bluuebunny/crossref_metadata_2025 huggingface dataset:
Iron oxide nanoparticles suppress the production of IL-1beta via the secretory lysosomal pathway in murine microglial cells
Authors: Wu Hsin-Ying , Chung Min-Chun , Wang Chia-Chi , Huang Chung-Hsiung , Liang Hong-Jen , Jan Tong-Rong
Published: September 2013

Background

Superparamagnetic iron oxide nanoparticles (IONPs) have been used as magnetic resonance imaging contrast agents for various research and diagnostic purposes, such as the detection of neuroinflammation and blood-brain-barrier integrity. As the central resident macrophage-like cells, microglia are responsible for managing foreign agents invading the CNS. The present study investigated the direct effect of IONPs on the production of pro-inflammatory cytokines by murine microglia stimulated with lipopolysaccharide (LPS).

Methods

Primary murine microglial cells were pretreated with IONPs (1–50 μg Fe/mL) for 30 min and then stimulated with LPS (100 ng/mL) for 24 h. Confocal microscopy is used to visualize the intracellular IONP distribution and secretory lysosomes after staining with LysoTracker and Rab27a, respectively. The production of interleukin (IL)-1β and tumor necrosis factor (TNF)-α was quantified by ELISA. The activity of IL-1β converting enzyme (ICE) and TNF-α converting enzyme (TACE) was measured by fluorescent microplate assay using specific substrates. The lysosomal number, alkalinity, permeability and cathepsin B activity were determined by flow cytometry with ectodermal dysplasia-1, lysosensor and acridine orange staining, and using cathepsin B specific substrate, respectively.

Results

Confocal imaging revealed that IONPs were markedly engulfed by microglia. Exposure to IONPs attenuated the production of IL-1β, but not TNF-α. Concordantly, the activity of ICE, but not the TACE, was suppressed in IONP-treated cells. Mechanistic studies showed that IONPs accumulated in lysosomes and the number of lysosomes was increased in IONP-treated cells. In addition, exposure to IONPs increased lysosomal permeability and alkalinity, but decreased the activity of cathepsin B, a secretory lysosomal enzyme involved in the activation of ICE.

Conclusions

Our results demonstrated a contrasting effect of IONPs on the production of IL-1β and TNF-α by LPS-stimulated microglia, in which the attenuation of IL-1β by IONPs was mediated by inhibiting the secretory lysosomal pathway of cytokine processing.
A comparison between experienced and inexperienced video game players’ perceptions
Authors: Christou Georgios
Published: September 2013

In this article we examine the relationship between usability, hedonic attributes and general appeal of two types of video games, first-person shooters, and massively multi-player online role playing games. Through the use of a successful example of a game from each genre, we examine the perceptions of both inexperienced and experienced players of each game, and draw conclusions on comparisons. We find that playing experience only affects usability and appeal perceptions, while type of game played not only affects usability and appeal, but also hedonic perceptions as well. We also find that the perception of appeal by players of a video game in the context of this study can be predicted from a linear combination of the same players’ perceptions of hedonic attributes and usability. We translate these findings into suggestions for game designers and developers.
Effect of sclerostin-neutralising antibody on periarticular and systemic bone in a murine model of rheumatoid arthritis: a microCT study
Authors: Marenzana Massimo , Vugler Alex , Moore Adrian , Robinson Martyn
Published: September 2013

Introduction

Patients with chronic inflammatory diseases have increased bone loss and bone fragility and are at increased risk of fracture. Although anti-resorptive drugs are effective in blocking inflammation-induced bone loss, they are less effective at rebuilding bone. We have previously shown that treatment with sclerostin antibody (Scl-AbI) builds bone and can prevent or restore bone loss in a murine model of inflammatory bowel disease. In this study, we tested the effect of Scl-AbI in a murine model of rheumatoid arthritis (the collagen-induced arthritis model, CIA). We hypothesised that sclerostin blockade can protect and restore bone both locally and systemically without affecting progression of inflammation.

Methods

CIA was induced in male DBA/1 mice, which were treated with either PBS or Scl-AbI (10 mg/kg, weekly) prophylactically for 55 days or therapeutically for 21 days (starting 14 days post onset of arthritis). Systemic inflammation was assessed by measuring the serum concentration of anti-CII IgG1, IgG2a and IgG2b by ELISA. Changes in bone mass and structure, either at sites remote from the joints or at periarticular sites, were measured using DEXA and microCT. Bone focal erosion was assessed in microCT scans of ankle and knee joints.

Results

Circulating anti-CII immunoglobulins were significantly elevated in mice with CIA and there were no significant differences in the levels of anti-CII immunoglobulins in mice treated with PBS or Scl-ABI. Prophylactic Scl-AbI treatment prevented the decrease in whole body bone mineral density (BMD) and in the bone volume fraction at axial (vertebral body) and appendicular (tibial proximal metaphysis trabecular and mid-diaphysis cortical bone) sites seen in PBS-treated CIA mice, but did not prevent the formation of focal bone erosions on the periarticular bone in the knee and ankle joints. In the therapeutic study, Scl-AbI restored BMD and bone volume fraction at all assessed sites but was unable to repair focal erosions.

Conclusions

Sclerostin blockade prevented or reversed the decrease in axial and appendicular bone mass in the murine model of rheumatoid arthritis, but did not affect systemic inflammation and was unable to prevent or repair local focal erosion.
Bond Strength of Diaphragm–Shotcrete Interface in the Vertical Direction
Authors: Mehta Sanjay S. , Cameron Donald G.
Published: September 2013

The steel sheet metal diaphragm used in AWWA D110, Type III, prestressed concrete tanks on the outside face of the precast concrete tank wall serves a dual purpose as a liquid barrier and as vertical reinforcement. Seismic restraint cables, located on the outside face of the diaphragm, are fully encapsulated in shotcrete before applying prestressing wires on the tank wall. Seismic load path from the center of gravity of precast concrete core wall to the base cables generates vertical shear stresses at the diaphragm-shotcrete interface, which are resisted by the bond strength of shotcrete–diaphragm interface. The concept of “development surface” of the diaphragm is presented based on the “diaphgram surface pull-out” tests in response to the concern that diaphragm-shotcrete interface may not have sufficient bond strength to develop full capacity of restraint cables. A design procedure based on bond strength test results ensures a ductile failure mode as specified in ASCE 7-05.
Influence of Soil Modeling Uncertainties on Site Response
Authors: Barani Simone , De Ferrari Roberto , Ferretti Gabriele
Published: September 2013

The scope of this work is to examine the influence of the uncertainty in soil modeling on numerical ground response estimates through a comprehensive sensitivity analysis. This allows identification of those parameters with the largest effect on both soil amplification (quantified here by a frequency-independent factor, Fa) and fundamental frequency, f0. Although extensively examined in previous articles, the effect of the input motion is also analyzed. The uncertainty affecting the shear wave velocity ( VS) profile was found to be the factor contributing most to the uncertainty of both Fa and f0. The soil thickness was also found to play a key role, particularly in those cases where bedrock depth is unknown or largely uncertain. Although of secondary importance compared to the effect of VS on Fa and f0, the influence of the input motion cannot be neglected; rather it becomes predominant with regard to the uncertainty affecting frequency-dependent shaking parameters.
Evaluation of Three-Dimensional Shape Signatures for Automated Assessment of Post-Earthquake Building Damage
Authors: Liu Wei , Dong Pinliang , Liu Jianbo , Guo Huadong
Published: September 2013

This paper proposes two new measures of three-dimensional shape signatures based on the slope and aspect of three-dimensional triangles, and evaluates the performance of three-dimensional shape signatures derived from distance, area, angle, volume, slope, and aspect for assessing post-earthquake building damage using simulated building models with flat, pent, gable and hip roofs. Three scenarios of post-earthquake building damage are tested using simulated light detection and ranging (LiDAR) points generated on the building roofs. Dissimilarity, sensitivity, and computational cost of the three-dimensional shape signatures are also discussed. The results show that a combination of three-dimensional shape signatures derived from slope and aspect can provide better detection of post-earthquake building damage compared with those derived from distance, area, angle, and volume. The paper demonstrates a promising method for rapid assessment of post-earthquake building damage using existing three-dimensional urban models and post-earthquake LiDAR data.
Natural Period and Seismic Idealization of Flexible Timber Diaphragms
Authors: Wilson Aaron , Quenneville Pierre , Ingham Jason
Published: September 2013

The current equations for diaphragm fundamental period determination and for diaphragm deformation determination published in commonly used seismic assessment documents are firstly reviewed to establish their origin. Using a validated analytical model that captures diaphragm deformation mechanics, three beam idealizations (a fixed-ended flexure beam, a pin-ended flexure beam, and a shear beam) are compared against true diaphragm behavior to determine which idealization is most suitable for the seismic assessment of diaphragm performance. Wherever necessary, recommendations have been made to update and to harmonize the current seismic assessment procedures for timber diaphragms in unreinforced masonry buildings. The presented analysis is specifically focused on straight-sheathed timber diaphragm configurations that are typically found in historic unreinforced masonry buildings.
Basis Risk of Earthquake Catastrophe Bond Trigger Using Scenario-Based versus Station Intensity–Based Approaches: A Case Study for Southwestern British Columbia
Authors: Goda Katsuichiro
Published: September 2013

This study investigates the effectiveness of two trigger mechanisms for parametric earthquake catastrophe bonds: scenario-based and station intensity–based approaches, in terms of basis risk. Advantages of the station intensity–based method are that balanced solutions with low total trigger errors and with similar positive and negative errors can be obtained. Two methods are applied to a case study for 2,000 conventional wood-frame houses in southwestern British Columbia. The results indicate that the station intensity–based method performs at least as well as the scenario-based method in terms of total trigger error. Moreover, model risks, as part of basis risk, are assessed by considering different spatial correlation models of peak ground motions. The use of incorrect spatial correlation models results in additional errors of the catastrophe bond trigger mechanisms.
Eccentric Rocking Bearings with a Designable Friction Property for Seismic Isolation: Experiment and Analysis
Authors: Lu Lyan-Ywan , Hsu Chia-Chiea
Published: September 2013

The friction coefficient plays a critical role in a friction-type isolator, since it determines the transmitted seismic force and the energy dissipation capacity of the isolator, simultaneously. However, the choice of feasible sliding materials that possess appropriate friction coefficients is very limited, and this has restricted the development and applications of friction-type isolators. To overcome this, an isolator called the eccentric rocking bearing (ERB) with the property of designable friction is introduced in this study. By using an eccentric rolling mechanism, the ERB bearing is self-centering and its effective friction coefficient is adjustable by a geometric parameter that can be designed by engineers. The results of a shaking table test conducted on an ERB-isolated full-scale structure have confirmed the feasibility and efficiency of the ERB bearings for seismic isolation. Additionally, the high consistency between the simulated and experimental dynamic responses verifies the method developed to analyze the ERB.
Floor Accelerations in Yielding Special Moment Resisting Frame Structures
Authors: Wieser Joseph , Pekcan Gokhan , Zaghi Arash E. , Itani Ahmad , Maragakis Manos
Published: September 2013

Severe damage to acceleration sensitive nonstructural components in recent earthquakes has resulted in unprecedented losses. Recent research has been aimed at increasing the understanding of acceleration demands on nonstructural components in buildings. This investigation subjects a set of four special moment resisting frame (SMRF) building models to a suite of 21 far-field ground motions using the incremental dynamic analysis procedure. Full three-dimensional models including floor slabs are used to extract both the horizontal and vertical responses. Floor acceleration response spectra are generated to assess the acceleration demands on elastic nonstructural components. Changes to the current code provisions that include the influence of structural period are proposed. An alternative design approach that directly amplifies the ground acceleration spectrum to achieve the desired floor acceleration spectrum is presented.
Story Damage Identification of Irregular Buildings Based on Earthquake Records
Authors: Wang Jer-Fu , Lin Chi-Chang , Lin Ging-Long , Yang Chun-Hao
Published: September 2013

In this paper, a story damage index was developed to evaluate the damage condition of a torsionally coupled building based on its dominant modal frequencies and mode shapes. This index has an analytical formula with a calculated value ranging from 0 (undamaged) to 1.0 (collapsed) to indicate the reduction of story lateral stiffness. The involved computation is simple once the modal parameters of any three modes are obtained through system identification techniques from few floor acceleration measurements. The damage region within a story can also be identified through tracking the change of eccentricity of center of rigidity. This index was verified by numerical simulations and a data analysis of the ASCE benchmark model. In addition, it was also applied to the damage assessment of a four-story reinforced concrete building in Taiwan, which experienced severe damage during the 2006 Taitung Beinan earthquake ( M = 6.2). The results agree fairly well with the visual inspection and show the applicability of the proposed damage assessment technique.
Cyclic Load Protocol for Anchored Nonstructural Components and Systems
Authors: Hutchinson Tara C. , Wood Richard L.
Published: September 2013

This work is motivated by the need to investigate the cyclic load response of restrained (via anchorage or other) nonstructural components and systems (NCSs). For this purpose, a load protocol is developed for capturing the behavior of the restraining element when subjected to seismic loading. The protocol incorporates numerical analyses of buildings designed to respond nonlinearly under design earthquake events, analysis of secondary systems located in these buildings and rainflow counting of time history results extracted from these analyses. Secondary system response results are used to develop tension and shear load protocols. Protocol statistics are presented and envisioned to be useful in anchor or other restraint system qualification tests.
eNOS derived nitric oxide regulates endothelial barrier function via VE cadherin and Rho GTPases
Authors: Di Lorenzo Annarita , Lin Michelle I. , Murata Takahisa , Landskroner-Eiger Shira , Schleicher Michael , Kothiya Milankumar , Iwakiri Yasuko , Yu Jun , Huang Paul L. , Sessa William C.
Published: September 2013

Transient disruption of endothelial adherens junctions and cytoskeletal remodeling are responsible for increases in vascular permeability induced by inflammatory stimuli and vascular endothelial growth factor (VEGF). Nitric oxide (NO) produced by endothelial NO synthase (eNOS) is critical for VEGF induced changes in permeability in vivo, however, the molecular mechanisms by which endogenous NO modulates endothelial permeability is not clear. Here we show that the lack of eNOS reduces VEGF induced permeability, an effect mediated by enhanced Rac-GTPase activation and stabilization of cortical actin. The loss of NO, increased the recruitment of the Rac-GEF, Tiam-1, to adherens junctions and VE-cadherin and reduced Rho-activation and stress fiber formation. In addition, NO deficiency reduced VEGF-induced VE-cadherin phosphorylation, and impaired the localization, but not the activation, of c-src to cell junctions. The physiological role of eNOS activation is clear since VEGF, histamine and inflammation induced vascular permeability is reduced in mice with bearing the knockin mutation of the key phosphorylation site S1176. Thus, NO is critical for Rho GTPase dependent regulation of cytoskeletal architecture leading to reversible changes in vascular permeability.
A functional siRNA screen identifies genes modulating angiotensin II-mediated EGFR transactivation
Authors: George Amee J. , Purdue Brooke W. , Gould Cathryn M. , Thomas Daniel W. , Handoko Yanny , Qian Hongwei , Quaife-Ryan Gregory A. , Morgan Kylie A. , Simpson Kaylene J. , Thomas Walter G. , Hannan Ross D.
Published: September 2013

The angiotensin type 1 receptor (AT1R) transactivates the epidermal growth factor receptor (EGFR) to mediate cellular growth, although the molecular mechanisms are not resolved. To address this, we performed a functional siRNA of the human kinome in human mammary epithelial cells that demonstrate a robust AT1R-EGFR transactivation. We identified a suite of genes that both positively and negatively regulate AT1R-EGFR transactivation. Many candidates comprised components of EGFR signalling networks, whereas others, including TRIO, BMX and CHKA, had not been previously linked to EGFR transactivation. Individual knockdown of TRIO, BMX or CHKA attenuated tyrosine phosphorylation of the EGFR by angiotensin II stimulation, but not following direct stimulation of the EGFR with EGF, indicating that these genes function between the activated AT1R and the EGFR. Further investigation of TRIO and CHKA revealed that their activity is likely to be required for AT1R-EGFR transactivation. CHKA also mediated EGFR transactivation in response to another GPCR ligand, thrombin, indicating a pervasive role for CHKA in GPCR-EGFR crosstalk. Our study reveals the power of unbiased, functional genomic screens to identify new signalling mediators important for cell biology related to tissue remodelling in cardiovascular disease and cancer.
The Mos-MAPK pathway regulates Diaphanous-related formin activity to drive cleavage furrow closure during polar body emission in starfish oocytes
Authors: Ucar Hasan , Tachibana Kazunori , Kishimoto Takeo
Published: September 2013

Maintenance of spindle attachment to the cortex and formation of the cleavage furrow around the protruded spindle are essential for polar body emission (PBE) during meiotic maturation of oocytes. Although spindle movement to the cortex has been well-studied, how the spindle is maintained at the cortex during PBE is unknown. Here, we show that activation of Diaphanous-related formin mediated by mitogen-activated protein kinase (MAPK) is required for tight spindle attachment to the cortex and cleavage furrow closure during PBE in starfish (Asterina pectinifera) oocytes. A. pectinifera Diaphanous-related formin (ApDia) had a distinct localization in immature oocytes and localized to the cleavage furrow during PBE. Inhibition of the Mos-MAPK pathway or the actin nucleating activity of formin homology 2 domain prevented cleavage furrow closure and resulted in PBE failure. In MEK/MAPK-inhibited oocytes, activation of ApDia by relief of its intramolecular inhibition restored PBE. In summary, this study elucidates a link between the Mos-MAPK pathway and diaphanous-related formins, that is responsible for maintaining tight spindle attachment to the cortex and cleavage furrow closure during PBE.
Sox4-mediated caldesmon expression facilitates skeletal myoblast differentiation
Authors: Jang Sang-Min , Kim Jung-Woong , Kim Daehwan , Kim Chul-Hong , An Joo-Hee , Choi Kyung-Hee , Rhee Sangmyung
Published: September 2013

Caldesmon (CaD), originally identified as an actin-regulatory protein, is involved in the regulation of diverse actin-related signaling processes, including cell migration and proliferation, in various cells. The cellular function of CaD has been studied primarily in the smooth muscle system; nothing is known about its function in skeletal muscle differentiation. In this study, we found that the expression of CaD gradually increased as C2C12 myoblast differentiation progressed. Silencing of CaD inhibited cell spreading and migration, resulting in a decrease in myoblast differentiation. Promoter analysis of the caldesmon gene (CALD1) and gel mobility shift assays identified Sox4 as a major trans-acting factor for the regulation of CALD1 expression during myoblast differentiation. Silencing of Sox4 decreased not only CaD protein synthesis but also myoblast fusion in C2C12 cells and myofibril formation in mouse embryonic muscle. Overexpression of CaD in Sox4-silenced C2C12 cells rescued the differentiation process. These results clearly demonstrate that CaD, regulated by Sox4 transcriptional activity, contributes to skeletal muscle differentiation.
Dynamin triple knockout cells reveal off target effects of commonly used dynamin inhibitors
Authors: Park Ryan , Shen Hongying , Liu Lijuan , Liu Xinran , Ferguson Shawn M. , De Camilli Pietro
Published: September 2013

Dynamin, which is encoded by three genes in mammals, is a GTPase implicated in endocytic membrane fission. Dynamin 1 and 3 are predominantly expressed in brain, while dynamin 2 is ubiquitously expressed. With the goal of assessing the impact of the lack of dynamin on cell physiology, we previously generated and characterized dynamin 1 and 2 double KO (DKO) fibroblasts. These DKO cells were unexpectedly viable in spite of a severe impairment of clathrin-mediated endocytosis. As low-level expression of the dynamin 3 gene in these cells could not be excluded, we have now engineered dynamin 1, 2, and 3 triple KO (TKO) fibroblasts. These cells did not reveal any additional defects beyond what was previously observed in DKO fibroblasts. Surprisingly, while fluid phase endocytosis and peripheral membrane ruffling were not impaired by the lack of all three dynamins, two structurally similar, widely used dynamin inhibitors, dynasore and Dyngo-4a, robustly inhibited these two processes both in wild type cells and TKO cells. Dynamin TKO cells will be useful tools for the further exploration of dynamin-dependent processes and the development of more specific dynamin inhibitors.
Group II intron–ribosome association protects intron RNA from degradation
Authors: Contreras Lydia M. , Huang Tao , Piazza Carol Lyn , Smith Dorie , Qu Guosheng , Gelderman Grant , Potratz Jeffrey P. , Russell Rick , Belfort Marlene
Published: September 2013

The influence of the cellular environment on the structures and properties of catalytic RNAs is not well understood, despite great interest in ribozyme function. Here we report on ribosome association of group II introns, which are ribozymes that are important because of their putative ancestry to spliceosomal introns and retrotransposons, their retromobility via an RNA intermediate, and their application as gene delivery agents. We show that group II intron RNA, in complex with the intron-encoded protein from the native Lactoccocus lactis host, associates strongly with ribosomes in vivo. Ribosomes have little effect on intron ribozyme activities; rather, the association with host ribosomes protects the intron RNA against degradation by RNase E, an enzyme previously shown to be a silencer of retromobility in Escherichia coli. The ribosome interacts strongly with the intron, exerting protective effects in vivo and in vitro, as demonstrated by genetic and biochemical experiments. These results are consistent with the ribosome influencing the integrity of catalytic RNAs in bacteria in the face of degradative nucleases that regulate intron mobility.
Drift and Adjustment in Organizational Rule Compliance: Explaining the “Regulatory Pendulum” in Financial Markets
Authors: Martinez-Moyano Ignacio J. , McCaffrey David P. , Oliva Rogelio
Published: September 2013

This article integrates research on rule development, compliance, and organizational change to model rule development and compliance in organizations, using causal-loop modeling from system dynamics to articulate explicitly a few key underlying processes. We focus on financial markets as a case area, suggesting that recurring regulatory problems in financial markets in the United States over the past 60 years, although differing in specifics, are structurally similar. At the heart of the model is the tension between production goals that focus on short-term, certain, salient benefits and required adherence to production-constraining rules that attempt to mitigate long-term, uncertain, nonsalient risks. It describes systemically how organizations attend to rules depending on the nature of the benefits of production compared with those of rule compliance. The model captures the operative mechanisms responsible for the development of pressures for production and for rule compliance in organizations, providing a structural explanation both for problem-prone organizations characterized by erosion of standards and increased violations and for organizations following rules more reliably. Drawing on studies of institutional work, we conclude by suggesting research on how agency, through strategic and tactical choice, potentially modifies structure in rule compliance.
An Agency Theory of the Division of Managerial Labor
Authors: Ross David Gaddis
Published: September 2013

Should responsibility for strategic planning and execution be assigned to the same manager? Should a firm have a chief operating officer with responsibilities distinct from those of the chief executive officer? How does the division of labor affect managerial opportunism? This paper uses a formal agency-theoretic model to address these questions and present a new theory of the division of managerial labor. Building on Penrose’s typology [ Penrose E (2009) The Theory of the Growth of the Firm, 4th ed. (Blackwell, Oxford, UK)], the theory identifies when to assign (i) entrepreneurial services, which relate to strategic planning and the acquisition of resources, and (ii) managerial services, which relate to execution, to the same generalist manager rather than to different specialists. The analysis reveals the critical importance of separability, i.e., whether a supervisor can separately observe the outcomes of entrepreneurial and managerial services. If managers and their supervisor have symmetric information about separability, hiring a generalist dominates because managerial services, which are easier to assess, reduce the scope for opportunism associated with entrepreneurial services, which are harder to assess. Conversely, if managers have better information regarding separability and the probability of separability is low, hiring specialists dominates because hiring a generalist allows the potential for opportunism associated with entrepreneurial services to contaminate the provision of managerial services. Even so, the benefits of hiring a generalist may be restored if the services are sequenced appropriately. An implication of such sequencing is that a firm will grow in fits and starts, giving rise to a “Penrose effect” even if labor market frictions do not impede the assimilation of new managers.
Perceptions of Organizational Politics: A Need Satisfaction Paradigm
Authors: Rosen Christopher C. , Ferris D. Lance , Brown Douglas J. , Chen Yuanyi , Yan Ming
Published: September 2013

Stressor and exchange relationship paradigms have developed in isolation from each other to explain the negative effects of perceived organizational politics. We outline how these different paradigms share a common basis—a focus on psychological need satisfaction—and develop a needs-based paradigm to account for the negative effects of perceived organizational politics. Moreover, we argue that psychological need satisfaction acts as an unmeasured third variable, which, once accounted for, should limit the utility of stressor and exchange relationship paradigms. Across four samples using a combination of multiple sources, operationalizations of constructs, and measurement occasions, we found full support for the needs-based paradigm as a mediator of the effects of politics on contextual performance, creativity, and proactive behavior, whereas strain and exchange relationship constructs by and large had no effect on outcomes once psychological need satisfaction was accounted for. Theoretical implications and future research directions are discussed.
Nalbuphine-Naloxone Mix-ups; Compounding Pharmacy Registration with the FDA; FDA Draft Guidance
Authors: Cohen Michael R. , Smetzer Judy L.
Published: September 2013

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs.

Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers’ names will be published if desired. ISMP may be contacted at the address shown below.

Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters’ wishes as to the level of detail included in publications.
Drug Monographs: Pomalidomide and Ponatinib
Authors: Butler Taylor W. , Waddell J. Aubrey , Solimando Dominic A.
Published: September 2013

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.
Oxandrolone: Pressure (Decubitis) Ulcers in Spinal Cord Injury
Authors: Generali Joyce A. , Cada Dennis J.
Published: September 2013

This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to jgeneral@ku.edu .
Methods to Promote Preceptor Scholarship through Resident Collaboration
Authors: Brown Jamie N. , Kemp Debra W. , Parker Mary H. , Wilkinson Samaneh T.
Published: September 2013

Preceptor participation in scholarly endeavors is recognized in the American Society of Health-System Pharmacists's (ASHP) residency accreditation standards as a method to demonstrate commitment and contribute to the profession of pharmacy. Although workplace demands and position responsibilities may not allow adequate time for preceptors to pursue scholarly activities, collaboration with pharmacy residents in a structured environment can be mutually beneficial and aid in the professional development of the resident and preceptor. The goal of this article is to provide preceptors with a description of activities suitable for collaboration with residents and with tips to ensure success within the residency year.
Cannabinoid Hyperemesis Syndrome
Authors: Sun Shusen , Zimmermann Anthony E.
Published: September 2013

Background

The purpose of this review is to describe cannabinoid hyperemesis syndrome (CHS), which is thought to be induced by long-term cannabis use, and provide clinical pharmacists with information to manage the hyperemetic phase of CHS.

Method

Published literature was searched and reviewed using PubMed.

Results

CHS is characterized by intractable nausea and vomiting without an obvious organic cause and associated learned compulsive hot water bathing behavior. Patients often seek care in the emergency department (ED) for symptomatic relief.

Conclusion

CHS is potentially underrecognized and underdiagnosed in the ED, and it should be considered in the differential diagnosis in long-term cannabis use patients with CHS symptoms to avoid unnecessary extensive diagnostic workup including invasive radiologic imaging. Pharmacists have an important role in CHS recognition, education, and symptom management.
Pharmacologic Options for Prevention and Management of Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage
Authors: Kiser Tyree H.
Published: September 2013

Background

Cerebral vasospasm and delayed cerebral ischemia continue to be major contributors to morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH).

Purpose

The purpose of this review was to evaluate the pharmacotherapy interventions for the prevention and management of cerebral vasospasm in patients with SAH.

Methods

A search of MEDLINE (January 1966-April 2012) and EMBASE (January 1974-April 2012) was conducted to retrieve relevant studies of pharmacotherapy options for prevention or treatment of cerebral vasospasm in SAH.

Results

Triple-H therapy (hypervolemia, hemodilution, hypertension) has been a widely accepted option by many clinicians for the management of cerebral vasospasm and delayed cerebral ischemia. However, implementation of Triple-H therapy varies considerably at individual institutions. Nimodipine and nicardipine have demonstrated the most dependable improvements in patient outcomes to date. High doses of intravenous magnesium have failed to show consistent benefits. Magnesium supplementation to prevent hypomagnesaemia should be employed. Statin therapy should be continued in patients who are taking statins prior to hospital admission. Use of statins in naive patients may be recommended when the results of an ongoing prospective study are available. Of the available locally administered pharmacologic therapies, nicardipine and thrombolytics appear to provide the most intriguing benefit-to-risk ratio. However, the data supporting the use of locally administered therapy are modest at best and require careful consideration prior to application.

Conclusions

Clinical studies have tested a variety of pharmacotherapy interventions for the prevention and treatment of cerebral vasospasm. Of available therapies, nimodipine has demonstrated consistent benefits and should be employed routinely. Demonstration of reduced cerebral vasospasm and improved neurological outcomes in larger prospective studies are needed for most pharmacologic therapy options prior to recommending their routine use.
Do You Know I Am Looking at You? Visual Pleasure and Body Politics in Tsai Ming-Liang's Films
Authors: Wu I-fen
Published: September 2013

The thematization of the change in socio-cultural patterns as a result of urbanization in many of Tsai Ming-Liang's films has been frequently acknowledged. Tsai's films often deal with urban alienation of a society in which people are emotionally blocked and seemingly afloat in a state of loss. His vision of contemporary culture is elaborated through his portrait of Taipei city as an urban malaise in which people are cut off from one another and from their feelings, moving around in drab, underlit apartments, cheap hotels, gay saunas, looking for sexual comfort to alleviate their loneliness and isolation. The city spectacle articulates the desires and emotions of modern people, which have been blocked and offered no spiritual escape routes.
My Name Is Khan and I'm Still Too Flamboyant
Authors: Ostepeev Lidia
Published: September 2013

Released in February 2010, My Name Is Khan -- a commercial Bollywood film directed by Karan Johar has the distinction of being the highest grossing Indian film in overseas markets. It is one of several recent Bollywood films to have sold distribution rights to divisions of transnational companies, in this case, to Fox Star for distribution in the United Kingdom, South Africa, Australia, Southeast Asia, the Middle East, and Europe and to Fox Searchlight for distribution in the U.S. With its global reach, My Name Is Khan has generated a range of critical reviews which often come with cultural bias preconceptions about what constitutes "good" cinema. By examining Western concerns about My Name Is Khan, it is possible to identify obstacles to Bollywood's ability to attract larger Western audiences.
The ‘De Santis case’: Screenwriting, political boycott and archival research
Authors: Russo Paolo
Published: September 2013

In the late 1940s and throughout the 1950s writer-director Giuseppe De Santis was the most successful Italian film-maker worldwide, thanks to box-office hits like the Oscar-nominated Riso amaro/Bitter Rice (1949). However, endless rows with producers, distributors and censorship soon forced him into professional exile until his creative voice was completely silenced. Over the years De Santis denounced a systematic boycott against him because of his social and political commitment. All scripts needed the central government film office approval; this system enforced a form of pre-emptive censorship by controlling the writing and packaging process. This article unveils the findings of comprehensive research conducted at the De Santis Fund in Rome. While De Santis’s official filmography lists only one title in the last 33 years of his life, his archive contains dozens of treatments and full scripts (and the film-maker’s correspondence) adding up to a total of almost 50 projects that were never made. The materials analysed here not only allow a thorough re-write of De Santis’s career, but also shed light on the intricate relations between politics and the Italian film industry in the post-war years.
‘It’s literature I want, Ivo, literature!’ Literature as screenplay as literature. Or, how to win a literary prize writing a screenplay
Authors: Geerts Ronald
Published: September 2013

Ivo Michiels, besides being one of the most acclaimed and radical experimental literary authors in Dutch literature, is arguably the first Flemish professional screenwriter.

These two occupations, that he continuously tried to combine, resulted in screenplays that either have been published as novels (and awarded important literary prizes) or repurposed as fragments in the Journal Brut cycle. Michiels developed a specific style for the screenplay by turning away from economical concrete descriptions. Instead he pursued a more literary way of writing, using narrative strategies aiming at certain effects in the mind of the reader, over conventional description. This article situates Michiels’ script writing as ‘performative’ in its intention and offers a case study of his work, as an expanded notion of the screenplay that elevates the form beyond mere description of what will be visible/audible on-screen. In Michiels’ practice, a screenplay is not just a text that ‘desires to become another text’, in the words of Pier Paolo Pasolini. In contrast, this article frames Michiels’ screenplays as ‘postdramatic’ texts which become artefacts, in and of themselves, claiming a certain independence from the film, whilst at the same time maintaining dialogue with the film (Bakhtin), realized or not.
Poetic dramaturgy in Andrey Tarkovsky’s Nostalgia (1983): A character without a goal?
Authors: Koivumäki Marja-Riitta
Published: September 2013

This article centres on the use of a character goal and a character arc as elements to express the theme and the meaning in Andrey Tarkovsky’s Nostalgia (1983). In classical dramaturgy, the goal of the character – what does the character want and what actions may he or she take in order to achieve this goal – is considered to be of the utmost importance. In Tarkovsky’s film, however, the character is passive and there does not seem to be any obvious goal to achieve. Through dramaturgical analysis my aim is to reveal the dramaturgical function of both the character goal and the character arc in Nostalgia. My contention is that a passive character forms part of an extensive dramaturgical system and that it carries more meaning than is apparent on the surface. Usually it is the character goal, what the character desires, that carries the spine of the narration and it is usually the starting point of the story design. I argue that the character arc (inner goal) can also assume this function and, accordingly, we can start the development of the screenplay from the perspective of considering how the character changes or why he/she might change. I also suggest that there is a need to reconsider the centrality of character goal, since the screenwriting theories of the twentieth century emphasize the importance of the character goal at the expense of the character arc. This article forms part of a larger study that aims to define certain characteristics of so-called poetic dramaturgy. As I’m interested in whether or not it is possible to define the features of poetic dramaturgy in a similar way as in classical dramaturgy so that they too can be incorporated into the writer’s craft, I also challenge the conventions of classical dramaturgy.
Screenwriting and emotional rhythm
Authors: David Ian
Published: September 2013

Recent advances in neuroscience have begun to unravel the part played by emotion in decision-making and creativity. All storytellers rely on emotion, but the screenwriter, conveying the essential narrative and technical information required to make a film, carries a unique burden. Screenplays must act as a bridge from the author to the audience, describing the narrative’s capacity to evoke emotion through action and image. In discussing a screenplay, the narrative is usually assessed in terms of its characters, plot, subplots, theme, dialogue, tone, style, etc. Yet, emotion, the quality that determines the screenplay’s (and ultimately the film’s) overall effect, is often poorly understood. This paper proposes Emotional Rhythm - that subliminal sequence of emotions underpinning all the dramatic components - as a means of evaluating the screenplay’s potency as it relates to the construction of the narrative.
Writing with images: The Film-Photo-Essay, the Left Bank Group and the pensive moment
Authors: Taylor Andrew
Published: September 2013

This article is focused on the film-photo-essay form. The first part of the article is a narrative account of my experiments ‘writing with images’ in the early and mid-2000s, using (the then) new digital tools to make film-photo-essays. My account reflects on how the change from analogue to digital affected my approach to photography, film-making and writing with images. I then look at the case study of Siberia (2009), an illustrated script that was written following my experimentation with the film-photo-essay form. The second part of this article is a more general enquiry into the film-photo-essay form and work that combines cinema and photography. I discuss the contemporary interest in work that falls on a spectrum between photography and cinema; often referred to as ‘still/moving’. I then focus on the ‘Left Bank Group’, whose work often combined cinema, photography and the literary and philosophical essay. Examples from the ‘cine-writing’ of Alain Resnais, Agnes Varda and Chris Marker highlight how Raymond Bellour’s idea of the ‘pensive moment’ is apt in relation to their work. I argue that still/moving forms allow more space for audience interaction and emotional response than conventional narrative cinema; and in a world saturated with information and cluttered with images, there is an important place for new pensive hybrid art forms.
Adventures in murky waters: The enactment and commemoration of Kon-Tiki
Authors: Wahlberg Malin
Published: September 2013

In 1947, Thor Heyerdahl and five crewmembers accomplished a 6900-km sea voyage on a reconstructed balsa wood raft to prove that Peruvian Indians could have settled in Polynesia. This short subject addresses the meanings of authenticity, enactment and cultural memory in relation to the expedition film by Heyerdahl and Nordemar, Kon-Tiki (1950). The film’s production history and its international success are part of a post-war media event, in itself a trans-Atlantic adventure that has only recently been the subject of scholarly attention.
Roald Amundsen and the documentary canon
Authors: Diesen Jan Anders , Iversen Gunnar
Published: September 2013

Newly restored documentaries about the polar expeditions of Norwegian explorer Roald Amundsen make it possible to re-examine and discuss the importance of these early travelogues. This article presents the Amundsen documentaries, films that have been inaccessible to researchers as well as the general public, but now are available on DVD in Norway in both Norwegian and English versions.
Septins in the glial cells of the nervous system
Authors: Patzig Julia , Dworschak Michelle S. , Martens Ann-Kristin , Werner Hauke B.
Published: September 2013

The capacity of cytoskeletal septins to mediate diverse cellular processes is related to their ability to assemble as distinct heterooligomers and higher order structures. However, in many cell types the functional relevance of septins is not well understood. This minireview provides a brief overview of our current knowledge about septins in the non-neuronal cells of the vertebrate nervous system, collectively termed ‘glial cells’, i.e., astrocytes, microglia, oligodendrocytes, and Schwann cells. The dysregulation of septins observed in various models of myelin pathology is discussed with respect to implications for hereditary neuralgic amyotrophy (HNA) caused by mutations of the human SEPT9-gene.