bluuebunny/crossref_metadata_2025 huggingface dataset:
Formation of surface layers on Ti–6Al–4V titanium alloy by laser alloying
Authors: Filip R. , Sieniawski J. , Pleszakov E.
Published: March 2006

This paper presents the results of the laser surface treatment of Ti–6Al–4V two phase titanium alloy. It was carried out in order to modify the microstructure and properties of the alloyed zone. Laser treatment was performed on samples coated by graphite and BN powders in stream of nitrogen in order to form martensitic phase, titanium nitrides, titanium carbides and borides as a consequence of the laser irradiation. The laser melted zone was examined and its microstructure and phase composition were determined. Microstructural analysis was carried out using Epiphot 300 optical microscope and Novascan 30 scanning electron microscope equipped with an EDS X-ray detector for compositional analysis. The phases were identified by X-ray diffractometry (Philips) with Cu Kα radiation. The Vickers microhardness under the load of 1.96 N and thermoelectric power were measured on the surface of cross-sections. The high hardness level (920–570 HV1.96) can be attributed to the formation of TiN, TiC and TiB phases. The laser melted zone displays ductile fracture.
Age hardening of Ni–P–Mo electroless deposit
Authors: Mendoza L. Vargas , Barba A. , Bolarín A. , Sánchez F.
Published: March 2006

A Ni–P–Mo autocatalytic coating was developed in order to study the structural changes according with the molybdenum codeposition and the effects of aging treatment. Results show that heat treatment induces structural changes that allow for total crystallisation of amorphous regions and the reordering of crystalline phases, to produce a Ni–Mo solid solution with precipitation of Ni3P and MoNi4 particles. Hardness of the as plated condition is similar to high phosphorous Ni–P deposits as mentioned in the literature, however the present work revealed that subsequent heat treatment was beneficial in enhancing the hardness of the metallic coating with a maximum of 1450 HV(100 g) being measured for coatings treated at 500°C for 2 h. This hardening can be interpreted as a consequence of amorphous to crystalline phase transformation and the aging processes of Ni–P–Mo ternary alloy. This enhancement is further reinforced by the precipitation of MoNi4 intermetallic particles.
Prediction of radio frequency power effect on silicon nitride deposition using a genetic algorithm based neural network
Authors: Kim B. , Bae J. , Han S. S.
Published: March 2006

Deposition rate of silicon nitride films was modelled using a neural network in conjunction with Box—Wilson experimental design. The films were deposited by a plasma enhanced chemical vapour deposition system. A neural network model was constructed and tested with 33 and 12 experiments respectively. Model prediction performance was significantly improved by applying genetic algorithm to training factor optimisation. To qualitatively estimate deposition mechanisms with the parameters, several plots were generated from the model and emphasis was placed on the investigation of the radio frequency power effect on the deposition rate under various plasma conditions. An increase in the deposition rate with increasing power was ascribed to more Si deposition near the reaction surface. The SiH4 effect was the most complex depending on the powers. In contrast, the power effect was insensitive to the variations in N2 flow rate. The power effect at high pressure was attributed to increased concentration of Si radicals in the gas phase. A comparison with a refractive index model facilitated to infer deposition mechanisms.
Deposition of cadmium sulphide and cadmium zinc sulphide thin films by photochemical deposition and their characterisation
Authors: Gunasekaran M. , Gopalakrishnan R. , Sivakumar R. , Ramasamy P. , Ichimura M.
Published: March 2006

CdS and CdZnS films were successfully deposited on glass/indium tin oxide (ITO) substrates from an aqueous solution. The ratio of Cd/Zn has been identified by auger electron spectroscopy (AES). The deposited films have been confirmed by X-ray diffraction (XRD) and were found to crystallise in the hexagonal crystal system. The surface of the as deposited and annealed films was analysed using SEM. The improvement of crystallinity was confirmed by Raman spectroscopy and XRD. Photoelectrochemical studies were carried out by fabricating a PEC cell of configuration CdS/0·1M Na2SO4/ITO and the physical parameters were studied. Current–voltage measurements were performed. The results of the present investigation are discussed in detail.
Inorganic materials and coatings produced by EBPVD
Authors: Movchan B. A.
Published: March 2006

The present paper describes the process of high speed electron beam evaporation of inorganic substances under vacuum and process parameters controlling the deposition, structure and properties of thick condensates (films). Considered are examples of single phase and multiphase metal, metal–ceramic, cermet and ceramic condensates of the thickness from several micrometres to several millimetres with dispersed, multilayer, porous and graded structures in a broad range of structural element dimensions. Dimensional effects in the structure and mechanical properties of thick condensates are noted. Areas of practical application of inorganic materials deposited from the vapour phase are described.
High deposition rate magnetrons: Key elements and advantages
Authors: Mitin V. S. , Sharipov E. I. , Mitin A. V.
Published: March 2006

An innovative coating technology based on ion plasma magnetron sputtering physical vacuum deposition (IMPS-PVD) method has been developed to produce new complex coatings to meet the constantly growing demand of advanced industries, with a view to replacing chemical coating methods owing to their ecology danger and to complement/replace high temperature PVD methods. The high deposition rate magnetron (HDRM) technology has initiated a rebirth of mosaic targets as the key component leading to a big increase in the design accuracy of both targets and coatings to be deposited.
Carbon nitride based hard multilayer films prepared by closed field unbalanced magnetron sputtering
Authors: Vyas A. , Li L. K. Y. , Zhou Z. F. , Shen Y. G.
Published: March 2006

Single layer a-CNx films as well as CNx/TiN multilayer films were deposited onto Si (100) and M42 high speed steel substrates by closed field unbalanced magnetron sputtering. In CNx/TiN multilayers, different bilayer (CNx + TiN layer) thickness could be attained in two ways: by changing the substrate rotation speed (1·3–20 rev min−1) and by varying the C target current only with substrate rotation speed fixed at 4 rev min−1 during the deposition process. The films were characterised by employing atomic force microscopy (AFM), nano/microindentation measurements, X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), pin on disc wear test, scratch tester and Rockwell C tester. The XPS results of CNx films suggest the formation of a major fraction of N–C sp2 bonds and a few N–C sp3 bonds. The nanohardness of CNx film about 11·7–20·8 GPa depends on the N/C ratio. In CNx/TiN multilayers, TiN, TiO2, TiC, C—N and C=N chemical and bonding states exist. The mechanical and tribological properties are influenced by different bilayer periods (about 10–1 nm). The root mean square (RMS) surface roughness measured by AFM was between 0·7 and 1·9 nm. High microhardness (∼50 GPa) of the multilayered structure depends on the bilayer thickness. The internal compressive stress is associated with the hardness of the multilayer which falls to about 3·3–7·7 GPa. The pin on disc tests under dry condition show a low friction coefficient between 0·11 and 0·15. Rockwell C and scratch tests show excellent adhesion results for the coating prepared at C target current of 0·5 A.
Evaluation of toughness of hard coatings
Authors: Bao M. D. , Zhu X. D. , He J. W.
Published: March 2006

Repeated impact has been introduced to evaluate different properties of hard coatings, such as impact wear resistance, bonding strength, fatigue, etc. The load and impact number relationships are similar to that of fatigue curves, and close to some real applications of coated parts. Cr–Cu–N coatings were performed on a hardened steel substrate and the repeated impact tests were conducted on the coating substrate system. At a low impact load, the intrinsic strength of the coating layer and the bonding strength between the coating and substrate are in competition. Coating layer cracking or delamination might occur and the strength plays an important role like that of high cycle fatigue. When the load is increased and towards the low cycle fatigue regime, toughness of the coating layer turns out to be predominant. The cohesive failure in high load regime preferentially depends on the toughness of the coating layer, and the failure cycles can be employed as a toughness criterion.
Are the protective effects of 17β-estradiol on splenic macrophages and splenocytes after trauma-hemorrhage mediated via estrogen-receptor (ER)-α or ER-β?
Authors: Hildebrand Frank , Hubbard William J , Choudhry Mashkoor A , Thobe Bjoern M , Pape Hans-Christoph , Chaudry Irshad H
Published: March 2006

The depression in cell-mediated immune function following trauma-hemorrhage is shown to be restored by 17β-estradiol (E2) administration. However, it remains unknown which of the two estrogen-receptors, (ER)-α or ER-β, plays the predominant role in mediating the beneficial effects of E2. Female B57BL/J6 ER-β−/− transgenic mice [knockout (KO)] and corresponding ovariectomized wild-type (WT) mice were subjected to laparotomy and hemorrhagic shock (35.0±5.0 mmHg for 90 min) and treated with E2 (50 μg/25 g) or ER-α agonist propyl pyrazole triol (PPT; 50 μg/25 g) following trauma-hemorrhage. Four hours after resuscitation, systemic cytokine concentrations and cytokine release by splenocytes and splenic macrophages were determined by cytometric bead array. Trauma-hemorrhage resulted in a significant increase in plasma tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-10. In contrast, the release of these cytokines by splenic macrophages was decreased significantly in WT and KO animals. Administration of E2 or PPT following trauma-hemorrhage produced a significant reduction in systemic TNF-α and IL-6 concentrations in WT and KO mice. Although the suppression in the productive capacity of these cytokines following trauma-hemorrhage by macrophages and splenocyte was also prevented in E2- and PPT-treated WT mice, the release of cytokines by macrophages and splenocytes in E2- and PPT-treated KO mice was not restored to the levels observed in sham animals. These findings collectively suggest that both receptors appear to play a significant role in mediating the immunoprotective effects of E2 in different tissue compartments following trauma-hemorrhage.
Systemic suppression of interferon-γ responses in Buruli ulcer patients resolves after surgical excision of the lesions caused by the extracellular pathogen Mycobacterium ulcerans
Authors: Yeboah-Manu Dorothy , Peduzzi Elisabetta , Mensah-Quainoo Ernestina , Asante-Poku Adwoa , Ofori-Adjei David , Pluschke Gerd , Daubenberger Claudia A
Published: March 2006

Buruli ulcer (BU), caused by Mycobacterium ulcerans, is the third most common mycobacterial infection in immunocompetent humans besides tuberculosis and leprosy. We have compared by ex vivo enzyme-linked immunospot analysis interferon-γ (IFN-γ) responses in peripheral blood mononuclear cells (PBMC) from BU patients, household contacts, and individuals living in an adjacent M. ulcerans nonendemic region. PBMC were stimulated with purified protein derivative (PPD) and nonmycobacterial antigens such as reconstituted influenza virus particles and isopentenyl-pyrophosphate. With all three antigens, the number of IFN-γ spot-forming units was reduced significantly in BU patients compared with the controls from a nonendemic area. This demonstrates for the first time that M. ulcerans infection-associated systemic reduction in IFN-γ responses is not confined to stimulation with live or dead mycobacteria and their products but extends to other antigens. Interleukin (IL)-12 secretion by PPD-stimulated PBMC was not reduced in BU patients, indicating that reduction in IFN-γ responses was not caused by diminished IL-12 production. Several months after surgical excision of BU lesions, IFN-γ responses of BU patients against all antigens used for stimulation recovered significantly, indicating that the measured systemic immunosuppression was not the consequence of a genetic defect in T cell function predisposing for BU but is rather related to the presence of M. ulcerans bacteria.
It takes nerve to tell T and B cells what to do
Authors: Kin Nicholas W , Sanders Virginia M
Published: March 2006

The existence of an association between the brain and immunity has been documented. Data show that the nervous and immune systems communicate with one another to maintain immune homeostasis. Activated immune cells secrete cytokines that influence central nervous system activity, which in turn, activates output through the peripheral nervous system to regulate the level of immune cell activity and the subsequent magnitude of an immune response. In this review, we will focus our presentation and discussion on the findings that indicate a regulatory role for the peripheral sympathetic nervous system in modulating the level of cytokine and antibody produced during an immune response. Data will be discussed from studies involving the stimulation of the β2 adrenergic receptor expressed on CD4+ T cells and B cells by norepinephrine or selective agonists. We will also discuss how dysregulation of this line of communication between the nervous and immune systems might contribute to disease development and progression.
Longitudinal robustness of variables predicting independent gait following severe middle cerebral artery stroke: a prospective cohort study
Authors: Kollen Boudewijn , Kwakkel Gert , Lindeman Eline
Published: March 2006

Objective: To determine within the first 10 weeks post onset the most robust variables in the prediction of recovery of independent gait at six months post stroke.

Design: A prospective cohort study.

Subjects: One hundred and one first ever ischaemic middle cerebral artery stroke patients. None of these patients were able to walk at onset and all suffered from a marked hemiplegia.

Setting: Twenty-four determinants, possibly related to recovery of gait at six months, were measured within 14 days following stroke onset. Based on Functional Ambulation Categories (FAC) independent gait was classified into present (FAC ≥ 4) or absent (FAC < 4). Bivariate logistic regression analysis was used to select determinants. Only significant determinants during the entire 10-week period were used for further weekly multivariate logistic prediction modelling of independent gait at six months post stroke.

Results: After six months post onset 62% ( N = 63) regained independent gait. Age, Barthel Index, Trunk Control Test, Motricity Index of arm and leg, Brunnstrom Fugl-Meyer stage of leg motor recovery, and type of intervention were significant determinants in bivariate analysis, but age of patient and Barthel Index were the most robust determinants in the final prediction model. Weekly re-evaluation produced sensitivity values between 89% and 96% and specificity values between 53% and 62%.

Conclusion: In initially non-ambulatory stroke patients age and Barthel Index were the most robust variables during the first 10-week poststroke period in the prediction of independent walking at six months. However, prediction of non-ambulation at six months proved to be less accurate.
Evaluating rehabilitation using cost-consequences analysis: an example in Parkinson's disease
Authors: Gage Heather , Kaye Julie , Owen Charles , Trend Patrick , Wade Derick
Published: March 2006

Objective: To use cost-consequences analysis to evaluate rehabilitation, and to discuss some practical limitations.

Design: Case study of a cost-consequences analysis.

Setting: Day hospital.

Subjects: People with Parkinson's disease without major cognitive loss, and their carers.

Intervention: A programme of multidisciplinary rehabilitation, delivered for one day per week over six weeks, and including 2 h of individual therapy (physical, occupational, speech and language, specialist nurse) and group activities on each occasion.

Main measures: Costs: direct and overhead costs of treatment; participant travel. Consequences: patient outcomes (mobility, speech and language, disability, psychological well-being, health-related quality of life); carer outcomes (psychological well-being, health-related quality of life, strain); social service utilization; satisfaction.

Results: In this example the main costs were facility's overheads and hospital-provided transport. The consequences of the intervention were improved immediate outcomes for patients that diminished over four months, discovery of unmet social services need, high satisfaction. No benefits for carers were observed.

Conclusion: A cost-consequences analysis provides a clear descriptive summary for decision-makers that is easier to interpret than cost-effectiveness, cost-utility and cost-benefit analysis. It is a useful technique in rehabilitation research where multiple outcomes and several perspectives (health service, patient, carer) are relevant. However limitations remain: it is difficult to capture all consequences because of data deficiencies and long-term effects; evaluations of individual interventions are partial and do not guarantee economic rationality; local studies may not be generalizable; fixed protocols impede the evaluation of alternative service configurations.
Mechanical Cell Injury
Authors: BARBEE KENNETH A.
Published: March 2006

Abstract: The tissues of the body are continually subjected to mechanical stimulation by external forces, such as gravity, and internally generated forces, such as the pumping of blood or muscle contraction. Within a physiological range, the forces elicit adaptive responses acutely (to rapidly alter function) and chronically (to remodel tissue structure to optimize load‐bearing capabilities). When the forces exceed certain thresholds, injury results. To understand the mechanisms of mechanical injury at the cellular level, we must analyze the structural response of the cell to various modes of deformation and examine the biological consequences of the structural alterations caused by the trauma. This chapter reviews the mechanics of cell membrane deformation and failure. Evidence for the strain‐rate‐dependent, transient disruption of cell membranes, or mechanoporation, is presented for a variety of cell types. The complex interactions between the structural damage and the biological sequelae are illustrated using clinically relevant forms of cell injury. Finally, novel therapeutic approaches targeting membrane integrity are described.
Cell Injury by Electric Forces
Authors: LEE RAPHAEL C.
Published: March 2006

Abstract: The molecular architecture of biological systems is heavily influenced by the highly polar interactions of water. Thus, macromolecules such as proteins that are highly water soluble must be electrically polar. Energy generation methods needed to support cell metabolic processes depend on compartmentalizing mobile ions and thus require electrical ion transport barriers such as membranes. One consequence of these biological design constraints is vulnerability to injury by electrical forces. Supraphysiological electric forces cause damage to cells and tissues by disrupting cell membranes and altering the conformation of biomolecules. In addition, prolonged passage of electrical current leads to damage by thermal mechanisms. This review will focus on the non‐thermal effects.
Cellular Response to DNA Damage
Authors: KAO JOHNNY , ROSENSTEIN BARRY S. , PETERS SHEILA , MILANO MICHAEL T. , KRON STEPHEN J.
Published: March 2006

Abstract: Eukaryotic cells, from yeast to man, possess evolutionarily conserved mechanisms to accurately and efficiently repair the overwhelming majority of DNA damage, thereby ensuring genomic integrity. Important repair pathways include base excision repair, nucleotide excision repair, mismatch repair, non‐homologous end‐joining, and homologous recombination. Defects in DNA repair processes generally result in susceptibility to cancer and, often, abnormalities in multiple organ systems. While signal transduction pathways have been intensely studied, epigenetic changes occurring in response to DNA damage are rapidly increasing in importance. Effective radiation and chemotherapy sensitization could result from selective inhibition of DNA repair in tumor cells. DNA damage repair is a dynamic field of research where the fruits of basic research often have important clinical implications.
The Role of Ca2+ in Muscle Cell Damage
Authors: GISSEL HANNE
Published: March 2006

Abstract: Skeletal muscle is the largest single organ of the body. Skeletal muscle damage may lead to loss of muscle function, and widespread muscle damage may have serious systemic implications due to leakage of intracellular constituents to the circulation. Ca2+ acts as a second messenger in all muscle and may activate a whole range of processes ranging from activation of contraction to degradation of the muscle cell. It is therefore of vital importance for the muscle cell to control [Ca2+] in the cytoplasm ([Ca2+]c). If the permeability of the sarcolemma for Ca2+ is increased, the muscle cell may suffer Ca2+ overload, defined as an inability to control [Ca2+]c. This could lead to the activation of calpains, resulting in proteolysis of cellular constituents, activation of phospholipase A2 (PLA2), affecting membrane integrity, an increased production of reactive oxygen species (ROS), causing lipid peroxidation, and possibly mitochondrial Ca2+ overload, all of which may further worsen the damage in a self‐reinforcing process. An increased influx of Ca2+ leading to Ca2+ overload in muscle may occur in a range of situations such as exercise, mechanical and electrical trauma, prolonged ischemia, Duchenne muscular dystrophy, and cachexia. Counteractions include membrane stabilizing agents, Ca2+ channel blockers, calpain inhibitors, PLA2 inhibitors, and ROS scavengers.
Autophagy
Authors: KELEKAR AMEETA
Published: March 2006

Abstract: Autophagy is a major intracellular pathway for the degradation and recycling of long‐lived proteins and cytoplasmic organelles. Like apoptotic programmed cell death, autophagy is an essential part of growth regulation and maintenance of homeostasis in multicellular organisms. Autophagic vacuole formation is also activated as an adaptive response to a variety of extracellular and intracellular stimuli, including nutrient deprivation, hormonal or therapeutic treatment, bacterial infection, aggregated and misfolded proteins and damaged organelles. Mediators of class I and class III PI3 kinase signaling pathways and trimeric G proteins play major roles in regulating autophagosome formation during the stress response. Defective autophagy is the underlying cause of a number of pathological conditions, including vacuolar myopathies, neurodegenerative diseases, liver disease, and some forms of cancer. This chapter provides an overview of the morphology and molecular basis of autophagosome formation and offers a glimpse into the role of autophagy in normal growth and development, while discussing the pathological implications of its deregulation.
The Mechanisms of Cell Membrane Repair
Authors: STEINHARDT RICHARD A.
Published: March 2006

Abstract: The best way to approach a new area is to study closely a sample of the key papers, and spread out from there. In this tutorial paper I present my personal selection of papers introducing concepts in the study of the mechanisms of cell membrane repair. For a more comprehensive review up to 2003, I refer the student to McNeil and Steinhardt (2003).
Membrane Sealing by Polymers
Authors: MASKARINEC STACEY A. , WU GUOHUI , LEE KA YEE C.
Published: March 2006

Abstract: An intact cell membrane serves as a barrier, controlling the traffic of materials going into and out of the cell. When the integrity of the membrane is compromised, its transport barrier function is also disrupted, leaving the cell vulnerable to necrosis. It has been shown that triblock copolymer surfactants can help seal structurally damaged membranes, arresting the leakage of intracellular materials. Using model lipid monolayers along with concurrent Langmuir isotherm and fluorescence microscopy measurements as well as surface X‐ray scattering techniques, the nature of the interaction between lipids and a particular family of triblock copolymers in the form poly(ethylene oxide)‐poly(propylene oxide)‐poly(ethylene oxide) is examined. The polymer is found to selectively insert into membranes where the lipid packing density is below that of an intact cell membrane, thus localizing its sealing effect on damaged portions of the membrane. The inserted polymer is “squeezed out” of the lipid film when the lipid packing density is increased, suggesting a mechanism for the cell to be rid of the polymer when the membrane integrity is restored.
Na+‐K+ Pump Stimulation Improves Contractility in Damaged Muscle Fibers
Authors: CLAUSEN TORBEN
Published: March 2006

Abstract: Skeletal muscles have a high content of Na+‐K+‐ATPase, an enzyme that is identical to the Na+‐K+ pump, a transport system mediating active extrusion of Na+ from the cells and accumulation of K+ in the cells. The major function of the Na+‐K+ pumps is to maintain the concentration gradients for Na+ and K+ across the plasma membrane. This generates the resting membrane potential, allowing the propagation of action potentials, excitation‐contraction coupling and force development. Muscles exposed to (1) high extracellular K+ or (2) low extracellular Na+ show a considerable loss of force. A similar force decline is elicited by (3) increasing Na+ permeability or (4) decreasing K+ permeability. Under all of these four conditions, stimulation of the Na+‐K+ pumps can restore contractility. Following exposure to electroporation or fatiguing stimulation, muscle cell membranes develop leaks to Na+ and K+ and a partially reversible loss of force. The restoration of force is abolished by blocking the Na+‐K+ pumps and markedly improved by stimulating the Na+‐K+ pumps with β2‐agonists, calcitonin gene‐related peptide, or dbcAMP. These observations indicate that the Na+‐K+ pumps are important for the functional compensation of the commonly occurring loss of muscle cell integrity. Stimulation of the Na+‐K+ pumps with β2‐agonists or other agents may be of therapeutic value in the treatment of muscle cell damage induced by electrical shocks, prolonged exercise, burns, or bruises.
Biological Water
Authors: DESPA FLORIN
Published: March 2006

Abstract: Water in tissues and cells is confined by intervening cellular components and is subject to structural effects that are not present in its bulk counterpart. The structuring effects lower the dielectric susceptibility of water molecules and induce a “red shift” of their relaxation frequency. This is also a source of polarization fields that contribute to the effective interactions between macromolecules. The behavior of water molecules at hydrophilic sites is different from that at hydrophobic sites, and this dissimilar behavior promotes the anisotropy of the hydration shell of proteins. The anisotropy of the hydration shell is essential for the enzyme function, but it is also important in detecting denaturation of the protein (i.e., proteins expose their hydrophobic parts to water during unfolding). The most significant differences between biological and ordinary water will be presented along with how this information can be used to decipher patterns in dynamical behavior of biological water and to detect possible structural changes of the cellular components.
Magnetic Resonance Imaging of Changes in Muscle Tissues after Membrane Trauma
Authors: GISSEL HANNE , DESPA FLORIN , COLLINS JOHN , MUSTAFI DEVKUMAR , ROJAHN KATHERINE , KARCZMAR GREG , LEE RAPHAEL
Published: March 2006

Abstract:A pure electroporation injury leads to cell membrane disruption and subsequent osmotic swelling of the tissue. The state of water in the injured area of a tissue is changed and differs from a healthy tissue. Magnetic resonance imaging (MRI), which is very sensitive to the quality of the interaction between mobile (water) protons and a restricted (protein) proton pool, is therefore a useful tool to characterize this injury. Here, we present a protocol designed to measure the difference between the values of the transverse magnetic relaxation time (T2) in MRIs of healthy and electrically injured tissue. In addition, we present a method to evaluate the two main contributions to the MRI contrast, the degree of structural alteration of the cellular components (including a major contribution from membrane pores), and edema. The approach is useful in assessing the level of damage that electric shocks produce in muscle tissues, in that edema will resolve in time whereas structural changes require active repair mechanisms.
The Physics of the Interactions Governing Folding and Association of Proteins
Authors: GUO WEIHUA , SHEA JOAN‐EMMA , BERRY R. STEPHEN
Published: March 2006

Abstract: The review discusses the molecular origins of the forces and free energies that determine several things about proteins, and how experiment and theory reveal this information. The first subject is the stability of the folded, native structures. The second is the range of molecular mechanisms by which proteins find their way to those folded structures in laboratory environments. The third is the much more complex problem of how folding occurs in the cellular environment. This topic includes a discussion of crowding and of the roles of chaperone molecules. The review concludes with a discussion of protein aggregation and fibril formation and of misfolding and therapies associated with it.
Heat Injury to Cells in Perfused Systems
Authors: ORGILL DENNIS P. , PORTER STACY A. , TAYLOR HELENA O.
Published: March 2006

Abstract: Tissue injury in response to excessive heat results in a clinical burn. Burns cause a range of physiologic derangements, including denaturation of macromolecular structures, leakage of cell membranes, activation of cytokines, and cessation of blood flow, all leading to tissue death. The purpose of this paper is to examine the mechanisms and consequences of burn injury and to discuss potential therapies based on these mechanisms. Knowledge of the thermal properties of tissues can predict the time‐temperature relationship necessary to cause a specified thermal insult. Changes in cell membrane biochemistry and the stabilization of proteins through the heat‐shock response can enable biomacromolecules to withstand supraphysiological temperatures. Mechanisms of cellular repair allow recovery of cellular function after thermal insult. An understanding of the response of proteins, cellular organelles, and cells to heat provides the foundation for understanding the pathophysiology and treatment of burn injury. The physics, biochemistry, and cellular biology behind the host response to thermal injury in perfused systems are reviewed.
Multimodal Strategies for Resuscitating Injured Cells
Authors: AGARWAL JAYANT , WALSH ALEXANDRA , LEE RAPHAEL C.
Published: March 2006

Abstract: Our cells and tissues are challenged constantly by exposure to extreme conditions that cause acute and chronic stress. Wounding at the cellular level is a common event, and results from cell exposure to supra‐physiologic forces, or is the consequence of action by reactive chemical agents. An individual cellular wound results from either the alteration of protein or DNA structure, or the disruption of molecular assemblies, the most important of which is the cell's membranes. Tissue healing at the macroscopic level is a complex and coordinated process involving many different cell types while, in contrast, the wounds of individual cells heal primarily via biomolecular interactions. Like tissue wound healing, cellular wound healing involves the upregulation or acceleration of processes that are constitutively expressed in routine physiologic repair of cellular structures In addition, recent advances have been made in the identification of pharmaceutical strategies to aid the cellular repair response. Many of these strategies offer promise for augmenting the already present cellular repair mechanisms.
Electroconformational Denaturation of Membrane Proteins
Authors: CHEN WEI
Published: March 2006

Abstract: Because of high electrical impedance of cell membrane, when living cells are exposed to an external electric field, the field‐induced voltage drops will mainly occur on the cell membrane. In addition to Joule heating damage and electroporation of the cell membrane, the electric field‐induced supraphysiological transmembrane potential may inevitably damage the membrane proteins, especially the voltage‐dependent membrane proteins. That is because the charged particles in the amino acid of the membrane proteins and, in particular, the voltage‐sensors in the voltage‐dependent membrane proteins are vulnerable to the membrane potential. An intensive, brief electric shock may induce electroconformational damage or denaturation in the membrane proteins. As a result, the cell functions are significantly reduced. This electric field‐induced denaturation in the membrane proteins strongly suggests a new underlying mechanism involved in electrical injury.
A Surfactant Copolymer Facilitates Functional Recovery of Heat‐Denatured Lysozyme
Authors: WALSH ALEXANDRA M. , MUSTAFI DEVKUMAR , MAKINEN MARVIN W. , LEE RAPHAEL C.
Published: March 2006

Abstract: The triblock copolymer poloxamer 188 is a non‐cytotoxic, nonionic surfactant with both hydrophobic and hydrophilic domains. We show that P188 is able to facilitate the recovery of catalytic activity of heat‐denatured lysozyme in dilute solution at low molar ratios of P188:enzyme. Heat‐denatured enzyme retained 55% of native activity. After treatment with P188, the enzyme's activity was 85% of native. Because of the low molar ratios used and the non‐cytotoxic nature of the compound, P188 may be of potential use in burn therapy.
Embedded Guideline Information without Patient Specificity in a Commercial Emergency Department Computerized Order‐entry System
Authors: Asaro Phillip V. , Sheldahl Amy L. , Char Douglas M.
Published: March 2006

Background:
Clinical practice guidelines and computerized provider order entry (CPOE) have potential for improving clinical care. Questions remain about feasibility and effectiveness of CPOE in the emergency department (ED). However, successful implementations in other settings typically incorporate decision support functions that are lacking in many commercially available ED information systems.

Objectives:
To compare acute coronary syndrome (ACS) guideline compliance before and after implementation of a locally implemented ACS guideline, first on paper and then in a commercially available ED information system without patient‐specific clinical decision support.

Methods:
Clinical data were abstracted retrospectively on patients seen before and after introduction of paper and, subsequently, CPOE versions of ACS guideline‐based order‐sets. Order‐set use was determined. Risk category assignments were made retrospectively using guideline criteria and compliance with the guideline regarding β‐blockers, heparin, and aspirin was determined. Association between order‐set use and compliance was determined.

Results:
The authors found increasing use of order‐sets over the period of study. However, there was poor association between the order‐sets used and risk stratification category. Some association between ED β‐blocker use and use of CPOE order‐sets was found, but there was no improvement in overall compliance with any of the guideline recommendations.

Conclusions:
Adherence to an ACS guideline did not improve with implementation of a commercial ED information system without provision for patient‐specific decision support. This suggests that the lack of patient‐specific decision‐support functionality in most current ED information system products may hamper progress in the development of effective decision support.
Multiple Centrally Acting Antidotes Protect against Severe Organophosphate Toxicity
Authors: Sivilotti Marco L.A. , Bird Steven B. , Lo Jean C.Y. , Dickson Eric W.
Published: March 2006

Background: Accumulation of acetylcholine in the central nervous system is believed to account for the rapid lethality of organophosphate pesticides and chemical nerve agents. Diazepam is known to supplement atropine therapy, but its specific mechanism of action is uncertain.

Objectives: To test four centrally acting agents for early antidotal efficacy in severe dichlorvos poisoning in the murine model.

Methods: The up‐and‐down method was used to dose four candidate antidotes: diazepam, xylazine, morphine, and ketamine. Antidotes were administered subcutaneously to unsedated adult Sprague‐Dawley rats who were pretreated with 3 mg/kg intraperitoneal glycopyrrolate. All animals received 20 mg/kg of dichlorvos subcutaneously 5 minutes later. A blinded observer adjudicated the outcomes of 10‐minute mortality and survival time.

Results: All animals pretreated with either no antidote (8/8 deaths) or glycopyrrolate alone (8/8) died within 10 minutes of dichlorvos injection. Pretreatment with diazepam (3/9 deaths), or xylazine (3/9), decreased lethality substantially (Fisher p = 0.007; median effective doses, 0.12 mg/kg and 3.0 mg/kg, respectively). Intermediate doses of morphine (3.1 to 5.5 mg/kg) resulted in survival, but higher doses did not, presumably because of excessive respiratory depression (7/11 deaths; p = 0.09). Ketamine (7/8 deaths) was ineffective as an antidote. Survival times also were prolonged in the diazepam and xylazine groups (log‐rank p < 0.001) and, to a lesser degree, the morphine group (p = 0.07).

Conclusions: Doses of diazepam, xylazine, and morphine below those used for deep sedation protect against severe dichlorvos poisoning, implying that several distinct central mechanisms are each sufficient to avert lethality. These findings suggest new possibilities for prophylaxis or therapy.
ST Segment Elevation Differs Depending on the Method of Measurement
Authors: Smith Stephen W.
Published: March 2006

Objectives:The literature seldom specifies the location or method of measurement of ST segment elevation (STE) for determining eligibility in reperfusion trials. The objective of this study was to assess if different methods of measurement of STE in precordial leads of patients with anterior acute myocardial infarction due to left anterior descending occlusion result in significantly different scores.

Methods:This was a retrospective review of diagnostic electrocardiograms (ECGs) of consecutive patients presenting to our emergency department with acute myocardial infarction who had emergent primary percutaneous coronary intervention, left anterior descending occlusion, and no bundle branch block. STE was measured at the J point and at 60 milliseconds after the J point, relative to the PR segment, in leads V1–V6. STE by the two methods was compared for each lead, as were ST scores (sum of STE in leads V1–V6) and the sum of the STE in V2–V4. Eligibility for reperfusion therapy using 1‐mm and 2‐mm STE criteria in two consecutive anterior leads, as well as ST scores and the sum of the STE in V2–V4, were evaluated.

Results:Thirty‐seven ECGs were analyzed. Mean ST measurements in every lead were significantly lower when measured at the J point versus 60 milliseconds after the J point, as were ST scores (9.7 ± 2.14 mm vs. 14.9 ± 2.69 mm; p < 0.00001). Fewer ECGs met enrollment criteria when based on STE at the J point versus at 60 milliseconds after the J point. Fewer ECGs met an ST score of 6 mm when measured at the J point (70% vs. 88%).

Conclusions:In anterior STE myocardial infarction, STE measurements produce different results depending on the method of measurement. Future clinical trials should specify the method of measurement.
Improving Communication Skills: Feedback from Faculty and Residents
Authors: Sherbino Jonathan , Bandiera Glen
Published: March 2006

Objectives:
To determine common themes in faculty and peer feedback for emergency medicine (EM) resident oral presentations.

Methods:
From January to July 2005, all EM residents received written feedback on communication skills from two faculty and two peer reviewers. The feedback forms were analyzed by using formal grounded theory. The two investigators independently reviewed 25% of the forms to generate a code of general categories and specific qualifiers. The independent codes were merged by consensus into a common code. All forms were independently coded by the two investigators using the common code. Coding disagreements were resolved by consensus, yielding a uniform inventory of feedback categories and qualifiers.

Results:
Twenty‐one of 23 residents participated. Three hundred seventy‐two data points were coded, with an interrater agreement of 85.7%. The five most common feedback themes were as follows: focus on key and relevant teaching points; increase audience participation; encourage higher level thinking; decrease content per slide; and add missing content relevant to teaching point. Peers differed from faculty, mentioning more frequently encourage higher level thinking and add missing content relevant to teaching point. Faculty differed from peers, mentioning increase clarity of teaching point and be engaging and enthusiastic more frequently. The difference in distribution of themes between faculty and peers was significant (χ2= 59.692; p = 0.01).

Conclusions:
The authors present a model for providing feedback to EM residents on communication skills that is individualized, behavior based, and includes peer comments. Faculty and peers differ in their recommendations. The findings may inform communication skills curricula for EM residents.
A Community Intervention by Firefighters to Increase 911 Calls and Aspirin Use for Chest Pain
Authors: Meischke Hendrika , Diehr Paula , Rowe Sharon , Cagle Anthony , Eisenberg Mickey
Published: March 2006

Objectives: To test the effectiveness of an intervention, delivered face‐to‐face by local firefighters, designed to increase utilization of 911 and self‐administration of aspirin for seniors experiencing chest pain.

Methods: King County, Washington was divided into 126 geographically distinct areas that were randomized to intervention and control areas. A mailing list identified households of seniors within these areas. More than 20,000 homes in the intervention areas were contacted by local firefighters. Data on all 911 calls for chest pain and self‐administration of aspirin were collected from the medical incident report form (MIRF). The unit of analysis was the area. Firefighters delivered a heart attack survival kit (that included an aspirin) and counseled participants on the importance of aspirin and 911 use for chest pain. Main outcome measures were 911 calls for chest pain and aspirin ingestion for a chest pain event, obtained from the MIRFs that are collected by emergency medical services personnel for 2 years after the intervention.

Results: There were significantly more calls (16%) among seniors on the mailing list in the intervention than control areas in the first year after the intervention. Among the seniors who were not on the mailing list, there was little difference in the intervention and control areas. The results were somewhat sensitive to the analytical model used and to an outlier in the treatment group.

Conclusions: A community‐based firefighter intervention can be effective in increasing appropriate response to symptoms of a heart attack among elders.
How Many Attempts Are Required to Accomplish Out‐of‐hospital Endotracheal Intubation?
Authors: Wang Henry E. , Yealy Donald M.
Published: March 2006

Background: An important goal of emergency airway management is to complete endotracheal intubation (ETI) correctly, safely, and quickly, and repeated ETI attempts can increase patient morbidity and mortality. Clinical protocols limiting the number of ETI attempts may minimize harm, but this strategy also may reduce the frequency of successful ETI.

Objectives: To characterize the relationship between the number of out‐of‐hospital ETI attempts and ETI success.

Methods: This study used prospective, multicenter data from 42 emergency medical services agencies from an 18‐month period. Out‐of‐hospital rescuers (paramedics, out‐of‐hospital nurses, and physicians) completed structured, closed‐response data forms describing clinical methods, course, and outcomes for all ETIs. An ETI attempt was defined as an insertion of the laryngoscope blade. Rescuers identified ETI outcome (success or failure) for each attempt. The authors defined overall success as ETI outcome (success or failure) on the last attempt, examining cardiac arrest, conventional nonarrest, sedation‐facilitated, and rapid‐sequence ETI separately. Univariate odds ratios (ORs) were used to identify the number of ETI attempts in which the cumulative ETI success rate approached the overall ETI success rate.

Results: Complete data were available for 1,941 cases. More than 30% of patients received more than one ETI attempt. For 1,272 cardiac arrest ETIs, cumulative success for the first three attempts were 69.9%, 84.9%, and 89.9%; cumulative success approached overall success (91.8%) after three attempts (OR, 0.79; 95% confidence interval [CI] = 0.61 to 1.04). For 463 conventional non‐arrest ETIs, cumulative success for the first three attempts were 57.6%, 69.2%, and 72.7%; cumulative success approached overall success (73.7%) after two attempts (OR, 0.95; 95% CI = 0.71 to 1.28). For 126 sedation‐facilitated ETIs, cumulative success for the first three attempts were 44.4%, 62.7%, and 75.4%; cumulative success approached overall success (77.0%) after three attempts (OR, 0.92; 95% CI = 0.51 to 1.64). For 80 rapid‐sequence ETI, cumulative ETI success for the first three attempts were 56.3%, 81.3%, and 91.3%; cumulative success approached overall success (96.3%) after three attempts (OR, 0.41; 95% CI = 0.10 to 1.65).

Conclusions: Out‐of‐hospital rescuers often require multiple attempts to accomplish ETI. A protocol limit of three attempts offers reasonable opportunity for accomplishing ETI within the constraints of the out‐of‐hospital environment.
An Emergency Department Intervention to Increase Booster Seat Use for Lower Socioeconomic Families
Authors: Gittelman Michael A. , Pomerantz Wendy J. , Laurence Susan
Published: March 2006

Objectives: To evaluate the effectiveness of booster seat education within an emergency department (ED) setting for families residing in lower socioeconomic neighborhoods.

Methods: This was a prospective, randomized study of families with children aged 4 to 7 years and weighing 40 to 80 lb who presented to a pediatric ED without a booster seat and resided in lower socioeconomic communities. Subjects were randomly assigned to one of three groups: 1) received standard discharge instructions, 2) received five‐minute booster seat training, and 3) received five‐minute booster seat training and free booster seat with installation. Automobile restraint practices were obtained initially and by telephone at one month.

Results: A total of 225 children were enrolled. Before randomization in the study, 79.6% of parents reported that their child was usually positioned in the car with a lap/shoulder belt and 13.3% with a lap belt alone. Some parents (16.4%) had never heard of a booster seat, and 44.9% believed a lap belt was sufficient restraint. A total of 147 parents (65.3%) were contacted for follow‐up at one month. Only one parent (1.3%) in the control group and four parents (5.3%) in the education group purchased and used a booster seat after their ED visit, while 55 parents (98.2%) in the education and installation group reported using the booster seat; 42 (75.0%) of these parents reported using the seat 100% of the time.

Conclusions: Education in a pediatric ED did not convince parents to purchase and use booster seats; however, the combination of education with installation significantly increased booster seat use in this population.