients, in particular phosphate, to the host. Therefore, understanding the mechanisms of phosphate acquisition and delivery in the fungi is critical for full appreciation of the mutualism in this association. Here, we provide updates on physical, chemical, and biological strategies of the fungi for phosphate acquisition, including interactions with phosphate‐solubilizing bacteria, and those on the regulatory mechanisms of phosphate homeostasis based on resurveys of published genome sequences and a transcriptome with reference to the latest findings in a model fungus. For the mechanisms underlying phosphate translocation and export to the host, which are major research frontiers in this field, not only recent advances but also testable hypotheses are proposed. Lastly, we briefly discuss applicability of the latest tools to gene silencing in the fungi, which will be breakthrough techniques for comprehensive understanding of the molecular basis of fungal phosphate metabolism.
Higher grain yield and higher grain protein deviation underline the potential of hybrid wheat for a sustainable agriculture
Authors: Thorwarth Patrick , Piepho Hans P. , Zhao Yusheng , Ebmeyer Erhard , Schacht Johannes , Schachschneider Ralf , Kazman Ebrahim , Reif Jochen C. , Würschum Tobias , Longin Carl Friedrich Horst
Published: April 2018

Grain yield and protein content are traits of major importance in wheat breeding, but their combination is challenging due to a tight negative correlation. Protein yield and grain protein deviation have been proposed as selection criteria to simultaneously improve both traits. Sedimentation volume is an indicator of protein quality, which plays an important role for bread‐making quality in wheat. All these traits have been investigated in our study with 135 parental inbred lines, their 1,604 hybrids and 10 commercial check varieties evaluated at five environments. The focus of our study was to investigate the usefulness of the grain protein deviation and to define a bivariate model for calculating the grain protein deviation. Further, we compared line and hybrid wheat for grain yield and quality‐related parameters such as protein content and sedimentation volume. The grain protein deviation determined with a bivariate model delivered robust estimates of variance components and enabled a balanced selection of genotypes with improved protein content and grain yield across different quality classes. Although heterosis for protein content and sedimentation volume was negative, hybrids had a higher grain protein deviation as well as higher grain yield at a given sedimentation volume or a given protein content than line varieties.
Bernard Williams on the Human Prejudice
Authors: Diamond Cora
Published: April 2018

In “The Human Prejudice”, Bernard Williams discusses our treating human beings differently in our moral thinking from the ways we treat other creatures. He criticises the idea that this expresses a prejudice, speciesism, analogous to racism and sexism. His essay has been misunderstood by some of its critics, including Peter Singer and Jeff McMahan. My essay sets out several questions one may have about Williams's essay, and explains how they can be answered. I make clear the connections between “The Human Prejudice” and some main elements in Williams's thinking about ethics, including his criticisms of moral theory.
How Do Consumers Choose between Multiple Product Generations and Conditions? An Empirical Study of iPad Sales on eBay
Authors: McKie Erin C. , Ferguson Mark E. , Galbreth Michael R. , Venkataraman Sriram
Published: April 2018

Many companies are reluctant to enter the remanufacturing market because of concern with cannibalization of new sales, competition from current remanufacturers, and the willingness of consumers to purchase remanufactured products. What is often missing, however, is an in‐depth understanding of how consumers make complex purchase decisions involving remanufactured items among numerous other options. This study examines how consumers evaluate remanufactured products when there are multiple conditions and generations of the item available, and evaluates the risk that remanufactured products pose to new product sales. We leverage transaction data of iPad sales from eBay and structural estimation techniques developed in the industrial organization literature to conduct our analysis. We find that product generation, condition, and seller attributes are all highly influential in shaping consumers’ purchasing decisions and that the relationship between new and remanufactured products is much more nuanced and context‐specific than previously shown. Counter to industry intuition, we find that remanufactured products pose the same amount of threat to new‐condition goods as do used goods. Through these and other findings, we provide insights on how CLSC participants and those exploring entry into the remanufacturing business may achieve more profitable remanufacturing strategies.
Psychopathic traits are differentially associated with efficiency of neural communication
Authors: Tillem Scott , van Dongen Josanne , Brazil Inti A. , Baskin‐Sommers Arielle
Published: April 2018

Recent advances in the application of graph theory made it possible to quantify the efficiency of communication within a neural network, going beyond traditional connectivity methods that only identify the degree to which neural regions are connected. Psychopathic traits, namely, interpersonal‐affective and impulsive‐antisocial traits, have been linked to widespread and distinct disruptions in neural connectivity. The efficiency of neural communication for individuals high on these psychopathic traits, though, is unknown. In the present study, resting‐state EEG was used to generate a connectivity matrix (i.e., weighted phase lag index) for multiple frequency bands. These connectivity matrices were examined using minimum spanning tree analysis, a graph theory approach that allows for the examination of neural efficiency, and regressed on Self‐Report Psychopathy‐Short Form scores (n = 158, unselected community sample). Results indicated that individuals with higher interpersonal‐affective traits had significantly less efficient communication within alpha1 (i.e., long‐range neural communication) and gamma (i.e., short‐range neural communication) frequency bands. Conversely, individuals with higher impulsive‐antisocial traits had more efficient communication within these same frequency bands. Overall, elevated psychopathic traits were related to alterations in the basic efficiency of neural communication. Moreover, this unique application of graph analysis provides a new avenue for inquiry into the mechanisms underlying the chronic and severe behavior of individuals with psychopathic traits.
M/XDR‐TB treatment perspective: How to avoid mountains of pills via digital technologies
Authors: Dudnyk Andrii , Burman Matthew , Kulyk Ludmyla , Rzhepishevska Olena
Published: April 2018

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Physiological characterization of ocular melanosis‐affected canine melanocytes
Authors: Dawson‐Baglien Ethan M. , Noland Erica L. , Sledge Dodd G. , Kiupel Matti , Petersen‐Jones Simon M.
Published: April 2018

Objective

Cairn terriers with ocular melanosis (OM) accumulate large, heavily pigmented melanocytes in the anterior uvea. Darkly pigmented plaques develop within the sclera, leading us to hypothesize that OM uveal melanocytes may have an abnormal migratory capacity.

Animals studied

Globes from OM‐affected Cairn terriers and unaffected control eyes enucleated for reasons unrelated to this study were used for immunohistochemistry and to culture melanocytes for in vitro cell behavior assays.

Procedures

The scleral plaques of six dogs were immunolabeled for HMB‐45, MelanA, PNL2, CD18, CD204, and Iba‐1 and compared with the pigment cells accumulated within the irides. Cultured uveal melanocytes from OM‐affected and control dogs were compared using conventional assays measuring cell proliferation, invasion capability, and melanin production.

Results

Melanocytes isolated from OM eyes had significantly elevated levels of per‐cell melanin content and production compared to controls. The majority of pigmented cells in the scleral plaques were HMB45 positive indicating a melanocytic origin. Many were also CD18 positive. No differences were observed between cultured melanocytes from OM‐affected and control uvea for standard in vitro proliferation or invasion assays.

Conclusion

Pigmented cells which accumulate in the sclera of OM‐affected Cairn terriers are predominantly melanocytes; however, in vitro assays of uveal melanocytes did not reveal differences in migratory behavior between OM and control cells. Migratory behavior of OM‐melanocytes may be environment‐dependent. We suggest that RNA sequencing and differential expression analysis would be a useful next step in understanding this disease.
A Non-Failing “NeoBlend-Digit” Schooling Free of Conventional Teachers: A Blueprint for a Futuristic Learning Open to Infinity
Authors: Hamdan M. Ziad
Published: April 2018

The practice of Blended learning in schooling for almost two decades has shown limited variations from what conventional education had breached hundreds of years ago. In that, continuing the use of large groups teaching, big chunks of required curriculum for learning and instruction, unified mandatory knowledge for all students, the lack of individual achievement pace, unified daily study schedules, and same backward assessment tools and formalities. Yet, ICTs exert every moment profound remote digital penetrating power into the deep privacy of human anatomy, actions, family and daily lives in what could be called the “Age of digital Information Nudity”. Moreover, resource teachers or students’ counselors are able by a click at a digital curriculum to reveal where learners’ locations are, how many times attempted reading, performing assignments, or what study difficulties they are facing. ICTs have dismantled all the psychological, social, educational and physical boundaries separating peoples, businesses and schooling communities. Students living currently in digital environments have a free will through digital means to decide, plan, in addition, to using types, tools, times and settings for their blended and online learnings, even without the pre-consent of school authorities. Hence, a new form of blended education deems crucial, that is “neoBlend-Digit” Schooling. This new hybrid methodology, when well served by developmental appropriate curriculum design, thoughtful treatment of curriculum content, a systemic implementation framework (diagnostic, formative and summative), and optional multi learning tracks, will lead to open ended learning free of failure, outdated teachers and school personnel, and environmental limitations. Consequently civic citizen students are graduating as literates, professional specialists, and academic pioneers.. Realizing as such what the American educator, William Glasser* wished for “Schools without Failure”. In current work however, the long waited dream of Glasser is presented in a concise digital language and concretely accountable educational evidences in field reality.
Nonequilibrium electron and lattice dynamics of strongly correlated Bi
2
Sr
2
CaCu
2
O
8+δ
single crystals
Authors: Konstantinova Tatiana , Rameau Jonathan D. , Reid Alexander H. , Abdurazakov Omadillo , Wu Lijun , Li Renkai , Shen Xiaozhe , Gu Genda , Huang Yuan , Rettig Laurenz , Avigo Isabella , Ligges Manuel , Freericks James K. , Kemper Alexander F. , Dürr Hermann A. , Bovensiepen Uwe , Johnson Peter D. , Wang Xijie , Zhu Yimei
Published: April 2018

Both electron and lattice dynamics are directly observed in the nonequilibrium state of strongly correlated Bi-2212.
Readily accessible shape-memory effect in a porous interpenetrated coordination network
Authors: Shivanna Mohana , Yang Qing-Yuan , Bajpai Alankriti , Sen Susan , Hosono Nobuhiko , Kusaka Shinpei , Pham Tony , Forrest Katherine A. , Space Brian , Kitagawa Susumu , Zaworotko Michael J.
Published: April 2018

An interpenetrated flexible metal-organic material exhibits only the second example of a shape-memory effect in a porous material.
Decline of adolescent smoking in Ireland 1995–2015: trend analysis and associated factors
Authors: Li Shasha , Keogan Sheila , Taylor Keishia , Clancy Luke
Published: April 2018

Objectives

The study examines trends in smoking among Irish adolescents aged 15–16 years between 1995 and 2015 and the factors associated with their smoking behaviours between 2007 and 2015.

Methods

Data were obtained from the European School Survey Project on Alcohol and Other Drugs Ireland between 1995 and 2015. To examine the gender gap, two-sample proportion tests were used. Multivariate logistic regression was performed to examine the factors associated with smoking behaviours. Dependent variable is whether a respondent is a smoker in last 30 days. Independent variables include gender, survey years, perceived ease of access to cigarettes, perceived risk of smoking, perceived relative wealth, parental monitoring, maternal relationship, family structure, truancy and peer smoking.

Results

Smoking prevalence has dropped from 41% in 1995 to 13% in 2015. The prevalence was much higher among girls than boys in 1995. The gender gap was closed by 2015. Multivariate regression results show that peer smoking, perceived access to cigarettes, perceived risks of smoking, parental monitoring, truancy, maternal relationship, perceived relative wealth and family structure were all significantly associated with adolescent smoking, and some of the factors had different effects for female and male students.

Conclusion

Ireland has successfully achieved a considerable decrease of adolescent smoking from 1995 to 2015, during which various tobacco control policies have been implemented. In addition, the gender gap on adolescent smoking has been closed during the period. Adolescent smoking could be further improved through strengthening enforcement on adolescent access to cigarettes and maintaining a high-intensity tobacco control media campaign targeting adolescents. Parents could also contribute by enhancing monitoring.