bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions between Private Health and Long‐term Care Insurance and the Effects of the Crisis: Evidence for Spain
Authors: Jiménez‐Martín Sergi , Labeaga‐Azcona José M. , Vilaplana‐Prieto Cristina
Published: November 2016

This paper analyzes the reasons for the scarce development of the private long‐term care insurance market in Spain, and its relationship with health insurance. We are also interested in the effects the crisis has had both on the evolution of the demand for long‐term care insurance and on the existence of regional disparities. We estimate bivariate probit models with endogenous variables using Spanish data from the Survey on Health and Retirement in Europe. Our results confirm that individuals wishing to purchase long‐term care insurance are, in a sense, forced to subscribe a health insurance policy. In spite of this restriction in the supply of long‐term care insurance contracts, we find its demand has grown in recent years, which we attribute to the budget cuts affecting the implementation of Spain's System of Autonomy and Attention to Dependent People. Regional differences in its implementation, as well as the varying effects the crisis has had across Spanish regions, lead to the existence of a crowding‐in effect in the demand for long‐term care insurance in those regions where co‐payment is based on income and wealth, those that have a lower percentage of public long‐term care beneficiaries, or those with a smaller share of cash benefits over total public benefits. Copyright © 2016 John Wiley & Sons, Ltd.
Have Standard VARS Remained Stable Since the Crisis?
Authors: Aastveit Knut Are , Carriero Andrea , Clark Todd E. , Marcellino Massimiliano
Published: November 2016

Small vector autoregressions are commonly used in macroeconomics for forecasting and evaluating shock transmission. This requires VAR parameters to be stable over the evaluation and forecast sample or modeled as time‐varying. Prior work has considered whether there were sizable parameter changes in the early 1980s and in the subsequent period until the beginning of the new century. This paper conducts a similar analysis focused on the period since the recent crisis. Using a range of techniques, we provide substantial evidence against parameter stability. The evolution of the unemployment rate seems particularly different relative to its past behavior. We also evaluate alternative methods to handle parameter instability in a forecasting context. Copyright © 2016 John Wiley & Sons, Ltd.
Relativistic (SR‐ZORA) quantum theory of atoms in molecules properties
Authors: Anderson James S. M. , Rodríguez Juan I. , Ayers Paul W. , Götz Andreas W.
Published: November 2016

The Quantum Theory of Atoms in Molecules (QTAIM) is used to elucidate the effects of relativity on chemical systems. To do this, molecules are studied using density‐functional theory at both the nonrelativistic level and using the scalar relativistic zeroth‐order regular approximation. Relativistic effects on the QTAIM properties and topology of the electron density can be significant for chemical systems with heavy atoms. It is important, therefore, to use the appropriate relativistic treatment of QTAIM (Anderson and Ayers, J. Phys. Chem. 2009, 115, 13001) when treating systems with heavy atoms. © 2016 Wiley Periodicals, Inc.
Sonographic measurement of fetal thymus size in uncomplicated singleton pregnancies
Authors: Tangshewinsirikul Chayada , Panburana Panyu
Published: November 2016

Purpose

To establish sonographic reference ranges of the normal fetal thymus size between 17 and 38 weeks of gestational age (GA).

Methods

The study was conducted between April 1 and December 31, 2013. Low‐risk singleton pregnancies without obstetrical and medical complications at the GAs between 17 and 38 weeks were recruited for thymus measurement. The fetal thymus was identified on transabdominal sonography at the three‐vessel view. Maximal transverse diameter, perimeter, and thymus/thoracic ratio were measured. The best‐fit models in predicting thymic dimensions as a function of GA and biparietal diameter (BPD) were determined using regression analysis, and percentile charts for predicting thymic dimensions were constructed.

Results

A total of 296 singleton pregnancies were recruited in this study. Maximal transverse diameter, perimeter, and thymus/thoracic ratio increased throughout pregnancy. The regression equation for maximal transverse diameter of the thymus as a function of GA was as follows: Predicted mean thymus diameter (mm) = −25.904 + 2.476 × GA − 0.019 × GA2 (r = 0.915; p < 0.001) with predicted standard deviations of thymus diameter (mm) = 1.428 + 0.044 × GA (r = 0.017; p < 0.001).

Conclusions

Sonographic reference ranges of the normal fetal thymic dimensions between 17 and 38 weeks of GA have been established. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:150–159, 2017
Internal jugular vein thrombosis with OHSS
Authors: Lee Seung Hyun , Park Jung‐Woo , Han Myoungseok , Bae Jong Woon , Cho Yeon Jean
Published: November 2016

Ovarian hyperstimulation syndrome (OHSS) includes ovarian enlargement and ascites. It is usually mild but can be, rarely, fatal. Deep vein thrombosis (DVT) is among the potentially fatal complications of OHSS. During pregnancy, DVT is more common in the lower extremities than in the upper part of the body, but OHSS‐related DVT occurs more frequently in the upper part. Internal jugular vein thrombosis is considered rare, and duplex ultrasound is the appropriate examination for its diagnosis. We present a rare case of internal jugular vein thrombosis following OHSS. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:450–452, 2017
A novel method for a high enrichment of human corneal epithelial stem cells for genomic analysis
Authors: Kasinathan Jhansi Rani , Namperumalsamy Venkatesh Prajna , Veerappan Muthukkaruppan , Chidambaranathan Gowri Priya
Published: November 2016

Understanding the molecular mechanisms that regulate the corneal epithelial stem cells (CESCs) in maintaining corneal homeostasis remains elusive largely due to the lack of a specific marker for their isolation. This study aims to enrich CESCs from human donor limbal epithelium and to evaluate the level of enrichment based on expression of ΔNp63α, a putative CESC marker. A two‐stage enrichment of CESCs was carried out. (a) The limbal basal epithelial cells were isolated by differential enzymatic treatment and five‐fold enrichment was achieved from 2% of CESCs present in the total limbal epithelium. The CESCs were quantified on the basis of two parameters—high expression of p63/ABCG2 and nucleus to cytoplasmic (N/C) ratio ≥0.7. (b) Cytospin smears of isolated basal cells were Giemsa stained and cells with N/C ratio ≥0.7 were separated by laser capture microdissection. This strategy resulted in an enrichment of CESCs to 78.57% based on two‐parameter analysis using p63 and 76.66% using ABCG2. RT‐PCR was carried out for ΔNp63 isoforms (α, β, and γ) and connexin‐43, with GAPDH for normalization. The expression of ΔNp63α was restricted to the enriched population of CESCs in contrast to its absence in limbal basal cells with N/C ratio <0.7 and CCECs. The unique expression of ΔNp63α and 5.9‐fold reduced connexin‐43 expression in the enriched population of CESCs indicates its high purity. Further analysis of these cells will help in elucidating the molecular mechanisms associated with stemness and also in identifying a specific marker for CESCs.
Morphological investigation of various orthodontic lingual bracket slots using scanning electron microscopy and atomic force microscopy
Authors: Choi Samjin , Kim Jae‐Hyung , Kim Nam‐Joon , Lee Seung‐Hoon , Kim Hyunsoo , Kim Kyung‐A , Park Ki‐Ho , Park Young‐Guk
Published: November 2016

Various labial and lingual orthodontic appliances with aesthetic materials have been developed due to an increased demand in aesthetic orthodontic treatment. However, there are few reports regarding the morphology of lingual orthodontic appliances. Therefore, this study evaluates the roughness of slot surfaces of various orthodontic lingual brackets using field emission scanning electron microscopy (FE‐SEM) and atomic force microscopy (AFM). Three types of stainless steel lingual brackets (Stealth®, 7th Generation®, and Clippy L®) and one gold lingual bracket (Incognito™) with a slot size of 0.018 inches × 0.025 inches (0.457 × 0.635 mm2) were selected as representative lingual materials. Both FE‐SEM and AFM examinations showed that the Stealth® and Clippy L® brackets had the lowest surface roughness, while the 7th Generation® bracket had the highest surface roughness. There was a significant difference in surface morphology between the types of lingual brackets, even when composed of the same material. The surface roughness of the bracket slot was dependent on the manufacturing process or surface polishing process rather than the fundamental properties of the bracket materials. There was no significant difference in the mean surface roughness of the slot floor between gold and stainless steel lingual brackets. These findings suggest that, although the gold lingual bracket is very expensive, it has great potential for use in patients with nickel allergy.
Antibodies to H1 histone from the sera of HIV‐infected patients recognize and catalyze site‐specific degradation of this histone
Authors: Baranova Svetlana V. , Dmitrienok Pavel S. , Ivanisenko Nikita V. , Buneva Valentina N. , Nevinsky Georgy A.
Published: November 2016

Histones and their posttranslational modifications have key roles in chromatin remodeling and gene transcription. Besides intranuclear functions, histones act as damage‐associated molecules when they are released into the extracellular space. Administration of histones to animals leads to systemic inflammatory and toxic responses. Autoantibodies with enzymatic activities (abzymes) are distinctive feature of some autoimmune and viral diseases. Electrophoretically and immunologically homogeneous IgGs containing no canonical enzymes were isolated from sera of human immunodeficiency virus–infected patients by chromatography on several affinity sorbents. In contrast to canonical proteases (trypsin, chymotrypsin, and proteinase K), IgGs from human immunodeficiency virus–infected patients purified by affinity chromatography on Sepharose containing immobilized histones specifically recognized and hydrolyzed only histones but not many other tested globular proteins. Using matrix‐assisted laser desorption/ionization mass spectrometry, the sites of H1 histone (193 amino acids [AAs]) cleavage by anti‐H1 histone IgGs were determined for the first time. It was shown that 1 cluster of 2 major and 4 moderate sites of cleavage is located at the beginning (106‐112 AAs) of the known antigenic determinants disposed at the long C‐terminal sequence of H1. Two clusters of minor and very weak sites of the protein cleavage correspond to middle (8 sites, 138‐158 AAs) and terminal (5 sites, 166‐176 AAs) parts of the antigenic determinants. It was shown that in contrast to canonical proteases, N‐terminal part of H1 histone (1‐136 AAs) containing no antigenic determinants is an unpredictably very resistant against hydrolysis by abzymes, while it can be easily cleavage by canonical proteases. Because histones act as damage‐associated molecules, abzymes against H1 and other histones can play important role in pathogenesis of acquired immune deficiency syndrome and probably other different diseases.
Zika virus: Global health challenge, threat and current situation
Authors: Aziz Hafsa , Zia Aadarash , Anwer Amania , Aziz Muneeba , Fatima Shazia , Faheem Muhammad
Published: November 2016

ZIKV has emerged as grave global health issue in the past few years. ZIKV was firstly isolated in 1947 from a rhesus sentinel monkey in the Zika forest in Uganda. It is usually transmitted by the bite of infected mosquitoes and infects skin fibroblasts, skin keratinocytes, etc. ZIKV until now was under reported because of its clinical similarity with the dengue and chikungunya. It is usually spread through the course of the sylvatic cycle. In this cycle, the virus or pathogen lifespan is spent between the wild animal and vectors. The intrinsic incubation period is not yet fully known but it is observed that the very first symptoms of ZIKV infection can appear or develop within 3–12 days of time period and usually subside within 7 days of time. There is a strong relationship between prenatal Zika virus infection and microcephaly; other serious brain anomalies to the infant or newborn are Guillain–Barré syndrome. To date no vaccines are available for ZIKV prevention hence only symptomatic treatment is recommended in infected patients. Usually ZIKV is detected by serologic (IgM ELISA), plaque reduction neutralization test (PRNT) along with in‐house” molecular techniques (RT‐PCR). ZIKV infection being imminent global health issue warrants strong protective measures to prevent it from becoming an epidemic. Early detection and prevention is the key to tackle this grave potential health hazard. J. Med. Virol. 89:943–951, 2017. © 2017 Wiley Periodicals, Inc.
Brain circuitry associated with the development of substance use in bipolar disorder and preliminary evidence for sexual dimorphism in adolescents
Authors: Lippard Elizabeth T.C. , Mazure Carolyn M. , Johnston Jennifer A.Y. , Spencer Linda , Weathers Judah , Pittman Brian , Wang Fei , Blumberg Hilary P.
Published: November 2016

Substance use disorders and mood disorders are highly comorbid and confer a high risk for adverse outcomes. However, data are limited on the neurodevelopmental basis of this comorbidity. Substance use initiation typically occurs during adolescence, and sex‐specific developmental mechanisms are implicated. In this preliminary study, we review the literature and investigate regional gray matter volume (GMV) associated with subsequent substance use problems in adolescents with bipolar disorder (BD) and explore these associations for females and males. Thirty adolescents with DSM‐IV–diagnosed BD and minimal alcohol/substance exposure completed baseline structural magnetic resonance imaging scans. At follow‐up (on average 6 years post baseline), subjects were administered the CRAFFT interview and categorized into those scoring at high ( ≥ 2: CRAFFTHIGH) vs. low ( < 2: CRAFFTLOW) risk for alcohol/substance problems. Lower GMV in prefrontal, insular, and temporopolar cortices were observed at baseline among adolescents with BD reporting subsequent alcohol and cannabis use compared to adolescents with BD who did not (P < 0.005, clusters ≥ 20 voxels). Lower dorsolateral prefrontal GMV was associated with future substance use in both females and males. In females, lower orbitofrontal and insula GMV was associated with future substance use, while in males, lower rostral prefrontal GMV was associated with future use. Lower orbitofrontal, insular, and temporopolar GMV was observed in those who transitioned to smoking tobacco. Findings indicate that GMV development is associated with risk for future substance use problems in adolescents with BD, with results implicating GMV development in regions subserving emotional regulation in females and regions subserving executive processes and attention in males. © 2016 Wiley Periodicals, Inc.
The effects of intra‐hippocampal L‐thyroxine infusion on long‐term potentiation and long‐term depression: A possible role for the αvβ3 integrin receptor
Authors: Bitiktaş Soner , Tan Burak , Kavraal Şehrazat , Yousef Marwa , Bayar Yeliz , Dursun Nurcan , Süer Cem
Published: November 2016

Although the effects of long‐term experimental dysthyroidism on long‐term potentiation (LTP) and long‐term depression (LTD) have been documented, the relationship between LTP/LTD and acute administration of L‐thyroxine (T4) has not been described. Here, we investigated the effects of intra‐hippocampal administration of T4 on synaptic plasticity in the dentate gyrus of the hippocampal formation. After a 15‐minute baseline recording, LTP and LTD were induced by application of high‐ and low‐frequency stimulation protocols, respectively. Infusions of saline or T4 and tetraiodothyroacetic acid (tetrac), a T4 analog that inhibits binding of iodothyronines to the integrin αvβ3 receptor, either alone or together, were made during the stimulation protocols. The averages of the excitatory postsynaptic potential (EPSP) slopes and population spike (PS) amplitudes, between 55 to 60 minutes, were used as a measure of the LTP/LTD magnitude and were analyzed by two‐way univariate ANOVA with T4 and tetrac as between‐subjects factors. The input–output curves of the infusion groups were comparable to each other, as shown by the non significant interaction observed between stimulus intensity and infused drug. The magnitude of the LTP in T4‐infused rats was significantly lower as compared to saline‐infused rats. Both the PS amplitude and the EPSP slope were depressed more markedly with T4 infusion than with saline, tetrac, and T4 + tetrac infusion. Data of this study provide in vivo evidence that T4 can promote LTD over LTP via the integrin αvβ3 receptor, and that the effect of endogenous T4 on this receptor can be suppressed by tetrac in the hippocampus. © 2016 Wiley Periodicals, Inc.
Complex Nonlinear Behavior in the Bromate–2‐Aminophenol Reaction
Authors: Tang Alexander , Bell Jeffrey G. , Green James R. , Wang Jichang
Published: November 2016

The bromate–2‐aminophenol reaction in a batch reactor was investigated in this research, in which both simple and sequential oscillations were observed. The occurrence of sequential oscillations were found to be very sensitive to changes of the initial concentrations, where decreasing the concentration of sulfuric acid or sodium bromate or increasing the 2‐aminophenol concentration caused the two oscillation windows to coalesce. Lowering the reaction temperature from 30 to 5°C also caused the two oscillation windows to merge into one. A phase diagram in the bromate–sulfuric acid concentration plane demonstrates that sequential oscillations only occur within a narrow band of conditions. Mechanistic studies of the system through employing 1H NMR and mass spectrometry suggest that a dibrominated ortho‐benzoquinone is a major product. The oxidation of 2‐aminophenol, on the other hand, can lead to the formation of pyrocatechol, which may be the substrate responsible for the second set of oscillations.
Solvent Influence on the Diels‐Alder Reaction Rates of 9‐(Hydroxymethyl)anthracene and 9,10‐Bis(hydroxymethyl)anthracene with Two Maleimides
Authors: Kiselev Vladimir D. , Kornilov Dmitry A. , Sedov Igor A. , Konovalov Alexander I.
Published: November 2016

The rates of the Diels–Alder reaction of 9‐(hydroxymethyl)anthracene and 9,10‐bis(hydroxymethyl)anthracene with maleic anhydride and two maleimides, N‐ethyl‐ and N‐phenylmaleimide, have been studied at various temperatures and pressures in different solvent media. A rate acceleration in water in comparison with organic solvents is observed. Thermodynamic functions of activation for the reaction of 9,10‐bis(hydroxymethyl)anthracene with N‐ethylmaleimide in binary 1,4‐dioxane–water mixtures are determined. From the observed tendencies, it can be concluded that acceleration of the Diels–Alder reactions in water is linked with an energetically favorable dehydration of the reaction centers of the reactants on the way to the activated complex. Addition of an organic cosolvent makes the desolvation of these centers less favorable.
Continental‐scale Impacts of Livestock Grazing on Ecosystem Supporting and Regulating Services
Authors: Eldridge David J. , Delgado‐Baquerizo Manuel
Published: November 2016

Grazing by livestock supports millions of people worldwide, particularly in drylands, but has marked negative effects on ecosystem services and functions. In Australia, its effects on ecosystem services have not been fully quantified. We examined the extent to which grazing by livestock influenced supporting (productivity, habitat for organisms and biodiversity) and regulating (carbon cycling and hydrological function) services, using data from published and unpublished studies on livestock grazing from a large number of sites across Australia. Grazing reduced our measure of supporting services by about 20% and regulatory services by 8%. On average, grazing reduced plant productivity by 40%, habitat value by 20%, and biodiversity, hydrological function and carbon sequestration by about 10%. Habitat and productivity showed strong declines with increasing grazing intensity, and carbon showed strong declines at the lowest and highest contrasts. Hydrological function and biodiversity did not decline with increasing grazing intensity. Overall, the results indicate that livestock grazing leads to substantial degradation at a continental scale by reducing ecosystem services associated with habitat provision, biodiversity, and soil and water functions. Management of livestock grazing will be critical if we are to retain functional levels of ecosystem services into the next century. Copyright © 2016 John Wiley & Sons, Ltd.
Multivalent Aptamer–RNA Conjugates for Simple and Efficient Delivery of Doxorubicin/siRNA into Multidrug‐Resistant Cells
Authors: Jeong Hyosook , Lee Soo Hyeon , Hwang Yeonju , Yoo Hyundong , Jung Heesun , Kim Sun Hwa , Mok Hyejung
Published: November 2016

Multivalent aptamer–siRNA conjugates containing multiple mucin‐1 aptamers and BCL2‐specific siRNA are synthesized, and doxorubicin, an anthracycline anticancer drug, is loaded into these conjugates through intercalation with nucleic acids. These doxorubicin‐incorporated multivalent aptamer–siRNA conjugates are transfected to mucin‐1 overexpressing MCF‐7 breast cancer cells and their multidrug‐resistant cell lines. Doxorubicin‐incorporated multivalent aptamer–siRNA conjugates exert promising anticancer effects, such as activation of caspase‐3/7 and decrease of cell viability, on multidrug‐resistant cancer cells because of their high intracellular uptake efficiency. Thus, this delivery system is an efficient tool for combination oncotherapy with chemotherapeutics and nucleic acid drugs to overcome multidrug resistance.

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Signal preprocessing, multivariate analysis and software tools for MA(LDI)‐TOF mass spectrometry imaging for biological applications
Authors: Ràfols Pere , Vilalta Dídac , Brezmes Jesús , Cañellas Nicolau , del Castillo Esteban , Yanes Oscar , Ramírez Noelia , Correig Xavier
Published: November 2016

Mass spectrometry imaging (MSI) is a label‐free analytical technique capable of molecularly characterizing biological samples, including tissues and cell lines. The constant development of analytical instrumentation and strategies over the previous decade makes MSI a key tool in clinical research. Nevertheless, most MSI studies are limited to targeted analysis or the mere visualization of a few molecular species (proteins, peptides, metabolites, or lipids) in a region of interest without fully exploiting the possibilities inherent in the MSI technique, such as tissue classification and segmentation or the identification of relevant biomarkers from an untargeted approach. MSI data processing is challenging due to several factors. The large volume of mass spectra involved in a MSI experiment makes choosing the correct computational strategies critical. Furthermore, pixel to pixel variation inherent in the technique makes choosing the correct preprocessing steps critical. The primary aim of this review was to provide an overview of the data‐processing steps and tools that can be applied to an MSI experiment, from preprocessing the raw data to the more advanced strategies for image visualization and segmentation. This review is particularly aimed at researchers performing MSI experiments and who are interested in incorporating new data‐processing features, improving their computational strategy, and/or desire access to data‐processing tools currently available. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 37:281–306, 2018
Reduction of GAPDH in lenses of Parkinson's disease patients: A possible new biomarker
Authors: Klettner Alexa , Tholey Andreas , Wiegandt Alena , Richert Elisabeth , Nölle Bernhard , Deuschl Günther , Roider Johann , Schneider Susanne A.
Published: November 2016

Background

We previously showed that the protein pattern of lenses removed in cataract surgery differs between patients with Parkinson's disease and age‐matched controls. In this study, we identified the protein reduced in abundance in the 34‐ to 37‐kDa gel band.

Methods

During cataract surgery (phacoemulsification), we collected the rinsing fluid and lens particles from the eyes of PD patients and controls. Residual lens fragments in the supernatant of 3 PD patients and aged‐matched controls were studied for protein profiles using liquid chromatography‐mass spectrometry and Western blots.

Results

We identified glyceraldehyde‐3‐phosphate dehydrogenase by mass spectrometry as the protein reduced in abundance and verified this finding in Western blots.

Conclusions

Glyceraldehyde‐3‐phosphate dehydrogenase has been implicated in PD development. The reduction of glyceraldehyde‐3‐phosphate dehydrogenase in the lenses of PD patients may be a new biomarker for PD and might also indicate an important role for this protein in PD development. © 2016 International Parkinson and Movement Disorder Society
Effects of ferric citrate supplementation on advanced glycation end products in a rat model of streptozotocin/nicotinamide‐induced diabetes
Authors: Chao Kuo‐Ching , Chen Seu‐Hwa , Chang Chun‐Chao , Lee Yu‐Chieh , Wang Chi‐Mei , Chang Jung‐Su
Published: November 2016

Scope

Diabetes is associated with the increased risks of anemia and activation of advanced glycation end products (AGEs) and the receptor for AGEs (RAGE). However, the effects of pharmacological doses of iron supplementation on AGE metabolism are less clear. The aim was to investigate the effect of ferric citrate supplementation on AGE metabolism.

Methods and results

Diabetes was induced in overnight starved rats by intraperitoneal injections of 40 mg/kg streptozotocin and 120 mg/kg nicotinamide. Diabetic rats were fed a standard diet or pharmacological doses of ferric citrate (0.5, 1, 2, and 3 g of ferric iron/kg diet) for 10 weeks. Ferric citrate supplementation showed a dose‐related effect on the hepatic steatosis score, malondialdehyde, cathepsin D, and glyoxalase I. A Western blot analysis revealed that >1 g of ferric iron suppressed hepatic AGE receptor 1 and high‐mobility group‐box 1 expressions but increased heme oxygenase‐1 and RAGE expressions. Further analysis showed that high doses of ferric iron triggered sterol regulatory element‐binding protein 1c, p38‐mitogen‐activated protein kinase, and nuclear factor‐κB protein expressions.

Conclusion

Overall, the present results suggest a dose‐related effect of ferric citrate supplementation on AGE metabolism, and this effect was more evident at high iron doses (>1 g of ferric iron/kg diet).
Stochastic call center staffing with uncertain arrival, service and abandonment rates: A Bayesian perspective
Authors: Aktekin Tevfik , Ekin Tahir
Published: November 2016

In this article, we introduce staffing strategies for the Erlang‐A queuing system in call center operations with uncertain arrival, service, and abandonment rates. In doing so, we model the system rates using gamma distributions that create randomness in operating characteristics used in the optimization formulation. We divide the day into discrete time intervals where a simulation based stochastic programming method is used to determine staffing levels. More specifically, we develop a model to select the optimal number of agents required for a given time interval by minimizing an expected cost function, which consists of agent and abandonment (opportunity) costs, while considering the service quality requirements such as the delay probability. The objective function as well as the constraints in our formulation are random variables. The novelty of our approach is to introduce a solution method for the staffing of an operation where all three system rates (arrival, service, and abandonment) are random variables. We illustrate the use of the proposed model using both real and simulated call center data. In addition, we provide solution comparisons across different formulations, consider a dynamic extension, and discuss sensitivity implications of changing constraint upper bounds as well as prior hyper‐parameters. © 2016 Wiley Periodicals, Inc. Naval Research Logistics 63: 460–478, 2016
Genome evolution in ductal carcinoma in situ: invasion of the clones
Authors: Casasent Anna K , Edgerton Mary , Navin Nicholas E
Published: November 2016

Ductal carcinoma in situ (DCIS) is the most frequently diagnosed early‐stage breast cancer. Only a subset of patients progress to invasive ductal carcinoma (IDC), and this presents a formidable clinical challenge for determining which patients to treat aggressively and which patients to monitor without therapeutic intervention. Understanding the molecular and genomic basis of invasion has been difficult to study in DCIS cancers due to several technical obstacles, including low tumour cellularity, lack of fresh‐frozen tissues, and intratumour heterogeneity. In this review, we discuss the role of intratumour heterogeneity in the progression of DCIS to IDC in the context of three evolutionary models: independent lineages, evolutionary bottlenecks, and multiclonal invasion. We examine the evidence in support of these models and their relevance to the diagnosis and treatment of patients with DCIS. We also discuss how emerging technologies, such as single‐cell sequencing, STAR‐FISH, and imaging mass spectrometry, are likely to provide new insights into the evolution of this enigmatic disease. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Perinatal factors associated with clinical presentation of osteosarcoma in children and adolescents
Authors: Endicott Alyson A. , Morimoto Libby M. , Kline Cassie N. , Wiemels Joseph L. , Metayer Catherine , Walsh Kyle M.
Published: November 2016

Background

Osteosarcoma typically develops during puberty with tumors arising at sites of rapid bone growth, suggesting a role for growth‐regulating pathways in tumor etiology. Birthweight is one measure of perinatal growth that has been investigated as an osteosarcoma risk factor. Whether birthweight affects clinical features of osteosarcoma remains unexplored.

Method

Six hundred seventy patients with osteosarcoma, aged 0–19 years, were identified through the California Cancer Registry. We analyzed birth certificate data from the California Department of Public Health vital statistics unit for these patients and 2,860 controls, matched by sex, birth‐year, and race/ethnicity. We examined the impact of birthweight on the risk, timing, and clinical presentation of pediatric osteosarcoma including tumor location, size, extension, differentiation, presence of metastasis, and age at onset. Regression models were adjusted for race, sex, gestational age, socioeconomic status, and tumor site.

Results

Higher birthweight was associated with more advanced tumor stage (P = 0.017), a trend toward greater tumor extension into surrounding tissues (P = 0.083), and with occurrence of tumors in sites other than the long bones of the arms/legs (P = 9.7 × 10−3). Higher birthweight was also associated with an increased likelihood of metastases present at diagnosis (P = 0.047), with each 200 g increase in birthweight associated with a 1.11‐fold increase in the odds of having metastatic disease (95% confidence interval: 1.01–1.22).

Conclusions

The association between higher birthweight and more aggressive osteosarcoma, frequently occurring at sites other than the long bones, suggests that growth pathways active during gestation may play an important role in future osteosarcoma progression, especially at anatomic sites with diminished rates of osteoblastic proliferation.
Spending on Hepatitis C Antivirals in the United States, 2009–2015
Authors: Suda Katie J. , Halbur Drew J. , Hunkler Robert J. , Matusiak Linda M. , Schumock Glen T.
Published: November 2016

Study objective

New hepatitis C virus (HCV) antivirals have been shown to be highly effective with minimal adverse effects, but they are costly. Little is known, however, about the impact of the new HCV antivirals on expenditures in the overall U.S. health care system or by health care sector. Thus the objective of this study was to describe HCV antiviral expenditures by agent, year, and health care sector.

Design

Retrospective cross‐sectional study.

Data source

QuintilesIMS National Sales Perspectives database.

Measurements and main results

QuintilesIMS National Sales Perspectives data for the period of January 1, 2009, to December 31, 2015, were used to describe HCV antiviral expenditures. HCV antiviral expenditures grew each year from $78 million in 2009 to $18 billion in 2015, except during 2013 when spending on HCV drugs dropped by $684 million (41%) compared with 2012. Although most expenditures in 2009 and 2010 were for interferons, this shifted to telaprevir in 2011–2013 and sofosbuvir‐containing regimens in 2014–2015. Mail service and community pharmacies were associated with most of the expenditures throughout the study period.

Conclusion

New HCV antivirals are driving the increased expenditures for this class. Decreased expenditures in 2013 may have been secondary to delaying HCV treatment until new therapies received approval from the U.S. Food and Drug Administration (termed “warehousing”). With continued drug development and approval of HCV therapies, expenditures are expected to continue to increase, barring actions by payers that may impede this trend. Medication policies guiding HCV treatment should focus on safety and efficacy while balancing the long‐term costs of HCV.
Computing an ensemble of variational data assimilations using its mean and perturbations
Authors: Lorenc Andrew C. , Jardak Mohamed , Payne Tim , Bowler Neill E. , Wlasak Marek A.
Published: November 2016

We show how to replace an ensemble of variational data assimilation minimizations by minimizations for the ensemble mean and the perturbations from it. Tests using the Met Office system show that this Mean–Pert method can give practically identical results at much reduced cost. This makes it a good candidate component when designing a cost‐effective system for hybrid ensemble‐variational data assimilation for numerical weather prediction.
The effect of passivated potential on the passive films formed on pure chromium in borate buffer solution
Authors: Jinlong Lv , Tongxiang Liang
Published: November 2016

The effect of passivated potential on corrosion resistance of the chromium in borate buffer solution was investigated. The electrochemical results showed that corrosion resistance of the passive film on the chromium electrode decreased with the increasing of passivated potential. The Mott–Schottky analysis showed that more acceptor concentrations in passive film due to higher passivated potential deteriorated corrosion resistance of the chromium electrode. The results from XPS showed that more chromium hydroxides were formed in higher passivated potential, while less chromium oxides were formed. More acceptor concentrations in passive films reduced corrosion resistance of the chromium electrode in borate buffer solution. Copyright © 2016 John Wiley & Sons, Ltd.
Prognostic Relevance of the Timing of Initiating and the Completion of Adjuvant Therapy in Patients with Resected Pancreatic Ductal Adenocarcinoma
Authors: Lee Woohyung , Yoon Yoo‐Seok , Han Ho‐Seong , Jang Jin Young , Cho Jai Young , Jung Woohyun , Kwon Wooil , Choi YoungRok , Kim Sun‐Whe
Published: November 2016

Background

Although the role of adjuvant therapy in patients with pancreatic ductal adenocarcinoma (PDAC) is well established, its optimal timing and duration are still controversial.

Methods

The study included 311 patients with PDAC who underwent curative resection followed by adjuvant therapy. We analyzed survival data according to the timing of initiation and completion of adjuvant therapy.

Results

There were no differences in 5‐year overall survival (OS) (32.8 vs. 35.4%, p = 0.539) and disease‐free survival (DFS) rates (26.2 vs. 23.3%, p = 0.865) between early (≤6 weeks) and late (>6 weeks) initiation of adjuvant therapy. However, the 5‐year OS (42.6 vs. 22.2%, p < 0.001) and DFS (29.2 vs. 18.4%, p = 0.042) rates were significantly greater in patients with complete versus incomplete adjuvant therapy. Multivariable analysis revealed that incomplete adjuvant therapy was an independent prognostic factor for decreased OS (p = 0.001; hazard ratio 1.850; 95% confidence interval 1.266–2.702).

Conclusions

The results show that complete adjuvant therapy is a more important prognostic factor than early initiation for improving the survival of patients with resected PDAC.
Communication about Congenital Adrenal Hyperplasia: Perspective of Filipino Families
Authors: Abad Peter James B. , Anonuevo Cora A. , Daack‐Hirsch Sandra , Abad Lorna R. , Padilla Carmencita D. , Laurino Mercy Y.
Published: November 2016

Congenital adrenal hyperplasia (CAH), like other genetic conditions, is a relational disease from both the biological and psychosocial perspectives since the diagnosis gives rise to a variety of health, reproductive, and psychosocial implications. It is in these contexts that family communication of genetic information is important to study. Hence, this research aimed to explore genetic information communication in Filipino families affected with CAH. Using a qualitative descriptive design, families with a child affected with CAH were recruited through the CAH parent support group and were interviewed. Semi‐structured interviews explored flow and content of genetic information communicated, the meanings the families attach to the communicated information, and the motivating and hindering factors in communication. Thematic analysis was used to analyze the findings. A total of five families participated, which included 11 individuals. Findings revealed that the diagnosis of CAH is not kept secret and it is openly shared with the family. The decision to communicate is influenced by several factors including the family's desire to seek further information about their family history. Initially, the focus of the communicated information is on the health implications and while communication about genetics occurs, this is almost always confined to the immediate family. The mother and grandmother serve as primary communicators in the family. The families have limited understanding of CAH especially its genetic implications including recurrence risk and carrier status. The findings can guide genetic counselors in supporting families in communicating information about CAH with the rest of the family.
Private Sales Clubs: A 21st Century Distribution Channel
Authors: Betancourt Roger R. , Chocarro Raquel , Cortiñas Monica , Elorz Margarita , Mugica Jose Miguel
Published: November 2016

Private sales clubs are a novel service institution arising out of the Internet's ability to allow an exclusively online channel to distribute out of season or out of fashion inventories to a large set of customers. They have become a thriving industry in the 21st century. In this paper we enhance understanding of this technology mediated institution as a distribution channel. Furthermore, we show how to measure the impact of the distribution services it provides through the Internet on customer satisfaction and of the latter on economic performance. We rely on the technique of quantile regressions in this endeavor. The latter allows for asymmetries in the response function that have been noted as a major issue to be addressed in the analysis of both customer satisfaction and economic performance variables. Our most important empirical finding is that the distortions introduced by ignoring asymmetries in the response function with respect to customer satisfaction are extremely misleading for managers of private sales clubs.
Regulatory cascading: Limitations of policy design in European banking structural reforms
Authors: Spendzharova Aneta B
Published: November 2016

This article examines banking structural reforms introduced in the European Union (EU), placed in an international context. The concept of ‘regulatory cascading’ is put forward to investigate how European policy-makers tackle complex multi-faceted problems, such as that of banks which are ‘too big to fail’. The article shows that partial solutions to the problem introduced in other areas of banking regulation, coupled with strategic activism at the domestic level by key EU member states have constrained the opportunities to design a coherent EU framework regulating bank structures. In response to the Commission's proposal for harmonised European banking structural reforms, the Council has stressed in its position two approaches that closely correspond to the measures adopted in France and Germany, on the one hand, and the UK, on the other hand.
Turbulent thermal convection driven by heated inertial particles
Authors: Zamansky R. , Coletti F. , Massot M. , Mani A.
Published: November 2016

The heating of particles in a dilute suspension, for instance by radiation, chemical reactions or radioactivity, leads to local temperature fluctuations in the fluid due to the non-uniformity of the disperse phase. In the presence of a gravity field, the fluid is set in motion by the resulting buoyancy forces. When the particle density is different than that of the fluid, the fluid motion alters the spatial distribution of the particles and possibly strengthens their concentration inhomogeneities. This in turn causes more intense local heating. Direct numerical simulations in the Boussinesq limit show this feedback loop. Various regimes are identified depending on the particle inertia. For very small particle inertia, the macroscopic behaviour of the system is the result of many thermal plumes that are generated independently of each other. For significant particle inertia, clusters of particles are observed and their dynamics controls the flow. The emergence of very intermittent turbulent fluctuations shows that the flow is influenced by the larger structures (turbulent convection) as well as by the small-scale dynamics that affect particle segregation and thus the flow forcing. Assuming thermal equilibrium between the particles and the fluid (i.e. infinitely fast thermal relaxation of the particle), we investigate the evolution of statistical observables with the change of the main control parameters (namely the particle number density, the particle inertia and the domain size), and propose a scaling argument for these trends. Concerning the energy density in the spectral space, it is observed that the turbulent energy and temperature spectra follow a power law, the exponent of which varies continuously with the Stokes number. Furthermore, the study of the spectra of the temperature and momentum forcing (and thus of the concentration/temperature and velocity/temperature correlations) gives strong support to the proposed feedback loop mechanism. We then discuss the intermittency of the flow, and analyse the effect of relaxing some of the simplifying assumptions, thus assessing the relevance of the original studied configuration.
A Sensitive Search for Predicted Methanol Maser Transitions with the Australia Telescope Compact Array
Authors: Chipman A. , Ellingsen S. P. , Sobolev A. M. , Cragg D. M.
Published: November 2016

We have used the Australia Telescope Compact Array to search for a number of centimetre wavelength methanol transitions which are predicted to show weak maser emission towards star formation regions. Sensitive, high spatial, and spectral resolution observations towards four high-mass star formation regions which show emission in a large number of class II methanol maser transitions did not result in any detections. From these observations, we are able to place an upper limit of ≲ 1300 K on the brightness temperature of any emission from the 31A+–31A−, 17−2–18−3 E (vt = 1), 124–133 A−, 124–133 A+, and 41A+–41A− transitions of methanol in these sources on angular scales of 2 arcsec. This upper limit is consistent with current models for class II methanol masers in high-mass star formation regions and better constraints than those provided here will likely require observations with next-generation radio telescopes.
Relations Between He I λ10830 Absorption Strength and Stellar Activity Amongst Dwarf Stars
Authors: Smith Graeme H.
Published: November 2016

Correlations are identified between the strength of the λ10830 He I triplet line and the following tracers of stellar activity amongst FGK dwarfs with colours of (B − V) > 0.47: coronal soft X-ray emission, emission in the λ1549 C IV and λ1335 C II lines originating from the transition region, and Ca II H and K emission from the chromosphere. No such correlations are present amongst dwarfs with spectral type earlier than F6. In addition, G and K dwarfs with strong triplet lines show evidence of excess flux in the GALEX FUV band compared to weak-triplet-line dwarfs. The X-ray spectra of late-F, G, and K dwarfs with He I triplets stronger than 160 mÅ have greater values of the ROSAT hardness ratio HR1 than are typical of weak-triplet dwarfs in the same range of spectral type. In other words, dwarfs later than F7V with strong He I triplet lines tend towards harder 0.1–2.0 keV X-ray spectra than weak-triplet dwarfs, although values of HR1 ~ −0.2 to +0.1 can still be encountered amongst a minority of weak-He-triplet stars. As regards, FGK main sequence stars the observational data on the λ10830 triplet line remains sparse. Progress could be made through spectroscopy of high resolution for samples of hundreds of stars, selected on the basis of having other measures of chromospheric and coronal activity available.
Moral Identity and Protest Cascades in Syria
Authors: Pearlman Wendy
Published: November 2016

Cascade models explain the roles of the intrepid few who initiate protest and the masses who join when the expected utility of dissent flips from negative to positive. Yet questions remain about what motivates participation between those points on the causal chain, or under any conditions of high risk. To explain these anomalies, this article employs theories of moral identity to explore the interdependence of a facet of decision making that rationalist models typically regard as fixed: individuals’ awareness of and need to express values central to their sense of self. Three mechanisms describe ways that individuals’ responses to early risers trigger moral identity-based motivations for protest. First, by conjuring normative ideals, first movers can activate bystanders’ urge to follow their example in order to earn their own self-respect. Secondly, by demonstrating the joy of agency, early risers can inspire bystanders’ desire to experience the same gratification. Thirdly, by absorbing punishments, early risers can activate onlookers’ sense of moral obligation to contribute to collective efforts. These mechanisms redouble bystanders’ sense of the inherent value of protest, apart from its instrumental utility, and intensify their acceptance of risks, independent of the actual risks anticipated. Original interviews with displaced Syrians about their participation in demonstrations illustrate these processes.