bluuebunny/crossref_metadata_2025 huggingface dataset:
Binding of Paeonol to Human Serum Albumin: A Hybrid Spectroscopic Approach and Conformational Study
Authors: Wang Juan
Published: January 2015

The purpose of this study was to elucidate the binding of paeonol to human serum albumin (HSA) through spectroscopic methods. The fluorescence quenching of HSA by paeonol was a result of the formation of the HSA–paeonol complex with low binding affinity (K = 4.45 × 103 M−1 at 298 K). Thermodynamic parameters (ΔG○ = –2.08 × 104 J·mol−1, ΔS○ = 77.9 J·mol−1·K−1, ΔH○ = 2.41 × 103 J·mol−1, kq = 9.67 × 1012 M−1·s−1) revealed that paeonol mainly binds HSA through hydrophobic force following a static quenching mode. The binding distance was estimated to be 1.91 nm by fluorescence resonant energy transfer. The conformation of HSA was changed and aggregates were formed in the presence of paeonol, revealed by synchronous fluorescence, circular dichroism, Fourier transform infrared spectroscopy, three‐dimensional fluorescence spectroscopy, and resonance light scattering results.
Epoxyeicosatrienoic Acids Regulate Macrophage Polarization and Prevent LPS‐Induced Cardiac Dysfunction
Authors: Dai Meiyan , Wu Lujin , He Zuowen , Zhang Shasha , Chen Chen , Xu Xizhen , Wang Peihua , Gruzdev Artiom , Zeldin Darryl C. , Wang Dao Wen
Published: January 2015

Macrophages, owning tremendous phenotypic plasticity and diverse functions, were becoming the target cells in various inflammatory, metabolic and immune diseases. Cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acid to form epoxyeicosatrienoic acids (EETs), which possess various beneficial effects on cardiovascular system. In the present study, we evaluated the effects of EETs treatment on macrophage polarization and recombinant adeno‐associated virus (rAAV)‐mediated CYP2J2 expression on lipopolysaccharide (LPS)‐induced cardiac dysfunction, and sought to investigate the underlying mechanisms. In vitro studies showed that EETs (1µmol/L) significantly inhibited LPS‐induced M1 macrophage polarization and diminished the proinflammatory cytokines at transcriptional and post‐transcriptional level; meanwhile it preserved M2 macrophage related molecules expression and upregulated anti‐inflammatory cytokine IL‐10. Furthermore, EETs down‐regulated NF‐κB activation and up‐regulated peroxisome proliferator‐activated receptors (PPARα/γ) and heme oxygenase 1 (HO‐1) expression, which play important roles in regulating M1 and M2 polarization. In addition, LPS treatment in mice induced cardiac dysfunction, heart tissue damage and infiltration of M1 macrophages, as well as the increase of inflammatory cytokines in serum and heart tissue, but rAAV‐mediated CYP2J2 expression increased EETs generation in heart and significantly attenuated the LPS‐induced harmful effects, which mechanisms were similar as the in vitro study. Taken together, the results indicate that CYP2J2/EETs regulates macrophage polarization by attenuating NF‐κB signaling pathway via PPARα/γ and HO‐1 activation and its potential use in treatment of inflammatory diseases. J. Cell. Physiol. 230: 2108–2119, 2015. © 2015 Wiley Periodicals, Inc.
Hospital course and discharge criteria for children hospitalized with bronchiolitis
Authors: Mansbach Jonathan M. , Clark Sunday , Piedra Pedro A. , Macias Charles G. , Schroeder Alan R. , Pate Brian M. , Sullivan Ashley F. , Espinola Janice A. , Camargo Carlos A. ,   for the MARC‐30 Investigators
Published: January 2015

BACKGROUND

For children hospitalized with bronchiolitis, there is uncertainty about the expected inpatient clinical course and when children are safe for discharge.

OBJECTIVES

Examine the time to clinical improvement, risk of clinical worsening after improvement, and develop discharge criteria.

DESIGN

Prospective multiyear cohort study.

SETTING

Sixteen US hospitals.

PARTICIPANTS

Consecutive hospitalized children age <2 years with bronchiolitis.

MEASUREMENT

We defined clinical improvement using: (1) retraction severity, (2) respiratory rate, (3) room air oxygen saturation, and (4) hydration status. After meeting improvement criteria, children were considered clinically worse based on the inverse of ≥1 of these criteria or need for intensive care.

RESULTS

Among 1916 children, the median number of days from onset of difficulty breathing until clinical improvement was 4 (interquartile range, 3–7.5 days). Of the total, 1702 (88%) met clinical improvement criteria, with 4% worsening (3% required intensive care). Children who worsened were age <2 months (adjusted odds ratio [AOR]: 3.51; 95% confidence interval [CI]: 2.07‐5.94), gestational age <37 weeks (AOR: 1.94; 95% CI: 1.13‐3.32), and presented with severe retractions (AOR: 5.55; 95% CI: 2.12‐14.50), inadequate oral intake (AOR: 2.54; 95% CI: 1.39‐4.62), or apnea (AOR: 2.87; 95% CI: 1.45‐5.68). Readmissions were similar for children who did and did not worsen.

CONCLUSIONS

Although children hospitalized with bronchiolitis had wide‐ranging recovery times, only 4% worsened after initial improvement. Children who worsened were more likely to be younger, premature infants presenting in more severe distress. For children hospitalized with bronchiolitis, these data may help establish more evidence‐based discharge criteria, reduce practice variability, and safely shorten hospital length‐of‐stay. Journal of Hospital Medicine 2015;10:205–211. © 2015 Society of Hospital Medicine
Before you call renal: Acute kidney injury for hospitalists
Authors: Cooper Cynthia M. , Fenves Andrew Z.
Published: January 2015

Acute kidney injury is a clinical problem of growing incidence in hospitalized patients. It increases the risk of poor outcomes, length of stay and the cost of hospitalization. Successful management of acute kidney injury requires early recognition and diagnosis through detailed medical history, careful physical exam, judicious use of laboratory and radiologic tests and timely renal consultation. Subsequent management is tailored to the likely mechanism of injury with emphasis on limiting both further injury and systemic consequences. A common sense approach to acute kidney injury is essential for hospitalists aiming to limit further injury, prevent acute complications and lessen the risk of chronic morbidity. Journal of Hospital Medicine 2015;10:403–408. © 2015 Society of Hospital Medicine
Data as a catalyst for change: Stories from the frontlines
Authors: Siegal Dana , Ruoff Gretchen
Published: January 2015

The landmark 1999 Institute of Medicine report, “To Err Is Human,” challenged us all to reduce the number of preventable medical errors. While vulnerabilities and patient harm continue at unacceptable rates, there are also many success stories. This article presents a series of case studies that illustrate how healthcare organizations have used data—quantitative, qualitative, and comparative—to address vulnerabilities and guide meaningful change to improve patient safety. These examples are drawn from the data‐sharing community of CRICO Strategies, a division of the Risk Management Foundation of the Harvard Medical Institutions, Inc. (CRICO). CRICO's data‐driven strategy uses intelligence from thousands of medical malpractice cases across the country to examine what has gone wrong and why, and to help members and clients manage their risk and provide better care.
Creating Capabilities through Maternal Mental Health Interventions: A Case Study at Hanover Park, Cape Town
Authors: Meintjes Ingrid , Field Sally , Van Heyningen Thandi , Honikman Simone
Published: January 2015

In South Africa, approximately one third of resource‐poor women experience mental illness during pregnancy. Prevalence is higher in low‐resource settings than in developed countries. The poverty–mental illness cycle is well documented. Through the capabilities approach, this paper locates maternal mental illness in a development framework and explores the deprivational impacts of mental illness. It describes a counselling intervention in South Africa as a case study and applies a qualitative content analysis to descriptive data of a sample of five typical clients. Findings suggest that integrated maternal mental health care may act as a strategic intervention for capability formation and sustainable development. Copyright © 2015 John Wiley & Sons, Ltd.
Nitrate content in a collection of higher mushrooms
Authors: Bóbics Renáta , Krüzselyi Dániel , Vetter János
Published: January 2015

BACKGROUND

Data of mushroom nitrate content from scientific studies is limited. There have been two such recent investigations (mainly regarding certain cultivated species). To obtain comparable analytical data, we analyzed 134 samples of 54 taxa gathered and prepared by our department.

RESULTS

The mushroom species were evaluated according to their nutritional types: saprotrophic, mycorrhizal and wood‐decaying groups. Low and relatively invariable contents were found in the mycorrhizal (216.5 mg kg−1 dry matter (DM) and wood‐decaying groups (228.6 mg kg−1 DM), but in the saprotrophic group we observed a wide variability (151.4–12 715 mg kg−1 DM).

CONCLUSION

A considerable nitrate content was found in samples of seven ‘accumulator’ species (Clitocybe nebularis, C. odora, Lepista nuda, L. personata, L. irina, Macrolepiota rachodes and M. procera). The toxicological relevance of daily uptake of acceptable nitrate content via mushrooms only is not presumable, but the ‘accumulator’ saprotrophic species can be ‘contributors’ to our nitrate intake in foods. © 2015 Society of Chemical Industry
Sleep Variability in Military‐Related PTSD: A Comparison to Primary Insomnia and Healthy Controls
Authors: Straus Laura D. , Drummond Sean P. A. , Nappi Carla M. , Jenkins Melissa M. , Norman Sonya B.
Published: January 2015

Sleep disturbances are prevalent in posttraumatic stress disorder (PTSD) and are associated with a number of adverse health consequences. Few studies have used comprehensive assessment methods to characterize sleep in Operation Iraqi Freedom/Operation Enduring Freedom/Operation New Dawn (OEF/OIF/OND) veterans with PTSD. OEF/OIF/OND veterans with PTSD and sleep disturbance (n = 45) were compared to patients with primary insomnia (n = 25) and healthy control subjects (n = 27). Participants were assessed using questionnaire‐based measures as well as daily subjective and objective measures of sleep. The 3 groups were compared with regard to (a) group means, (b) intraindividual (i.e., night‐to‐night) variability of sleep, and (c) interindividual (i.e., within‐group) variability of sleep. In terms of group means, only objective sleep efficiency was significantly worse with PTSD than with primary insomnia (d = 0.54). Those with PTSD differed from those with primary insomnia on measures of intraindividual as well as interindividual variability (d = 0.48–0.73). These results suggested sleep symptoms in OEF/OIF/OND veterans with PTSD are more variable across nights and less consistent across patients relative to sleep symptoms in insomnia patients without PTSD. These findings have implications for research, as well as for personalizing treatment for individuals with PTSD.
A widespread allergic reaction to black tattoo ink caused by laser treatment
Authors: Bernstein Eric F.
Published: January 2015

Background and Objective

This is the first reported case of a local and widespread reaction in a 39 year old woman, to black tattoo ink, induced by Q‐switched laser treatment.

Study Design/Patients and Methods

A 39 year old woman was treated with the Q‐switched Nd:YAG laser for removal of a decorative tattoo of her lower back.

Results

Subsequent to laser treatment, a severe, widespread allergic reaction developed within and surrounding the treated tattoo.

Conclusions

Tattoo reactions subsequent to laser treatment should be considered in addition to reactions to topical antibiotics or wound dressings, following laser treatment of tattoos. Lasers Surg. Med. 47:180–182, 2015. © 2015 Wiley Periodicals, Inc.
Labeling as a Social Practice in Online Consumption Communities
Authors: Dinhopl Anja , Gretzel Ulrike , Whelan Andrew
Published: January 2015

The present research explores how consumers use labeling in online consumption communities as a social practice. Through the analysis of conversations in an online consumption community of vegetarians, this paper presents a typology of strategies for using labels to serve specific functions. (1) Construction strategy: Consumers invent new practices under one label to account for the variety of practices associated with a label while benefiting from the awareness surrounding it. Its purpose is to accommodate and promote emerging practices. (2) Reconstruction strategy: Consumers use static definitions of a label that selectively exclude community members they do not perceive to be “true” to the label for policing and demarcating community boundaries. (3) Conversion strategy: Consumers maintain use of a label despite conflicts to promote group cohesion and unity. (4) Invalidation strategy: Consumers abandon a label, because it has lost meaning for the practice to which they adhere. This paper presents a theoretical framework for when, how, and why online consumption community members use labels to describe themselves, their consumption activity, and the community to which they belong. This also provides marketers with insights into when and how to use such community‐based labels to communicate with consumers.
Health Communities as Permissible Space: Supporting Negotiation to Balance Asymmetries
Authors: Keeling Debbie Isobel , Laing Angus , Newholm Terry
Published: January 2015

Online communities provide promising opportunities to support patient–professional negotiations that address the asymmetries characterizing health services. This study addresses the lack of in‐depth understanding of these negotiations, what constitutes successful negotiation outcomes, and the potential impact of negotiation on offline health behaviors. Adopting a netnographic approach, two threads were observed from each of the four online health communities focusing on breast cancer, prostate cancer, depression, and diabetes, respectively. This analysis was supplemented with 45 in‐depth interviews. The evidence suggests that online health communities can be constructed as permissible spaces. Such virtual spaces facilitate the type of patient–professional negotiations that can redress asymmetries. The critical elements of the negotiation process are identified as occupation, validation, advocacy, and recording. These support patients and professionals as they debate and resolve conflicts in how they experience health. Direct tangible offline negotiation outcomes are reported (e.g., changes in treatment plans). Implications for professional–patient partnerships are also explored.
Hexavalent chromium induces expression of mesenchymal and stem cell markers in renal epithelial cells
Authors: Li Wei‐Jen , Yang Cheng‐Lin , Chow Kuan‐Chih , Kuo Ting‐Wei
Published: January 2015

Cr(VI) causes severe kidney damage. The patient's renal function could gradually recover by spontaneous kidney regeneration. The molecular effect of Cr(VI) on recovery of kidney cells, however, has not been clearly elucidated. Here we show that Cr(VI) induces expression of mesenchymal and stem cell markers, cell markers, such as paxillin, vimentin, α‐SMA, nanog, and CD133 of HK‐2 cells. Moreover, Cr(VI) activates epithelial‐to‐mesenchymal transition (EMT). By revealing that levels of dihydrodiol dehydrogenase were promptly reduced following Cr(VI) challenge, our data suggested that DDH could be involved in a Cr(VI)‐related oxidation to generate massive reactive oxygen species and H2O2, and to create intracellular hypoxia, which then increased levels of SUMO‐1 activating enzyme subunit 2, and sumoylation of eukaryotic elongation factor‐2, to mediate the subsequent molecular and cellular responses, e.g., expression of mesenchymal and stem cell markers. Pretreatment with vitamin C reduced Cr(VI)‐related cellular effects. However, no evident effect was observed when vitamin C was added following Cr(VI) challenge. © 2015 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc.
CD38 is a putative functional marker for side population cells in human nasopharyngeal carcinoma cell lines
Authors: Zheng Danwei , Liao Shan , Zhu Guangchao , Luo Gengqiu , Xiao Songshu , He Junyu , Pei Zhen , Li Guiyuan , Zhou Yanhong
Published: January 2015

Cancer stem cells (CSCs) are thought to be responsible for cancer progression and therapeutic resistance but identification of this subpopulation requires selective markers. Fortunately, side population (SP) cells analysis brings a novel method to CSCs study. In this study, we identified SP cells, which are demonstrated rich in CSCs, in four nasopharyngeal carcinoma (NPC) cell lines. We investigated SP cells from HK‐1 NPC cell line and showed CSCs characteristics in this subpopulation. SP cells displayed greater proliferation and invasion and expressed high levels of CSCs markers than NSP cells. Furthermore, our microRNA microarray analysis of SP versus NSP cells revealed that CD38‐related miRNAs were down‐regulated in SP cell, but the mRNA and protein level of CD38 were highly expressed in SP cells. We further searched for molecules interacting with CD38 and identified ZAP70, which was also well expressed in SP cells at both mRNA and protein levels. Our results uncover a CD38 pathway that may regulate the proliferation and migration of SP cells from HK‐1 NPC cell line. © 2015 Wiley Periodicals, Inc.
Development of the Work Intention Inventory Short–Form
Authors: Nimon Kim , Zigarmi Drea
Published: January 2015

The Work Intention Inventory (WII: Zigarmi, Nimon, Houson, Witt, & Diehl, 2012) was designed to assess five measures of work intention. Measuring employee intentions is important to consider when evaluating outcomes associated with employee engagement or work passion as research indicates intentions are strong predictors of behavior. Following scale reduction procedures developed by Stanton, Sinar, Balzer, and Smith (2002), we used inter–item covariance matrices from Zigarmi et al. (2012) and data resulting from the field test of the WII–Short Form (WII–SF) in a manufacturing company to develop a short form of the WII and provide initial evidence of construct validity. There is preliminary evidence to indicate that the WII–SF may offer practitioners and researchers an efficient way to reliably and validly assess employee work intentions
Writing for Publication While in Graduate School: An Accessible Reality
Authors: Collins Joshua C.
Published: January 2015

The purpose of this Writer's Forum is to share eight tips about writing for publication as a graduate student. These tips demonstrate writing for publication as an accessible reality for students. This Writer's Forum advances ideas, advice, and anecdotes focused on helping graduate students to see themselves as valued experts who are capable of writing, dealing with feedback and criticism, and using time in a thoughtful and productive manner.
A multiscale coupling approach between discrete element method and finite difference method for dynamic analysis
Authors: Li Mingguang , Yu Haitao , Wang Jianhua , Xia Xiaohe , Chen Jinjian
Published: January 2015

The coupling between two distinct numerical methods presents a major challenge, especially in the case of discrete‐continuum coupling for dynamic simulations. This paper presents a general multiscale framework for coupling the discrete element method (DEM) and the finite difference method (FDM). DEM has been shown to be particular suitable for capturing physical phenomena at small length scales where continuum mechanics description no longer applies. Its efficiency, however, is limited because of the computational power required. A multidomain analysis coupling DEM and FDM is thus proposed to reduce the computational cost. To couple overlapping DEM and FDM, a bridging scale term is introduced such that compatibility of dynamic behavior between the DEM‐based and the FDM‐based models is enforced. This multiscale method couples two commercial packages: the DEM‐based code, particle flow code, and the FDM‐based code, fast lagrangian analysis of continua. The new method is applied to several reference dynamic tests. Results using the proposed method compare well with benchmark simulations from FDM and DEM. Copyright © 2015 John Wiley & Sons, Ltd.
Computational structural and material stability analysis in finite electro‐elasto‐statics of electro‐active materials
Authors: Miehe C. , Vallicotti D. , Zäh D.
Published: January 2015

Dielectric materials like electro‐active polymers (EAPs) exhibit coupled electro‐mechanical behavior at large strains. They respond by a deformation to an applied electrical field and are used in advanced industrial environments as sensors and actuators, for example, in robotics, biomimetics and smart structures. In field‐activated or electronic EAPs, the electric activation is driven by Coulomb‐type electrostatic forces, resulting in Maxwell stresses. These materials are able to provide finite actuation strains, which can even be improved by optimizing their composite microstructure. However, EAPs suffer from different types of instabilities. This concernsglobal structural instabilities, such as buckling and wrinkling of EAP devices, as well aslocal material instabilities, such as limit‐points and bifurcation‐points in the constitutive response, which induce snap‐through and fine scale localization of local states. In this work, we outline variational‐based definitions for structural and material stability, and design algorithms for accompanying stability checks in typical finite element computations. The formulation starts from stability criteria for acanonical energy minimization principleof electro‐elasto‐statics, and then shifts them over to representations related to anenthalpy‐based saddle point principlethat is considered as the most convenient setting for numerical implementation. Here, global structural stability is analyzed based on aperturbation of the total electro‐mechanical energy, and related to statements of positive definiteness of incremental finite element tangent arrays. We base the local material stability on anincremental quasi‐convexity conditionof the electro‐mechanical energy, inducing the positive definiteness of both the incremental electro‐mechanical moduli as well as a generalized acoustic tensor. It is shown that the incremental arrays to be analyzed in the stability criteria appear within the enthalpy‐based setting in adistinct diagonal form, with pure mechanical and pure electrical partitions. Applications of accompanying stability analyses in finite element computations are demonstrated by means of representative model problems. Copyright © 2015 John Wiley & Sons, Ltd.
Extended finite element method coupled with face‐based strain smoothing technique for three‐dimensional fracture problems
Authors: Jiang Y. , Tay T. E. , Chen L. , Zhang Y. W.
Published: January 2015

In this work, the extended finite element method (XFEM) is for the first time coupled with face‐based strain‐smoothing technique to solve three‐dimensional fracture problems. This proposed method, which is called face‐based smoothed XFEM here, is expected to combine both the advantages of XFEM and strain‐smoothing technique. In XFEM, arbitrary crack geometry can be modeled and crack advance can be simulated without remeshing. Strain‐smoothing technique can eliminate the integration of singular term over the volume around the crack front, thanks to the transformation of volume integration into area integration. Special smoothing scheme is implemented in the crack front smoothing domain. Three examples are presented to test the accuracy, efficiency, and convergence rate of the face‐based smoothed XFEM. From the results, it is clear that smoothing technique can improve the performance of XFEM for three‐dimensional fracture problems. Copyright © 2015 John Wiley & Sons, Ltd.
Successful Electronic Implementation of Discharge Referral Decision Support Has a Positive Impact on 30‐ and 60‐day Readmissions
Authors: Bowles Kathryn H. , Chittams Jesse , Heil Eric , Topaz Maxim , Rickard Kathy , Bhasker Mrinal , Tanzer Matt , Behta Maryam , Hanlon Alexandra L.
Published: January 2015

In a quasi‐experimental study, decision support software was installed in three hospitals to study the ability to scale (spread) its use from one hospital on paper to three hospitals as software, and to examine the effect on 30‐ and 60‐day readmissions. The Discharge Decision Support System (D2S2) software analyzes data collected by nurses on admission with a proprietary risk assessment tool, identifies patients in need of post‐acute care, and alerts discharge planners. On six intervention units, with a concurrent comparison group of 76 units, we examined the implementation experience and compared readmission outcomes before and after implementation. The software implementation finished one month ahead of schedule, and the software performed reliably. High‐risk patients admitted in the experimental phase after implementation of D2S2 decision support had significantly fewer 30‐day readmissions (a decrease from 22.2% to 9.4%). When high‐ and low‐risk patients were analyzed together, D2S2 achieved a 33% relative reduction in 30‐day readmissions (13.1 to 8.8%) and sustained a 37% relative reduction at 60 days. The software, available commercially through RightCare Solutions, was adopted by the health system and remains in use after 22 months. The D2S2 risk assessment tool can be installed easily in existing EHR systems. Future research will focus on how the tool influences discharge decision‐making and how its accuracy can be improved in specific settings. © 2015 Wiley Periodicals, Inc.
Comparable efficacy with varying dosages of glucarpidase in pediatric oncology patients
Authors: Scott Jeffrey R. , Zhou Yinmei , Cheng Cheng , Ward Deborah A. , Swanson Hope D. , Molinelli Alejandro R. , Stewart Clinton F. , Navid Fariba , Jeha Sima , Relling Mary V. , Crews Kristine R.
Published: January 2015

Background

Glucarpidase rapidly reduces methotrexate plasma concentrations in patients experiencing methotrexate‐induced renal dysfunction. Debate exists regarding the role of glucarpidase in therapy given its high cost. The use of reduced‐dose glucarpidase has been reported, and may allow more institutions to supply this drug to their patients. This report explores the relationship between glucarpidase dosage and patient outcomes in pediatric oncology patients.

Methods

The authors evaluated data from 26 patients who received glucarpidase after high‐dose methotrexate. Decrease in plasma methotrexate concentrations and time to renal recovery were evaluated for an association with glucarpidase dosage, which ranged from 13 to 90 units/kg.

Results

No significant relationship was found between glucarpidase dosage (units/kg) and percent decrease in methotrexate plasma concentrations measured by TDx (P > 0.1) or HPLC (P > 0.5). Patients who received glucarpidase dosages <50 units/kg had a median percent reduction in methotrexate plasma concentration of 99.4% (range, 98–100) measured by HPLC compared to a median percent reduction of 99.4% (range, 77.2–100) in patients who received ≥50 units/kg. Time to SCr recovery was not related to glucarpidase dosage (P > 0.8).

Conclusions

The efficacy of glucarpidase in the treatment of HDMTX‐induced kidney injury was not dosage‐dependent in this retrospective analysis of pediatric oncology patients. Pediatr Blood Cancer 2015;62:1518–1522. © 2015 Wiley Periodicals, Inc.
Beginning and duration of pregnancy in automated health care databases: review of estimation methods and validation results
Authors: Margulis Andrea V. , Palmsten Kristin , Andrade Susan E. , Charlton Rachel A. , Hardy Janet R. , Cooper William O. , Hernández‐Díaz Sonia
Published: January 2015

Purpose

To describe methods reported in the literature to estimate the beginning or duration of pregnancy in automated health care data, and to present results of validation exercises where available.

Methods

Papers reporting methods for determining the beginning or duration of pregnancy were identified based on Pubmed searches, by consulting investigators with expertise in the field and by reviewing conference abstracts and reference lists of relevant papers. From each paper or abstract, we extracted information to characterize the study population, data sources, and estimation algorithm. We then grouped these studies into categories reflecting their general methodological approach.

Results

Methods were classified into 5 categories: (i) methods that assign a uniform duration for all pregnancies, (ii) methods that assign pregnancy duration based on preterm‐delivery or health care related codes, or codes for other pregnancy outcomes, (iii) methods based on the timing of prenatal care, (iv) methods based on birth weight, and (v) methods that combine elements from 2 and 3. Validation studies evaluating these methods used varied approaches, with results generally reporting on the mistiming of the start of pregnancy, incorrect estimation of the duration of pregnancy, or misclassification of drug exposure during pregnancy or early pregnancy.

Conclusions

In the absence of accurate information on the beginning or duration of pregnancy, several methods of varying complexity are available to estimate them. Validation studies have been performed for many of them and can serve as a guide for method selection for a particular study. Copyright © 2015 John Wiley & Sons, Ltd.
Factors influencing quality decision‐making: regulatory and pharmaceutical industry perspectives
Authors: Donelan Ronan , Walker Stuart , Salek Sam
Published: January 2015

Purpose

Currently, there is no qualified understanding of the influences, behaviours and other factors that impact the decision‐making of individuals and organisations involved in the development of new medicines. The aim of this qualitative study was to investigate and identify the important issues that influence quality decision‐making.

Methods

Semi‐structured interviews were carried out with 29 senior decision‐makers from the pharmaceutical industry and regulatory authorities. The study participants were invited to discuss and review their perception of decision‐making within their organisation, its role in drug development and the regulatory review and their awareness and use of decision‐making techniques and the impact and monitoring of decisions.

Results

The analyses (using NVivo 8© software) resulted in the identification of 32 major and 97 sub‐themes that were consolidated into 19 overarching themes. These included items such as quality and validity of data, time considerations, organisational and cultural influences, analytical and logical approach, qualification and experience, subjective and personal considerations, political influences, precedents for similar previous decisions, understanding of the decision in question, impact analyses, audit trail, education and awareness, individual versus corporate decision‐making and frameworks. Relationships between themes were identified. The 19 overarching decision‐making themes were integrated into a framework for quality decision‐making.

Conclusion

This study has achieved its aim of exploring decision‐making from the perspective of the individual and the organisation working in drug development and the regulatory review and has identified issues and considerations relating to making good quality decisions and allowed for the generation of a framework to aid quality decision‐making. Copyright © 2015 John Wiley & Sons, Ltd.
Synthesis and characterization of polylactides with different branched architectures
Authors: Nouri Sahar , Dubois Charles , Lafleur Pierre G.
Published: January 2015

Star‐shaped and comb‐like poly(L‐Lactide)s (PLA) are produced by employing multifunctional initiators, and hyperbranched structure is prepared using a cyclic co‐monomer with hydroxyl group. FTIR, size exclusion chromatography, and H‐NMR techniques are employed to characterize the synthesized polymers, validating the formation of desired structures with chain lengths above the critical length for entanglement. After characterization of the synthesized polymers, the effect of branching on PLA properties is investigated by comparing the crystallization and rheological behavior of branched PLAs to those of a linear commercial grade. Differential scanning calorimetry and optical microscopy observations reveal a remarkable improvement in PLA crystallization due to the nucleation role of branching points. Moreover, synthesized polylactides exhibit strain hardening behavior during elongational viscosity measurements by a sentmanat extension rheometer platform. Significant improvements in crystallization and elongational rheology behavior of the synthesized polymers support the achievement of branched polymer structures. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015, 53, 522–531
Nonspecific shielding of unfavorable electrostatic intramolecular interactions in the erythropoietin native‐state increase conformational stability and limit non‐native aggregation
Authors: Banks Douglas D.
Published: January 2015

Previous equilibrium and kinetic folding studies of the glycoprotein erythropoietin indicate that sodium chloride increases the conformational stability of this therapeutically important cytokine, ostensibly by stabilizing the native‐state [Banks DD, (2011) The Effect of Glycosylation on the Folding Kinetics of Erythropoietin. J Mol Biol 412:536–550]. The focus of the current report is to determine the underlying cause of the salt dependent increase in erythropoietin conformational stability and to understand if it has any impact on aggregation, an instability that remains a challenge to the biotech industry in maintaining the efficacy and shelf‐life of protein therapeutics. Isothermal urea denaturation experiments conducted at numerous temperatures in the absence and presence of sodium chloride indicated that salt stabilizes erythropoietin primarily by increasing the difference in enthalpy between the native and unfolded sates. This result, and the finding that the salt induced increases in erythropoietin melting temperatures were independent of the identity of the salt cation and anion, indicates that salt likely increases the conformational stability of erythropoietin at neutral pH by nonspecific shielding of unfavorable electrostatic interaction(s) in the native‐state. The addition of salt (even low concentrations of the strong chaotrope salt guanidinium hydrochloride) also exponentially decreased the initial rate of soluble erythropoietin non‐native aggregation at 37 °C storage.
The prognostic value of reactive stroma on prostate needle biopsy: A population‐based study
Authors: Sæter Thorstein , Vlatkovic Ljiljana , Waaler Gudmund , Servoll Einar , Nesland Jahn M. , Axcrona Karol , Axcrona Ulrika
Published: January 2015

BACKGROUND

Reactive tumor stroma has been shown to play an active role in prostatic carcinogenesis. A grading system for reactive stroma in prostate cancer (PC) has recently been established and found to predict biochemical recurrence and prostate cancer‐specific mortality (PCSM) in prostatectomized patients. To the best of our knowledge, there has been no study investigating the prognostic value of reactive stromal grading (RSG) with regard to PCSM when evaluated in diagnostic prostate needle biopsies.

METHODS

A population‐based study on 318 patients, encompassing all cases of PC diagnosed by needle biopsies and without evidence of systemic metastasis at the time of diagnosis in Aust–Agder County in the period 1991–1999. Patients were identified by cross‐referencing the Cancer Registry of Norway. Clinical data were obtained by review of medical charts. The endpoint was PCSM. RSG was evaluated on haematoxylin and eosin stained sections according to previously described criteria; grade 0, 0–5% reactive stroma; grade 1, 6–15%; grade 2, 16–50%; grade 3, 51–100%.

RESULTS

RSG could be evaluated in 278 patients. The median follow‐ up time was 110 months (interquartile range: 51–171). The 10‐year PC ‐ specific survival rate for RSGs of 0, 1, 2, and 3 was 96%, 81%, 69%, and 63%, respectively (P < 0.005). RSG remained independently associated with PCSM in a multivariate Cox regression analysis adjusting for prostate–specific antigen level, clinical stage, Gleason score, and mode of treatment. The concordance index of the multivariate model was 0.814

CONCLUSIONS

Our study demonstrates that RSG in diagnostic prostate needle biopsies predicts PCSM independently of other evaluable prognostic factors. Hence, RSG could be used in addition to traditional prognostic factors for prognostication and treatment stratification of PC patients. Prostate 75: 662–671, 2015. © 2015 Wiley Periodicals, Inc.
The role of atmospheric uncertainty in Arctic summer sea ice data assimilation and prediction
Authors: Yang Qinghua , Losa Svetlana N. , Losch Martin , Jung Thomas , Nerger Lars
Published: January 2015

The role of atmospheric uncertainty for the assimilation and prediction of Arctic sea ice is explored by running the Massachusetts Institute of Technology general circulation model (MITgcm) in data assimilation (DA) and prediction mode for summer 2010. The atmospheric ensemble forcing is taken from the UK Met Office (UKMO) system available through the TIGGE (THORPEX Interactive Grand Global Ensemble) database. The DA system is based on a Local Singular Evolutive Interpolated Kalman (LSEIK) filter, and Special Sensor Microwave Imager/Sounder (SSMIS) sea ice concentration operational products from the National Snow and Ice Data Center (NSIDC) are assimilated. Two kinds of experiments are carried out differing in the LSEIK configuration and forcing used: the first one uses a single deterministic control forcing and a forgetting factor necessary to inflate the ensemble spread in the DA phase; the second one uses 23 members from the UKMO atmospheric ensemble prediction system, thereby avoiding any additional ensemble inflation and making further tuning unnecessary. With both systems the model data misfit improves as expected, but the ensemble approach outperforms the deterministic filter. The ice concentration of 24 h forecasts is consistently closer to observations with the ensemble approach, because a larger and more realistic ensemble spread, representing model uncertainty, leads to a better adjustment. Fifteen‐day forecasts are also better with ensemble forcing than with deterministic forcing, because of both the larger spread and the better initial state in the ensemble forced system. The ensemble forcing can also improve poor initial states obtained with the deterministic control forcing, because the ensemble forcing introduces a larger spread that spans a larger range of model simulations. Ice thickness forecasts cannot be significantly improved with the ensemble forcing.
How quantum chemistry can solve fundamental problems in bioenergetics
Authors: Blomberg Margareta R. A.
Published: January 2015

Three different enzymes are discussed, cytochrome c oxidase, involved in aerobic respiration, cytochrome c dependent nitric oxide reductase, involved in denitrification (anaerobic respiration), and photosystem II, involved in photosynthesis. For all three systems, free energy profiles for the entire catalytic cycle are obtained from quantum mechanical calculations on large cluster models of the active sites, using hybrid density functional theory with the B3LYP* functional. The free energy profiles are used to solve different fundamental problems concerning energy conservation, enzymatic reaction mechanisms and structure, and also to explain experimental results that seem to be in conflict with each other. Possible future applications to related problems using similar methodology are suggested. © 2015 Wiley Periodicals, Inc.
Large‐scale plant growth chamber design for elevated pCO2 and δ13C studies
Authors: Hagopian William M. , Schubert Brian A. , Jahren A. Hope
Published: January 2015

Rationale

Throughout at least the next century, CO2 fertilization and environmental stresses (e.g. nutrient, moisture, insect herbivory) are predicted to affect yields of economically important crop species. Stable isotopes of carbon are used to study plant stresses, which affect yields, but a growth chamber design that can be used to isolate the effects of environmental stresses on crop‐sized species through precise maintenance of pCO2 levels and the δ13C values of atmospheric CO2 (δ13CCO2) is lacking.

Methods

We designed and built low‐cost plant growth chambers for growing staple crop species under precise pCO2 and δ13CCO2 conditions. Over the course of 14 hours, we assessed for pCO2 stability at two targeted levels (ambient, ~400 ppm; and 2×, ~800 ppm) and measured the δ13CCO2 value within the two chambers using a stable isotope ratio mass spectrometer. We also compared the temperature and relative humidity conditions within the two growth chambers, and in the ambient, outside air.

Results

Across our experimental period, we achieved δ13CCO2 stability (ambient: –8.05 ± 0.17‰; elevated: –12.99 ± 0.29‰) that showed nearly half the variability of any previously reported values for other chamber designs. The stability of the pCO2 conditions (ambient: 406 ± 3 ppm; elevated: 793 ± 54 ppm) was comparable with that in previous studies, but our design provided ~8 times more growing space than previous chamber designs. We also measured nearly identical temperature and relative humidity conditions for the two chambers throughout the experiment.

Conclusions

Our growth chamber design marks a significant improvement in our ability to test for plant stress across a range of future pCO2 scenarios. Through significant improvement in δ13CCO2 stability and increased chamber size, small changes in carbon isotope fractionation can be used to assess stress in crop species under specific environmental (temperature, relative humidity, pCO2) conditions. Copyright © 2015 John Wiley & Sons, Ltd.
Unexpected benzimidazole ring formation from a quinoneimide species in the presence of ammonium acetate as supporting electrolyte used in the coupling of electrochemistry with mass spectrometry
Authors: Bussy Ugo , Jurva Ulrik , Boisseau Renaud , Andresen‐Bergström Moa , Silvestre Virginie , Galland Nicolas , Jacquemin Denis , Boujtita Mohammed
Published: January 2015

Rationale

Electrochemistry (EC) coupled to mass spectrometry (MS) has been used to study different phase‐I reactions. Despite of the versatility of EC/MS, the effect of the nature of the supporting electrolyte on the formation of oxidation products has seldom been discussed during EC/MS experiments. Here, we present a comparison of two different supporting electrolytes and their effect on the identification of unstable intermediate oxidation species is discussed.

Methods

The oxidation of acebutolol was performed with a coulometric cell in the presence of two supporting electrolytes namely ammonium acetate and lithium acetate. Ultra‐performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry (UPLC/QTOFMS) using a binary gradient (water/acetonitrile) with positive electrospray ionization was used to identify the oxidation products in the presence and absence of glutathione. Chemical structure elucidations of the oxidation products were performed by high‐resolution mass spectrometry (HRMS) and were also supported by nuclear magnetic resonance (NMR) measurements.

Results

From the electrochemical study and HRMS measurements, we demonstrate that the quinoneimide species resulting from the oxidative hydrolyses of acebutolol gives a benzimidazole ring product in the presence of ammonium acetate. Through the example of the oxidation of acebutolol, a correlation between the supporting electrolyte nature and oxidation product formation was established. The obtained results were supported by quantum mechanical calculations.

Conclusions

We present here evidence of the side reactions induced by the presence of ammonia as supporting electrolyte during EC/MS measurements. Acebutolol was used as a model to postulate an uncommon and unexpected side reaction leading to benzimidazole ring formation. The findings may help to understand the identification of the intermediate species in the oxidative degradation process. Copyright © 2015 John Wiley & Sons, Ltd.
Distributed node‐to‐node consensus of multi‐agent systems with stochastic sampling
Authors: Wan Ying , Wen Guanghui , Cao Jinde , Yu Wenwu
Published: January 2015

This paper is concerned with the mean square node‐to‐node consensus tracking problem for multi‐agent systems with nonidentical nonlinear dynamics and directed topologies. The randomly occurred uncertainties in the sampling devices may result in stochastically varied sampling periods, which lead to the investigation of node‐to‐node consensus problem under stochastic sampling. By employing the input‐delay method and discontinuous Lyapunov functional approach, it arrives at some sufficient conditions under which the state of each follower can track that of the corresponding leader asymptotically in the mean square sense. Finally, some numerical simulations are provided to verify the effectiveness of the theoretical results. Copyright © 2015 John Wiley & Sons, Ltd.
A general two‐party bi‐input private function evaluation protocol
Authors: Sun Yi , Wen Qiaoyan
Published: January 2015

In the past, researchers have discussed the problem of two‐party single‐input private function evaluation (PFE), where P1 holds a private input x while P2 holds a private circuit Cf, and their goal is to securely compute Cf(x) without revealing x and Cf. Herein, we further consider a more general case, two‐party bi‐input PFE, where P2 also participates in the PFE by contributing a private input y. The research in this general case is of great value not only in theory but also in practice. In this paper, we focus on this problem and propose the first constant‐round two‐party bi‐input PFE protocol, which is with linear complexity and without relying on universal circuit or fully homomorphic encryption. Copyright © 2015 John Wiley & Sons, Ltd.
A Bayesian dose‐finding design for phase I/II clinical trials with nonignorable dropouts
Authors: Guo Beibei , Yuan Ying
Published: January 2015

Phase I/II trials utilize both toxicity and efficacy data to achieve efficient dose finding. However, due to the requirement of assessing efficacy outcome, which often takes a long period of time to be evaluated, the duration of phase I/II trials is often longer than that of the conventional dose‐finding trials. As a result, phase I/II trials are susceptible to the missing data problem caused by patient dropout, and the missing efficacy outcomes are often nonignorable in the sense that patients who do not experience treatment efficacy are more likely to drop out of the trial. We propose a Bayesian phase I/II trial design to accommodate nonignorable dropouts. We treat toxicity as a binary outcome and efficacy as a time‐to‐event outcome. We model the marginal distribution of toxicity using a logistic regression and jointly model the times to efficacy and dropout using proportional hazard models to adjust for nonignorable dropouts. The correlation between times to efficacy and dropout is modeled using a shared frailty. We propose a two‐stage dose‐finding algorithm to adaptively assign patients to desirable doses. Simulation studies show that the proposed design has desirable operating characteristics. Our design selects the target dose with a high probability and assigns most patients to the target dose. Copyright © 2015 John Wiley & Sons, Ltd.