bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions between fawns and does of farmed fallow deer Dama dama in the postnatal period
Authors: Janiszewski Paweł , Cilulko‐Dołęga Justyna , Murawska Daria , Bogdaszewski Marek
Published: October 2017

The aim of the present study was to describe the suckling behavior of the offspring of farmed European fallow deer Dama dama in the postnatal period. Video surveillance footage from the first 18 days postpartum was analyzed in detail to reveal that the duration of interactions between the mother and the offspring changed with the fawns’ age. The duration of mother‐offspring interactions was longest between postpartum days 12 and 18. The frequency of interactions at different times of the day varied in the analyzed periods. The results of the study could be used to increase the welfare of farmed deer.
Optimal dosing and delivery of parathyroid hormone and its analogues for osteoporosis and hypoparathyroidism – translating the pharmacology
Authors: Tay Donovan , Cremers Serge , Bilezikian John P.
Published: October 2017

In primary hyperparathyroidism (PHPT), bone loss results from the resorptive effects of excess parathyroid hormone (PTH). Under physiological conditions, PTH has actions that are more targeted to homeostasis and to bone accrual. The predominant action of PTH, either catabolic, anabolic or homeostatic, can be understood in molecular and pharmacokinetic terms. When administered intermittently, PTH increases bone mass, but when present continuously and in excess (e.g. PHPT), bone loss ensues. This dual effect of PTH depends not only on the dosing regimen, continuous or intermittent, but also on how the PTH molecule interacts with various states of its receptor (PTH/PTHrP receptor) influencing downstream signalling pathways differentially. Altering the amino‐terminal end of PTH or PTHrP could emphasize the state of the receptor that is linked to an osteoanabolic outcome. This concept led to the development of a PTHrP analogue that interacts preferentially with the transiently linked state of the receptor, emphasizing an osteoanabolic effect. However, designing PTH or PTHrP analogues with prolonged state of binding to the receptor would be expected to be linked to a homeostatic action associated with the tonic secretory state of the parathyroid glands that is advantageous in treating hypoparathyroidism. Ideally, further development of a drug delivery system that mimics the physiological tonic, circadian, and pulsatile profile of PTH would be optimal. This review discusses basic, translational and clinical studies that may well lead to newer approaches to the treatment of osteoporosis as well as to different PTH molecules that could become more advantageous in treating hypoparathyroidism.
How we diagnose and treat systemic mastocytosis in adults
Authors: Scherber Robyn M. , Borate Uma
Published: October 2017

Rapid advances in the understanding of the molecular biology, data from translational and clinical trials, and retrospective analyses has influenced the diagnosis and treatment of systemic mastocytosis (SM). Many options have existed for the symptomatic management of SM patients, but recent evolution in regards to the molecular underpinnings of this disease and our ability to distinguish clonal mastocytosis from mast cell activation syndrome has changed our treatment paradigm and opened new opportunities for understanding genetic risk, transformation to mast cell leukaemia, and treatment choices. Key to this change has been the discovery of the KIT mutation and the use of next generation sequencing to evaluate for co‐existing molecular mutations that may define the disease course. Careful diagnosis, judicious symptom management and close surveillance of those who may have yet undiagnosed disease is paramount in providing optimal management. In this article, we review the diagnosis and provide a paradigm for the management of SM patients.
Realgar nanoparticles versus ATO arsenic compounds induce in vitro and in vivo activity against multiple myeloma
Authors: Cholujova Danka , Bujnakova Zdenka , Dutkova Erika , Hideshima Teru , Groen Richard W. , Mitsiades Constantine S. , Richardson Paul G. , Dorfman David M. , Balaz Peter , Anderson Kenneth C. , Jakubikova Jana
Published: October 2017

Multiple myeloma (MM), a B cell malignancy characterized by clonal proliferation of plasma cells in the bone marrow, remains incurable despite the use of novel and conventional therapies. In this study, we demonstrated MM cell cytotoxicity triggered by realgar (REA; As4S4) nanoparticles (NREA) versus Arsenic trioxide (ATO) against MM cell lines and patient cells. Both NREA and ATO showed in vivo anti‐MM activity, resulting in significantly decreased tumour burden. The anti‐MM activity of NREA and ATO is associated with apoptosis, evidenced by DNA fragmentation, depletion of mitochondrial membrane potential, cleavage of caspases and anti‐apoptotic proteins. NREA induced G2/M cell cycle arrest and modulation of cyclin B1, p53 (TP53), p21 (CDKN1A), Puma (BBC3) and Wee‐1 (WEE1). Moreover, NREA induced modulation of key regulatory molecules in MM pathogenesis including JNK activation, c‐Myc (MYC), BRD4, and histones. Importantly, NREA, but not ATO, significantly depleted the proportion and clonogenicity of the MM stem‐like side population, even in the context of the bone marrow stromal cells. Finally, our study showed that both NREA and ATO triggered synergistic anti‐MM activity when combined with lenalidomide or melphalan. Taken together, the anti‐MM activity of NREA was more potent compared to ATO, providing the preclinical framework for clinical trials to improve patient outcome in MM.
Effect of ultrasonic nanocrystal surface modification on residual stress and fatigue cracking in engineering alloys
Authors: Khan M.K. , Fitzpatrick M.E. , Wang Q.Y. , Pyoun Y.S. , Amanov A.
Published: October 2017

The effects of ultrasonic nanocrystal surface modification (UNSM) on residual stresses and fatigue crack initiation were investigated in various engineering alloys. It was found that higher contact force and smaller pin in UNSM produced higher compressive residual stresses at the surface and subsurface of the alloys. The compressive residual stresses were found to be higher in high yield strength alloys. A deeper compressive residual stress field was observed in alloys with higher elastic modulus and strain hardening exponent. Fatigue crack initiation was found to occur subsurface in the material where the effect of UNSM hardening was saturated. It was concluded that deeper UNSM hardening produces higher fatigue life.
Analysis of the stress intensity factor along the thickness: The concept of pivot node on straight crack fronts
Authors: Garcia‐Manrique J. , Camas‐Peña D. , Lopez‐Martinez J. , Gonzalez‐Herrera A.
Published: October 2017

This paper focuses on calculating and analysing the thickness and load level influence on the stress intensity factor distribution along the thickness, both individually and together. The main objective is improving the knowledge about the small region existing near the surface where the stress intensity factor results remain independent of external factor as load level or thickness. It is found that this phenomenon occurs around a pivot node within the crack front (PI) that presents advantages for the correlation of numerical and experimental studies.

The work evaluates the finite element model of an Al 2024‐T35 compact tension specimen with no plastic wake effect introduced. The three‐dimensional behaviour near the crack front is simulated through numerical analysis with ANSYS code, and J‐integral method is used to determinate the curves of K evolution along the thickness.

The results are studied according to a series of parameters that characterize the curves. Conclusions are presented on the areas of influence of each factor involved.
Very high‐cycle fatigue behaviour ofTi‐6Al‐4Valloy under corrosive environment
Authors: Zhao P.‐C. , Li S.‐X. , Jia Y.‐F. , Zhang C.‐C. , Zhang X.‐C. , Tu S.‐T.
Published: October 2017

Rotary‐bending fatigue tests of Ti‐6Al‐4V alloy at very high‐cycle regime were performed in air and 3.5% NaCl solution, respectively. The S‐N curves exhibited the characteristic of horizontal asymptote (traditional fatigue limit) in laboratory air, while a lower fatigue limit was shown in 3.5% NaCl solution after around 3 × 108cycles. The decrease of fatigue life was due to the generation of small surface defects in comparison with that in air. These defects were ascribed to the hydrogen‐induced cracking and fatigue loading. The number of fatigue crack initiation sites decreases with increasing cycles. Only one crack origin site, dominated by slip mechanism, exists in each specimen at very high‐cycle regime. The existing experimental S‐N data of Ti‐6Al‐4V alloy from very high‐cycle fatigue tests were also reviewed. It was shown that the fatigue life (R = −1) of Ti‐6Al‐4V alloy was predominantly influenced by the microstructure and not strongly sensitive to the loading mode and frequency (in the range from 52.5 Hz to 20 kHz) under air condition at room temperature.
Environmental insights from high‐resolution (SIMS) sulfur isotope analyses of sulfides in Proterozoic microbialites with diverse mat textures
Authors: Gomes M. L. , Fike D. A. , Bergmann K. D. , Jones C. , Knoll A. H.
Published: October 2017

In modern microbial mats, hydrogen sulfide shows pronounced sulfur isotope (δ34S) variability over small spatial scales (~50‰ over <4 mm), providing information about microbial sulfur cycling within different ecological niches in the mat. In the geological record, the location of pyrite formation, overprinting from mat accretion, and post‐depositional alteration also affect both fine‐scale δ34S patterns and bulk δ34Spyrite values. We report μm‐scale δ34S patterns in Proterozoic samples with well‐preserved microbial mat textures. We show a well‐defined relationship between δ34S values and sulfide mineral grain size and type. Small pyrite grains (<25 μm) span a large range, tending toward high δ34S values (−54.5‰ to 11.7‰, mean: −14.4‰). Larger pyrite grains (>25 μm) have low but equally variable δ34S values (−61.0‰ to −10.5‰, mean: −44.4‰). In one sample, larger sphalerite grains (>35 μm) have intermediate and essentially invariant δ34S values (−22.6‰ to −15.6‰, mean: −19.4‰). We suggest that different sulfide mineral populations reflect separate stages of formation. In the first stage, small pyrite grains form near the mat surface along a redox boundary where high rates of sulfate reduction, partial closed‐system sulfate consumption in microenvironments, and/or sulfide oxidation lead to high δ34S values. In another stage, large sphalerite grains with low δ34S values grow along the edges of pore spaces formed from desiccation of the mat. Large pyrite grains form deeper in the mat at slower sulfate reduction rates, leading to low δ34Ssulfide values. We do not see evidence for significant 34S‐enrichment in bulk pore water sulfide at depth in the mat due to closed‐system Rayleigh fractionation effects. On a local scale, Rayleigh fractionation influences the range of δ34S values measured for individual pyrite grains. Fine‐scale analyses of δ34Spyrite patterns can thus be used to extract environmental information from ancient microbial mats and aid in the interpretation of bulk δ34Spyrite records.
Reading Australian modernity: Unsettled settlers and cultures of mobility
Authors: Rees Anne
Published: October 2017

What did Australian modernity look like? Over the last two decades, Australia's entrenched reputation for ‘cultural belatedness’ has been displaced by the study of ‘colonial modernity’. No longer beholden to the idea that a singular modernity was disseminated from core to periphery, scholars now speak of many localised modernities that arose across colonial and provincial sites. According to this new ‘multiple modernities’ paradigm, Australia was home to its own home‐grown incarnation of modern life. But what was distinctively ‘Australian’ about Australian modernity? Although widely discussed in recent historiography, scholars have yet to delineate its distinguishing features. This article posits mobility as a central component of the Australian modern. Drawing upon new scholarship in settler colonial studies and transnational history, it argues that early twentieth‐century Australia was home to intense cultures of both domestic and global mobility that were entangled with the geographies and anxieties of the settler colonial project. It shows how the nation's ‘unsettled settlers’ also became its chief agents of modernity, and in doing so draws together several strands in recent historiography. Although mobility also signified modernity beyond Australia, it was within this settler colonial nation tyrannised by distance that the modern appetite for motion reached especial heights.
The story continues: an overview of the ‘Dissertations into Practice’ feature
Authors: Marshall Audrey
Published: October 2017

The ‘Dissertations into practice’ feature began life in March 2012 with a dual aim: to encourage students, recent graduates and new professionals to write for publication and to highlight the impact of student research on policy and practice. This article reflects on the initiative and demonstrates that it has been extremely successful in achieving both aims. It highlights the diverse range of contributions to the feature so far and proves that student research can and does influence policy and practice. It also demonstrates that, with the right encouragement and support, students are willing and able to write for academic publication and that they gain a lot from the experience.

A. M.
Dental pulp regeneration via cell homing
Authors: Eramo S. , Natali A. , Pinna R. , Milia E.
Published: October 2017

The typical treatment for irreversibly inflamed/necrotic pulp tissue is root canal treatment. As an alternative approach, regenerative endodontics aims to regenerate dental pulp‐like tissues using two possible strategies: cell transplantation and cell homing. The former requires exogenously transplanted stem cells, complex procedures and high costs; the latter employs the host's endogenous cells to achieve tissue repair/regeneration, which is more clinically translatable. This systematic review examines cell homing for dental pulp regeneration, selecting articles on in vitro experiments, in vivo ectopic transplantation models and in situ pulp revascularization. MEDLINE/PubMed and Scopus databases were electronically searched for articles without limits in publication date. Two reviewers independently screened and included papers according to the predefined selection criteria. The electronic searches identified 46 studies. After title, abstract and full‐text examination, 10 articles met the inclusion criteria. In vitro data highlighted that multiple cytokines have the capacity to induce migration, proliferation and differentiation of dental pulp stem/progenitor cells. The majority of the in vivo studies obtained regenerated connective pulp‐like tissues with neovascularization. In some cases, the samples showed new innervation and new dentine deposition. The in situ pulp revascularization regenerated intracanal pulp‐like tissues with neovascularization, innervation and dentine formation. Cell homing strategies for pulp regeneration need further understanding and improvement if they are to become a reliable and effective approach in endodontics. Nevertheless, cell homing currently represents the most clinically viable pathway for dental pulp regeneration.
Addition of dipeptidyl peptidase‐4 inhibitors to insulin treatment in type 2 diabetes patients: A meta‐analysis
Authors: Yang Wenjia , Cai Xiaoling , Gao Xueying , Chen Yifei , Chen Ling , Ji Linong
Published: October 2017

Aims/Introduction

To evaluate the efficacy and safety of combining insulin therapy with dipeptidyl peptidase‐4 (DPP‐4) inhibitors compared with combining insulin therapy with a placebo or other antihyperglycemic agents.

Materials and Methods

A literature search was carried out via electronic databases. The inclusion criteria were randomized controlled trials comparing the addition of DPP‐4 inhibitors to insulin with the addition of a placebo or other active hypoglycemic agents to insulin therapy, study duration of no less than 12 weeks carried out in type 2 diabetes patients and the availability of outcome data to evaluate a change in the glycated hemoglobin.

Results

The glycated hemoglobin‐lowering efficacy was significantly greater with DPP‐4 inhibitor/insulin (DPP‐4i/INS) than with placebo/insulin (weighted mean difference −0.53%, 95% confidence interval −0.63, −0.43, P < 0.01). The postprandial plasma glucose‐lowering efficacies was also significantly greater with DPP‐4i/INS than with placebo/insulin (weighted mean difference −1.65 mmol/L, 95% CI: −2.34, −0.96, P < 0.05). The risk of hypoglycemia or severe hypoglycemia was similar for DPP4i/INS and placebo/insulin treatments. There was no significant difference in the glycemia‐lowering efficacy between DPP‐4i/INS and alpha‐glucosidase inhibitors/insulin, thiazolidinedione/insulin and glucagon‐like peptide‐1 receptor agonist/insulin. Sodium–glucose cotransporter 2 inhibitor/insulin treatment achieved better placebo‐corrected efficacy in lowering postprandial plasma glucose, with less weight gain and no higher risk of hypoglycemia.

Conclusions

Treatment with DPP‐4 inhibitors combined with insulin improved glycemic control without an increased risk of hypoglycemia or weight gain compared with insulin treatment alone.
Regulatory connection between the expression level of classical protein kinase C and pruning of climbing fibers from cerebellar Purkinje cells
Authors: Takahashi Nobutaka , Shuvaev Anton N. , Konno Ayumu , Matsuzaki Yasunori , Watanave Masashi , Hirai Hirokazu
Published: October 2017

Cerebellar Purkinje cells (PCs) express two members of the classical protein kinase C (cPKC) subfamily, namely, PKCα and PKCγ. Previous studies on PKCγ knockout (KO) mice have revealed a critical role of PKCγ in the pruning of climbing fibers (CFs) from PCs during development. The question remains as to why only PKCγ and not PKCα is involved in CF synapse elimination from PCs. To address this question, we assessed the expression levels of PKCγ and PKCα in wild‐type (WT) and PKCγ KO PCs using PC‐specific quantitative real‐time reverse transcription‐polymerase chain reaction, western blotting, and immunohistochemical analysis. The results revealed that the vast majority of cPKCs in PCs were PKCγ, whereas PKCα accounted for the remaining minimal fraction. The amount of PKCα was not up‐regulated in PKCγ KO PCs. Lentiviral expression of PKCα in PKCγ KO PCs resulted in a 10‐times increase in the amount of PKCα mRNA in the PKCγ KO PCs, compared to that in WT PCs. Our quantification showed that the expression levels of cPKC mRNA in PKCγ KO PCs increased roughly from 1% to 22% of that in WT PCs solely through PKCα expression. The up‐regulation of PKCα in PKCγ KO PCs significantly rescued the impaired CF synapse elimination. Although both PKCα and PKCγ are capable of pruning supernumerary CF synapses from developing PCs, these results suggest that the expression levels of cPKCs in PKCγ KO PCs are too low for CF pruning.

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Mutations in the genes for keratin‐4 and keratin‐13 in Swedish patients with white sponge nevus
Authors: Westin Maria , Rekabdar Elham , Blomstrand Lena , Klintberg Per , Jontell Mats , Robledo‐Sierra Jairo
Published: October 2017

Background

White sponge nevus is a rare autosomal dominant disorder that affects the non‐keratinised stratified squamous epithelium. Mutations in the genes that encode mucosa‐specific keratin‐4 and keratin‐13 are strongly linked to the manifestation of white sponge nevus. This study involved mutational analysis of the genes encoding keratin‐4 and keratin‐13 in two Swedish families with white sponge nevus.

Methods

The diagnosis of white sponge nevus was based on disease history, clinical characteristics of the lesions and, in the majority of the cases, histopathological examination. Samples were collected from the affected buccal mucosa using buccal swabs. DNA was subsequently extracted and amplified using touchdown‐PCR. The keratin‐4 and keratin‐13 genes were sequenced, and a genetic analysis was performed.

Results

A novel heterozygous missense mutation was identified in exon 1A of the keratin‐4 gene in Family 2. In addition, previously reported heterozygous missense mutations were identified in the keratin‐4 (E449K, A72V, Q156R, R208H) and keratin‐13 (L115P) genes in both families.

Conclusion

We describe a novel heterozygous missense mutation in the keratin‐4 gene of a Swedish family with white sponge nevus. Our results support the notion that mutations in keratin‐4 and keratin‐13 are the underlying cause of white sponge nevus.
Exploring the nature of illness perceptions in people with end‐stage kidney disease
Authors: Rees Jessica , Chilcot Joseph , Donnellan Warren , Soulsby Laura
Published: October 2017

Background

Diagnosis and treatment for End‐Stage Kidney Disease (ESKD) results in vast lifestyle changes. Despite the high prevalence of depression in people with ESKD, the psychosocial impacts of ESKD are still often overlooked. Illness perceptions enable people to make sense of their illness and are closely associated with depression. Due to the high levels of depression within ESKD, this study sought to understand the nature of illness perceptions in people with ESKD.

Methodology

In this qualitative study, eleven participants were identified through hospital and online patient support groups. Semi‐structured interviews were audio‐taped, transcribed and analysed using grounded theory techniques.

Results

Three themes emerged from the data: Renal Conflicts, Forced Adjustment and Coping. The main dimensions of illness perception discussed by participants were Consequences, Control, Timeline and Identity.

Conclusion

The results of this study have practical implications for informing practitioners about the psychosocial effects of ESKD diagnosis and treatment.
Effects of Prescription Drug Insurance on Hospitalization and Mortality: Evidence from Medicare Part D
Authors: Kaestner Robert , Schiman Cuping , Alexander G. Caleb
Published: October 2017

We used Medicare administrative data (2002–2009) and an instrumental variables design that exploits the natural experiment created by the implementation of Medicare Part D to estimate the effect of prescription drug coverage insurance on the use and costs of inpatient services. We find that gaining prescription drug insurance through Part D caused approximately a 4 percent decrease in hospital admission rate, a 2–5 percent decrease in Medicare inpatient payments per person, and a 10–15 percent decrease in inpatient charges. Among specific types of admissions, gaining insurance was associated with significant decreases in admissions for CHF and COPD.
Candidate genes associated with resistance to Valsa canker identified via quantitative trait loci in apple
Authors: Tan Yi , Shen Fei , Chen Ruiting , Wang Yi , Wu Ting , Li Tianhong , Xu Xuefeng , Han Zhenhai , Zhang Xinzhong
Published: October 2017

Valsa canker is a destructive fungal disease for the apple industry, especially in Asian regions. Here, individuals in “Jonathan” × “Golden Delicious” hybrid population were phenotyped by off situ inoculation with Valsa mali isolates 03‐8 and xc56 from 2012 to 2015. Thirty‐one QTLs for the resistance were detected using high‐density genetic maps. Based on year‐stable and isolate‐robust QTLs, resistant loci G13‐1 and G13‐2 were mapped on chromosome 13 of the male parent, meanwhile locus J15‐1 was mapped on chromosome 15 of the female parent. Using the parental whole‐genome resequencing SNP databases, eighteen SNPs that could change predicted cis‐elements of gene or led to non‐synonymous substitution were screened in the three loci. After segregation analysis in hybrids and gene expression verification, three SNPs in an RNA‐binding protein gene, a serine/threonine‐protein kinase gene and a MYB transcription factor gene showed a close relationship to Valsa canker resistance in apple. These results will be useful for the application of marker‐assisted selection for Valsa canker resistance in apple.
Caesarean delivery and anaemia risk in children in 45 low‐ and middle‐income countries
Authors: Wilunda Calistus , Yoshida Satomi , Blangiardo Marta , Betran Ana Pilar , Tanaka Shiro , Kawakami Koji
Published: October 2017

Caesarean delivery (CD) may reduce placental transfusion and cause poor iron‐related haematological indices in the neonate. We aimed to explore the association between CD and anaemia in children aged <5 years utilising data from Demographic and Health Surveys conducted between 2005 and 2015 in 45 low‐ and middle‐income countries (N = 132,877). We defined anaemia categories based on haemoglobin levels, analysed each country's data separately using propensity‐score weighting, pooled the country‐specific odds ratios (ORs) using random effects meta‐analysis, and performed meta‐regression to determine whether the association between CD and anaemia varies by national CD rate, anaemia prevalence, and gross national income. Individual‐level CD was not associated with any anaemia (OR 0.95, 95% confidence interval (CI) [0.86, 1.06]; I2 = 40.2%), mild anaemia (OR 0.91, 95% CI [0.81, 1.02]; I2 = 24.8%), and moderate/severe anaemia (OR 0.97, 95% CI [0.85, 1.11]; I2 = 47.7%). CD tended to be positively associated with moderate/severe anaemia in upper middle‐income countries and negatively associated with mild anaemia in lower middle‐income countries; however, meta‐regression did not detect any variation in the association between anaemia and CD by the level of income, CD rate, and anaemia prevalence. In conclusion, there was no evidence for an association between CD and anaemia in children younger than 5 years in low‐ and middle‐income countries. Our conclusions were consistent when we looked at only countries with CD rate >15% with data stratified by individual‐level wealth status and type of health facility of birth.
The association between a genetic risk score for allergy and the risk of developing allergies in childhood—Results of the WHISTLER cohort
Authors: Arabkhazaeli Ali , Ahmadizar Fariba , Leusink Maarten , Arets Hubertus G. M. , Raaijmakers Jan A. M. , Uiterwaal Cuno S. P. M. , van der Ent Cornelis K. , Maitland‐van der Zee Anke‐Hilse , Vijverberg Susanne J. H.
Published: October 2017

Background

Several genetic variants have been associated with the susceptibility to allergic disease in adults, but it remains unclear whether these genetic variants are also associated with the onset of allergic disease early in life. The aim of this study was to develop a genetic risk score (GRS) for allergy based on findings in adults and study its predictive capacity for allergy in children.

Methods

A GRS was constructed based on 10 SNPs previously associated with allergies in adults. The GRS was tested in children who participated in a population‐based newborn cohort (WHISTLER) and were followed from birth to school age. Logistic regression analysis was used to study the association between the GRS and the parental‐reported allergies at age 5 (based on a reported allergy to ≥1 of the following allergens: pollen, house dust mites, or pets). A Cox regression model was used to study the association between GRS and a physician‐diagnosed allergy during follow‐up (allergic conjunctivitis, allergic rhinitis, and eczema/dermatitis). Cohen's kappa coefficient was calculated to study the agreement between physician‐diagnosed allergy and parental‐reported allergy at age 5.

Results

The GRS was significantly associated with parental‐reported allergy (odds ratio: 15.9, 95% confidence interval (CI): 1.07‐233.73) at age 5, as well as with a physician‐diagnosed allergy during follow‐up (hazard ratio: 1.89, 95% CI: 1.05‐3.41). The overall agreement between physician‐diagnosed and parental‐reported allergies was 70.5% (kappa: 0.10, 95% CI: 0.03‐0.18).

Conclusions

An adult‐derived GRS for allergy predicts the risk of developing allergies in childhood.
Non‐immediate‐reading skin tests and prolonged challenges in non‐immediate hypersensitivity to beta‐lactams in children
Authors: Lezmi G. , Alrowaishdi F. , Bados‐Albiero A. , Scheinmann P. , de Blic J. , Ponvert C.
Published: October 2017

Background

A minority of children reporting non‐immediate reactions to beta‐lactams (BLs) are allergic. Allergy workup usually includes late‐reading (48‐72 hours) skin tests (ST) and short (1‐3 days) drug provocation tests (DPT), regardless of the chronology of the index reaction. The sensitivity of hyper‐late‐reading (≥6‐7 days) ST and of prolonged DPT for the diagnosis of non‐immediate hypersensitivity to BLs is yet to be determined.

Objectives

To establish the diagnostic values of late‐reading ST and hyper‐late‐reading ST and of prolonged DPT in children reporting non‐immediate reactions to BLs.

Methods

Prospective assessment of children reporting non‐immediate reactions to BLs with late‐ and additional hyper‐late‐reading intradermal (ID) and patch tests, and if negative, with prolonged DPT.

Results

Five hundred and fifty children reporting reactions to a single or several BLs (674 suspected BLs) were included. Non‐immediate hypersensitivity to BLs was diagnosed in 63 children (11.5%), reporting 66 reactions (9.8%), based on responses in ST (n = 17, 25.8%: 5 to ID, 8 to patch tests, and 4 to both tests), DPT (n = 43, 65.2%), and clinical history (n = 6, 9.1%), including 3/9 children with severe cutaneous adverse reactions. Skin test positivity was observed after the 6‐7th day in 14/17 children, and DPT positivity after a median time of 3 days. No severe reaction was observed after ST or during prolonged DPT.

Conclusion

Additional hyper‐late‐reading of ST enhanced their positivity. However, their overall sensitivity remained weak, especially in non‐severe cases. Prolonged DPT are safe and may improve the performance of DPT in the diagnosis of non‐immediate hypersensitivity to BLs.
Metabolic strategies of melanoma cells: Mechanisms, interactions with the tumor microenvironment, and therapeutic implications
Authors: Fischer Grant M. , Vashisht Gopal Y. N. , McQuade Jennifer L. , Peng Weiyi , DeBerardinis Ralph J. , Davies Michael A.
Published: October 2017

Melanomas are metabolically heterogeneous, and they are able to adapt in order to utilize a variety of fuels that facilitate tumor progression and metastasis. The significance of metabolism in melanoma is supported by growing evidence of impact on the efficacy of contemporary therapies for this disease. There are also data to support that the metabolic phenotypes of melanoma cells depend upon contributions from both intrinsic oncogenic pathways and extrinsic factors in the tumor microenvironment. This review summarizes current understanding of the metabolic processes that promote cutaneous melanoma tumorigenesis and progression, the regulation of cancer cell metabolism by the tumor microenvironment, and the impact of metabolic pathways on targeted and immune therapies.
Flavonoids inhibit chronically exposed arsenic‐induced proliferation and malignant transformation of HaCaT cells
Authors: Rajput Mohit , Kujur Praveen Kumar , Mishra Abhijeet , Singh Rana P.
Published: October 2017

Background

Apart from exposure to UV‐radiation, studies show relationship between skin cancer and chronic ingestion of arsenic through drinking water. Chemopreventive strategies could help in reducing the toxic effects of arsenic and arsenic‐induced skin cancer.

Methods

Cytotoxicity of arsenic on human skin keratinocytes HaCaT cells was evaluated using MTT and trypan blue assays. Arsenic‐induced malignant transformant HaCaT cells were selected through soft agar colony assay. Cell cycle progression was analyzed through FACS. The expressions of genes modulated by arsenic were studied through RT‐PCR.

Results

The lower concentrations (0.1‐0.5 μmol/L) of arsenic were non‐toxic and transformed HaCaT cells on chronic exposure, and also enhanced the cell proliferation. Silibinin and fisetin reduced the arsenic‐induced cell proliferation and malignant transformation. A slight increase in G2‐M phase cell population was also observed. The anti‐proliferation effects of flavonoids on HaCaT transformants were further enhanced when combined with gamma radiation. Chronic and acute exposure to arsenic modulated the expression of transformation‐associated genes including Bcl‐2A1, IGFL‐1, Rab31, and TNC in HaCaT cells.

Conclusions

Chronic exposure to lower arsenic concentrations caused malignant transformation of skin keratinocytes and that effect was attenuated by flavonoids silibinin and fisetin. Thus, chemoprevention could reduce arsenic‐caused detrimental effects on skin cells.
Optimal Dynamic Taxation with Distinctive Forms of Social Status Attainment
Authors: Chang Juin‐Jen , Tsai Hsueh‐Fang , Tsai Tsung‐Sheng
Published: October 2017

We examine the role of both consumption‐ and wealth‐induced social comparisons in setting dynamic optimal income taxation. Under complete information, state‐invariant labor income taxes are used to remedy the externality caused by consumption‐induced social comparisons, while state‐contingent capital income taxes are used to remedy the externalities caused by both consumption‐ and wealth‐induced social comparisons. Under incomplete information, distinct types of agents are subject to an identical marginal capital income tax, which removes social comparisons. To solve the information problem, low‐productivity agents could be subject to a lower marginal labor tax than high‐productivity agents, which contradicts the traditional result in the Mirrlees–Stiglitz models.
Who runs away from home and why? How families, schools, and bullying influence youth runaways
Authors: Radu Monica Bixby
Published: October 2017

While prior research establishes that youth who experience family problems are more likely to leave home before reaching adulthood, we know less regarding how peer victimization in the form of bullying may influence youths' likelihood of becoming runaways. Youth often run away from home to escape family conflict or abusive home environments. Mental illness, behavioral problems, and delinquent peers are also powerful forces predicting the likelihood of running away from home. Additionally, recent literature suggests that negative experiences at school may increase youths' decisions to leave home prematurely. In this article, I review literature that addresseswhoruns away from home, including variations by age, race/ethnicity, sexual orientation, gender, family structure, mental health, problem behaviors, and peer networks. I also suggest directions for future research, including an approach that considers how families and schools individually and collectively affect youths' likelihood of running away from home. Finally, I recommend a focus on bully victimization to better understand how victimization outside of the family affects the likelihood that youth will become runaways.
Urban politics and the study of urban poverty: Promising developments and future directions
Authors: Levine Jeremy R.
Published: October 2017

The study of urban poverty is alive and well in sociology. The study of urban politics, by contrast, has stagnated. Though scholars agree that politics shapes the creation and durability of urban poverty, analytical connections between the two subfields are rarely made explicit. In this article, I make the case for a more integrated body of research. I first illustrate how urban poverty scholars implicitly discuss politics, and conversely, how urban politics scholars implicitly discuss poverty. I then highlight recent developments in the literature and propose two paths forward—by no means the only paths forward, but two ways to jumpstart greater conversation across both subfields. For the urban poverty literature, a focus on organizations can help scholars analyze political dynamics more directly. And for the urban politics literature, an emphasis on political mechanisms rather than overarching perspectives can disrupt the current theoretical malaise. These two moves can advance both literatures while drawing them closer together.
Solid-State Microjoining Mechanisms of Wire Bonding and Flip Chip Bonding
Authors: Takahashi Yasuo , Fukuda Hiroki , Yoneshima Yasuhiro , Kitamura Hideki , Maeda Masakatsu
Published: October 2017

Low-temperature microjoining, such as wire (or ribbon) bonding, tape automated bonding (TAB), and flip chip bonding (FCB), is necessary for electronics packaging. Each type of microjoining takes on various aspects but has common bonding mechanisms regarding friction slip, plastic deformation, and friction heating. In the present paper, solid-state microjoining mechanisms in Au wire (ball) bonding, FCB, Al wire bonding (WB), and Al ribbon bonding are discussed to systematically understand the common bonding mechanisms. Ultrasonic vibration enhances friction slip and plastic deformation, making it possible to rapidly obtain dry interconnects. Metallic adhesion at the central area of the bonding interface is mainly produced by the friction slip. On the other hand, the folding of the lateral side surfaces of the Au bump, Au ball, and Al wire is very important for increasing the bonded area. The central and peripheral adhesions are achieved by a slip-and-fold mechanism. The solid-state microjoining mechanisms of WB and FCB are discussed based on experimental results.
Hierarchical Fuzzy Primitive Surface Classification From Tessellated Solids for Defining Part-to-Part Removal Directions
Authors: Rafibakhsh Nima , Campbell Matthew I.
Published: October 2017

This paper is arranged in three main sections: the first section is a hierarchical method based on clustering and a fuzzy membership system where the tessellated three-dimensional (3D) models are classified into their containing primitives: cylinder, cone, sphere, and flat. In the second section, automated assembly planning (AAP) is considered as the main application of our novel hierarchical primitive classification approach. The classified primitives obtained from the first section are used to define the removal directions between mating parts in an assembly model. Finally, a fuzzification method is used to express the uncertainty of the detected connections between every pair of parts. The acquired uncertainties are used in a user interaction process to approve, deny, or modify the connections with higher uncertainties.
An Alternative Method to Characterize the Quasi-Static, Nonlinear Material Properties of Murine Articular Cartilage
Authors: Kotelsky Alexander , Woo Chandler W. , Delgadillo Luis F. , Richards Michael S. , Buckley Mark R.
Published: October 2017

With the onset and progression of osteoarthritis (OA), articular cartilage (AC) mechanical properties are altered. These alterations can serve as an objective measure of tissue degradation. Although the mouse is a common and useful animal model for studying OA, it is extremely challenging to measure the mechanical properties of murine AC due to its small size (thickness < 50 μm). In this study, we developed novel and direct approach to independently quantify two quasi-static mechanical properties of mouse AC: the load-dependent (nonlinear) solid matrix Young's modulus (E) and drained Poisson's ratio (ν). The technique involves confocal microscope-based multiaxial strain mapping of compressed, intact murine AC followed by inverse finite element analysis (iFEA) to determine E and ν. Importantly, this approach yields estimates of E and ν that are independent of the initial guesses used for iterative optimization. As a proof of concept, mechanical properties of AC on the medial femoral condyles of wild-type mice were obtained for both trypsin-treated and control specimens. After proteolytic tissue degradation induced through trypsin treatment, a dramatic decrease in E was observed (compared to controls) at each of the three tested loading conditions. A significant decrease in ν due to trypsin digestion was also detected. These data indicate that the method developed in this study may serve as a valuable tool for comparative studies evaluating factors involved in OA pathogenesis using experimentally induced mouse OA models.
The Influence of Cutting Fluid Concentration on Surface Integrity of VP80 Steel and the Influence of Cutting Fluid Flow Rate on Surface Roughness of VPATLAS Steel After Grinding
Authors: de Paiva Raphael Lima , da Silva Rosemar Batista , Jackson Mark J. , Abrão Alexandre Mendes
Published: October 2017

The application of cutting fluid in grinding operations is crucial to control temperature levels and prevent thermal damage to the workpiece. Water-based (emulsions and solutions) coolants are used in grinding operations owing to their excellent cooling capability and relatively lower cost compared to neat oils. However, the cutting fluid efficiency is not only dependent on its type, but also on other parameters including its concentration and flow rate. In this context, this work aims to analyze the influence of the coolant concentration and flow rate on the grinding process. Two different workpiece materials for the production of plastic injection moulds were machined: VP80 and VPATLAS steel grades. Six grinding conditions (combinations of depth of cut values of 5, 15, and 25 μm with coolant concentration of 3% and 8%, respectively) were employed in the former, while two grinding conditions were used for the latter. The output parameter used to assess the influence of coolant concentration and flow rate on the grinding operation focused on the integrity of the workpiece materials (surface roughness and microhardness below the ground surface). The results showed that the surface integrity of VP80 after grinding was more sensitive to depth of cut than to cutting fluid concentration. Furthermore, the highest coolant concentration outperformed the lowest one when grinding under more severe conditions. With regard VPATLAS steel, no influence of the coolant flow rate on surface roughness was observed.
Measuring Water Film Thickness in a Wet Gas Compressor Diffuser—Design, Calibration, and Testing of Electromagnetic Probes
Authors: Nolen Craig , Poerner Melissa
Published: October 2017

The distribution of water in the diffuser of a wet gas compressor is not well understood. Measurements of water film thickness across the diffuser surface would improve the understanding of two-phase flow phenomena in wet gas compressors. Electromagnetic probes were designed in order to measure water film thickness in the diffuser of a SwRI-designed wet gas compressor. The probes consisted of two electrode foils plated on a thin insulating substrate, allowing them to be bonded in place without drilling through the diffuser. An AC signal was passed between the electrodes, and the voltage across a resistor in series with the electrodes was recorded. As the water level covering the electrodes increased, the recorded voltage increased. A method of calibrating the probes was developed and used prior to installation in the diffuser. Testing showed the probes to be effective at detecting the presence of water in the diffuser and indicating the general water level. Improvements in probe design, calibration, and installation are needed to provide more precise water film thickness data.
Design of Complex Engineered Systems Using Multi-Agent Coordination
Authors: Soria Zurita Nicolás F. , Colby Mitchell K. , Tumer Irem Y. , Hoyle Christopher , Tumer Kagan
Published: October 2017

In complex engineering systems, complexity may arise by design, or as a by-product of the system's operation. In either case, the cause of complexity is the same: the unpredictable manner in which interactions among components modify system behavior. Traditionally, two different approaches are used to handle such complexity: (i) a centralized design approach where the impacts of all potential system states and behaviors resulting from design decisions must be accurately modeled and (ii) an approach based on externally legislating design decisions, which avoid such difficulties, but at the cost of expensive external mechanisms to determine trade-offs among competing design decisions. Our approach is a hybrid of the two approaches, providing a method in which decisions can be reconciled without the need for either detailed interaction models or external mechanisms. A key insight of this approach is that complex system design, undertaken with respect to a variety of design objectives, is fundamentally similar to the multi-agent coordination problem, where component decisions and their interactions lead to global behavior. The results of this paper demonstrate that a team of autonomous agents using a cooperative coevolutionary algorithm (CCEA) can effectively design a complex engineered system. This paper uses a system model of a Formula SAE racing vehicle to illustrate and simulate the methods and potential results. By designing complex systems with a multi-agent coordination approach, a design methodology can be developed to reduce design uncertainty and provide mechanisms through which the system level impact of decisions can be estimated without explicitly modeling such interactions.
Large Eddy Simulation Study on Forced Convection Heat Transfer to Water at Supercritical Pressure in a Trapezoid Annulus
Authors: Amin Muhsin Mohd , Duan Yu , He Shuisheng
Published: October 2017

It is now well known that heat transfer to fluid at supercritical pressure in a confined channel shows complex behaviors. This is due to the strong variations of the thermal–physical properties resulting from the changes of pressure and temperature. To improve the reliability and efficiency of the supercritical water-cooled reactors (SCWRs) to be designed, the understanding of supercritical fluid flow in the fuel assemblies is very important. The study reported here reconsiders a simplified geometry made of a trapezoid channel enclosing an inner rod to simulate the triangular arrangement of a fuel assembly. Large eddy simulation (LES) with the wall adapting local eddy viscosity (WALE) model is used to simulate the forced convection flow in the channel. Supercritical water at 25 MPa is used as the working fluid. The Reynolds number of flow based on the hydraulic diameter and the bulk velocity is 10,540, while the heat flux from the inner rod wall has been varied from 10 kW/m2 to 75 kW/m2. Large unsteady flow structures are observed to be present due to the nonuniformity of the cross section of the flow channel. The characteristics of the flow structures and their effect on the local heat transfer are analyzed using instantaneous velocities, spectrum analysis, and correlation analysis. The swinging flow structures in the wide gap are much weaker than those in the narrow gap. The behaviors of such large flow structures are influenced by the strong spatial and temporal variations of the properties. When the temperature distribution follows Tb < Tpc < Tw, the mixing parameters due to the large flow structures, including mixing coefficient and effective mixing velocity in the gap, are also significantly influenced.