bluuebunny/crossref_metadata_2025 huggingface dataset:
The Magnetron and the Beginnings of the Microwave Age
Authors: Brittain James E.
Published: January 2008

In the autumn of 1940, a British technical and scientific mission, headed by Sir Henry Tizard, brought to the United States a famous black tin trunk containing, among other things, an electronic device that exerted a profound influence on the outcome of the war. This device, the cavity magnetron, was developed by two British physicists, Henry A. Boot and John T. Randall, and was built at the British General Electric Laboratory at Wembley. The British at first hesitated to divulge the design of the magnetron to Americans for fear that it would fall into the hands of German intelligence, but the subsequent developments completely justified the Tizard commission's actions. The disclosure of this device led to the formation later that year of the Radiation Laboratory at Massachusetts Institute of Technology. An elite group of scientists and engineers recruited from universities and industry developed there a variety of magnetrons during the war years and incorporated them into more than 100 radar systems, giving the Allied forces a decisive technical lead. More than two billion dollars was invested in the development and production of radar systems by the United States during the war, and a momentum in microwave technology was created that persisted in the postwar period.
A New Level of Structure
Authors: Greenberg O. W.
Published: January 2008

The history of the physics of the small is in great measure the story of the discovery of new levels of structure, each associated with the development of a new set of experimental tools, and ultimately with a new discipline. We have repeatedly categorized some set of particles as the elementary constituents of matter, only to discover later that these should properly be considered as composed of yet-more-fundamental particles. Discounting the prescientific view of matter as composed of Air, Fire, Earth, and Water, five levels of structure have been discovered so far, as shown in table 1. Most readers of this article are probably familiar with the evidence for each level of structure; a good review of this evidence can be found in reference 1.
What is the Lithosphere?
Authors: Maxwell John C.
Published: January 2008

In simpler times, natural philosophers recognized a tripartite division of the Earth into concentric zones: the atmosphere, the hydrosphere and the lithosphere, the latter being Earth's stony outer portion. As techniques for observation and measurement advanced, geologists identified various lithospheres, with thicknesses depending upon the physical or chemical characteristics that define them:
Multiscale complex network of protein conformational fluctuations in single-molecule time series
Authors: Li Chun-Biu , Yang Haw , Komatsuzaki Tamiki
Published: January 2008

Conformational dynamics of proteins can be interpreted as itinerant motions as the protein traverses from one state to another on a complex network in conformational space or, more generally, in state space. Here we present a scheme to extract a multiscale state space network (SSN) from a single-molecule time series. Analysis by this method enables us to lift degeneracy—different physical states having the same value for a measured observable—as much as possible. A state or node in the network is defined not by the value of the observable at each time but by a set of subsequences of the observable over time. The length of the subsequence can tell us the extent to which the memory of the system is able to predict the next state. As an illustration, we investigate the conformational fluctutation dynamics probed by single-molecule electron transfer (ET), detected on a photon-by-photon basis. We show that the topographical features of the SSNs depend on the time scale of observation; the longer the time scale, the simpler the underlying SSN becomes, leading to a transition of the dynamics from anomalous diffusion to normal Brownian diffusion.
Promiscuous gene expression patterns in single medullary thymic epithelial cells argue for a stochastic mechanism
Authors: Derbinski Jens , Pinto Sheena , Rösch Stefanie , Hexel Klaus , Kyewski Bruno
Published: January 2008

Promiscuous expression of tissue-restricted autoantigens in medullary thymic epithelial cells (mTECs) imposes central T cell tolerance. The molecular regulation of this unusual gene expression is not understood, in particular its delineation from cell lineage-specific gene expression control remains unclear. Here, we compared the expression profile of the casein gene locus in mTECs and mammary gland epithelial cells by single cell PCR. Mammary gland cells showed highly correlated intra- and interchromosomal coexpression of milk proteins (the casein genes, lactalbumin-α and whey acidic protein) and one of its transcriptional regulators (Elf5). In contrast, coexpression of these genes in mature CD80himTECs was rarely observed and no pattern of gene expression in individual mTECs was discernible. The apparent stochastic expression pattern of genes within the casein locus, the lower mRNA levels compared with mammary gland cells in conjunction with frequent coexpression of insulin in single mTECs clearly delineates the molecular mechanism(s) of promiscuous gene expression from cell lineage-specific gene control.
Rapid cell-cycle reentry and cell death after acute inactivation of the retinoblastoma gene product in postnatal cochlear hair cells
Authors: Weber Thomas , Corbett Mary K. , Chow Lionel M. L. , Valentine Marcus B. , Baker Suzanne J. , Zuo Jian
Published: January 2008

Unlike lower vertebrates, mammals are unable to replace damaged mechanosensory hair cells (HCs) in the cochlea. Recently, ablation of the retinoblastoma protein (Rb) in undifferentiated mouse HC precursors was shown to cause cochlear HC proliferation and the generation of new HCs, raising the hope that inactivation of Rb in postmitotic HCs could trigger cell division and regenerate functional HCs postnatally. Here, we acutely inactivated Rb in nearly all cochlear HCs of newborn mice, using a newly developed HC-specific inducible Cre mouse line. Beginning 48 h after
Rb
deletion, ≈40% of HCs were in the S and M phases of the cell cycle, demonstrating an overriding role for Rb in maintaining the quiescent state of postnatal HCs. Unlike
Rb
-null HC precursors, such HCs failed to undergo cell division and died rapidly. HC clusters were restricted to the less differentiated cochlear regions, consistent with differentiation-dependent roles of Rb. Moreover, outer HCs expressed the maturation marker prestin, suggesting an embryonic time window for Rb-dependent HC specification. We conclude that Rb plays essential and age-dependent roles during HC proliferation and differentiation, and, in contrast to previous hypotheses, cell death after forced cell-cycle reentry presents a major challenge for mammalian HC regeneration from residual postnatal HCs.
Role for lysosomal enzyme β-hexosaminidase in the control of mycobacteria infection
Authors: Koo Ingrid Chou , Ohol Yamini M. , Wu Ping , Morisaki J. Hiroshi , Cox Jeffery S. , Brown Eric J.
Published: January 2008

The pathogenic mycobacteria that cause tuberculosis (TB) and TB-like diseases in humans and animals elude sterilizing immunity by residing within an intracellular niche in host macrophages, where they are protected from microbicidal attack. Recent studies have emphasized microbial mechanisms for evasion of host defense; less is known about mycobactericidal mechanisms that remain intact during initial infection. To better understand macrophage mechanisms for restricting mycobacteria growth, we examined
Mycobacterium marinum
infection of
Drosophila
S2 cells. Among ≈1,000 host genes examined by RNAi depletion, the lysosomal enzyme β-hexosaminidase was identified as an important factor in the control of mycobacterial infection. The importance of β-hexosaminidase for restricting mycobacterial growth during mammalian infections was confirmed in macrophages from β-hexosaminidase knockout mice. β-Hexosaminidase was characterized as a peptidoglycan hydrolase that surprisingly exerts its mycobactericidal effect at the macrophage plasma membrane during mycobacteria-induced secretion of lysosomes. Thus, secretion of lysosomal enzymes is a mycobactericidal mechanism that may have a more general role in host defense.
Demonstration of inflammation-induced cancer and cancer immunoediting during primary tumorigenesis
Authors: Swann Jeremy B. , Vesely Matthew D. , Silva Anabel , Sharkey Janelle , Akira Shizuo , Schreiber Robert D. , Smyth Mark J.
Published: January 2008

Here we report the effects of loss of the Toll-like receptor-associated signaling adaptor myeloid-differentiation factor 88 (MyD88) on tumor induction in two distinct mouse models of carcinogenesis. The 7,12-dimethylbenz[
a
]anthracene (DMBA)/12-
O
-tetradecanoylphorbol 13-acetate (TPA)-induced skin papilloma model depends on proinflammatory processes, whereas the 3′-methylcholanthrene (MCA) induction of fibrosarcoma has been used by tumor immunologists to illustrate innate and adaptive immune surveillance of cancer. When exposed to a combination of DMBA/TPA, mice lacking MyD88 formed fewer skin papillomas than genetically matched WT controls treated in a similar manner. Unexpectedly, however, fewer MyD88
−/−
mice formed sarcomas than WT controls when exposed to MCA. In contrast, MyD88-deficient mice did not show a defective ability to reject highly immunogenic transplanted tumors, including MCA sarcomas. Despite the reported role of TNF in chronic inflammation, TNF-deficient mice were significantly more susceptible to MCA-induced sarcoma than WT mice. Overall, these data not only confirm the key role that MyD88 plays in promoting tumor development but also demonstrate that inflammation-induced carcinogenesis and cancer immunoediting can indeed occur in the same mouse tumor model.
Allosteric cooperativity in protein kinase A
Authors: Masterson Larry R. , Mascioni Alessandro , Traaseth Nathaniel J. , Taylor Susan S. , Veglia Gianluigi
Published: January 2008

Allosteric signaling in proteins requires long-range communication mediated by highly conserved residues, often triggered by ligand binding. In this article, we map the allosteric network in the catalytic subunit of protein kinase A using NMR spectroscopy. We show that positive allosteric cooperativity is generated by nucleotide and substrate binding during the transitions through the major conformational states: apo, intermediate, and closed. The allosteric network is disrupted by a single site mutation (Y204A), which also decouples the cooperativity of ligand binding. Because protein kinase A is the prototype for the entire kinome, these findings may serve as a paradigm for describing long-range coupling in other protein kinases.
Cell-specific nitrogen responses mediate developmental plasticity
Authors: Gifford Miriam L. , Dean Alexis , Gutierrez Rodrigo A. , Coruzzi Gloria M. , Birnbaum Kenneth D.
Published: January 2008

The organs of multicellular species consist of cell types that must function together to perform specific tasks. One critical organ function is responding to internal or external change. Some cell-specific responses to changes in environmental conditions are known, but the scale of cell-specific responses within an entire organ as it perceives an environmental flux has not been well characterized in plants or any other multicellular organism. Here, we use cellular profiling of five
Arabidopsis
root cell types in response to an influx of a critical resource, nitrogen, to uncover a vast and predominantly cell-specific response. We show that cell-specific profiling increases sensitivity several-fold, revealing highly localized regulation of transcripts that were largely hidden from previous global analyses. The cell-specific data revealed responses that suggested a coordinated developmental response in distinct cell types or tissues. One example is the cell-specific regulation of a transcriptional circuit that we showed mediates lateral root outgrowth in response to nitrogen via microRNA167, linking small RNAs to nitrogen responses. Together, these results reveal a previously cryptic component of cell-specific responses to nitrogen. Thus, the results make an important advance in our understanding of how multicellular organisms cope with environmental change at the cell level.
Conformational changes of calmodulin upon Ca
2+
binding studied with a microfluidic mixer
Authors: Park Hye Yoon , Kim Sally A. , Korlach Jonas , Rhoades Elizabeth , Kwok Lisa W. , Zipfel Warren R. , Waxham M. Neal , Webb Watt W. , Pollack Lois
Published: January 2008

A microfluidic mixer is applied to study the kinetics of calmodulin conformational changes upon Ca
2+
binding. The device facilitates rapid, uniform mixing by decoupling hydrodynamic focusing from diffusive mixing and accesses time scales of tens of microseconds. The mixer is used in conjunction with multiphoton microscopy to examine the fast Ca
2+
-induced transitions of acrylodan-labeled calmodulin. We find that the kinetic rates of the conformational changes in two homologous globular domains differ by more than an order of magnitude. The characteristic time constants are ≈490 μs for the transitions in the C-terminal domain and ≈20 ms for those in the N-terminal domain of the protein. We discuss possible mechanisms for the two distinct events and the biological role of the stable intermediate, half-saturated calmodulin.
In vitro
reconstitution of the human RISC-loading complex
Authors: MacRae Ian J. , Ma Enbo , Zhou Min , Robinson Carol V. , Doudna Jennifer A.
Published: January 2008

Targeted gene silencing by RNAi requires the RNA-induced silencing complex (RISC), whose core component is the protein Argonaute (Ago) bound to a microRNA (miRNA) or an siRNA. In humans, Ago2 is loaded with miRNAs by the action of a specialized assembly called the RISC-loading complex (RLC), comprising the proteins Ago2, Dicer, and TRBP. Here we show that the human RLC assembles spontaneously
in vitro
from purified components. No cofactors or chaperones are required for the complex to form. The reconstituted RLC, containing one copy of each protein, has the dicing, slicing, guide-strand selection, and Ago2-loading activities observed for the endogenous RLC. Furthermore, once Ago2 is loaded with an miRNA, it tends to dissociate from the rest of the complex. These results lay the groundwork for future structural and functional dissection of RISC loading in humans.
Unfolded protein response transcription factor XBP-1 does not influence prion replication or pathogenesis
Authors: Hetz Claudio , Lee Ann-Hwee , Gonzalez-Romero Dennisse , Thielen Peter , Castilla Joaquín , Soto Claudio , Glimcher Laurie H.
Published: January 2008

The unfolded protein response (UPR) is a conserved adaptive reaction that increases cell survival under endoplasmic reticulum (ER) stress conditions. X-box-binding protein-1 (XBP-1) is a key transcriptional regulator of the UPR that activates genes involved in protein folding, secretion, and degradation to restore ER function. The occurrence of chronic ER stress has been extensively described in neurodegenerative conditions linked to protein misfolding and aggregation. However, the role of the UPR in the CNS has not been addressed directly. Here we describe the generation of a brain-specific XBP-1 conditional KO strain (XBP-1
Nes−/−
). XBP-1
Nes−/−
mice are viable and do not develop any spontaneous neurological dysfunction, although ER stress signaling in XBP-1
Nes−/−
primary neuronal cell cultures was impaired. To assess the function of XBP-1 in pathological conditions involving protein misfolding and ER stress, we infected XBP-1
Nes−/−
mice with murine prions. To our surprise, the activation of stress responses triggered by prion replication was not influenced by XBP-1 deficiency. Neither prion aggregation, neuronal loss, nor animal survival was affected. Hence, this most highly conserved arm of the UPR may not contribute to the occurrence or pathology of neurodegenerative conditions associated with prion protein misfolding despite predictions that such diseases are related to ER stress and irreversible neuronal damage.
Characterization of a late transitional B cell population highly sensitive to BAFF-mediated homeostatic proliferation
Authors: Meyer-Bahlburg Almut , Andrews Sarah F. , Yu Karl O.A. , Porcelli Steven A. , Rawlings David J.
Published: January 2008

We have characterized a distinct, late transitional B cell subset, CD21int transitional 2 (T2) B cells. In contrast to early transitional B cells, CD21int T2 B cells exhibit augmented responses to a range of potential microenvironmental stimuli. Adoptive transfer studies demonstrate that this subset is an immediate precursor of both follicular mature and marginal zone (MZ) B cells. In vivo, a large percentage of CD21int T2 B cells has entered the cell cycle, and the cycling subpopulation exhibits further augmentation in mitogenic responses and B cell-activating factor of the TNF family (BAFF) receptor expression. Consistent with these features, CD21int T2 cells exhibit preferential responses to BAFF-facilitated homeostatic signals in vivo. In addition, we demonstrate that M167 B cell receptor (BCR) idiotypic-specific B cells are first selected within the cycling CD21int T2 population, ultimately leading to preferential enrichment of these cells within the MZ B cell compartment. These data, in association with the coordinate role for BAFF and microenvironmental cues in determining the mature BCR repertoire, imply that this subset functions as a unique selection point in peripheral B cell development.
Mannose-binding lectin enhances Toll-like receptors 2 and 6 signaling from the phagosome
Authors: Ip W.K. Eddie , Takahashi Kazue , Moore Kathryn J. , Stuart Lynda M. , Ezekowitz R. Alan B.
Published: January 2008

Innate immunity is the first-line defense against pathogens and relies on phagocytes, soluble components, and cell-surface and cytosolic pattern recognition receptors. Despite using hard-wired receptors and signaling pathways, the innate immune response demonstrates surprising specificity to different pathogens. We determined how combinatorial use of innate immune defense mechanisms defines the response. We describe a novel cooperation between a soluble component of the innate immune system, the mannose-binding lectin, and Toll-like receptor 2 that both specifies and amplifies the host response to Staphylococcus aureus. Furthermore, we demonstrate that this cooperation occurs within the phagosome, emphasizing the importance of engulfment in providing the appropriate cellular environment to facilitate the synergy between these defense pathways.
Pogostemon cablin as ROS Scavenger in Oxidant‐Induced Cell Death of Human Neuroglioma Cells
Authors: Kim Hyung Woo , Cho Su Jin , Kim Bu-Yeo , Cho Su In , Kim Young Kyun
Published: January 2008

Reactive oxygen species (ROS) have been implicated in the pathogenesis of a wide range of acute and long‐term neurodegenerative diseases. This study was undertaken to examine the efficacy of Pogostemon cablin, a well‐known herb in Korean traditional medicine, on ROS‐induced brain cell injury. Pogostemon cablin effectively protected human neuroglioma cell line A172 against both the necrotic and apoptotic cell death induced by hydrogen peroxide (H2O2). The effect of Pogostemon cablin was dose dependent at concentrations ranging from 0.2 to 5 mg ml−1. Pogostemon cablin significantly prevented depletion of cellular ATP and activation of poly ADP‐ribose polymerase induced by H2O2. The preservation of functional integrity of mitochondria upon the treatment of Pogostemon cablin was also confirmed by 3‐(4,5‐dimethyl‐2‐thiazyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide assay. Furthermore, Pogostemon cablin significantly prevented H2O2‐induced release of cytochrome c into cytosol. Determination of intracellular ROS showed that Pogostemon cablin might exert its role as a powerful scavenger of intracellular ROS. The present study suggests the beneficial effect of Pogostemon cablin on ROS‐induced neuroglial cell injury. The action of Pogostemon cablin as a ROS‐scavenger might underlie the mechanism.
Body Acupuncture for Nicotine Withdrawal Symptoms: A Randomized Placebo‐Controlled Trial
Authors: Hyun Min-Kyung , Lee Myeong Soo , Kang Kyungwon , Choi Sun-Mi
Published: January 2008

This study evaluated whether improvements in nicotine withdrawal symptoms (NWS), depression and anxiety are greater for body acupuncture than for sham acupuncture. Smoking volunteers from the public were randomized to receive six sessions of either real or sham acupuncture for 2 weeks. The primary outcome measure was NWS measured by the Minnesota Nicotine Withdrawal Score, and the secondary measures were scores on the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). Eighty volunteers were randomized into real acupuncture (n = 38) and sham acupuncture (n = 42) groups, of which 46 subjects (22 and 24 in the real and sham acupuncture groups, respectively) completed the treatment and the 2‐week follow‐up. An intention‐to‐treat analysis revealed that the NWS did not differ significantly between the real and sham acupuncture groups immediately after the treatment (12.2 ± 9.7 and 12.8 ± 7.7, respectively; mean ± SD) and at the 2‐week follow‐up (11.7 ± 10.2 and 12.6 ± 7.8). Both groups also showed similar improvements in BDI and BAI scores. These results indicate that the real acupuncture treatment tested in this trial was no more effective than sham acupuncture at reducing NWS, depression and anxiety for smoking cessation.
The Type B Phosphatidylinositol-4-Phosphate 5-Kinase 3 Is Essential for Root Hair Formation inArabidopsis thaliana
Authors: Stenzel Irene , Ischebeck Till , König Sabine , Hołubowska Anna , Sporysz Marta , Hause Bettina , Heilmann Ingo
Published: January 2008

Root hairs are extensions of root epidermal cells and a model system for directional tip growth of plant cells. A previously uncharacterized Arabidopsis thaliana phosphatidylinositol-4-phosphate 5-kinase gene (PIP5K3) was identified and found to be expressed in the root cortex, epidermal cells, and root hairs. Recombinant PIP5K3 protein was catalytically active and converted phosphatidylinositol-4-phosphate to phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2]. Arabidopsis mutant plants homozygous for T-DNA–disrupted PIP5K3 alleles were compromised in root hair formation, a phenotype complemented by expression of wild-type PIP5K3 cDNA under the control of a 1500-bp PIP5K3 promoter fragment. Root hair–specific PIP5K3 overexpression resulted in root hair deformation and loss of cell polarity with increasing accumulation of PIP5K3 transcript. Using reestablishment of root hair formation in T-DNA mutants as a bioassay for physiological functionality of engineered PIP5K3 variants, catalytic activity was found to be essential for physiological function, indicating that PtdIns(4,5)P2 formation is required for root hair development. An N-terminal domain containing membrane occupation and recognition nexus repeats, which is not required for catalytic activity, was found to be essential for the establishment of root hair growth. Fluorescence-tagged PIP5K3 localized to the periphery of the apical region of root hair cells, possibly associating with the plasma membrane and/or exocytotic vesicles. Transient heterologous expression of full-length PIP5K3 in tobacco (Nicotiana tabacum) pollen tubes increased plasma membrane association of a PtdIns(4,5)P2-specific reporter in these tip-growing cells. The data demonstrate that root hair development requires PIP5K3-dependent PtdIns(4,5)P2 production in the apical region of root hair cells.
Can default rates in colposcopy really be reduced?
Authors: Balasubramani L , Orbell S , Hagger M , Brown V , Tidy J
Published: January 2008

A prospective postal questionnaire study aimed to identify variables that predict a woman’s intention to attend and her subsequent attendance/default at colposcopy clinics. One thousand two hundred and fifty‐eight women attending colposcopy clinics of a university hospital were sent a postal questionnaire 3 weeks before their second appointment at colposcopy. An intention to attend the colposcopy clinic was the most significant predictor for colposcopy attendance during the next 15 months. Smoking and a longer travel time were associated with default. Our study shows that while interventions tried by service providers can reduce default rates, there will remain a cohort of women who do not fully participate in the screening programme.
Tetralogy of Fallot: maternal and neonatal outcomes
Authors: Gelson E , Gatzoulis M , Steer PJ , Lupton M , Johnson M
Published: January 2008

We performed a retrospective cohort study of 26 pregnancies in 16 women with repaired tetralogy of Fallot (rTOF) delivering at the Chelsea and Westminster Hospital and compared them with 104 controls. The rate of antenatal complications was significantly higher in the rTOF group (30 cf. 13%). Use of epidural anaesthesia was higher (67 cf. 25%) in the rTOF group compared with controls, and the length of the second stage was shorter in both spontaneous and assisted deliveries. However, the mode of delivery and neonatal outcomes were similar in both groups. Mean birthweight centile was lower in the tetralogy of Fallot group, 26 versus 58 in the control group (P = 0.000001, Wilcoxon rank sum test). All women whose babies were <10th centile weight for gestational age had moderate to severe pulmonary regurgitation.
Interobserver Variability among Faculty in Evaluations of Residents Clinical Skills
Authors: LaMantia Joseph , Rennie William , Risucci Donald A. , Cydulka Rita , Spillane Linda , Graff Louis , Becher John , Kleinschmidt Kurt
Published: January 2008

Objective: To describe interobserver variability among emergency medicine (EM) faculty when using global assessment (GA) rating scales and performance‐based criterion (PBC) checklists to evaluate EM residents clinical skills during standardized patient (SP) encounters. Methods: Six EM residents were videotaped during encounters with SPs and subsequently evaluated by 38 EM faculty at four EM residency sites. There were two encounters in which a single SP presented with headache, two in which a second SP presented with chest pain, and two in which a third SP presented with abdominal pain, resulting in two parallel sets of three. Faculty used GA rating scales to evaluate history taking, physical examination, and interpersonal skills for the initial set of three cases. Each encounter in the second set was evaluated with complaint‐specific PBC checklists developed by SAEM's National Consensus Group on Clinical Skills Task Force. Results: Standard deviations, computed for each score distribution, were generally similar across evaluation methods. None of the distributions deviated significantly from that of a Gaussian distribution, as indicated by the Kolmogorov‐Smirnov goodness‐of‐fit test. On PBC checklists, 80% agreement among faculty observers was found for 74% of chest pain, 45% of headache, and 30% of abdominal pain items. Conclusions: When EM faculty evaluate clinical performance of EM residents during videotaped SP encounters, interobserver variabilities are similar, whether a PBC checklist or a GA rating scale is used.
Storage Temperatures of Out‐of‐hospital Medications
Authors: Allegra John R. , Brennan John , Lanier Vicki , Lavery Robert , MacKenzie Bruce
Published: January 2008

Objectives: To determine whether temperatures inside drug boxes used in the out‐of‐hospital setting are within the U.S. Pharmacopeia recommendations for “controlled room temperature,” which is defined as a temperature maintained between 15°C and 30°C with a mean kinetic temperature less than 25°C, and to determine whether time—temperature indicator labels can reliably monitor mean kinetic temperatures. Methods: Two methods were used to monitor temperatures: miniature electronic temperature recorders and color‐changing time—temperature indicator labels. These were placed in drug storage boxes of advanced life support units over three summer months and two winter months. Results: In summer, the electronic recorders logged temperatures exceeding 30°C in all drug storage boxes, ranging from 3% to 29% of the total time. The mean kinetic temperatures by location for the whole period ranged from 21°C to 30°C. In the winter, the electronic recorders logged temperatures exceeding 30°C at one location 2% of the total time. There were significant temperature excursions below 15°C at all locations, ranging from 16% to 90% of the total time. At one location, there were temperature readings below 0°C for 9% of the total time. The mean kinetic temperatures obtained from the electronic recorders and the indicator labels differed by less than 1°C. Conclusions: This study demonstrates that out‐of‐hospital medications are subject to temperatures both above and below recommended storage temperatures. Time—temperature indicator labels can reliably monitor exposure to elevated temperatures.
The Prevalence and Effects of Hunger in an Emergency Department Patient Population
Authors: Kersey Margaret A. , Beran Mary Sue , McGovern Paul G. , Biros Michelle H. , Lurie Nicole
Published: January 2008

Objectives: Little is known about the prevalence and health effects of hunger among ED patients. The objectives of this study were to determine the prevalence of hunger among patients in a large urban ED and to examine whether it has adverse health effects. Methods: A survey about hunger, choices between buying food and buying medicine, and adverse health outcomes related to food adequacy over the preceding 12 months was administered to a convenience sample of adult non‐critically ill ED patients from afternoon and evening shifts. The study was conducted in the ED of Hennepin County Medical Center in Minneapolis, Minnesota. Results: Of the 302 eligible patients who were asked to participate, 297 (98%) agreed. Eighteen percent reported not having enough to eat at least once in the preceding 12 months: 14% reported that they had “gotten sick” as a result of not being able to afford their medicine, resulting in an ED visit or hospital admission 50% of the time. Predictors of making choices about buying food vs medicine include having a chronic health condition, lack of private health insurance, having a reduction in food stamps, having an annual income less than 10,000, and lack of alcohol use. By patient report, a reduction in food stamps was a predictor of ED visits and hospitalizations as a result of making choices about buying food over medicine. Conclusion: The ED patients in this urban setting have high rates of hunger and many must make choices between buying food and medicine, which patients report results in otherwise preventable ED visits and hospitalization. Loss or reduction of food stamps is associated with increased hunger and increased perceived adverse health outcomes as a result of not being able to afford medicine.
Population‐based Incidence and Outcome of Acetaminophen Poisoning by Type of Ingestion
Authors: Bond G. Randall , Hite Ladonna K.
Published: January 2008

Objectives: 1) To determine, in a population‐based sample, the observed frequency of acetaminophen overdose‐related ED evaluation and hospitalization. 2) To examine the relative frequency of hospitalization by pattern of ingestion, the outcome of each group, and the presence or absence of postulated risk factors. Methods: This study was a 46‐month, retrospective chart review of all acetaminophen‐related visits, by patients at least 10 years of age, to either of the two hospitals that serve a four‐county region of central Virginia. Results: Of 636 charts identified for review, only 137 involved acute or chronic acetaminophen overdose. One hundred twenty‐six patients presented after an acute ingestion; 122 of these patients gave a history of a single, supratherapeutic ingestion of acetaminophen. Twenty‐five patients were hospitalized for treatment. Eighteen of these were treated with N‐acetylcysteine (NAC) based on the Rumack‐Matthew nomogram; one suffered significant hepatic injury. The other seven presented at least 18 hours after ingestion, with no measurable serum acetaminophen. Two of these suffered significant hepatic injury. Four additional patients presented after multiple ingestions within 24 hours. Three were hospitalized, but none experienced significant injury. Only 11 patients were evaluated for chronic acetaminophen overmedication for pain (more than 6 g/day over a period of more than 24 hours). Four were admitted for treatment; three suffered significant hepatic injury. Thus, the observed incidence of acute acetaminophen ingestion in this region was 21.4/100,000/yr (95% CI = 17.7 to 25.2). The observed incidence of hospitalization for acute acetaminophen toxicity was 4.8/100,000/yr (95% CI = 3.0 to 6.5). The observed incidence of hospitalization for all acetaminophen poisoning was 5.5/100,000/yr (95% CI = 4.1 to 7.0). High ethanol consumption was present more frequently in those who suffered hepatic injury. Conclusions: Most patients evaluated for acetaminophen ingestion present early following acute single overdose. Relatively few of these patients require hospitalization and, for those hospitalized, the outcome is good. More significantly, acetaminophen overdose patients whose risk cannot be estimated using the Rumack‐Matthew nomogram represented 44% of those hospitalized and 83% of those who suffered significant hepatic injury. Emergency physicians need to determine how they can impact the outcome of these patients. Efforts should be directed at further characterizing historical, physical, and biochemical markers of risk and at determining in which circumstances hospitalization for NAC or other therapies is justified.
Intradermal Anti‐Loxosceles Fab Fragments Attenuate Dermonecrotic Arachnidism
Authors: Gomez Hernan F. , Miller Mark J. , Trachy Joseph W. , Marks Rory M. , Warren Jeffrey S.
Published: January 2008

Objective: Bites from the brown recluse spider and other arachnids from the genus Loxosceles frequently induce necrotic skin lesions that can be recalcitrant to treatment and disfiguring. The authors used a rabbit model of dermonecrotic arachnidism to address the therapeutic efficacy of intradermal (id) polyclonal anti‐Loxosceles Fab fragments (αLoxd Fab) raised against Loxosceles deserta spider venom. Methods: Fab fragments were prepared by papain digestion and affinity chromatography from the IgG fraction of L. deserta antivenom raised in rabbits. Eighteen inbred New Zealand white rabbits were assigned to six groups of three. The rabbits received L. deserta venom (3 μg, id) injections into each flank. Cohorts of rabbits received single id injections (at one venom site/rabbit) of 30 μg αLoxd Fab at different times (T = 0, 1, 2, 4, 8, and 12 hours) after venom injection. In each rabbit the opposite flank was left untreated. As an additional control, one group of rabbits (T = 0) received nonspecific Fab (30 μg, id) in the opposite flank. Dermal lesions were quantified as a function of time through the use of a series of digital photographs and imaging software. In addition, myeloperoxidase (MPO) activity, a measure of neutrophil accumulation, was determined in lesion biopsies. Lesion areas and MPO activities were analyzed by repeated‐measures analysis of variance (ANOVA). Results: Lesion areas and MPO activity were markedly reduced when αLoxd Fab was administered very early after venom injections. As the interval between venom inoculation and antivenom treatment increased, the therapeutic benefit of αLoxd Fab decreased. The final time tested that demonstrated therapeutic efficacy of αLoxd Fab was T = 4 hours. Lesion attenuation was no longer apparent when αLoxd Fab was given 8 hours post inoculation. Conclusions: Intradermal administration of αLoxd Fab attenuates Loxosceles‐induced dermonecrotic lesion formation when given up to 4 hours after venom inoculation in this rabbit model.
Effect of a Practice Guideline on the Process of Emergency Department Care of Falls in Elder Patients
Authors: Baraff Larry J. , Lee Thomas J. , Kader Susan , Penna Richard Della
Published: January 2008

Objective: To determine the effect of a practice guideline on the process of ED care in a health maintenance organization. Methods: A pre—post‐intervention comparison with a one‐year pre‐intervention phase followed by a one‐year post‐educational intervention phase was used to study the effect of the guideline on ED care. Emergency physicians and nurses were provided the details of the guideline during a two‐week interval between the two periods. Results: During the two years of the study, 1,140 preintervention and 759 post‐intervention patients met study eligibility criteria. More patients were diagnosed as having had falls due to loss of consciousness, stroke, and seizures during the post‐intervention period (pre‐intervention 3.8% vs post‐intervention 8.4%, p < 0.001). There was a significant improvement in documentation of six of ten history items: cause of fall (64.5% vs 72.9%), location of fall (54.7% vs 60.5%), ability to get up unassisted (5.4% vs 12.5%), long lie after fall (1.5% vs 10.1%), prescription medications (79.0% vs 92.2%), and Pneumovax immunization status (20.8% vs 43.0%); and two of the four physical examination items: visual acuity (1.5% vs 3.2%) and the “get up and go test” (1.3% vs 11.2%). Prescribing of calcium and vitamin D increased from 0% to 6.6%. Conclusions: The educational intervention to the practice guideline for the ED management of falls in elders led to small but significant improvements in the documentation of selected history and physical examination items and the prescribing of calcium and vitamin D, and to a greater consideration of the causes of falls.
Computers and Connectivity in Illinois Emergency Departments
Authors: Handler Jonathan A. , Gillam Michael , Wang Ernest E. , Feied Craig F. , Yarnold Paul R. , Bose Sudip , Smith Mark S.
Published: January 2008

Although the Internet has been described as “ubiquitous,” little is known about the extent to which physicians have access to the Internet while providing clinical care. Objective: To assess the extent of Internet connectivity within the clinical area of every ED within the state of Illinois. Methods: This was a prospective observational study. Each Illinois ED listed in a published directory was called by telephone, and a responsible party was identified to provide information regarding the type and size of the ED, patient demographics, the types of personal computers (PCs) available in the ED (if any), the types of operating systems used, the availability of access to the World Wide Web (Web), and the highest speed at which an Internet connection could be established. Responses regarding the presence and types of PCs and the types of operating systems used were assessed using one‐factor chi‐square. Univariate and multivariate predictors of the type of PC used, the presence or absence of Web access, and the highest speed of Internet access were evaluated using optimal discriminant analysis and nonlinear classification tree analysis, respectively. Results: One hundred ninety‐eight of the 199 EDs in the state of Illinois (99.5%) completed the survey. Of the responding EDs, 50.5% had PCs, but only 17.6% had Web access. When Web access was available, it was most often available through a high‐speed Internet connection that was faster than a dial‐up modem. Most departments (68.1%) with PCs used the Windows 95 or Windows 98 operating systems. A majority (62.5%) used the Netscape browser exclusively. Larger EDs (more than six ED beds) in rural or suburban areas were more likely to have a PC compared with smaller EDs (six or fewer beds). Large EDs (more than 12 ED beds) in private tertiary care or academic hospitals were most likely to have Web access. Conclusions: Although half of Illinois EDs have PCs, only one in six has access to the Internet; thus, most emergency physicians do not have ready access to the Web from the site where they deliver clinical care.
Feasibility of an Emergency Department‐based Tuberculosis Counseling and Screening Program
Authors: Kirsch Thomas D. , Chanmugam Arjun , Keyl Penelope , Regan Linda A. , Shahan Judy , Hexter David A. , Kelen Gabor D.
Published: January 2008

Objective: To assess the feasibility and effectiveness of an ED‐based tuberculosis (TB) screening program. Methods: A TB screening program of adult ED patients was conducted at a university hospital ED with 46,000 annual visits that serves a poor urban community. Patients were screened on weekdays during business hours. ED patients were counseled about the disease and the screening procedure and, after consent, purified protein derivative (PPD) tests were placed. Patients returned in 48‐72 hours for reaction reading and post‐test counseling. PPD‐positive patients received a physical examination, chest x‐ray, and HIV testing and were referred to a city TB clinic for possible treatment. Results: Overall, 873 patients were counseled, 630 were eligible for screening, and 374 (59.4%) consented to PPD testing. Of the 203 (54.1%) who returned, 32 (15.8%) were PPD‐positive. No active case was detected, but 26 patients were referred to the health department. Eighteen kept their appointments and all 13 who were started on therapy completed treatment. Targeted screening of groups aged 55 years or more, nonwhite groups, and those with other high‐risk factors would detect 84% of PPD‐positive cases while testing only 48% of eligible patients. Conclusion: An ED‐based TB screening program is feasible and can identify many patients requiring treatment. Targeted screening of high‐risk groups could reduce the program cost, but would miss some cases.
The Effect of Abbreviations on MEDLINE Searching
Authors: Federiuk Carol S.
Published: January 2008

Abstract. Objective: To determine the effect of the use of abbreviations and acronyms on citation retrieval in MEDLINE searches. Methods: Twenty common medical abbreviations that retrieved a minimum of 400 citations each in MEDLINE text word searches were studied. Each abbreviation was entered in a MEDLINE subject search to determine whether it mapped to an appropriate medical subject heading (MeSH) term. The MeSH category and the number of citations retrieved were recorded. The abbreviation and its definition were each entered in separate text word searches, and the number of citations retrieved was recorded. Sets were combined to determine the number of identical and unique citations retrieved in the searches. Results: MEDLINE recognized all 20 abbreviations and mapped them to appropriate MeSH headings. MeSH term assignment, however, may be case‐ and space‐sensitive. MeSH term searches retrieved more citations than text word searches for 18 of 20 abbreviations. Comparison of the document sets yielded by each search method revealed a subset of citations common to each. Although all sets retrieved showed overlap, no two were identical. In addition, each citation set contained a proportion of unique documents. Conclusion: Retrieval of all unique citations required three searches; subject with abbreviation, text word with abbreviation, and text word with definition. These results have important implications for MEDLINE users.
Authorship: “Law” and Order
Authors: Gaeta Theodore J.
Published: January 2008

Abstract. Publication is a marker of academic success. In academia, appointments and promotions are in many cases strongly linked to the candidate's bibliography. The “publish or perish” mindset has placed extraordinary pressures on scientists and academic physicians alike. Authorship controversies have received considerable attention in the medical literature. Although guidelines are available to help determine how attribution should be acknowledged, anecdotal experiences with disputes associated with authorship continue to exist. This paper addresses several key problems facing authorship. A discussion of who should be given authorship, the responsibilities of an author, and a method for assigning authorship in a multiauthored publication is provided.
Evaluating Professionalism in Emergency Medicine: Clinical Ethical Competence
Authors: Larkin Gregory Luke
Published: January 2008

Abstract. While the teaching and assessing of technical skills have been an integral part of residency training, the demonstration of ethical and humanistic skills has been more or less left to chance. Only in the last two decades has the formal teaching of bioethics become an accepted component of Western medical education. In spite of the many ethics lectures, discussions, conferences, and courses, the clinical impact of this educational paradigm shift remains unclear. Most ethics assessments to date are conducted retrospectively by risk managers and attorneys. The few prospective evaluations of trainees have focused on single‐researcher observations or student attitude surveys that are fraught with observer and recall biases, respectively. More reliable and valid methods of identifying clinical ethical competence are needed. This paper reviews a variety of evaluative tools and suggests a three‐level approach to monitoring the ethical knowledge, capacity, and real‐time performance of emergency medicine residents.
A Comparison of Australasian and United States Emergency Medicine Training Programs**
Authors: Taylor David McD. , Jelinek George A.
Published: January 2008

Abstract. Training programs in emergency medicine differ from country to country. This article compares the allopathic training programs of Australasia and the United States. The perceived advantages of these programs are highlighted, but no attempt is made to determine which is the better program. The Australasian program is significantly longer and places a greater emphasis on the basic clinical sciences, physical examination skills, and academic output. Australasian College for Emergency Medicine (ACEM) regulations are relatively flexible and allow trainees to design their own programs. Trainees are encouraged to arrange accredited positions in a variety of hospitals. Overseas and part‐time training may be acceptable. In the United States, trainees rotate within and from one parent institution, which provides a rigid teaching structure for a “critical mass” of trainees, based on a “core” curriculum. Rotations tend to be much shorter but ensure exposure to a broader range of clinical experience. Evaluation of trainees and teaching faculty is more frequent and documentation of procedural and resuscitation skills is required. Trainees are under the close supervision of teaching faculty at all times when working in an ED.