bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring socioeconomic status in multicountry studies: results from the eight-country MAL-ED study
Authors: Psaki Stephanie R , Seidman Jessica C , Miller Mark , Gottlieb Michael , Bhutta Zulfiqar A , Ahmed Tahmeed , Ahmed AM Shamsir , Bessong Pascal , John Sushil M , Kang Gagandeep , Kosek Margaret , Lima Aldo , Shrestha Prakash , Svensen Erling , Checkley William ,   MAL-ED Network Investigators
Published: March 2014

Background

There is no standardized approach to comparing socioeconomic status (SES) across multiple sites in epidemiological studies. This is particularly problematic when cross-country comparisons are of interest. We sought to develop a simple measure of SES that would perform well across diverse, resource-limited settings.

Methods

A cross-sectional study was conducted with 800 children aged 24 to 60 months across eight resource-limited settings. Parents were asked to respond to a household SES questionnaire, and the height of each child was measured. A statistical analysis was done in two phases. First, the best approach for selecting and weighting household assets as a proxy for wealth was identified. We compared four approaches to measuring wealth: maternal education, principal components analysis, Multidimensional Poverty Index, and a novel variable selection approach based on the use of random forests. Second, the selected wealth measure was combined with other relevant variables to form a more complete measure of household SES. We used child height-for-age Z-score (HAZ) as the outcome of interest.

Results

Mean age of study children was 41 months, 52% were boys, and 42% were stunted. Using cross-validation, we found that random forests yielded the lowest prediction error when selecting assets as a measure of household wealth. The final SES index included access to improved water and sanitation, eight selected assets, maternal education, and household income (the WAMI index). A 25% difference in the WAMI index was positively associated with a difference of 0.38 standard deviations in HAZ (95% CI 0.22 to 0.55).

Conclusions

Statistical learning methods such as random forests provide an alternative to principal components analysis in the development of SES scores. Results from this multicountry study demonstrate the validity of a simplified SES index. With further validation, this simplified index may provide a standard approach for SES adjustment across resource-limited settings.
Blood-brain barrier damages and intrathecal synthesis of anti-N-methyl-D-aspartate receptor NR2 antibodies in diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus
Authors: Hirohata Shunsei , Arinuma Yoshiyuki , Yanagida Tamiko , Yoshio Taku
Published: March 2014

Introduction

Although neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the recalcitrant complications of the disease, its pathogenesis still remains unclear. Previous studies revealed that antibodies reactive with NMDA (N-methyl-D-aspartate) receptor NR2 (anti-NR2) are elevated in cerebrospinal fluid (CSF) of patients with diffuse psychiatric/neuropsychological syndromes (diffuse NPSLE), which is usually more recalcitrant than neurologic syndromes of NPSLE (focal NPSLE). Two mechanisms have been implicated for the elevation of CSF IgG, including intrathecal synthesis and transudation through the damaged blood-brain barrier (BBB). The present study was designed in order to elucidate the roles of BBB function and intrathecal synthesis of anti-NR2 in the elevation of CSF anti-NR2 with regard to the severity in NPSLE.

Methods

Paired serum and CSF samples were obtained from 81 systemic lupus erythematosus (SLE) patients when they presented active neuropsychiatric manifestations, and from 22 non-SLE control patients with non-inflammatory neurological diseases. The 81 SLE patients consisted of 55 patients with diffuse NPSLE, including 23 patients with acute confusional state (ACS), the severest form of diffuse NPSLE, and 26 patients with neurologic syndromes or peripheral nervous system involvement (focal NPSLE). IgG anti-NR2 and albumin were measured by ELISA. BBB function and intrathecal synthesis of anti-NR2 were evaluated by Q albumin and by CSF anti-NR2 index, respectively.

Results

CSF anti-NR2 levels, Q albumin and CSF anti-NR2 index were significantly higher in NPSLE than in non-SLE control. CSF anti-NR2 levels and Q albumin were significantly higher in ACS than in non-ACS diffuse NPSLE (anxiety disorder, cognitive dysfunction, mood disorder and psychosis) or in focal NPSLE, whereas there was no significant difference in CSF anti-NR2 index among the 3 groups. CSF anti-NR2 levels were significantly correlated with Q albumin in diffuse NPSLE (r = 0.3754, P = 0.0053).

Conclusions

These results demonstrate that the severity of BBB damages plays a crucial role in the development of ACS, the severest form of diffuse NPSLE, through the accelerated entry of larger amounts of anti-NR2 into the central nervous system.
Genomic occupancy of Runx2 with global expression profiling identifies a novel dimension to control of osteoblastogenesis
Authors: Wu Hai , Whitfield Troy W , Gordon Jonathan A R , Dobson Jason R , Tai Phillip W L , van Wijnen Andre J , Stein Janet L , Stein Gary S , Lian Jane B
Published: March 2014

Background

Osteogenesis is a highly regulated developmental process and continues during the turnover and repair of mature bone. Runx2, the master regulator of osteoblastogenesis, directs a transcriptional program essential for bone formation through genetic and epigenetic mechanisms. While individual Runx2 gene targets have been identified, further insights into the broad spectrum of Runx2 functions required for osteogenesis are needed.

Results

By performing genome-wide characterization of Runx2 binding at the three major stages of osteoblast differentiation - proliferation, matrix deposition and mineralization - we identify Runx2-dependent regulatory networks driving bone formation. Using chromatin immunoprecipitation followed by high-throughput sequencing over the course of these stages, we identify approximately 80,000 significantly enriched regions of Runx2 binding throughout the mouse genome. These binding events exhibit distinct patterns during osteogenesis, and are associated with proximal promoters and also non-promoter regions: upstream, introns, exons, transcription termination site regions, and intergenic regions. These peaks were partitioned into clusters that are associated with genes in complex biological processes that support bone formation. Using Affymetrix expression profiling of differentiating osteoblasts depleted of Runx2, we identify novel Runx2 targets including Ezh2, a critical epigenetic regulator; Crabp2, a retinoic acid signaling component; Adamts4 and Tnfrsf19, two remodelers of the extracellular matrix. We demonstrate by luciferase assays that these novel biological targets are regulated by Runx2 occupancy at non-promoter regions.

Conclusions

Our data establish that Runx2 interactions with chromatin across the genome reveal novel genes, pathways and transcriptional mechanisms that contribute to the regulation of osteoblastogenesis.
Enzymatic synthesis of epothilone A glycosides
Authors: Parajuli Prakash , Pandey Ramesh Prasad , Koirala Niranjan , Yoon Yeo Joon , Kim Byung-Gee , Sohng Jae Kyung
Published: March 2014

Epothilones are extremely cytotoxic chemotherapeutic agents with epoxide, thiazole, and ketone groups that share equipotent kinetic similarity with taxol. The in vitro glycosylation catalyzed by uridine diphosphate glucosyltransferase (YjiC) from Bacillus licheniformis generated six novel epothilone A glycoside analouges including epothilone A 7-O-β-D-glucoside, epothilone A 7-O-β-D-galactoside, epothilone A 3,7-O-β-D-digalactoside, epothilone A 7-O-β-D-2-deoxyglucoside, epothilone A 7-O-β-L-rhamnoside, and epothilone A 7-O-β-L-fucoside. Epothilone A 7-O-β-D-glucoside was structurally elucidated by ultra-high performance liquid chromatography-photo diode array (UPLC-PDA) conjugated with high resolution quantitative time-of-flight-electrospray ionization mass spectroscopy (HR-QTOF ESI-MS/MS) supported by one-and two-dimensional nuclear magnetic resonance studies whereas other epothilone A glycosides were characterized by UPLC-PDA and HR-QTOF ESI-MS/MS analyses. The time dependent conversion study of epothilone A to epothilone A 7-O-β-D-glucoside found to be maximum (~26%) between 3 h to 5 h incubation.
Induction of PGF2α Synthesis by Cortisol Through GR Dependent Induction of CBR1 in Human Amnion Fibroblasts
Authors: Guo Chunming , Wang Wangsheng , Liu Chao , Myatt Leslie , Sun Kang
Published: March 2014

Abundant evidence indicates a pivotal role of prostaglandin F2α (PGF2α) in human parturition. Both the fetal and maternal sides of the fetal membranes synthesize PGF2α. In addition to the synthesis of PGF2α from PGH2 by PGF synthase (PGFS), PGF2α can also be converted from PGE2 by carbonyl reductase 1 (CBR1). Here, we showed that there was concurrent increased production of cortisol and PGF2α in association with the elevation of CBR1 in human amnion obtained at term with labor versus term without labor. In cultured primary human amnion fibroblasts, cortisol (0.01–1μM) increased PGF2α production in a concentration-dependent manner, in parallel with elevation of CBR1 levels. Either siRNA-mediated knockdown of glucocorticoid receptor (GR) expression or GR antagonist RU486 attenuated the induction of CBR1 by cortisol. Chromatin immunoprecipitation (ChIP) showed an increased enrichment of both GR and RNA polymerase II to CBR1 promoter. Knockdown of CBR1 expression with siRNA or inhibition of CBR1 activity with rutin decreased both basal and cortisol-stimulated PGF2α production in human amnion fibroblasts. In conclusion, CBR1 may play a critical role in PGF2α synthesis in human amnion fibroblasts, and cortisol promotes the conversion of PGE2 into PGF2α via GR-mediated induction of CBR1 in human amnion fibroblasts. This stimulatory effect of cortisol on CBR1 expression may partly explain the concurrent increases of cortisol and PGF2α in human amnion tissue with labor, and these findings may account for the increased production of PGF2α in the fetal membranes prior to the onset of labor.
Novel Vasotocin-Regulated Aquaporins Expressed in the Ventral Skin of Semiaquatic Anuran Amphibians: Evolution of Cutaneous Water-Absorbing Mechanisms
Authors: Saitoh Yasunori , Ogushi Yuji , Shibata Yuki , Okada Reiko , Tanaka Shigeyasu , Suzuki Masakazu
Published: March 2014

Until now, it was believed that only one form of arginine vasotocin (AVT)-regulated aquaporin (AQP) existed to control water absorption from the ventral skin of semiaquatic anuran amphibians, eg, AQP-rj3(a) in Rana japonica. In the present study, we have identified a novel form of ventral skin-type AQP, AQP-rj3b, in R. japonica by cDNA cloning. The oocyte swelling assay confirmed that AQP-rj3b can facilitate water permeability. Both AQP-rj3a and AQP-rj3b were expressed abundantly in the ventral hindlimb skin and weakly in the ventral pelvic skin. For the hindlimb skin, water permeability was increased in response to AVT, although the hydroosmotic response was not statistically significant in the pelvic skin. Isoproterenol augmented water permeability of the hindlimb skin, and the response was inhibited by propranolol. These events were well correlated with the intracellular trafficking of the AQPs. Immunohistochemistry showed that both AQP-rj3 proteins were translocated from the cytoplasmic pool to the apical membrane of principal cells in the first-reacting cell layer of the hindlimb skin after stimulation with AVT and/or isoproterenol. The type-b AQP was also found in R. (Lithobates) catesbeiana and R. (Pelophylax) nigromaculata. Molecular phylogenetic analysis indicated that the type-a is closely related to ventral skin-type AQPs from aquatic Xenopus, whereas the type-b is closer to the AQPs from terrestrial Bufo and Hyla, suggesting that the AQPs from terrestrial species are not the orthologue of the AQPs from aquatic species. Based on these results, we propose a model for the evolution of cutaneous water-absorbing mechanisms in association with AQPs.
Cryptosporidium parvum-induced ileo-caecal adenocarcinoma and WNT signaling in a rodent model
Authors: Benamrouz Sadia , Conseil Valerie , Chabe Magali , Praet Marleen , Audebert Christophe , Blervaque Renaud , Guyot Karine , Gazzola Sophie , Mouray Anthony , Chassat Thierry , Delaire Baptiste , Goetinck Nathalie , Gantois Nausicaa , Osman Marwan , Slomianny Christian , Dehennaut Vanessa , Lefebvre Tony , Viscogliosi Eric , Cuvelier Claude , Dei-Cas Eduardo , Creusy Colette , Certad Gabriela
Published: March 2014

Cryptosporidium species are worldwide spread apicomplexan protozoan. These parasites constitute a significant risk to humans and animals. They cause self-limited diarrhea in immunocompetent hosts and a life threatening disease in immunocompromised hosts. Interestingly, Cryptosporidium parvum has been related to digestive carcinogenesis in humans. Consistently with a potential tumorigenic role of this parasite, in an original reproducible animal model of chronic cryptosporidiosis based on dexamethasone-treated or untreated adult SCID mice, we formerly reported that C. parvum (strains of animal and human origin) is able to induce digestive adenocarcinoma even in infections induced with very low inoculum. The aim of this study was to further characterize this animal model and to explore metabolic pathways potentially involved in the development of C. parvum-induced ileo-caecal oncogenesis. We searched for alterations in genes or proteins commonly involved in cell cycle, differentiation or cell migration, such as β-catenin, Apc, E-cadherin, Kras and p53. After infection of animals with C. parvum we demonstrated immunohistochemical abnormal localization of Wnt signaling pathway components and p53. Mutations in the selected loci of studied genes were not found after high-throughput sequencing. Furthermore, alterations in the ultrastructure of adherens junctions of the ileo-caecal neoplastic epithelia of C. parvum infected mice were recorded using transmission electron microscopy. In conclusion, we found for the first time that the Wnt signaling pathway, and particularly the cytoskeleton network seems to be pivotal for the development of C. parvum-induced neoplastic process and cell migration of transformed cells. Furthermore, this model is a valuable tool to contribute to the comprehension of the host-pathogen interactions associated to the intricate infection process due to this parasite, which is able to modulate host cytoskeleton activities and several host-cell biological processes and that remains a significant cause of infection worldwide.
Yeti, aDrosophila melanogasteressential gene, encodes a protein required for chromatin organization
Authors: Messina Giovanni , Damia Elisabetta , Fanti Laura , Atterrato Maria Teresa , Celauro Emanuele , Mariotti Francesca Romana , Accardo Maria Carmela , Walther Matthias , Vernì Fiammetta , Picchioni Daria , Moschetti Roberta , Caizzi Ruggiero , Piacentini Lucia , Cenci Giovanni , Giordano Ennio , Dimitri Patrizio
Published: March 2014

The evolutionarily conserved family of Bucentaur (BCNT) proteins exhibits a widespread distribution in animal and plants, yet its biological role remains largely unknown. Using Drosophila melanogaster as a model organism, we investigated the in vivo role of the Drosophila BCNT member called YETI. We report that loss of YETI causes lethality before pupation and defects in higher order chromatin organization, evidenced by severe impairment in the association of histone H2A.V, nucleosomal histones and epigenetic marks with polytene chromosomes. We also find that YETI binds to polytene chromosomes through its conserved BCNT domain and interacts with the histone variant H2A.V, HP1a and Domino-A (DOM-A), the ATPase subunit of the DOM/Tip60 chromatin remodeling complex. Furthermore, we identify YETI as a novel downstream target of the Drosophila DOM-A. Based on these results, we propose that YETI interacts with H2A.V-exchanging machinery, as a chaperone or as a new subunit of the DOM/Tip60 remodeling complex, and contributes to regulate the accumulation of H2A.V at chromatin sites. Overall, our findings suggest an unanticipated role of YETI protein in chromatin organization and provide for the first time mechanistic clues on how BCNT proteins may control development in multicellular organisms.
Interaction between Underexpanded Supersonic Jet and Obstacle
Authors: Kashimura Hideo , Yasunobu Tsuyoshi , Otobe Yumiko
Published: March 2014

When an underexpanded supersonic jet impinges on an obstacle, a self-induced flow oscillation occurs. This oscillation depends on the pressure ratio in the flowfield, the position of an obstacle and is related to the noise problems of aeronautical and other industrial engineering. The characteristic and the mechanism of self-induced flow oscillation, therefore, have to be understood to control the various noise problems. The characteristics of the oscillatory flowfield and the mechanism of an oscillation have to be studied further to control the oscillation. This paper aims to clarify the effect of the pressure ratio and the obstacle position on the mechanism of self-induced flow oscillation by the numerical analysis and the experiment, when the underexpanded supersonic jet impinges on the cylindrical body. From the result of this study, it is clear that occurrence of self-induced flow oscillation depends on the pressure balance in the flowfield.
Analytical Solution for Generating a Wave from a Wall with Changing Temperature
Authors: Takahashi S. , Sakurai A.
Published: March 2014

We consider the problem of wave generation from a wall with changing temperature to analytically solve the linear Boltzmann-BGK equation with diffuse reflection at a wall by successive approximation and to provide a foundation for the numerical approach. Convergence is verified, and approximate solutions used in its proof are utilized to demonstrate its wave-like features observed in the numerical solution.
Factors Affecting the Use of Outside, Intermittent Resources during NPD
Authors: Marion Tucker , Fixson Sebastian
Published: March 2014

Information technology, globalization, and digital design have all contributed to the changing composition of new product development (NPD). These developments have led to a paradigm shift where continuous resources can be replaced by outsourced resources that are used intermittently throughout the entire innovation process. These resources can be plugged into the project at opportune times thereby lowering fixed costs and speeding commercialization. However, this intermittent use of resources requires appropriate management actions. This study reports on longitudinal, ethnographic case research performed over the span of the product development cycle of two projects. We look at multiple factors that can influence the effective coordination of outside, intermittent resources on the project. We explore critical characteristics of intermittent resources employed by new ventures, focusing on project management, the product development process, and the role of technology enablers such as IT collaboration. We find that technology's role in coordination of resources is less important than the robustness of interaction. Our qualitative study suggests that only when skilled project coordination is combined with precise communication can intermittent resources be effective. We conclude the article with the limitations and directions for further research.
Drugs acting on central nervous system (CNS) targets as leads for non-CNS targets
Authors: Kharkar Prashant S.
Published: March 2014

Innovative drug discovery approaches are currently needed to rejuvenate the shrinking product pipelines of the pharmaceutical companies across the globe. Here a theme is presented – the use of central nervous system (CNS) drugs as leads for non-CNS targets. The approach is related to the use of existing drugs for new indications. Suitable chemical modifications of the CNS drugs abolish their CNS penetration. These novel analogs may then be screened for activity against non-CNS targets. Careful selection of the appropriate structural modifications remains the key to success.
Electronic Textbook: Pros and Cons
Authors: Виноградова  , Vinogradova Natalya
Published: March 2014

Discussion materials on an actual problem related to use of an electronic version of textbook for elementary school have been presented in this

publication. Various opinions of authoritative experts concerning informational security ensuring of junior school pupils, and functions which

electronic editions should carry out in educational process, and requirements imposed to them are expressed.
Editorial—Report of the Marketing Science Editorial Review Committee
Authors: Fader Peter S. , Bronnenberg Bart J. , Iyer Ganesh , Neslin Scott A. , Netzer Oded , Srinivasan Kannan
Published: March 2014

This is an abridged version of an evaluation report for Marketing Science, which was commissioned by the INFORMS Publications Committee as part of its periodic review of every INFORMS journal. The coauthors listed here comprised the task force that conducted the research project and strategic analysis described below.
Connective Tissue Disease following Hepatitis B Vaccination; Topiramate-Associated Fatal Heat Stroke; Ramelteon-Induced Autoimmune Hepatitis; Acute Oxaliplatin-Induced Thrombotic Thrombocytopenic Purpura
Authors: Mancano Michael A.
Published: March 2014

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers.
Role of Corticosteroids during Cardiopulmonary Bypass
Authors: Kristeller Judith L. , Jankowski Arthur , Reinaker Travis
Published: March 2014

Corticosteroids are commonly used in the peri-operative setting for patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). The inflammatory response to CPB is associated with organ dysfunction and increased mortality. Corticosteroids reduce biochemical inflammatory markers associated with CPB, however the impact on clinical outcomes is mixed. The purpose of this article is to evaluate the evidence of changes in clinical outcomes associated with the peri-operative administration of corticosteroids in patients undergoing cardiac surgery with CPB. Randomized, placebo-controlled trials and meta-analyses were reviewed for evidence evaluating the impact of corticosteroids on clinical outcomes including mortality, myocardial infarction, atrial fibrillation (AF), duration of intubation, length of intensive care unit (ICU) or hospital stay, hyperglycemia, and gastrointestinal complications. Most of the relevant studies are underpowered to assess major clinical outcomes. Although corticosteroids likely reduce the risk of AF, this needs to be evaluated when used in addition to or in lieu of other anti-arrhythmic agents. Evidence does not equivocally support the use of corticosteroids to improve clinical outcomes in cardiac surgery patients.
Drug Monographs: Afatinib and Obinutuzumab
Authors: Mancheril Benjamin G. , Waddell J. Aubrey , Solimando Dominic A.
Published: March 2014

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases.
Accountable Care Organizations: Impact on Pharmacy
Authors: Amara Shilpa , Adamson Robert T. , Lew Indu , Slonim Anthony
Published: March 2014

The Patient Protection and Affordable Care Act (PPACA) has considerably transformed the approaches being used to deliver health care in the United States. It was enacted to expand health insurance access, improve funding for health professions education, and reform patient care delivery. The traditional fee-for-service payment system has been criticized for overspending and providing substandard quality of care. The Accountable Care Organization (ACO) was developed as a payment reform mechanism to slow rising health care costs and improve quality. Under this concept, networks of clinicians and hospitals share responsibility for a population of patients and are held accountable for the financial and clinical outcomes. Due to high rates of medication misuse, nonadherence to therapeutic medication regimens, and preventable adverse drug events, pharmacists are in an ideal position to manage drug therapy and reduce health care expenditures; as such, they may be valuable assets to the ACO team. This article discusses the role of the pharmacist in the era of ACOs specifically and health care reform globally. It outlines pharmacy-related quality of care measures, medication therapy management (MTM) programs (which may provide the foundation for pharmacist involvement in ACOs), and pharmacist functions in patient-centered medical homes (through which ACO services may be organized). The article concludes with a description of successful ACO models that have incorporated pharmacists into their programs.
Implementation of Pharmacist-Managed Anticoagulation Clinic in a Saudi Arabian Health Center
Authors: Dib Jean G. , Mohammed Khurram , Momattin Hisham I. , Alshehri Ali M.
Published: March 2014

Background

During the past 2 decades, a paradigm shift in the management of oral anticoagulation therapy has occurred. A multidisciplinary approach has been used and has proved beneficial from both a cost and quality perspective. However, this approach to anticoagulation therapy is not well established in Saudi Arabia and the Middle East, and the traditional way of managing anticoagulation patients is still the mainstay of care. The Pharmacy Services Division (PSD) in collaboration with physician, nursing, and medical support enterprises at the Dhahran Health Center established the pharmacy-managed anticoagulation clinic (ACC).

Objective

To describe the implementation process of the first pharmacist-managed anticoagulation clinic in the eastern province of Saudi Arabia and its impact on patient care.

Methods

The PSD in collaboration with medical staff successfully created a care delivery model utilizing clinical pharmacists’ expertise to provide comprehensive anticoagulation management services at Saudi Aramco Medical Services Organization (SAMSO). Planning included analyzing existing practices, reviewing the relevant literature, obtaining physician input, formulating a business proposal, and developing clinical protocols and guidelines. Collaborative relationships were established with the center laboratory, scheduling services, and nursing and medical departments. Clinic services include patient assessment, anticoagulation monitoring, warfarin dosage adjustment, medication dispensing at the clinic, patient education, and feedback to referring physicians. Data (2 years before and after clinic inception) for all patients enrolled at the anticoagulation clinic were reviewed to evaluate the impact of the clinic on anticoagulation management, adverse events, and patient satisfaction.

Results

A total of 578 patients were enrolled in the ACC. The total percentage of international normalized ratio (INR) within the target range was 59% versus 48% when compared to the previous traditional practice. The number of INR tests per patient dropped by 19%. Minor and major adverse events occurred in 10% and 1.5% of patients, respectively. Overall, the patients were very satisfied with the new clinic compared to the previous practice.

Conclusion

Implementation of the pharmacist-managed ACC in the eastern province of Saudi Arabia had a positive impact on patient care based on the improvements in the number of patients whose INR was within therapeutic range and patient satisfaction scores.
Evolving Biosimilars Marketplace
Authors: McBride Ali
Published: March 2014

Biologic therapies represent a drug class toward which there is continued development and production in a number of disease states. The development of an approval pathway allowing for the introduction of biosimilars into the US pharmaceutical market poses new challenges for health care systems and institutions. The potential difference in cost is a major driver for the development and use of biosimilars in practice. The manufacturing process for biosimilar compounds is complicated and requires specific detailing of each step, including development of the large-molecular component. Requirements for safe manufacturing of these therapies are crucial, as downstream effects may influence clinical efficacy and immunological properties. As these therapies enter the US marketplace, health care professionals will be asked to take prudent measures as they consider and evaluate these therapies for substitution into their formularies.
Enhanced Appreciation of Life Following Acquired Brain Injury: Posttraumatic Growth at 6 Months Postdischarge
Authors: Silva Jennifer , Ownsworth Tamara , Shields Cassandra , Fleming Jennifer
Published: March 2014

Preliminary research supports that acquired brain injury (ABI) can act as a catalyst for positive psychological changes, and that such posttraumatic growth (PTG) increases with time since injury. In this study, posttraumatic growth refers to positive psychological changes in domains including interpersonal relationships, new possibilities, personal strength, spirituality and appreciation for life. This study aimed to identify associations between levels of subjective impairment and depressive symptoms at discharge, and PTG at 6-months postdischarge following ABI. Sixty participants (73% male) with ABI (Mean days of hospitalisation = 32.92, SD = 40.74) were consecutively recruited from an inpatient rehabilitation unit at discharge and were administered measures of subjective impairment (Mayo-Portland Adaptability Index–4; MPAI-4) and depression (Depression, Anxiety Stress Scales; DASS). Participants were followed up at 6-months postdischarge and administered the Post-Traumatic Growth Inventory, DASS and MPAI-4. The results indicated that levels of PTG reported at six months postdischarge were relatively modest and ranged between no to very small degree of change (‘spirituality’) and a small to moderate degree of change (‘a greater appreciation of life’). Level of subjective impairment at discharge significantly predicted overall level of PTG at 6-months follow-up (β =.40, p < .05, sr2 = .28). Further, at 6-months postdischarge, individuals with a greater appreciation for life reported significantly higher levels of subjective impairment (r = .35; p < .01) and depressive symptoms (r = .34, p < .01) at that time point. These findings indicate that individuals who perceive greater functional consequences of their ABI are more likely to experience PTG. Further, the process of reevaluating priorities and values in life after ABI may be associated with emotional distress during the early stages of community reintegration.
A Double-Blind, Randomised, Placebo-Controlled Trial of Cytisine for Smoking Cessation in Medium-Dependent Workers
Authors: Vinnikov Denis , Brimkulov Nurlan , Burjubaeva Aichurek
Published: March 2014

Among many studies on cytisine only a few have been controlled trials, and the aim of this study was to assess the efficacy of cytisine in a randomized controlled double-blind trial compared to placebo in medium-dependent smoking men working in mining industry. Materials and methods: 171 middle-aged smokers were randomised to either cytisine (25-days regimen) or placebo; both groups received individual counseling with brochure. Self-reported continuous abstinence was assessed at 8 and 26 weeks. Results: At the end of week 8 there were no differences in number of abstinent subjects, but at 26 weeks 10.6% of subjects were abstinent in cytisine group compared to 1.2% in placebo (p = .01). In both groups, we did not find any weight increase, but quality of life improved in both groups, and physical and social functioning improved in cytisine group. Conclusions: Cytisine may be an effective medication to help smokers quit even for those working in difficult working conditions with high relapse rate.
Reviews
Authors: Mcluhan Eric , Drucker Susan , Grabowski Michael
Published: March 2014

Farrell, Thomas. Walter Ong’s Contributions to Cultural Studies: The Phenomenology of the World and I-Thou Communication. Cresskill, NJ: Hampton, 2000. 309 pp. Cloth $75.00, ISBN 1-57273-249-0. Paper $27.50, ISBN 1-57273-250-5.

Rosen, Jonathan. The Talmud and the Internet: A Journey Between Worlds. New York: Farrar Straus & Giroux, 2001. 132 pp. Cloth $16.00, ISBN 0-374-27238-7. Paper $10.00, ISBN 0-312-42017-X.

Rushkoff, Douglas, correspondent. Frontline: The Merchants of Cool. Dir. Barak Goodman. Prod. Barak Goodman and Rachel Dretzin. Written by Rachel Dretzin. Videocassette. PBS Home Video, 2001. 56 min.
Properties of wood-plastic composites (WPCs) reinforced with extracted and delignified wood flour
Authors: Chen Yao , Stark Nicole M. , Tshabalala Mandla A. , Gao Jianmin , Fan Yongming
Published: March 2014

The water sorption and mechanical properties of wood-plastic composites (WPCs) made of extracted and delignified wood flour (WF) has been investigated. WF was prepared by extraction with the solvent systems toluene/ethanol (TE), acetone/water (AW), and hot water (HW), and its delignification was conducted by means of sodium chlorite/acetic acid (AA) solution. A 24 full-factorial experimental design was employed to determine the effects of treatments and treatment combinations. WPCs were prepared with high-density polyethylene (HDPE) and treated WF was prepared by means of extrusion followed by injection molding, and the water absorption characteristics and mechanical properties of the products were evaluated. WPCs produced with extracted WF had lower water absorption rates and better mechanical properties than those made of untreated WF. WPCs containing delignified WF had higher water absorption rates and improved mechanical performance compared with those made of untreated WF.
Identification of key residues in the formate channel FocA that control import and export of formate
Authors: Hunger Doreen , Doberenz Claudia , Sawers R. Gary
Published: March 2014

The formate-nitrite transporter (FNT) family comprises pentameric channels that transport monovalent anions. The prototype of this family is the formate channel (FocA), which was originally identified as a formate channel in Escherichia coli. Each protomer in the channel has a pore with structural features that include periplasmic and cytoplasmic constriction sites, which are likely important for bi-directional gating of substrate passage. Highly conserved amino acid residues within FocA previously identified in structural studies are predicted to be important in the control of formate translocation. Here we present a first detailed in vivo analysis of these residues using a combined targeted amino acid exchange and formate-responsive lacZ fusion-based reporter approach. Sixteen exchanges were made and each variant was shown to be largely unaffected in its secondary and quaternary structure. The invariant H209 and T91 residues, which form part of the lower constriction site linking the Ω-loop with the pore cavity, proved to be important in governing the directionality of formate passage through the pore. A predicted salt-bridge triad of E208-K156-N213 along with the cytoplasmically-oriented N-terminal helix are also involved in pH-dependent gating of the channel. Together, our data are consistent with passive export and import of formate or formic acid through the channel.
Analysis and Prediction of End Milling Characteristics of Al-SiC
p
Metal Matrix Composite Using RSM and ANN
Authors: Jayakumar K. , Mathew Jose , Joseph M. A.
Published: March 2014

The study focused on analysis and prediction of cutting force and surface roughness during end milling of aluminium based Metal Matrix Composite using Artificial Neural Network (ANN) and Response Surface Methodology (RSM). The chosen material, Al-SiC composites were synthesized through Powder Metallurgy route, by mixing A356 Aluminium alloy powder of 25–50 μm average size with 10 volume % SiC particles of three different sizes (1, 12.5 and 25 μm). The mixed powders were compacted using Vacuum Hot Press to achieve near theoretical densities. The influence of SiC particle size on the composites in terms of density and microstructure were investigated. The effect of cutting speed, feed, depth of cut and SiC particle size on cutting force and surface roughness were also investigated. The results revealed that the cutting force and surface finish were decreased with increasing cutting speed. On the other hand, increase in feed, depth of cut and size of SiC particle decreased both the responses. The 4-10-2 multi layer feed forward neural network model predicts both responses with high accuracy in terms of higher correlation coefficient and lower mean square error compared to the regression model.
Investigation of Continuous Casting Slag Films Sampled on Site and Comparison with Laboratory Results
Authors: Marschall Irmtraud , Kölbl Nathalie , Harmuth Harald , Xia Guangmin
Published: March 2014

Slag film samples together with their associated mold fluxes were collected after service during tail out at the voestalpine Stahl GmbH continuous casting machine. The slag films were obtained after casting steel grades different in Al or Ti content and mineralogically investigated. Three distinctive layers could be determined within the slag films. A so called glassy layer, a crystalline layer and a layer, which has been liquid during casting and solidified afterwars, could be observed. Cuspidine (Ca4Si2O7F2) is the prevailing crystal phase in the crystalline layer. Casting alloyed steel grades the structure of the crystalline layer will be modified. With increasing Al2O3 content of the slag, due to interactions with the steel, nepheline ((Na,K)AlSiO4) was formed besides cuspidine. Here the distinctive needle like shaped cuspidine is remarkable. With casting steel grades with even more elevated Al content, the slag composition shows a strong decrease of silica and an increase of alumina. Therefore no longer cuspidine but fluorite (CaF2) and a so far unknown phase rich in alumina are the main crystal phases. When casting steel grades with increased Ti content, perovskite (CaTiO3) will be formed additionally to cuspidine in the crystalline layer.

In addition quench tests of the original mold powders as well as DTA and viscosity measurements of the original mold powder and the slag films were performed. The methods revealed the impact of the Al2O3 and TiO2 pick-up on the crystallization temperature, the phase composition and the viscosity.
Interaction between Molten Steel, Alumina Lining Refractory and Slag Phase
Authors: Wang Jiling , Zhang Lifeng , Yang Shufeng , Chen Yongfeng , Li Jingyu , Wachsman Alexander
Published: March 2014

Laboratory experiments exploring the interaction between molten steel, slag and lining refractory were performed. The transient erosion and reaction over time were investigated, and the transient change of the reaction layer and inclusions generated in the molten steel were evaluated using optical microscopy and SEM-EDS. Without slag addition before remelting, the FeO from reoxidation entered the space between the lining refractory and the steel and strengthened the erosion of the lining refractory. Several layers were found from the steel to the original lining refractory layer: steel phase, FeO layer, a FeO-rich lining layer and an Original Lining (OL)-rich lining layer. The thickness of the reaction layer increased nearly linearly with the reaction time at an erosion rate of 4.2 µm/min. With slag addition before remelting, the reaction layer between the steel and the original lining materials included several sub-layers: a gap, a slag layer, an FeO-rich lining layer and an Original Lining (OL)-rich lining layer. The thickness of the reaction layer nearly linearly increased with the reaction time and with an erosion rate of 5.7 µm/min. Slags were entrained into the steel occasionally.
An Evaluation of Thermochemical Property Models for CaO-MnO-SiO2-Al2O3-MgO Slag
Authors: Muller J. , Steenkamp J.D.
Published: March 2014

The modeling of thermochemical properties is important in studying the physical behavior of slag in the operation of pyrometallurgical smelters. To study the flow of slag through a submerged-arc furnace (SAF) tap-hole, knowledge of thermochemical properties such as viscosity, thermal conductivity, density and heat capacity are required. In literature various models exist for silicate slags that enable thermochemical properties to be predicted as functions of chemical composition and temperature. This paper reports on the application of models in the CaO-MnO-SiO2-Al2O3-MgO slag system to be used in future CFD modeling of slag tapped from SAFs producing high-carbon ferromanganese (HCFeMn) or silicomanganese (SiMn). FactSage 6.2 is used to estimate the phase composition of slags with varying chemical composition and temperature. The dependence of thermochemical property models on chemical composition and temperature is illustrated in the form of ternary diagrams showing the predicted property values as a function of basicity (chemical composition) and temperature. Slag compositions typical of HCFeMn and SiMn processes are used. Each thermochemical property is calculated at 1400, 1500 and 1600 °C at a fixed weight percentage ratio Al2O3/SiO2 of 0.57 and 6% MgO. Ternary phase diagrams (1400, 1500 and 1600 °C) and a ternary liquidus temperature diagram are also presented for the system. Since viscosity has the most significant influence on flow behavior, results from various viscosity models have been compared with measured data. Predictions for thermal conductivity, density, and heat capacity are also discussed.
Optimization of Correlated Quality Characteristics in WEDM Process using Taguchi Approach Coupled with Principal Component Analysis
Authors: Padhi P.C. , Mahapatra S.S. , Yadav S.N. , Tripathy D.K.
Published: March 2014

In the present work, an attempt has been made to solve the correlated multi-response optimization problem of wire electrical discharge machining (WEDM) of EN-31 steel. The experimental investigation have been carried out to evaluate the best process environment which could simultaneously satisfy multiple quality characteristics such as material removal rate (MRR), surface roughness (Ra) and dimensional deviation (DD). In view of the fact that traditional Taguchi method cannot solve a multi response optimization problem, weighted principal component analysis (WPCA) has been coupled with Taguchi method to overcome this limitation. The multiple responses are converted into a single response using principal component analysis so that influence of correlation among the responses can be eliminated. Values of individual principal components multiplied by their priority weight were added to calculate the composite principal component defined as multi-response performance index (MPI). MPI is used as response for optimization using Taguchi's L27 orthogonal array. From analysis of variance, pulse on time was found to be the most significant parameter. Finally, the optimal result obtained was verified through confirmatory test.
A Finite Element Analysis of Temperature Profiles and Cooling Rates of ERW Pipes during TIG Welding
Authors: Bhattacharya Tathagata , Bandyopadhyay Asish , Pal Pradip Kumar
Published: March 2014

The present investigation deals with the determination of temperature profile and subsequent cooling rates of certain points on the external surface of an ERW pipe with the help of ANSYS Finite Element Modeling and Analysis method, under simulated TIG welding conditions. A TIG welding condition for an ERW pipe is first simulated through ANSYS Finite Element Modeling. The physical and material properties along with the dimensions and size of the ERW pipe are all included in the modeling part. The TIG welding arc is simulated as a point heat source of a given power traversing the periphery of the pipe surface during welding. In the ANSYS program, after modeling the TIG welding problem, the same is run in the post – processing analysis part to get the temperature profile along the external surface of the pipe at various time intervals from the start of the welding. The rate of cooling of a few particular nodes on the modeled pipe surface, from the start of welding to the completion of one welding pass is also studied and results are indicated in graphical form. Later, these cooling rates on the modeled pipe surface are compared with those of an exactly similar ERW pipe, physically welded by TIG welding method in the workshop under similar welding conditions and welding parameters.
ALS-Linked Mutations Enlarge TDP-43-Enriched Neuronal RNA Granules in the Dendritic Arbor
Authors: Liu-Yesucevitz LiQun , Lin Amy Y. , Ebata Atsushi , Boon Joon Y. , Reid Whitney , Xu Ya-Fei , Kobrin Kendra , Murphy George J. , Petrucelli Leonard , Wolozin Benjamin
Published: March 2014

Trans-activating response region (TAR) DNA-binding protein of 43 kDa (TDP-43) is an RNA-binding protein that is mutated in familial amyotrophic lateral sclerosis (ALS). Disease-linked mutations in TDP-43 increase the tendency of TDP-43 to aggregate, leading to a corresponding increase in formation of stress granules, cytoplasmic protein/RNA complexes that form in response to stress. Although the field has focused on stress granules, TDP-43 also forms other types of RNA granules. For example, TDP-43 is associated with RNA granules that are prevalent throughout the dendritic arbor in neurons. Because aggregation of TDP-43 is also important for the formation of these neuronal RNA granules, we hypothesized that disease-linked mutations might alter granule formation even in the absence of stress. We now report that ALS-linked mutations in TDP-43 (A315T and Q343R) increase the size of neuronal TDP-43 granules in the dendritic arbor of rat hippocampal neurons. The mutations correspondingly reduce the granule density, movement, and mobility of TDP-43 granules. Depolarization of rat hippocampal neurons with KCl stimulates TDP-43 granule migration into dendrites, but A315T and Q343R TDP-43 granules migrate shorter distances and into fewer dendrites than wild-type TDP-43. These findings highlight novel elements of TDP-43 biology that are affected by disease-linked mutations and suggest a neuronally selective mechanism through which TDP-43 mutations might elicit neuronal dysfunction.
Intracellular Bicarbonate Regulates Action Potential Generation via KCNQ Channel Modulation
Authors: Jones Ryan T. , Faas Guido C. , Mody Istvan
Published: March 2014

Bicarbonate (HCO3−) is an abundant anion that regulates extracellular and intracellular pH. Here, we use patch-clamp techniques to assess regulation of hippocampal CA3 pyramidal cell excitability by HCO3−in acute brain slices from C57BL/6 mice. We found that increasing HCO3−levels enhances action potential (AP) generation in both the soma and axon initial segment (AIS) by reducing Kv7/KCNQ channel activity, independent of pH (i.e., at a constant pH of 7.3). Conversely, decreasing intracellular HCO3−leads to attenuation of AP firing. We show that HCO3−interferes with Kv7/KCNQ channel activation by phosphatidylinositol-4,5-biphosphate. Consequently, we propose that, even in the presence of a local depolarizing Cl−gradient, HCO3−efflux through GABAAreceptors may ensure the inhibitory effect of axoaxonic cells at the AIS due to activation of Kv7/KCNQ channels.