bluuebunny/crossref_metadata_2025 huggingface dataset:
It just took a blank sheet of paper: changing the job plan of an adult psychiatrist
Authors: Hampson Michele
Published: August 2003

Many good ideas seemingly come out of the blue – in my case, dreaming of early retirement. If work felt like a painful sprint, at least it would be short-lived. I considered the impact of a stressed, adult psychiatrist on recruitment, for medical students and junior trainees spend the majority of their training with such consultants. Early retirement can increase the workload of the remaining psychiatrists, given the existing unfilled posts, which can create a domino effect. Previously, the idea of jogging along had felt self-indulgent. Now, it seemed as essential for the profession as for myself.
Seismic Isolation: New Zealand Applications
Authors: McKay G. R. , Chapman H. E. , Kirkcaldie D. K.
Published: August 2003

Seismic isolation of structures has been applied in New Zealand since 1973. To date approximately 45 bridges, 3 large buildings and a few other structures have been protected with this technique. These include 40 bridges and 2 buildings designed by Works and Development Services Corporation (NZ) Ltd (WORKS). Numerous energy dissipating devices have been developed and tested by New Zealand researchers. Six of these designs have proved to be convenient and economical and have been incorporated in the seismic isolation systems of the structures built. Development work on seismic isolation devices is continuing in New Zealand and contact with specialists from other countries - in particular from Japan and the United States of America - is being maintained. Seismic isolation has been found to be a cost effective means of mitigating earthquake effects, particularly if the long term benefits of reduced seismic damage and disruption are taken into consideration.
Earthquake Hazard Mitigation: The Need for Human Resources Development and Research
Authors: Kuntz Robert J.
Published: August 2003

Most of California's population and industry are located in zones of high seismicity, and the Federal Emergency Management Agency (FEMA) estimated that a 7.5 to 8.3 Richter magnitude earthquake in an urban area could cause up to $60 billion in damage (1). Such an earthquake could cripple the state's public and private economies, and, as California's economy is the sixth largest in the world, have a negative effect on the world market. Building practices in California offer only minimal protection from seismic damage, however new technologies, such as seismic isolation, can mitigate damage and are becoming available to government and industry. There is a need for design professionals, building officials, planners, and building owners to become aware of these new technologies, and the legal constraints to their use, and incorporate them into practice, and for engineering and architectural educators to include new seismic design technologies in undergraduate curricula.
Impediments to the Implementation of Seismic Isolation
Authors: Mayes Ronald L. , Jones Lindsay R. , Buckle Ian G.
Published: August 2003

There are over 125 civil engineering structures worldwide that have been constructed using the principles of seismic isolation and 15 of these are in the United States. Although use of the technology is increasing in the United States it is significantly less than that seen in Japan and New Zealand. Some of the impediments that have been encountered, such as design codes, economics and government leadership are discussed and the paper provides a summary of the status of some of the solutions required for its more widespread use in the United States. A comparison with the Japanese implementation process is also provided.
Seismic Rehabilitation of the Mackay School of Mines, Phase III, with Base Isolation
Authors: Way Douglas , Howard Jack
Published: August 2003

The original Mackay School of Mines Building was constructed in 1908. It is one of the original buildings of the University of Nevada, and is situated at the north end of the main quadrangle within the campus. Prominent in its location at University of Nevada and in appearance, the building is designated as a national historic monument. During the years of 1926 and 1956, significant structural alterations were made to the original building. Phase III work at the original Mackay School of Mines Building involves adding a library at the basement, with the balance of the building being remodeled for similar-type functions. Constructed mainly of unreinforced masonry, the seismic rehabilitation of the structure warrants careful attention. During the schematic phase of the work, both conventional strengthening and Base Isolation were explored as potential techniques with which to mitigate damage from earthquakes. Cost estimate of both schemes were also developed. From a preservationist point of view, there were definite advantages in the isolation design. Since the isolation system could filter out most of the damaging forces associated with earthquakes, none of the unreinforced masonry walls required strengthening. As a result, many of the original architectural features of the original building can be salvaged, maintaining the original quality of the building and its identity. For these reasons the Base Isolation option was selected as the seismic retrofit scheme. This paper illustrates the Base Isolation design for the Mackay School of Mines, a historical structure constructed of unreinforced masonry. The isolation system consists of high-damping rubber bearings in combination with sliding elements.
Comparison of Earthquake Simulator Test Results with the SEAONC Tentative Seismic Isolation Design Requirements
Authors: Griffith Michael C. , Aiken Ian D. , Kelly James M.
Published: August 2003

Earthquake simulator tests were performed on a 1/5-scale, 6-story reinforced concrete shear-wall structure and a 1/4-scale, 9-story braced steel frame structure. The structures were supported by five different base isolation systems which consisted of various types and combinations of elastomeric bearings. The main objective of this study was to compare the peak experimental displacements of the base isolation systems tested with values given by the tentative base isolation design provisions proposed by the Seismology Committee of the Structural Engineers Association of Northern California (SEAONC). Comparisons of experimental results and values from the SEAONC base isolation design formula for displacements indicated that the formula is generally conservative, even for predominantly low frequency earthquake motions, provided the ground motion coefficient Av (based on the effective peak velocity as defined by ATC 3-06) is used in the design equation for base-isolated structures with periods greater than 1 second.
Impact of Helical Computed Tomography on the Outcomes of Emergency Department Patients with Suspected Appendicitis
Authors: Torbati Sam S. , Guss David A.
Published: August 2003

Objectives: To assess the impact of an emergency department (ED) guideline employing selective use of helical computed tomography (CT) on clinical outcomes of female patients with suspected appendicitis. Methods: All patients presenting with suspected appendicitis were prospectively enrolled and managed in accordance with a guideline incorporating selective use of helical CT. Although not the objective of this investigation, male patients were included for purposes of comparison. Patients with clinically evident appendicitis were referred to the surgical service, and patients with equivocal presentations were studied with helical CT. Patients were followed to final surgical or clinical outcomes. Outcome measures included time from ED presentation to laparotomy and rate of appendiceal perforation. These measures were compared with those of a historical cohort of patients preceding the use of helical CT. Results: A total of 310 consecutive patients with suspected appendicitis were enrolled; 92 had appendicitis. Sixty patients were referred to the surgical service without helical CT, and 41 had appendicitis (68%). Helical CT was performed on 250 patients; 51 had appendicitis (20%). For males, the mean interval from ED presentation to laparotomy was 559 minutes (95% CI = 444 to 674 minutes) during guideline use and 480 minutes (95% CI = 405 to 555 minutes) before. This interval for females was 433 minutes (95% CI = 326 to 540 minutes) during guideline use and 710 minutes (95% CI = 558 to 862 minutes) before. Appendiceal perforation rate for males was 0.25 (95% CI = 0.14 to 0.36) during guideline use and 0.38 (95% CI = 0.29 to 0.47) before; perforation rate for females was 0.06 (95% CI =−0.05 to 0.17) during guideline use and 0.23 (95% CI = 0.14 to 0.32) before. Helical CT had 92% sensitivity, 97% specificity, and 96% accuracy in diagnosing appendicitis. Conclusions: Helical CT is highly accurate in detecting appendicitis in patients with equivocal ED presentations. The use of a guideline employing selective helical CT was associated with a decline in the time from ED presentation to operative intervention in females.
Arterial Blood Gas Results Rarely Influence Emergency Physician Management of Patients with Suspected Diabetic Ketoacidosis
Authors: Ma O. John , Rush Micheal D. , Godfrey Michelle M. , Gaddis Gary
Published: August 2003

Objectives: To test the hypothesis that arterial blood gas (ABG) results for patients with suspected diabetic ketoacidosis (DKA) do not influence emergency physicians' management decisions and to assess correlation and precision between venous pH and arterial pH. Methods: Prospective, observational study of emergency physicians' decision making for consecutive ED patients with suspected DKA. Inclusion criteria were capillary blood glucose equal to or greater than 200 mg/dL, ketonuria, and clinical signs and symptoms of DKA. Venous pH, chemistry panel, and ABGs were drawn before treatment. Attending emergency physicians indicated planned management and disposition on a standardized form before and after reviewing ABG and venous pH results. This study was powered to detect a 10% difference in management decisions (n= 195). Pearson's correlation and Bland‐Altman bias plot were used to compare venous pH and arterial pH. Results: ABG analysis changed the emergency physicians' diagnosis in 2/200 cases (1.0%; 95% confidence interval [95% CI] = 0.3% to 3.6%), altered treatment in 7/200 cases (3.5%; 95% CI = 1.7% to 7.1%), and changed disposition in 2/200 cases (1.0%; 95% CI = 0.3% to 3.6%). The pH value of the ABGs changed the treatment or disposition in 5/200 patients (2.5%; 95% CI = 1.1% to 5.7%). The Po 2 and Pco 2 results of the ABGs altered treatment and disposition in 2/200 patients (1.0%; 95% CI = 0.3% to 3.6%). Venous pH correlated well with arterial pH (r= 0.951), and bias plotting yielded a bias value of −0.015 (± 0.006 pH units). Conclusions: ABG results rarely influenced emergency physicians' decisions on diagnosis, treatment, or disposition in suspected DKA patients. Venous pH correlated well and was precise enough with arterial pH to serve as a substitute.
Information Technology in Emergency Medicine Residency–Affiliated Emergency Departments
Authors: Pallin Daniel , Lahman MeeMee , Baumlin Kevin
Published: August 2003

Objectives: To describe acquisition and implementation of information technology (IT) in U.S. emergency medicine (EM) residency–affiliated emergency departments (EDs), including automatic medication error checking. Methods: This was a survey of all U.S. EM residencies active in September 2000. Respondents specified whether specific IT tools had been “acquired” and “implemented fully.” EDs were categorized according to primary versus affiliated training site, trauma level, and census. Numbers of “yes” responses were compared according to ED type (Kruskal‐Wallis test, p ≤ 0.05 significant). Results: Of 121 residency programs, data were obtained from 93 (77%) for a total of 149 EDs. The percentages of EDs that reported full implementation for each technology are as follows: medication error checking, 7%; medication order entry, 18%; nonmedication orders, 7%; clinical documentation, 21%; old electrocardiograms, 62%; laboratory results, 84%; radiography order entry, 62%; image retrieval, 29%; radiologists' interpretations, 67%; cardiology reports, 62%; pathology reports, 70%; surgical reports/dictations, 60%; triage, 34%; tracking, 46%; electronic reference materials, 56%; registration, 84%; accounts, 72%; patient management software package, 20%; voice recognition, 7%. Trauma centers reported more IT tools than nontrauma centers (p = 0.01), and primary training sites reported fewer IT tools than affiliated EDs (p = 0.027). Conclusions: Incorporation of IT is not uniform in EDs where EM residents train. Acquisition of effective IT tools varies, and implementation lags behind acquisition. Fully implemented IT for medication error checking was reported in 7% of EDs; an additional 12% had acquired IT without implementing it fully.
Neighborhood Characteristics and Emergency Department Utilization
Authors: Li Guohua , Grabowski Jurek G. , McCarthy Melissa L. , Kelen Gabor D.
Published: August 2003

Objectives: Neighborhood environments have been linked to the prevalence and incidence rates of a variety of diseases and injuries. This study assessed the relations between neighborhood demographic and socioeconomic characteristics and emergency department (ED) utilization. Methods: Billing data for the calendar year 2000 for adult patients residing within a one‐mile radius of the study ED were geo‐coded based on home addresses and merged with neighborhood data from the U.S. Census Bureau. Annual ED visit rates per 100 population were computed for each census block within the study area and analyzed in relation to neighborhood characteristics. Results: The study area consisted of 714 census blocks and 42,278 adult residents, with a total of 16,427 visits to the study ED. Annual ED visit rates increased from 17 visits per 100 population for neighborhoods where less than 50% of the population were African American to 51 visits per 100 population for neighborhoods where all residents were African American (p < 0.001). Annual ED visit rates decreased from 53% for neighborhoods where <20% of housing units were owner‐occupied to 27% for neighborhoods with >45% owner‐occupied housing units (p < 0.001). Multivariate linear regression modeling revealed that proportions of African American residents and owner‐occupied housing units were significantly associated with ED utilization, independent of age and gender compositions and the distance between residence and the study ED. Conclusions: Even within a small geographic area, ED utilization may vary greatly by neighborhood characteristics. Neighborhood racial composition and housing tenure are independent predictors of ED visit rates in this urban community.
Emergency Department Presentations of Naltrexone‐accelerated Detoxification
Authors: Armstrong Jason , Little Mark , Murray Lindsay
Published: August 2003

Objectives: To analyze emergency department (ED) presentations after naltrexone‐accelerated detoxification. Methods: This was a retrospective cohort analysis of patient presentations to Sir Charles Gairdner Hospital Emergency Department over a six‐month period (November 2000 to April 2001). Results: During the six‐month study period, 42 patients presented to the ED after naltrexone‐accelerated detoxification. This represented 7% of patients treated at a single clinic over the same period. Presentation occurred within 24 hours in 40% of cases and within 48 hours in 74%. Clinical features on presentation included gastrointestinal (GI) symptoms (vomiting, 60%; abdominal pain, 55%; diarrhea, 45%), central nervous system [CNS] symptoms (excessive drowsiness, 55%; agitation requiring sedation, 50%), and respiratory symptoms (tachypnea, 33%; respiratory difficulties, 19%). Gastrointestinal symptoms were managed adequately with supportive therapy in most cases (intravenous fluids; antiemetics). Agitation sometimes required large doses of intravenous benzodiazepines (up to 730 mg in 44 hours), one‐to‐one nursing, and security staff. Two of 14 patients presenting with predominantly CNS disturbance required intubation (14%). Mean in‐hospital stay for all patients was 18 hours (range 1 to 92 hours). Conclusions: A few patients undergoing outpatient naltrexone‐accelerated detoxification during a six‐month period subsequently required ED management. The clinical features encountered in this group of patients can be subdivided into GI or CNS predominance, with different management strategies. Most presentations can be managed in the ED or an associated observation ward, but departmental resources must be available for one‐to‐one nursing and security personnel. Patients presenting with agitation should be sedated with benzodiazepines; large doses may be required. Close monitoring of respiratory function is mandatory, and advanced airway management may be required.
Prospective Study of Accuracy and Outcome of Emergency Ultrasound for Abdominal Aortic Aneurysm over Two Years
Authors: Tayal Vivek S. , Graf Christian D. , Gibbs Michael A.
Published: August 2003

Determination of the presence of an abdominal aortic aneurysm (AAA) is essential in the management of the symptomatic emergency department (ED) patient. Objectives: To identify whether emergency ultrasound of the abdominal aorta (EUS‐AA) by emergency physicians could accurately determine the presence of AAA and guide ED disposition. Methods: This was a prospective, observational study at an urban ED with more than 100,000 annual patient visits with consecutive patients enrolled over a two‐year period. All patients suspected to have AAA underwent standard ED evaluation consisting of EUS‐AA, followed by a confirmatory imaging study or laparotomy. AAA was defined as any measured diameter greater than 3 cm. Demographic data, results of confirmatory testing, and patient outcome were collected by retrospective review. Results: A total of 125 patients had EUS‐AA performed over a two‐year period. The patient population had the following characteristics: average age 66 years, male 54%, hypertension 56%, coronary artery disease 39%, diabetes 22%, and peripheral vascular disease 14%. Confirmatory tests included radiology ultrasound, 28/125 (22%); abdominal computed tomography, 95/125 (76%); abdominal magnetic resonance imaging, 1/125 (1%); and laparotomy, 1/125 (1%). AAA was diagnosed in 29/125 (23%); of those, 27/29 patients had AAA on confirmatory testing. EUS‐AA had 100% sensitivity (95% CI = 89.5 to 100), 98% specificity (95% CI = 92.8 to 99.8), 93% positive predictive value (27/29), and 100% negative predictive value (96/96). Admission rate for the study group overall was 70%. Immediate operative management was considered in 17 of 27 (63%) patients with AAA; ten patients were taken to the operating room. Conclusions: EUS‐AA in a symptomatic population for AAA is sensitive and specific. These data suggest that the presence of AAA on EUS‐AA should guide urgent consultation. Emergency physicians were able to exclude AAA regardless of disposition from the ED.
Comparative Analysis of Adult versus Adolescent Sexual Assault: Epidemiology and Patterns of Anogenital Injury
Authors: Jones Jeffrey S. , Rossman Linda , Wynn Barbara N. , Dunnuck Chris , Schwartz Natalie
Published: August 2003

Objectives: To compare the characteristics of sexual assault in pubertal girls (<18 years old) and adults in a community‐based population of women presenting to an urban sexual assault clinic. Methods: This case‐series analysis evaluated consecutive female patients presenting to a sexual assault clinic during a three‐year study period. The clinic is associated with a university‐affiliated emergency medicine residency program and is staffed by forensic nurses trained to perform medicolegal examinations using colposcopy with nuclear staining. Patient demographics, assault characteristics, and injury patterns were recorded using a standardized classification system. Data from the two patient groups (adolescents vs. women ≥18 years of age) were analyzed using chi‐square test and t‐test. Results: A total of 766 cases were identified: 43% of the victims were 13 to 17 years old (mean 15.0 years old), and 57% were older than 17 years old (mean 30.8 years old). Adolescents were more likely to be assaulted by an acquaintance or relative (84% vs. 50%, p < 0.001) and to delay medical evaluation (17 hours vs. 12 hours, p < 0.001) than were older women. Adolescent sexual assault was less likely to involve weapons or physical coercion (29% versus 57%, p < 0.001) and was associated with fewer nongenital injuries (33% vs. 55%, p < 0.001). Adolescents had a greater frequency of anogenital injuries (83% vs. 64%, p < 0.001), however, compared with older women. Common sites of injury in adolescents were posterior, including the fossa navicularis, hymen, fourchette, and labia minora. The injuries showed consistent topologic features, varying with the site and nature of tissue. Adult victims of sexual assault had a less consistent pattern of anogenital injuries with fewer hymenal injuries, greater injury to the perianal area, and widespread erythema. Conclusions: Of women presenting to an urban sexual assault clinic, 43% were adolescents. The epidemiology of sexual trauma and the pattern of anogenital trauma in this age group are unique and may pose special challenges to emergency health care providers.
Faculty Development: How to Evaluate the Effectiveness of a Faculty Development Program in Emergency Medicine
Authors: Ramalanjaona Georges
Published: August 2003

Evaluation of the effectiveness of any faculty development program (FDP) is crucial to provide assessment of existing programs and to yield valid recommendations for designing future programs that better address the needs of individual faculty members and the sponsoring institutions. The author chose the validated Kirkpatrick's model with four levels of program outcomes (satisfaction data, learning data, performing data, and career change) to evaluate the effectiveness of an FDP in emergency medicine. Assessment of the effectiveness of this FDP can be performed by sponsoring organizations or by independent evaluators experienced in the field for better objectivity.
Factors Affecting the Risk of Blood Bank Specimen Hemolysis
Authors: Tanabe Paula , Kyriacou Demetrious N. , Garland Franklyn
Published: August 2003

Objectives: To evaluate simultaneously several possible risk factors for blood bank specimen hemolysis. Methods: This was a prospective cohort study of emergency department and labor and delivery patients to estimate the effect of various factors on the risk of blood bank specimen hemolysis. Study variables included patient demographics, type and gauge of needle or catheter, anatomic location of venipuncture, and patient care area. Hemolysis was determined by blood bank laboratory technicians. Cox proportional hazards multivariate regression modeling was performed to estimate the adjusted relative risks for hemolysis. Results: Of the 605 subjects with complete data, 194 (32.1%) subjects had blood specimens drawn directly with a steel needle, and 411 (69.1%) had specimens drawn through a Vialon (BD Medical Systems, Inc., Sandy, UT) intravenous (IV) angiocatheter. The overall risk of hemolysis for all was 7%, 10% for Vialon IV angiocatheters and 1.5% for steel needles. In the multivariate analysis, the factors most closely associated with hemolysis were the use of Vialon IV catheters and sampling from an anatomic site other than the antecubital area. Conclusions: Blood bank specimens drawn from Vialon IV catheters (particularly smaller gauge catheters) and from veins outside the antecubital area are at significantly increased risk to hemolyze.
U.S. Allopathic Emergency Medicine Residency Programs: A Descriptive Review
Authors: Lathrop George R. , Wilkinson Keith C.
Published: August 2003

Objective: To use collected data from all 124 allopathic emergency medicine residency (EMR) programs in existence in 2001 to describe allopathic EMR training programs in the United States. Methods: The authors performed a cross‐sectional review of all 124 EMRs using self‐reported, standardized data from regularly updated sources: the SAEM Residency Catalog and the AMA's FREIDA (Fellowship and Residency Electronic Interactive Database Access). The authors report median values, ranges, and interquartile ranges (IQRs) on a variety of variables. Results: Median values for EMR programs included a class size of 10 per year; a total faculty‐to‐resident ratio of 0.78 (1:1.29); an annual primary emergency department (ED) census of 66,000 (IQR = 53,000 to 80,000), with an annual combined primary and secondary ED census of 95,500 (IQR = 75,000 to 126,000); a combined pediatric census of 20,000 (IQR = 15,000 to 32,500) at the primary and secondary sites; an annual combined ED visit per resident of 3,181 (IQR = 2,542 to 3,949), including 733 pediatric visits per resident, at the primary and secondary sites; an admission rate of 20% (IQR = 17% to 23%); and an intensive care unit admission rate of 13% (IQR = 5% to 20%). Despite a wide variability in ranges and IQR in most characteristics pertaining to training setting, the overall reported completion rate of training for residents was high (99%). Conclusions: This summary description provides median values and ranges for important components of the emergency medicine training environment and provides a basis of comparison for medical students and graduate medical educators.
Development and Implementation of a Relative Value Scale for Teaching in Emergency Medicine: The Teaching Value Unit
Authors: Khan Naghma S. , Simon Harold K.
Published: August 2003

Relative value units exist for measuring clinical productivity. Limited objective measures exist, however, for nonclinical activities, specifically teaching.Objective:To develop an objective measure of teaching productivity linked to a performance‐based incentive plan.Methods:Teaching goals and objectives were identified before the 1998–1999 academic year. Teaching value units (TVUs), objective measures for quantifying teaching activities, were developed and assigned based on an estimation of time needed to complete each activity and weighted for importance to the teaching mission. Each physician was allocated teaching time based on past performance and future goals. Targeted TVUs necessary to meet expectations were proportionate to allocated teaching time. Teaching productivity was defined as a percentage of targeted TVUs achieved. Incentive dollars for teaching were distributed based on percentage of targeted TVUs achieved, weighted individually for teaching load.Results:Teaching productivity was evaluated over a three‐year period. In year 1, mean TVUs allocated/physician were 181 units (range 25 to 449). Four of 18 physicians (22%) met expectations. The mean individual TVUs achieved were 54% of expected (range 0% to 114%). By year 3, mean TVUs allocated/physician were 179 (range 45 to 629). Twelve of 22 physicians (55%) met expectations. The mean individual TVUs achieved were 82% of expected (range 11% to 146%). Between year 1 and year 3, group productivity increased from 73% to 88%, and mean individual productivity increased from 54% to 82% (p = 0.01).Conclusions:The development of a TVU‐based system enabled objective quantification and monitoring of a broad range of teaching activities. The TVU‐based system linked to an incentive plan helped to increase individual and group teaching productivity.
ECM-induced gap junctional communication enhances mammary epithelial cell differentiation
Authors: El-Sabban Marwan E. , Sfeir Agnel J. , Daher Myriam H. , Kalaany Nada Y. , Bassam Rola A. , Talhouk Rabih S.
Published: August 2003

The relationship between gap junctional intercellular communication (GJIC)and mammary cell (CID-9) differentiation in vitro was explored. CID-9 cells differentiate and express β-casein in an extracellular matrix (ECM)- and hormone-dependent manner. In response to interaction with the ECM, cells in culture modulated the expression of their gap junction proteins at the transcriptional and post-translational levels. In the presence of EHS-matrix,connexins (Cx)26, 32 and 43 localized predominantly to the plasma membrane,and enhanced GJIC [as measured by Lucifer Yellow (LY) dye transfer assays] was noted. Inhibition of GJIC of cells on EHS-matrix with 18α glycyrrhetinic acid (GA) resulted in reversible downregulation of β-casein expression. In the presence of cAMP, cells cultured on plastic expressed β-casein,upregulated Cx43 and Cx26 protein levels and enhanced GJIC. This was reversed in the presence of 18α GA. cAMP-treated cells plated either on a non-adhesive PolyHEMA substratum or on plastic supplemented with function-blocking anti-β1 integrin antibodies, maintainedβ-casein expression. These studies suggest that cell-ECM interaction alone may induce differentiation through changes in cAMP levels and formation of functional gap junctions. That these events are downstream of ECM signalling was underscored by the fact that enhanced GJIC induced partial differentiation in mammary epithelial cells in the absence of an exogenously provided basement membrane and in a β1-integrin- and adhesion-independent manner.
DrosophilaRheb GTPase is required for cell cycle progression and cell growth
Authors: Patel Parthive H. , Thapar Nitika , Guo Lea , Martinez Monica , Maris John , Gau Chia-Ling , Lengyel Judith A. , Tamanoi Fuyuhiko
Published: August 2003

Precise body and organ sizes in the adult animal are ensured by a range of signaling pathways. In a screen to identify genes affecting hindgut morphogenesis in Drosophila, we identified a P-element insertion in dRheb, a novel, highly conserved member of the Ras superfamily of G-proteins. Overexpression of dRheb in the developing fly (using the GAL4:UAS system) causes dramatic overgrowth of multiple tissues: in the wing,this is due to an increase in cell size; in cultured cells, dRheboverexpression results in accumulation of cells in S phase and an increase in cell size. Using a loss-of-function mutation we show that dRheb is required in the whole organism for viability (growth) and for the growth of individual cells. Inhibition of dRheb activity in cultured cells results in their arrest in G1 and a reduction in size. These data demonstrate that dRheb is required for both cell growth (increase in mass) and cell cycle progression; one explanation for this dual role would be that dRheb promotes cell cycle progression by affecting cell growth. Consistent with this interpretation, we find that flies with reduced dRheb activity are hypersensitive to rapamycin, an inhibitor of the growth regulator TOR. In cultured cells, the effect of overexpressing dRheb was blocked by the addition of rapamycin. These results imply that dRheb is involved in TOR signaling.
Myosin VI: two distinct roles in endocytosis
Authors: Hasson Tama
Published: August 2003

Actin is found at the cortex of the cell where endocytosis occurs, but does it play a role in this essential process? Recent studies on the unconventional myosin, myosin VI, an actin-based molecular motor, provide compelling evidence that this myosin and therefore actin is involved in two distinct steps of endocytosis in higher eukaryotes: the formation of clathrin-coated vesicles and the movement of nascent uncoated vesicles from the actin-rich cell periphery to the early endosome. Three distinct adapter proteins - GIPC, Dab2 and SAP97 - that associate with the cargo-binding tail domain of myosin VI have been identified. These proteins may recruit myosin VI to its sites of action.
Immune semaphorins: a new area of semaphorin research
Authors: Kumanogoh Atsushi , Kikutani Hitoshi
Published: August 2003

The semaphorin family comprises soluble and membrane-bound proteins originally identified as axonal guidance cues that function during neuronal development. Emerging evidence suggests that a subset of semaphorins, called'immune semaphorins', function in the immune system. The class IV semaphorins Sema4D/CD100 and Sema4A use CD72 and Tim-2, respectively, as receptors during immune responses; these receptors comprise a set distinct from those used by semaphorins in the nervous system. Sema4D/CD100, which is expressed constitutively by T cells, is involved in the activation of B cells and dendritic cells, whereas Sema4A is preferentially expressed on B cells and dendritic cells, and is involved in the activation of T cells. Additionally,increasing evidence suggests that some other semaphorins, including viral-encoded semaphorins, might also play important roles in the immune system.
Leading the way: directional sensing through phosphatidylinositol 3-kinase and other signaling pathways
Authors: Merlot Sylvain , Firtel Richard A.
Published: August 2003

Chemoattractant-responsive cells are able to translate a shallow extracellular chemical gradient into a steep intracellular gradient resulting in the localization of F-actin assembly at the front and an actomyosin network at the rear that moves the cell forward. Recent evidence suggests that one of the first asymmetric cellular responses is the localized accumulation of PtdIns(3,4,5)P3, the product of class I phosphoinositide 3-kinase (PI3K) at the site of the new leading edge. The strong accumulation of PtdIns(3,4,5)P3 results from the localized activation of PI3K and also from feedback loops that amplify PtdIns(3,4,5)P3 synthesis at the front and control its degradation at the side and back of cells. These different pathways are temporally and spatially regulated and integrate with other signaling pathways during directional sensing and chemotaxis.
Prediction of Milk/Plasma Concentration Ratio of Drugs
Authors: Larsen Line Alleslev , Ito Shinya , Koren Gideon
Published: August 2003

OBJECTIVE:

The milk to plasma (m/p) concentration ratio of drugs is used to estimate the amount of drug offered to the suckling infant. Published literature was reviewed to identify drugs for which sufficient data exist for calculation of m/p ratio and to examine whether the existing empiric data agree with the published method of Atkinson for mathematical prediction of m/p ratios based on physiochemical characteristics.

METHODS:

Using a comprehensive reference text, we identified studies reporting sufficient data to calculate m/p ratio based on the AUC for milk and plasma. Subsequently, we calculated the m/p ratio with Atkinson's formula based on pKa, lipophilicity, and protein binding. We then correlated the empiric versus predicted (calculated) m/p ratios.

RESULTS:

Of 192 drugs of which at least some data on milk accumulation have been published, there were sufficient data to quantify m/p ratios for only 69 medications (78 studies). There was no significant correlation between the empiric m/p ratios and the predicted values using the Atkinson's model.

CONCLUSIONS:

Reliable data on m/p concentration ratios exist for few medications. Presently, there is no appropriate model to predict milk concentrations of drugs in humans.
Long-Acting Inhaled β2-Agonists for Stable COPD
Authors: Dougherty John A , Didur Bethany L , Aboussouan Loutfi S
Published: August 2003

OBJECTIVE:

To describe the pathogenesis of chronic obstructive pulmonary disease (COPD) and mechanisms of benefit, formulations available, drug costs, pharmacokinetic profiles, and pertinent clinical studies for long-acting β2-agonists.

DATA SOURCES:

A MEDLINE search was conducted from July 1966 through October 2002.

STUDY SELECTION AND DATA EXTRACTION:

Pertinent articles related to COPD and long-acting β2-agonists.

DATA SYNTHESIS:

The incidence and subsequent morbidity and mortality of COPD have increased during the last 4 decades, prompting worldwide initiatives to formulate guidelines to decrease the burden of this disease. COPD is a progressive, irreversible disease state characterized by chronic cough, dyspnea, sputum production, and wheezing, in which no medication has been shown to decrease mortality, excluding oxygen supplementation. Bronchodilators have been a mainstay of COPD treatment through their ability to work by both smooth- and non–smooth-muscle mechanisms. Long-acting β2-agonists (i.e., formoterol, salmeterol) dosed twice daily provide more convenient dosing than 4-times-daily regimens of traditional short-acting bronchodilators. Both formoterol and salmeterol have acceptable adverse event profiles when used at recommended doses. There have been no direct clinical outcome studies comparing formoterol and salmeterol, but both have shown some benefits over ipratropium and theophylline in improving the symptoms, spirometric indices, exacerbations, and quality of life of patients with COPD.

CONCLUSIONS:

Based on current evidence, long-acting β2-agonists are acceptable first-line agents for patients with COPD.
Successful Meropenem Desensitization in a Patient with Cystic Fibrosis
Authors: Wilson Diana L , Owens Robert C , Zuckerman Jonathan B
Published: August 2003

Objective

To report a case of successful meropenem desensitization in a patient with cystic fibrosis (CF) with documented hypersensitivity to multiple antibiotics including carbapenems.

Case Summary

A 20-year-old white man with CF was admitted to the hospital for treatment of an acute pulmonary exacerbation caused by multidrug-resistant Burkholderia cepacia complex and methicillin-resistant Staphylococcus aureus (MRSA). Past treatments of his CF exacerbations were complicated by urticarial eruptions following administration of β-lactams, including meropenem, and ototoxicity from aminoglycosides. Skin testing revealed hypersensitivity reactions to β-lactam antibiotics including penicillin, piperacillin/tazobactam, ceftazidime, and imipenem. A literature review (MEDLINE, January 3, 2002) and communication with the manufacturer of meropenem revealed no specific information on desensitizing patients to this agent. Because of meropenem's activity against B. cepacia complex alone and in combination with other antimicrobials, a desensitization protocol was adapted and applied to meropenem in an effort to provide the most beneficial treatment available. A 12-dose escalation protocol was successfully employed without incident.

Discussion

Antimicrobial therapy is limited in CF patients by susceptibility profiles of common infecting organisms (e.g., Pseudomonas spp., B. cepacia complex, MRSA). Unfortunately, host responses may further reduce the utility of many effective antibiotic classes due to hypersensitivity and/or adverse reactions. Desensitization is a useful alternative that allows the administration of beneficial medications to patients with documented allergy histories.

Conclusions

Meropenem is an important treatment option in the CF population, particularly due to its activity against B. cepacia complex. Successful desensitization using a dose-escalation protocol in patients with a documented carbapenem allergy will allow the most beneficial therapy to continue.
Increased Topical Tacrolimus Absorption in Generalized Leukemic Erythroderma
Authors: Teshima Daisuke , Ikesue Hiroaki , Itoh Yoshinori , Urabe Kazunori , Furue Masutaka , Oishi Ryozo
Published: August 2003

Objective

To report a case of elevated blood tacrolimus concentration after application of topical tacrolimus ointment in an erythrodermic patient.

Case Summary

A 44-year-old man developed generalized erythroderma and itching due to infection with human T-cell lymphotropic virus. Despite application of strong glucocorticosteroid ointments, the symptoms and area of erythroderma were not alleviated. Daily topical application of tacrolimus 0.1% ointment was added and therapeutic drug monitoring was started. The dose and applied area of tacrolimus were gradually increased from 2.5 to 12.5 g/d and from 10% to 90% of body surface area, respectively. Because the trough concentration of tacrolimus in whole blood increased from 7.5 ng/mL on treatment day 9 to 15.4 ng/mL on day 13, the dose was reduced to 10 g/d. However, the concentration further elevated to 16.5 ng/mL. Therefore, the applied area was reduced to 20% of body surface area, and the tacrolimus concentration decreased gradually thereafter. Although the transient increase of blood tacrolimus concentration was observed on day 23, treatment with 20% applied area and 5 g/d were maintained.

Discussion

Topically applied tacrolimus was substantially absorbed with the expansion of its applied area and dose. Increased tacrolimus concentrations may have a tendency to depend on the increase of the percent of body surface area per dose. Our findings showing the elevation of blood tacrolimus concentration after application of the ointment to a large area of the body suggest that the applied area should be as narrow as possible in a barrier-disrupted condition such as erythroderma. However, the safety of tacrolimus ointment has not been established in patients with generalized erythroderma.

Conclusions

Tacrolimus concentrations in whole blood should be carefully monitored to prevent nephrotoxicity. Based on the results of that monitoring, the application area and dose of tacrolimus ointment should be closely adjusted, especially in generalized erythrodermic cases.
Modular stability tools for distributed computation and control
Authors: Slotine Jean‐Jacques E.
Published: August 2003

Much recent functional modelling of the central nervous system, beyond traditional ‘neural net’ approaches, focuses on its distributed computational architecture. This paper discusses extensions of our recent work aimed at understanding this architecture from an overall non‐linear stability and convergence point of view, and at constructing artificial devices exploiting similar modularity. Applications to synchronization and to schooling are also described. The development makes extensive use of non‐linear contraction theory. Copyright © 2003 John Wiley & Sons, Ltd.
A robust on‐line learning algorithm for intelligent control systems
Authors: Efe Mehmet Önder , Kaynak Okyay , Wilamowski Bogdan M. , Yu Xinghuo
Published: August 2003

This paper describes a novel error extraction approach for exploiting the strength of Levenberg–Marquardt (LM) optimization technique in intelligent control systems. Since the target value of the control signal is unknown, tuning of the controller parameters becomes a tedious task if the knowledge about the system and the environment is limited. The suggested methodology utilizes the sliding model control (SMC) technique. The error extraction scheme postulates the form of error on the applied control signal using the discrepancy from the prescribed reaching dynamics. The devised approach has been tested on the non‐linear Duffing oscillator, which has been forced to follow a periodic orbit radically different from the natural one. The results obtained through a series of simulations have confirmed the high precision and robustness advantages without knowing the analytical details of the system under investigation. The issues of observation noise and the stability in the parametric space have approximately been addressed from the point of SMC perspective. Copyright © 2003 John Wiley & Sons, Ltd.
Adaptive critic design using non‐linear network structures
Authors: Kuljaca Ognjen , Lewis Frank L.
Published: August 2003

A neural net (NN)/fuzzy logic (FL) adaptive critic controller is described. This structure takes advantage of the decision‐making properties of a FL system to critique and tune a NN action‐generating network. The stability of the proposed structure is proven. NN and fuzzy weight tuning algorithms are given that do not require complicated initialization procedures or any off‐line learning phase. Tracking and bounded NN weights and control signals are guaranteed. The adaptive fuzzy critic controller given here is a model‐free controller' in the sense that it works for any system in a prescribed class without the need for extensive modeling and preliminary analysis to find a regression matrix'. There is no linearity in the parameter (LIP) requirement. Copyright © 2003 John Wiley & Sons, Ltd.
Novel mutation in the gene encoding c‐Abl‐binding protein SH3BP2 causes cherubism
Authors: Lo Bryan , Faiyaz‐Ul‐Haque M. , Kennedy S. , Aviv R. , Tsui L.‐C. , Teebi Ahmad S.
Published: July 2003

Cherubism is a rare autosomal dominant inherited condition caused by mutations in the c‐Abl‐binding protein SH3BP2. It is characterized by multiple cystic giant cell lesions of the jaw appearing in early childhood with stabilization and remission after puberty. In the present study, we used direct sequence analysis of the SH3BP2 gene of several individuals from a family with cherubism to search for additional SH3BP2 mutations resulting in cherubism. In affected relatives, we found a previously unreported G to A transition in exon 9 leading to a Gly to Arg substitution at amino acid position 420. G420R has been reported previously with a G to C transversion. To date there have been no disease causing mutations outside exon 9. Therefore, the amino acid sequence from positions 415 to 420 may represent a specific protein domain which, when disrupted, leads to the cherubism phenotype. © 2003 Wiley‐Liss, Inc.
Clinical features of boys with fragile X premutations and intermediate alleles
Authors: Aziz Monica , Stathopulu Eleni , Callias Maria , Taylor Catherine , Turk Jeremy , Oostra Ben , Willemsen Rob , Patton Mike
Published: July 2003

Fragile X syndrome has a characteristic behavioural and physical phenotype. Clinical experience and case reports suggest that boys with premutations and intermediate alleles may have similar, but possibly milder, clinical features than those with the full mutation. We conducted detailed physical, psychiatric, psychological and speech and language evaluations on a clinical series of 10 boys, with either premutation or intermediate CGG triplet expansions. Wherever possible we measured the levels of FMR1 protein in participants' hair roots. Many participants demonstrated striking resemblance in their clinical picture, behavioural and physical, to individuals with the fragile X syndrome full mutation. However, protein expression was normal in all participants where it was assessed, despite large variation in CGG triplet repeats. We propose that the findings are unlikely to be attributable to ascertainment bias alone. Replication on larger independent samples is required to confirm our impression that fragile X premutations and intermediate alleles may be associated with important developmental disabilities and physical features. © 2003 Wiley‐Liss, Inc.
Association of the C766T polymorphism of the low‐density lipoprotein receptor‐related protein gene with Alzheimer's disease
Authors: Kölsch Heike , Ptok Ursula , Mohamed Iman , Schmitz Sandra , Rao Marie Luise , Maier Wolfgang , Heun Reinhard
Published: July 2003

The low‐density lipoprotein receptor‐related protein (LRP) is one of the most important cholesterol receptors in the brain. Gene variation of its ligand, apolipoprotein E, is a major genetic risk‐factor for Alzheimer's disease (AD). The C‐allele of the silent C766T polymorphism in exon 3 of the LRP gene might be associated with AD, however, results are conflicting and thus discussed controversially. Consequently, we compared the prevalence of this polymorphism in a homogenous cohort of patients with AD and control subjects. We found that carriers of a C‐allele were at lower risk of AD; in agreement with this observation, AD patients who were carriers of a C‐allele presented with a later age at onset of the disease than carriers of the TT genotype. These data suggest that LRP polymorphism influences the risk as well as the age at onset of AD. Our results contrast with other studies which described the C‐allele to be a risk‐factor for AD, but are in line with a recent publication on the effect of LRP polymorphism on longevity and on the risk for coronary artery disease. Further research on LRP polymorphisms is needed to evaluate their effects on the risk of AD, on coronary artery disease and on longevity. © 2003 Wiley‐Liss, Inc.