bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the Storz Video Macintosh Laryngoscope for Use in Difficult Airways: A Human Simulator Study
Authors: Bair Aaron E. , Olmsted Kalani , Brown Calvin A. , Barker Tobias , Pallin Daniel , Walls Ron M.
Published: October 2010

Objectives:  Video laryngoscopy has been shown to improve glottic exposure when compared to direct laryngoscopy in operating room studies. However, its utility in the hands of emergency physicians (EPs) remains undefined. A simulated difficult airway was used to determine if intubation by EPs using a video Macintosh system resulted in an improved glottic view, was easier, was faster, or was more successful than conventional direct laryngoscopy.

Methods:  Emergency medicine (EM) residents and attending physicians at two academic institutions performed endotracheal intubation in one normal and two identical difficult airway scenarios. With the difficult scenarios, the participants used video laryngoscopy during the second case. Intubations were performed on a medium‐fidelity human simulator. The difficult scenario was created by limiting cervical spine mobility and inducing trismus. The primary outcome was the proportion of direct versus video intubations with a grade I or II Cormack‐Lehane glottic view. Ease of intubation (self‐reported via 10‐cm visual analog scale [VAS]), time to intubation, and success rate were also recorded. Descriptive statistics as well as medians with interquartile ranges (IQRs) are reported where appropriate. The Wilcoxon matched pairs signed‐rank test was used for comparison testing of nonparametric data.

Results:  Participants (n = 39) were residents (59%) and faculty. All had human intubation experience; 51% reported more than 100 prior intubations. On difficult laryngoscopy, a Cormack‐Lehane grade I or II view was obtained in 20 (51%) direct laryngoscopies versus 38 (97%) of the video‐assisted laryngoscopies (p < 0.01). The median VAS score for difficult airways was 50 mm (IQR = 28–73 mm) for direct versus 18 mm (IQR = 9–50 mm) for video (p < 0.01). The median time to intubation in difficult airways was 25 seconds (IQR = 16–44 seconds) for direct versus 20 seconds (IQR = 12–35 seconds) for video laryngoscopy (p < 0.01). All intubations were successful without need for an invasive airway.

Conclusions:  In this simulation, video laryngoscopy was associated with improved glottic exposure, was perceived as easier, and was slightly faster than conventional direct laryngoscopy in a simulated difficult airway. Absence of secretions and blood limits the generalizability of our findings; human studies are needed.

ACADEMIC EMERGENCY MEDICINE 2010; 17:1134–1137 © 2010 by the Society for Academic Emergency Medicine
Safety of Intravenous Thrombolytic Use in Four Emergency Departments Without Acute Stroke Teams
Authors: Scott Phillip A. , Frederiksen Shirley M. , Kalbfleisch John D. , Xu Zhenzhen , Meurer William J. , Caveney Angela F. , Sandretto Annette , Holden Ann B. , Haan Mary N. , Hoeffner Ellen G. , Ansari Sameer A. , Lambert David P. , Jaggi Michael , Barsan William G. , Silbergleit Robert
Published: October 2010

Objectives:  The objective was to evaluate safety of intravenous (IV) tissue plasminogen activator (tPA) delivered without dedicated thrombolytic stroke teams.

Methods:  This was a retrospective, observational study of patients treated between 1996 and 2005 at four southeastern Michigan hospital emergency departments (EDs) with a prospectively defined comparison to the National Institute of Neurological Disorders and Stroke (NINDS) tPA stroke study cohort. Main outcome measures were mortality, intracerebral hemorrhage (ICH), systemic hemorrhage, neurologic recovery, and guideline violations.

Results:  A total of 273 consecutive stroke patients were treated by 95 emergency physicians (EPs) using guidelines and local neurology resources. One‐year mortality was 27.8%. Unadjusted Cox model relative risk (RR) of mortality compared to the NINDS tPA treatment and placebo groups was 1.20 (95% confidence interval [CI] = 0.87 to 1.64) and 1.04 (95% CI = 0.76 to 1.41), respectively. The rate of significant ICH by computed tomography (CT) criteria was 6.6% (odds ratio [OR] = 1.03, 95% CI = 0.56 to 1.90 compared to the NINDS tPA treatment group). The proportions of symptomatic ICH by two other prespecified sets of clinical criteria were 4.8 and 7.0%. The rate of any ICH within 36 hours of treatment was 9.9% (RR = 0.94, 95% CI = 0.58 to 1.51 compared to the NINDS tPA group). The occurrence of major systemic hemorrhage (requiring transfusion) was 1.1%. Functional recovery by the modified Rankin Scale score (mRS = 0 to 2) at discharge occurred in 38% of patients with a premorbid disability mRS < 2. Guideline deviations occurred in the ED in 26% of patients and in 25% of patients following admission.

Conclusions:  In these EDs there was no evidence of increased risk with respect to mortality, ICH, systemic hemorrhage, or worsened functional outcome when tPA was administered without dedicated thrombolytic stroke teams. Additional effort is needed to improve guideline compliance.

ACADEMIC EMERGENCY MEDICINE 2010; 17:1062–1071 © 2010 by the Society for Academic Emergency Medicine
Characteristics and Outcomes of Polymicrobial Bloodstream Infections in the Emergency Department: A Matched Case–control Study
Authors: Lin Jiun‐Nong , Lai Chung‐Hsu , Chen Yen‐Hsu , Chang Lin‐Li , Lu Po‐Liang , Tsai Shang‐Shyue , Lin Hsing‐Lin , Lin Hsi‐Hsun
Published: October 2010

Objectives:  Polymicrobial bloodstream infection (BSI) is a critical condition and has been increasingly reported; however, the authors were unable to find an emergency department (ED) patient‐based study in the literature.

Methods:  A retrospective matched case–control study with a ratio of 1:3 among patients with polymicrobial BSIs in an ED was conducted. The case group was patients aged > 16 years with polymicrobial BSIs. Patients matched for age and sex with monomicrobial BSIs were sampled as the control group. Demographic information, underlying conditions, microbiologic data, and outcomes were collected for further analysis.

Results:  From January 2005 to December 2007, a total of 112 episodes of polymicrobial BSIs among 109 patients were included. Two pathogens were isolated among 87 (77.7%) episodes and three were found among 25 (22.3%) episodes. A history of hospitalization within 90 days was an independent risk factor for polymicrobial BSIs (p = 0.003). Intraabdominal infection (p < 0.001) and respiratory tract infection (p = 0.017) were more likely to be associated with polymicrobial BSIs. Gram‐negative and Gram‐positive bacteria were documented in 95.5 and 46.4% episodes of polymicrobial BSIs, respectively. Inappropriate antimicrobial treatment was observed in 53.6% of polymicrobial BSIs, but only accounted for 23.8% of monomicrobial BSIs (p < 0.001). The overall 30‐day mortality rate of the polymicrobial group was significantly higher than those with monomicrobial BSIs (30.3 and 11.6%, respectively; p < 0.001).

Conclusions:  Patients with polymicrobial BSIs had a high mortality rate. Acknowledgment of the clinical and microbiologic characteristics and recognition of patients at risk for polymicrobial BSIs are critical in EDs.

ACADEMIC EMERGENCY MEDICINE 2010; 17:1072–1079 © 2010 by the Society for Academic Emergency Medicine
Identifying Infected Emergency Department Patients Admitted to the Hospital Ward at Risk of Clinical Deterioration and Intensive Care Unit Transfer
Authors: Kennedy Maura , Joyce Nina , Howell Michael D. , Lawrence Mottley J. , Shapiro Nathan I.
Published: October 2010

Objectives:  An important challenge faced by emergency physicians (EPs) is determining which patients should be admitted to an intensive care unit (ICU) and which can be safely admitted to a regular ward. Understanding risk factors leading to undertriage would be useful, but these factors are not well characterized.

Methods:  The authors performed a secondary analysis of two prospective, observational studies of patients admitted to the hospital with clinically suspected infection from an urban university emergency department (ED). Inclusion criteria were as follows: adult ED patient (age 18 years or older), ward admission, and suspected infection. The primary outcome was transfer to an ICU within 48 hours of admission. Using multiple logistic regression, independent predictors of early ICU transfer were identified, and the area under the curve for the model was calculated.

Results:  Of 5,365 subjects, 93 (1.7%) were transferred to an ICU within 48 hours. Independent predictors of ICU transfer included respiratory compromise (odds ratio [OR] = 2.5, 95% confidence interval [CI] = 1.4 to 4.3), congestive heart failure (CHF; OR = 2.2, 95% CI = 1.4 to 3.6), peripheral vascular disease (OR = 2.0, 95% CI = 1.1 to 3.7), systolic blood pressure (sBP) < 100 mm Hg (OR = 1.9, 95% CI = 1.2 to 2.9), heart rate > 90 beats/min (OR = 1.8, 95% CI = 1.1 to 2.8), and creatinine > 2.0 (OR = 1.8, 95% CI = 1.1 to 2.8). Cellulitis was associated with a lower likelihood of ICU transfer (OR = 0.33, 95% CI = 0.15 to 0.72). The area under the curve for the model was 0.73, showing moderate discriminatory ability.

Conclusions:  In this preliminary study, independent predictors of ICU transfer within 48 hours of admission were identified. While somewhat intuitive, physicians should consider these factors when determining patient disposition.

ACADEMIC EMERGENCY MEDICINE 2010; 17:1080–1085 © 2010 by the Society for Academic Emergency Medicine
Parametric Versus Nonparametric Statistical Tests: The Length of Stay Example
Authors: Qualls Munirih , Pallin Daniel J. , Schuur Jeremiah D.
Published: October 2010

Objectives:  This study examined selected effects of the proper use of nonparametric inferential statistical methods for analysis of nonnormally distributed data, as exemplified by emergency department length of stay (ED LOS). The hypothesis was that parametric methods have been used inappropriately for evaluation of ED LOS in most recent studies in leading emergency medicine (EM) journals. To illustrate why such a methodologic flaw should be avoided, a demonstration, using data from the National Hospital Ambulatory Medical Care Survey (NHAMCS), is presented. The demonstration shows how inappropriate analysis of ED LOS increases the probability of type II errors.

Methods:  Five major EM journals were reviewed, January 1, 2004, through December 31, 2007, and all studies with ED LOS as one of the reported outcomes were reviewed. The authors determined whether ED LOS was analyzed correctly by ascertaining whether nonparametric tests were used when indicated. An illustrative analysis of ED LOS was constructed using 2006 NHAMCS data, to demonstrate how inferential testing for statistical significance can deliver differing conclusions, depending on whether nonparametric methods are used when indicated.

Results:  Forty‐nine articles were identified that studied ED LOS; 80% did not perform a test of normality on the ED LOS data. Data were not normally distributed in all 10 of the studies that did perform such tests. Overall, 43% failed to use appropriate nonparametric methods. Analysis of NHAMCS data confirmed that failure to use nonparametric bivariate tests results in type II statistical error and in multivariate models with less explanatory power (a smaller R2 value).

Conclusions:  ED LOS, a key ED operational metric, is frequently analyzed incorrectly in the EM literature. Applying parametric statistical tests to such nonnormally distributed data reduces power and increases the probability of a type II error, which is the failure to find true associations. Appropriate use of nonparametric statistics should be a core component of statistical literacy because such use increases the validity of ED research and quality improvement projects.

ACADEMIC EMERGENCY MEDICINE 2010; 17:1113–1121 © 2010 by the Society for Academic Emergency Medicine
Clinicopathological Conference: A 71‐year‐old Female With Neurological Deficits, Chest Pain, and Electrocardiographic Changes
Authors: Narang Aneesh T. , Alian Andrus
Published: October 2010

The authors present a case of a 71‐year‐old female who presented to the emergency department with slurred speech, left sided facial droop, and right arm and leg weakness. During her ED stay, she developed left sided chest pain and right arm numbness in the setting of EKG changes. The patient's clinical course is outlined and a discussion of the potential etiologies as well as the clinical management is provided.

ACADEMIC EMERGENCY MEDICINE 2010; 17:e102–e109 © 2010 by the Society for Academic Emergency Medicine
Direct Observation Evaluations by Emergency Medicine Faculty Do Not Provide Data That Enhance Resident Assessment When Compared to Summative Quarterly Evaluations
Authors: Ryan James G. , Barlas David , Sharma Manish
Published: October 2010

Objectives:  The purpose of this study was to compare quarterly global evaluations with direct observation evaluations to determine if direct observation evaluations provide unique data compared to those obtained from quarterly global evaluations.

Methods:  This observational, cohort study was performed at a 3‐year emergency medicine (EM) residency program with 10 residents per year. Faculty used an online Web‐based evaluation system to complete quarterly global evaluations and patient‐specific direct observation evaluations. Two scores were collected for each resident within each quarterly evaluation period: 1) the quarterly evaluation score was the mean score across all faculty who performed a quarterly evaluation and, 2) the direct observation score was the mean score across all faculty who performed a direct observation evaluation. Pearson correlation coefficients were performed across these two groups of evaluations.

Results:  Over the 4‐year period of the study 296 complete data sets were available for the analysis. When the quarterly evaluation score was correlated with the direct observation score for each resident at the same evaluation period, we found a very high correlation for each of the eight evaluation questions (r = 0.95–0.96, p < 0.0001). When these evaluations were stratified based on the number of direct observation evaluations that were performed during the evaluation period of interest, the correlation between the quarterly evaluation and the direct observation scores increased as the number of direct observations in the evaluation period increased. The evaluation scores from the faculty who had performed both direct observation and quarterly evaluation methods during the same resident evaluation period were highly correlated even with small numbers of evaluators.

Conclusions:  Direct observations are highly correlated with quarterly evaluations when there are greater than three direct observation evaluations completed; however, this correlation drops significantly when the number of direct observations is lower. Direct observation evaluations provide similar data when compared with data obtained from quarterly global evaluations.

ACADEMIC EMERGENCY MEDICINE 2010; 17:S72–S77 © 2010 by the Society for Academic Emergency Medicine
Anatomy of a Clerkship Test
Authors: Senecal Emily L. , Askew Kim , Gorney Barbara , Beeson Michael S. , Manthey David E.
Published: October 2010

Written examinations are frequently used to assess medical student performance. Within emergency medicine (EM), a National Board of Medical Examiners (NBME) subject examination for EM clerkships does not exist. As a result, clerkship directors frequently generate examinations within their institution. This article reviews the literature behind the use of standardized examinations in evaluating medical student performance, describes methods for generating well‐written test questions, reviews the statistical concepts of reliability and validity that are necessary to evaluate an examination, and proposes future directions for testing EM students.

ACADEMIC EMERGENCY MEDICINE 2010; 17:S31–S37 © 2010 by the Society for Academic Emergency Medicine
Risk Factors for Acute Adverse Events During Ultrasound‐guided Central Venous Cannulation in the Emergency Department
Authors: Theodoro Daniel , Krauss Missy , Kollef Marin , Evanoff Bradley
Published: October 2010

Background:  Ultrasound (US) greatly facilitates cannulation of the internal jugular vein. Despite the ability to visualize the needle and anatomy, adverse events still occur. The authors hypothesized that the technique has limitations among certain patients and clinical scenarios.

Objectives:  The purpose of this study was to identify characteristics of adverse events surrounding US‐guided central venous cannulation (CVC).

Methods:  The authors assembled a prospective observational cohort of emergency department (ED) patients undergoing consecutive internal jugular CVC with US. The primary outcome of interest was a composite of acute mechanical adverse events including hematoma, arterial cannulation, pneumothorax, and unsuccessful placement. Physicians performing the CVC recorded anatomical site, reason for insertion, and acute complications. The patients with catheters were followed until the catheters were removed based on radiographic evidence or hospital nursing records. ED charts and pharmacy records contributed variables of interest. A self‐reported online survey provided physician experience information. Logistic regression was used to calculate the odds of an adverse outcome.

Results:  Physicians attempted 289 CVCs on 282 patients. An adverse outcome occurred in 57 attempts (19.7%, 95% confidence interval [CI] = 15.5 to 24.7), the most common being 31 unsuccessful placements (11%, 95% CI = 7.7 to 14.8). Patients with a history of end‐stage renal disease (odds ratio [OR] = 3.54, 95% CI = 1.59 to 7.89), and central lines placed by operators with intermediate experience (OR = 2.26, 95% CI = 1.19 to 4.32), were most likely to encounter adverse events. Previously cited predictors such as body mass index (BMI), coagulopathy, and pulmonary hyperinflation were not significant in our final model.

Conclusions:  Acute adverse events occurred in approximately one‐fifth of US‐guided internal jugular central line attempts. The study identified both patient (history of end‐stage renal disease) and physician (intermediate experience level) factors that are associated with acute adverse events.

ACADEMIC EMERGENCY MEDICINE 2010; 17:1055–1061 © 2010 by the Society for Academic Emergency Medicine
Scholarly Tracks in Emergency Medicine
Authors: Regan Linda , Stahmer Sarah , Nyce Andrew , Nelson Bret P. , Moscati Ronald , Gisondi Michael A. , Hopson Laura R.
Published: October 2010

Over the past decade, some residency programs in emergency medicine (EM) have implemented scholarly tracks into their curricula. The goal of the scholarly track is to identify a niche in which each trainee focuses his or her scholarly work during residency. The object of this paper is to discuss the current use, structure, and success of resident scholarly tracks. A working group of residency program leaders who had implemented scholarly tracks into their residency programs collated their approaches, implementation, and early outcomes through a survey disseminated through the Council of Emergency Medicine Residency Directors (CORD) list‐serve. At the 2009 CORD Academic Assembly, a session was held and attended by approximately 80 CORD members where the results were disseminated and discussed. The group examined the literature, discussed the successes and challenges faced during implementation and maintenance of the tracks, and developed a list of recommendations for successful incorporation of the scholarly track structure into a residency program. Our information comes from the experience at eight training programs (five 3‐year and three 4‐year programs), ranging from 8 to 14 residents per year. Two programs have been working with academic tracks for 8 years. Recommendations included creating clear goals and objectives for each track, matching track topics with faculty expertise, protecting time for both faculty and residents, and providing adequate mentorship for the residents. In summary, scholarly tracks encourage the trainee to develop an academic or clinical niche within EM during residency training. The benefits include increased overall resident satisfaction, increased success at obtaining faculty and fellowship positions after residency, and increased production of scholarly work. We believe that this model will also encourage increased numbers of trainees to choose careers in academic medicine.

ACADEMIC EMERGENCY MEDICINE 2010; 17:S87–S94 © 2010 by the Society for Academic Emergency Medicine
The CORD Academy for Scholarship in Education in Emergency Medicine
Authors: LaMantia Joseph , Kuhn Gloria J. , Searle Nancy S.
Published: October 2010

In 2010 the Council of Emergency Medicine Residency Directors (CORD) established an Academy for Scholarship in Education in Emergency Medicine to define, promote, recognize, and reward excellence in education, education research, and education leadership in emergency medicine. In this article we describe the mission and aims of the Academy.  Academies for medical educators are widespread in medical schools today and have produced many benefits both for faculty and for educational programs. Little effort, however, has been devoted to such a model in graduate medical education specialty societies. While CORD and other emergency medicine organizations have developed numerous initiatives to advance excellence in education, we believe that this effort will be accelerated if housed in the form of an Academy that emphasizes scholarship in teaching and other education activities.  The CORD Academy for Scholarship in Education in Emergency Medicine is a new model for promoting excellence in education in graduate medical education specialty societies.

ACADEMIC EMERGENCY MEDICINE 2010; 17:S13–S15 © 2010 by the Society for Academic Emergency Medicine
Emergency Medicine in the Medical School Curriculum
Authors: Wald David A. , Lin Michelle , Manthey David E. , Rogers Rob L. , Zun Leslie S. , Christopher Theodore
Published: October 2010

Emergency medicine (EM) is a dynamic specialty that continues to define itself as a fertile training ground for medical students. Throughout the years, a number of U.S. medical schools have incorporated topics germane to EM training (basic cardiac life support, principles of wound care, splinting, basic procedural skills training, etc.) into the medical school curriculum. By virtue of their broad‐based training and the unique patient care environment that they practice in, EM specialists can serve a multitude of educational roles in the medical school. Whether serving as a problem‐based learning facilitator, collaborating with basic scientists, or teaching medical history‐taking and physical examination skills in the emergency department (ED), EM faculty can effectively teach future physicians in training. Although opportunities for teaching will vary by institution, often all it takes to get involved is asking. Teaching can take place in the ED, classroom, or simulation center, both in the preclinical and in the clinical curriculum. EM faculty may be well suited to help teach procedural skills to students as they enter their clinical clerkships. A formal rotation in EM can also assist the medical school in achieving their institutional objectives or in identifying ways to satisfy the Liaison Committee on Medical Education’s objectives. Patients presenting to the ED span the entire spectrum: young and old, sick and not sick. It is this variety of cases that makes the ED a truly valuable setting for educating students.

ACADEMIC EMERGENCY MEDICINE 2010; 17:S26–S30 © 2010 by the Society for Academic Emergency Medicine
Critical Appraisal of Emergency Medicine Educational Research: The Best Publications of 2009
Authors: Kuhn Gloria J. , Shayne Philip , Coates Wendy C. , Fisher Jonathan , Lin Michelle , Maggio Lauren A. , Farrell Susan E.
Published: October 2010

Objectives:  The objective was to critically appraise and highlight methodologically superior medical education research specific to emergency medicine (EM) published in 2009.

Methods:  A search of the English language literature in 2009 querying Ovid MEDLINE In‐Process & Other Non‐Indexed Citations, Ovid MEDLINE 1950 to Present, Web of Science, Education Resources Information Center (ERIC), and PsychInfo identified 36 EM studies that used hypothesis‐testing or observational investigations of educational interventions. Six reviewers independently ranked all publications based on 10 criteria, including four related to methodology, that were chosen a priori to standardize evaluation by reviewers. This was a refinement of the methods used to appraise medical education published in 2008.

Results:  Seven studies met the standards as determined by the averaged rankings and are highlighted and summarized here. This year, 16 of 36 (44%) identified studies had funding, compared to 11 of 30 (36%) identified last year; five of seven (71%) highlighted publications were funded in 2009 compared to three of five (60%) highlighted in 2008. Use of technology in medical education was reported in 14 identified and four highlighted publications, with simulation being the most common technology studied. Five of the seven (71%) featured publications used a quasi‐experimental or experimental design, one was observational, and one was qualitative. Practice management topics, including patient safety, efficiency, and revenue generation, were examined in seven reviewed studies.

Conclusions:  Thirty‐six medical education publications published in 2009 focusing on EM were identified. This critical appraisal reviews and highlights seven studies that met a priori quality indicators. Current trends are noted.

ACADEMIC EMERGENCY MEDICINE 2010; 17:S16–S25 © 2010 by the Society for Academic Emergency Medicine
Influence of water stress on the glucosinolate profile of Brassica oleracea var. italica and the performance of Brevicoryne brassicae and Myzus persicae
Authors: Khan M.A.M. , Ulrichs Christian , Mewis Inga
Published: October 2010

Drought stress alters the chemical composition of plants, which can influence their tolerance to insect herbivory. To evaluate plant chemical responses to drought stress, broccoli, Brassica oleracea L. var. italica Plenck (Brassicaceae), was grown under well‐watered, drought, and water‐logged conditions. The glucosinolate (GS) levels and the performance of two aphid species, the specialist Brevicoryne brassicae (L.) and the generalist Myzus persicae (Sulzer) (both Hemiptera: Aphididae), in relation to water stress conditions were studied. High Performance Liquid Chromatography analysis showed that water stress changed the levels of GS in broccoli plants. Plants grown for 2 weeks under drought stress were significantly smaller and showed decreased levels of total GS when compared with GS contents of well‐watered plants, whereas water‐logged conditions led to a slight increase in the GS contents. A substantial decrease in indolyl GS was detected in water‐deficient plants, whereas aliphatic GS decreased slightly. Analysis of sugar levels in phloem sap of broccoli plants revealed that plants under water‐logged conditions contained the highest amounts of sugars followed by drought‐stressed and well‐watered plants. The two aphid species responded differently to water stress‐induced changes in their host plants. Significantly larger populations of M. persicae were recorded on plants with a limited water supply than on plants grown under well‐watered or water‐logged conditions. Brevicoryne brassicae was less affected by water stress, and similar population sizes were found on plants that were subject to different treatments. Analysis of covariance showed a significant effect of the plants’ water condition but no significant effect of GS content on the performance of M. persicae. However, the specialist B. brassicae remained unaffected by changes induced under water stress conditions.
Telocytes in human isolated atrial amyloidosis: ultrastructural remodelling
Authors: Mandache E. , Gherghiceanu M. , Macarie C. , Kostin S. , Popescu L. M.
Published: October 2010

The human heart can be frequently affected by an organ‐limited amyloidosis called isolated atrial amyloidosis (IAA). IAA is a frequent histopathological finding in patients with long‐standing atrial fibrillation (AF). The aim of this paper was to investigate the ultrastructure of cardiomyocytes and telocytes in patients with AF and IAA. Human atrial biopsies were obtained from 37 patients undergoing cardiac surgery, 23 having AF (62%). Small fragments were harvested from the left and right atrial appendages and from the atrial sleeves of pulmonary veins and processed for electron microscopy (EM). Additional fragments were paraffin embedded for Congo‐red staining. The EM examination certified that 17 patients had IAA and 82% of them had AF. EM showed that amyloid deposits, composed of characteristic 10‐nm‐thick filaments were strictly extra‐cellular. Although, under light microscope some amyloid deposits seemed to be located within the cardiomyocyte cytoplasm, EM showed that these deposits are actually located in interstitial recesses. Moreover, EM revealed that telopodes, the long and slender processes of telocytes, usually surround the amyloid deposits limiting their spreading into the interstitium. Our results come to endorse the presumptive association of AF and IAA, and show the exclusive, extracellular localization of amyloid fibrils. The particular connection of telopodes with amyloid deposits suggests their involvement in isolated atrial amyloidosis and AF pathogenesis.
Characterisation of zuclopenthixol metabolism by in vitro and therapeutic drug monitoring studies
Authors: Davies S. J. C. , Westin A. A. , Castberg I. , Lewis G. , Lennard M. S. , Taylor S. , Spigset O.
Published: October 2010

Davies SJC, Westin AA, Castberg I, Lewis G, Lennard MS, Taylor S, Spigset O. Characterisation of zuclopenthixol metabolism by in vitro and therapeutic drug monitoring studies.

Objective:  Zuclopenthixol pharmacokinetics is incompletely characterised. We investigated potential interactions mediated through cytochrome P450 enzymes.

Method:  In vitro, we examined the impact of CYP2D6 and CYP3A4 inhibitors on zuclopenthixol metabolism in microsomes from six human livers. Subsequently, we compared dose‐corrected serum zuclopenthixol concentrations in 923 samples from a therapeutic drug monitoring database from patients prescribed oral (n = 490) or injected (n = 423) zuclopenthixol alone or with fluoxetine, paroxetine, levomepromazine or carbamazepine.

Results:  In vitro fluoxetine, paroxetine, ketoconazole and quinidine all significantly inhibited zuclopenthixol metabolism. Ketoconazole and quinidine together abolished zuclopenthixol disappearance. Clinically, dose‐corrected oral zuclopenthixol serum concentrations increased significantly, after adjustment, by 93%, 78% and 46% during co‐treatment with fluoxetine, paroxetine and levomepromazine and decreased 67% with carbamazepine. Carbamazepine caused dose‐dependent reductions in the oral zuclopenthixol concentration–dose ratio (P < 0.001), fluoxetine (P < 0.001) and paroxetine (P = 0.011) dose‐dependent increases and levomepromazine an increase related to its serum concentration (P < 0.001). Results for injected zuclopenthixol were similar but not all reached statistical significance.

Conclusion:  The In vitro study suggests zuclopenthixol is metabolised primarily by CYP2D6 and CYP3A4. The clinical study supports this, demonstrating the impact of co‐prescribed inhibitors or inducers. Guidelines should incorporate these interactions noting the potential for zuclopenthixol‐related toxicity or treatment failure.
Dalteparin, a low‐molecular‐weight heparin, promotes angiogenesis mediated by heparin‐binding VEGF‐A in vivo
Authors: NORRBY KLAS , NORDENHEM ARVID
Published: October 2010

Norrby K, Nordenhem A. Dalteparin, a low‐molecular‐weight heparin, promotes angiogenesis mediated by heparin‐binding VEGF‐A in vivo. APMIS 2010; 118: 949–57.

Tumors are angiogenesis dependent and vascular endothelial growth factor‐A (VEGF‐A), a heparin‐binding protein, is a key angiogenic factor. As chemotherapy and co‐treatment with anticoagulant low‐molecular‐weight heparin (LMWH) are common in cancer patients, we investigated whether angiogenesis in vivo mediated by VEGF‐A is modulated by metronomic‐type treatment with: (i) the LMWH dalteparin; (ii) low‐dosage cytostatic epirubicin; or (iii) a combination of these two drugs. Using the quantitative rat mesentery angiogenesis assay, in which angiogenesis was induced by intraperitoneal injection of very low doses of VEGF, dalteparin sodium (Fragmin®) and epirubicin (Farmorubicin®) were administered separately or in combination by continuous subcutaneous infusion at a constant rate for 14 consecutive days. Dalteparin was administered at 27, 80, or 240 IU/kg/day, i.e., doses that reflect the clinical usage of this drug, while epirubicin was given at the well‐tolerated dosage of 0.4 mg/kg/day. While dalteparin significantly stimulated angiogenesis in an inversely dose‐dependent manner, epirubicin did not significantly affect angiogenesis. However, concurrent treatment with dalteparin and epirubicin significantly inhibited angiogenesis. The effect of dalteparin is the first demonstration of a proangiogenic effect of any LMWH in vivo. The fact that co‐treatment with dalteparin and epirubicin significantly inhibited angiogenesis suggests a complex drug effect.
Fusobacterium necrophorum– detection and identification on a selective agar
Authors: BANK STEFFEN , NIELSEN HANNE MERETE , HOYER MATHIASEN BORIS , CHRISTIANSEN LETH DORTE , HAGELSKJÆR KRISTENSEN LENA , PRAG JØRGEN
Published: October 2010

Bank S, Nielsen HM, Hoyer Mathiasen B, Christiansen Leth D, Hagelskjær Kristensen L, Prag J. Fusobacterium necrophorum– detection and identification on a selective agar. APMIS 2010; 118: 994–9.

Within the last decade, Fusobacterium necrophorum subsp. funduliforme has been considered a clinically important pathogen causing pharyngitis especially in adolescents and young adults. F. necrophorum pharyngitis can progress into Lemierre’s syndrome, which is a severe and life‐threatening infection. However, throat swabs are not cultured anaerobically in the routine and even if cultured anaerobically, it can be difficult to identify F. necrophorum from the normal flora of the throat. F. necrophorum is therefore often overlooked as the cause of pharyngitis. In our laboratory, a F. necrophorum selective agar has been developed containing vancomycin and nalidixin, which inhibit the growth of most Gram‐positive and many Gram‐negative bacteria, respectively. β‐haemolysis of horse blood can be detected, which further facilitates the detection and identification of F. necrophorum. The F. necrophorum selective agar was evaluated against a quantitative real‐time polymerase chain reaction assay and shown to have a significantly higher sensitivity for detecting F. necrophorum than the anaerobic agar commonly used in Denmark. Furthermore, the F. necrophorum selective agar does not require experienced laboratory technicians, require fewer subcultures, is probably less expensive and is faster to perform than other culture methods.
Differential susceptibility to lethal endotoxaemia in mice deficient in IL‐1α, IL‐1β or IL‐1 receptor type I
Authors: JOOSTEN LEO A.B. , VAN DE VEERDONK FRANK L. , VONK ALIEKE G. , BOERMAN OTTO C. , KEUTER MONIQUE , FANTUZZI GIAMILLA , VERSCHUEREN INEKE , VAN DER POLL TOM , DINARELLO CHARLES A. , KULLBERG BART JAN , VAN DER MEER JOS W.M. , NETEA MIHAI G.
Published: October 2010

Joosten LAB, van de Veerdonk F, Vonk AG, Boerman OC, Keuter M, Fantuzzi G, Verschueren I, van der Poll T, Dinarello CA, Kullberg BJ, Van der Meer JWM, Netea MG. Differential susceptibility to lethal endotoxaemia in mice deficient in IL‐1α, IL‐1β or IL‐1 receptor type I. APMIS 2010; 118: 1000–7.

The role of intereukin‐1 (IL‐1) in mortality caused by endotoxaemia remains controversial. While IL‐1 receptor antagonist (IL‐1Ra) protects mice from lethal endotoxaemia, mice deficient in IL‐1β (IL‐1β− /−) display normal susceptibility to lipopolysaccharide (LPS). The aim of this study was to identify the source of these discrepancies. Mice deficient in IL‐1α, IL‐1β or IL‐1R type I were injected intraperitoneally with Escherichia coli or Salmonella typhimurium LPS. Survival of the mice was examined and compared with C57/Bl6 wild‐type mice. In addition, serum cytokine concentrations were determined after LPS challenge and in vitro cytokine production by peritoneal macrophages was analysed. Clearance of radioactive IL‐1α was examined in IL‐1α−/− and wild‐type mice. IL‐1β−/− mice were normally susceptible to endotoxaemia and cytokine production did not differ from that in control mice. Surprisingly, LPS mortality in IL‐1α−/− mice was significantly greater than that in control mice, accompanied by higher interferon‐γ release. These effects were mediated by a distorted homeostasis of IL‐1RI receptors, as shown by a strongly delayed clearance of IL‐1α. In contrast to the IL‐1α−/− and IL‐1β−/− mice, IL‐1RI−/− mice were completely resistant to high doses of LPS. In conclusion, IL‐1RI‐mediated signals are crucial in mediating mortality occurring as a result of lethal endotoxaemia. Investigation of IL‐1‐mediated pathways in IL‐1 knock‐out mice is complicated by a distorted homeostasis of IL‐1Rs.
Static and dynamic expression of life history traits in the northern fulmar Fulmarus glacialis
Authors: Orzack Steven Hecht , Steiner Ulrich K. , Tuljapurkar Shripad , Thompson Paul
Published: October 2010

Understanding the static and dynamic expression of life history traits is a prerequisite for the development of a causal theory of the evolution of aging and of life histories. We analyzed the statics and dynamics of reproduction and survival in a wild population of the northern fulmar, Fulmarus glacialis (Procellaridae). Survival rate is most influenced by year as compared to age and cohort. When temporal variation is ignored, survival rate increases slowly with age and then declines more rapidly at late ages. Survival rate contingent upon reproductive ‘stratum’ (producing an egg, hatching an egg, fledging a hatchling) also exhibits this pattern. Survival and reproduction have a positive static association in that survival rate increases as the apparent energy allocated to reproduction increases (as indexed by stratum). There is a broad distribution of realized lifetime reproductive success, which could be due to ‘fixed’ heterogeneity, with some individuals always having low survival and reproduction and others always having high survival and reproduction, or be due to ‘dynamic’ heterogeneity, with all individuals having the same expected reproductive and survival rates. Analysis of stochastic stratum dynamics indicates that individuals do not remain long in any given stratum and suggest that the variation among individuals with respect to lifetime reproductive success is due to dynamic heterogeneity. The probability of producing an egg increases with age for both sexes, whereas the probability of producing a fledgling initially declines with age and then increases. These results underscore the necessity of understanding the static and dynamic expression of demographic traits when making a causal claim about their evolution.
Food abundance determines distribution and density of a frugivorous bird across seasons
Authors: Crampton Lisa H. , Longland William S. , Murphy Dennis D. , Sedinger James S.
Published: October 2010

Although food abundance is a principal determinant of distribution and abundance of many animals, most previous studies have not quantitatively assessed its importance relative to other factors that may also determine species distributions. We estimated frugivorous phainopeplaPhainopepla nitensoccupancy and density, food density, and vegetation structure on transects in fragmented mesquite and acacia woodlands over three years in non‐breeding and breeding seasons. Using an AIC framework and controlling for detection probability, we determined relative impacts of food abundance, vegetation structure, and habitat fragmentation on patch occupancy and density, and concomitant extinction and colonization probabilities of phainopeplas. Initial occupancy in winter 2002 was high (0.87 ± 0.047), and primarily positively correlated with food abundance and woodland area (Akaike weights wi= 0.998 and 0.750 respectively). Woodland area more strongly influenced occupancy where food was scarcer. Phainopepla density in both seasons was strongly positively correlated with food abundance, especially in the 2002 drought when density was higher (wi=1.0 for food and year). Density was higher in acacia than mesquite woodlands (wi= 1.0), and moderately negatively correlated with elevation (wi= 0.789). Extinction probability (patches vacated) was low (0.078 ± 0.040), and principally influenced by phainopepla density (wi= 0.968) and tree height (wi= 0.749). Colonization probability was low (0.15 ± 0.034) and determined by vegetation structure (wi= 1.0). Much recorded colonization was reoccupancy of woodlands previously occupied by single males in winter, then vacated in a breeding season. These results suggest that for an animal occupying a highly fragmented landscape, distributions and densities at the habitat patch scale are driven by food abundance, are moderately affected by habitat fragmentation, and are slightly influenced by vegetation structure.
Response of feather moss associated N2fixation and litter decomposition to variations in simulated rainfall intensity and frequency
Authors: Jackson Benjamin G. , Martin Pablo , Nilsson Marie‐Charlotte , Wardle David A.
Published: October 2010

Feather mosses in boreal forests form a dense ground‐cover that is an important driver of both nutrient and carbon cycling. While moss growth is highly sensitive to moisture availability, little is known about how moss effects on nutrient and carbon cycling are affected by the dynamics of moisture input to the ecosystem. We experimentally investigated how rainfall regimes affected ecosystem processes driven by the dominant boreal feather mossPleurozium schreberiby manipulating total moisture amount, frequency of moisture addition and moss presence/absence. Moisture treatments represented the range of rainfall conditions that occur in Swedish boreal forests as well as shifts in rainfall expected through climate change. We found that nitrogen (N) fixation by cyanobacteria in feather mosses (the main biological N input to boreal forests) was strongly influenced by both moisture amount and frequency, and their interaction; increased frequency had greater effects when amounts were higher. Within a given moisture amount, N fixation varied up to seven‐fold depending on how that amount was distributed temporally. We also found that mosses promoted vascular litter decomposition rates, concentrations of litter nutrients, and active soil microbial biomass, and reduced N release into soil solution. These effects were usually strongest under low moisture amount and/or frequency, and revealed a buffering effect of mosses on the decomposer subsystem under moisture limitation. These results highlight that both the amount and temporal distribution of rainfall, determine the effect of feather mosses on ecosystem N input and the decomposer subsystem. They also emphasize the role of feather mosses in mediating moisture effects on decomposer processes. Finally, our results suggest that projected shifts in precipitation in the Swedish boreal forest through climate change will result in increased moss growth and N2fixation but a reduced dependency of the decomposer subsystem on feather moss cover for moisture retention.
Scaling down from species to individuals: a flower–visitation network between individual honeybees and thistle plants
Authors: Dupont Y. L. , Trøjelsgaard K. , Olesen J. M.
Published: October 2010

Studies of ecological networks usually focus upon interaction patterns among species. However, linkage among species is mediated by their constituting individuals. Thus, every linked species pair in a network encapsulates a new network of interacting individuals. Very few studies outside the sociology of larger animals have investigated networks at the level of the individual. Here, we analyse the structure of a flower–visitation network of individual thistles Cirsium arvense and honeybees Apis mellifera in a small meadow patch in Denmark. We marked and numbered 62 honeybees and 32 thistle stems and monitored all floral visits. The constructed bipartite network of individual plants and bees had a high connectance and low nestedness, but it was not significantly modular. Frequency distributions of number of links per species (i.e. linkage level) had their best fit to a truncated power law, and interactions were asymmetrical. Unipartite networks of either plants or bees had exceedingly short average path length and high clustering. Linkage level of plants increased with their number of flower heads and height of inflorescence (floral display parameters). Overall, the individual network of honeybees and thistles was denser linked than what is known from species pollination networks. Characteristics of both plants (e.g. floral display) and animals (e.g. foraging behaviour) are likely to generate this intra–specific, inter–individual link pattern. Such features of individual–individual networks may scale up and become important drivers of the structure and dynamics of species–species networks.
Climate and topography drives macroscale biodiversity through land‐use change in a human‐dominated world
Authors: Yamaura Yuichi , Amano Tatsuya , Kusumoto Yoshinobu , Nagata Hisashi , Okabe Kimiko
Published: October 2010

Drivers of biodiversity at macroscales have long been of interest in ecology, and climate and topography are now considered to be major drivers. Because humans have transformed most of the Earth's land surface, land use may play a significant role as a driver of biodiversity at a macroscale. Here we disentangle the relationships among climate, topography, land use, available energy (measured by the normalized difference vegetation index [NDVI]), and species richness of Japanese forest birds. Species richness was better explained at 40‐ and 80‐km resolutions than at 5‐, 10‐ and 20‐km resolutions; it was explained by climate, topography, and land use, and the effects of land use were fully incorporated into those of climate and topography. As temperature increased and elevation decreased, natural forest area decreased, and this decrease intensified in warm lowland areas. With the loss of natural forest, species richness decreased below a certain threshold. As temperature increased and elevation decreased, species richness and NDVI increased slightly or were unchanged in cool highland areas and decreased in warm lowland areas. Species richness increased linearly with the increase in NDVI. Most effects of climate/topography on species richness in warm lowland areas were shared by those of land use, suggesting that the decrease in species richness in warm lowland areas has been caused by loss of natural forest. Therefore, it is suggested that climate and topography determined land use intensity, which in turn, drove species richness through the depletion of available energy. Increasing temperature and decreasing elevation leads to both benefits (increase in potential available energy) and costs (depletion of energy by human land‐use change) for forest birds. These costs seem to override benefits in warm lowland areas.