bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantification of the Genetic Component of Basal C‐Reactive Protein Expression in SLE Nuclear Families
Authors: Rhodes B. , Meek J. , Whittaker J. C. , Vyse T. J.
Published: March 2008

C‐reactive protein (CRP) is a heritable acute‐phase plasma protein also expressed at low, basal, levels in healthy individuals. Elevated basal CRP has been associated with increased cardiovascular risk, while CRP dysregulation may be a feature of systemic lupus erythematosus (SLE). In this cohort of 496 Caucasian SLE families we estimated basal CRP heritability, h2= 27.7%. We typed a dense map of CRP single nucleotide polymorphisms (SNPs) and found that seven were associated with basal CRP using both a regression approach and an orthogonal family‐based test (P = 0.001–0.011), as were haplotypes carrying the minor allele of these SNPs. SNPs in the interleukin‐1β and interleukin‐6 genes were associated with basal CRP. No association was seen between CRP genotype and SLE. Using a variance components approach we estimated that the CRP genotype accounted for only 15% of the total genetic component of basal CRP variation, perhaps explaining the limited evidence of association between CRP and disease. Most of the genetic determinants of basal CRP variation therefore remain unknown. Multiple genes may be involved and identifying them will provide an insight into pathways regulating CRP expression, highlight potential cardiovascular disease and SLE candidates and improve the ability of basal CRP to predict cardiovascular risk.
Sustainable liquid biofuels from biomass: the writing's on the walls
Authors: Gomez Leonardo D. , Steele‐King Clare G. , McQueen‐Mason Simon J.
Published: March 2008

Domination of the global biosphere by human beings is unprecedented in the history of the planet, and our impact is such that substantive changes in ecosystems, and the global environment as a whole, are now becoming apparent. Our activity drives the steady increase in global temperature observed in recent decades. The realization of the adverse effects of greenhouse gas emissions on the environment, together with declining petroleum reserves, has ensured that the quest for sustainable and environmentally benign sources of energy for our industrial economies and consumer societies has become urgent in recent years. Consequently, there is renewed interest in the production and use of fuels from plants. The ‘first‐generation’ biofuels made from starch and sugar appear unsustainable because of the potential stress that their production places on food commodities. Second‐generation biofuels, produced from cheap and abundant plant biomass, are seen as the most attractive solution to this problem, but a number of technical hurdles must be overcome before their potential is realized. This review will focus on the underpinning research necessary to enable the cost‐effective production of liquid fuels from plant biomass, with a particular focus on aspects related to plant cell walls and their bioconversion.

Contents

Summary
473

I.
Historical context
474

II.
The case for liquid biofuels in the context of human energy consumption
474

III.
Liquid biofuels
474

IV.
Converting plant biomass into liquid fuels
475

V.
General composition of plant biomass
478

VI.
Overcoming the saccharification barrier
482

VII.
Tools for cell wall disassembly
483

VIII.
Prospects for biofuels
483

References
484
Survey of academic veterinarians' attitudes toward provision of cardiopulmonary–cerebral resuscitation and discussion of resuscitation with clientele
Authors: Hofmeister Erik H. , Thompson Brian F. , Brainard Benjamin M. , Kegge Samantha , Kube Stephanie , Egger Christine M. , Kimura Yoshio M. , Jehn Carl , Green Brad
Published: March 2008

Objective: To examine the impact of stress on veterinarians resulting from both the provision of cardiopulmonary–cerebral resuscitation (CPCR) and the discussion of CPCR and do not attempt resuscitation (DNAR) with affected clients.

Design: Descriptive cross‐sectional with survey methodology.

Setting: Eight colleges of veterinary medicine in the United States.

Subjects: Two hundred and one academic veterinarians.

Interventions: The survey was distributed by the authors to small animal faculty, residents, and interns. Demographic variables and Likert‐style questions about comfort discussing and performing CPCR and affective impact of CPCR events were included. Multiple linear regression models were constructed to determine the effect of the questions on different target variables of interest.

Measurements and Main Results: Ninety‐six percent of veterinarians experienced stress when performing CPCR and reported that positive emotions after a successful CPCR were statistically greater than the negative emotions of an unsuccessful CPCR. Veterinarians trained in CPCR reported lower scores for stress and negative emotional impact from a failed CPCR.

Conclusions: Veterinarians experience stress during CPCR and when discussing CPCR and DNAR choices with owners. Steps can be taken to reduce the likelihood of having a negative affect from CPCR efforts, such as improved training of CPCR supervisors and increased competence of CPCR supervisors.
Survey of academic veterinarians' clinical practice in cardiopulmonary–cerebral resuscitation
Authors: Hofmeister Erik H. , Thompson Brian F. , Brainard Benjamin M. , Kegge Samantha , Kube Stephanie , Egger Christine M. , Jehn Carl , Green Brad
Published: March 2008

Objective:To document the clinical practice of cardiopulmonary–cerebral resuscitation (CPCR) among academic veterinarians.

Design:Survey.

Setting:Eight colleges of veterinary medicine in the United States.

Subjects:Two hundred and one academic veterinarians.

Interventions:The survey was distributed by hand by the authors into the mailboxes of small animal faculty, residents, and interns. Demographic variables, questions regarding number of cardiopulmonary arrests (CPA) supervised and number successful, do not attempt resuscitation discussions, and Likert‐style questions about client presence during CPCR, appropriateness of CPCR, and CPCR decision‐making were included. Multiple linear regression models were constructed to determine the effect of multiple questions on different target variables of interest.

Measurements and main results:Numerous differences were noted based on institution, gender, specialty, and position. Most institutions did not have a standard resuscitation consent form. Most respondents believed the client, house officer, and senior clinician should determine whether to perform resuscitation or not. Quality of life was the most significant determinant of whether to resuscitate or not, followed by long‐term prognosis, then short‐term prognosis.

Conclusions:Veterinarians differ in many aspects of their approach to CPA and resuscitation. Creating consensus within the veterinary profession would benefit client service and patient care.
Successful cardiopulmonary resuscitation and use of short‐term mechanical ventilation following inadvertent ketamine overdose in a cat
Authors: Cortés Yonaira E. , Holm Jennifer L.
Published: March 2008

Objective: To describe the clinical manifestations and successful outcome following an inadvertent overdose of ketamine to a cat.

Case summary: A 4‐year‐old neutered male domestic shorthair cat was evaluated for a urethral obstruction. Because of an inadvertent miscalculation of ketamine, 20 times the intended dose was administered intravenously, which resulted in cardiopulmonary arrest. Cardiopulmonary‐cerebral resuscitation was successful, and short‐term mechanical ventilation, fluids and intensive monitoring were utilized to achieve full recovery and subsequent discharge of the animal.

New or unique information provided: Ketamine is a common anesthetic agent used in cats that is considered to have a wide therapeutic index and minimal cardiopulmonary depressant effects at recommended doses. Successful management of inadvertent ketamine overdose has been reported in children, but not in cats. Prompt CPCR and short‐term mechanical ventilation may be necessary to treat a significant ketamine overdose. In cats, yohimbine may act as a partial antagonist of ketamine.
Myocardial perforation by a stick foreign body in a dog
Authors: Pelosi Augusta , Hauptman Joseph G. , Eyster George E. , Beal Matthew W. , Anderson Lorel K. , Olivier N. Bari
Published: March 2008

Objective: To report a case of myocardial perforation by a stick foreign body in a dog.

Case Summary: A 3‐year‐old castrated male Labrador Retriever was examined because of a puncture wound seen after an unsupervised run in the woods. The wound was suspected to penetrate into the thoracic cavity on the basis of physical exam and radiographs. Uniform ventricular premature complexes (VPCs) and junctional beats were noted on electrocardiogram (ECG). Thoracotomy was performed and a 6‐cm wooden stick was seen protruding from the right ventricle through the pericardium toward the sternum. The stick was removed while purse string sutures were tied around the resultant myocardial defect. Follow‐up echocardiography revealed intact intracardiac structures. VPCs were treated with lidocaine and resolved completely within 24 hours of presentation.

New or Unique Information Provided: Thoracic trauma can result in myocardial injury; penetration into the myocardium represents a life‐threatening situation for the emergency clinician. Cardiac injury should be included in the differential diagnoses of penetrating thoracic foreign bodies.
Direct Cost Burden Among Insured US Employees With Migraine
Authors: Hawkins Kevin , Wang Sara , Rupnow Marcia
Published: March 2008

Objective.— To provide a current estimate of the national direct health‐care cost burden of illness associated with migraine among a US insured population.

Background.— Individuals with migraine use health‐care resources more than those without migraine, incurring substantial costs to US employers.

Methods.— The Thomson Medstat's Commercial Claims and Encounters 2004 database was utilized for this study. Only paid claims were analyzed. The migraine cohort had a primary migraine diagnosis and/or a migraine‐specific abortive drug prescription during 2004. A matched control cohort with no evidence of migraine was generated using propensity score techniques. Demographic characteristics and overall comorbidities were similar between cohorts. A second‐stage regression controlled for any remaining significant intergroup differences. The burden of illness of migraine was defined as the difference in average total health‐care expenditures per person between cohorts. The national burden of illness was defined as the average expenditure for migraine of national population estimates of privately insured individuals, and was estimated by projecting the migraine prevalence rate and average expenditure using Medical Expenditure Panel Survey population estimates.

Results.— Patients with migraine (n = 215,209) had significantly higher average health‐care expenditures compared with matched controls ($7007 vs $4436 per person per year; difference of $2571; P < .001). Migraine‐associated national expenditure estimates: outpatient care, $5.21 billion; prescriptions, $4.61 billion; inpatient care, $0.73 billion; and emergency department care, $0.52 billion.

Conclusions.— The direct costs associated with patients with migraine were found to be $2571 per person per year higher than in matched nonmigraine controls. The projected national burden of migraine of $11.07 billion is substantially higher than previous estimates.
Spontaneous Intracranial Hypotension Syndrome in a Patient With Marfan Syndrome and Autosomal Dominant Polycystic Kidney Disease
Authors: Albayram Sait , Baş Ahmet , Ozer Harun , Dikici Suleyman , Gulertan Serap Yavuz , Yuksel Adnan
Published: March 2008

Intracranial hypotension is typically manifested by orthostatic headache. The most frequent underlying factor is cerebrospinal fluid leakage. It has been suggested that dural structural weakness in some connective tissue diseases may be responsible for dural tears and diverticula and consequently leakage. We present a case of spontaneous intracranial hypotension associated with Marfan syndrome and autosomal dominant polycystic kidney disease. The patient was treated successfully with epidural autologous blood patch. Dural involvements of these hereditary connective tissue diseases are also discussed.
Associations Between Frequent Headaches, Persistent Smoking, and Attempts to Quit
Authors: Waldie Karen E. , McGee Rob , Reeder Anthony I. , Poulton Richie
Published: March 2008

Background.— Recent studies have found a strong relationship between tobacco smoking and headache pain. It remains unclear whether smoking behavior leads to headache or visa versa, mainly due to the cross‐sectional nature of the majority of this research.

Objective.— To help clarify the direction of the relation between smoking and frequent headaches in a representative cohort study.

Design and Methods.— Members of the Dunedin Multidisciplinary Health and Development Study (N = 980) were asked about their cigarette smoking and headache history at ages 11 and 13 (childhood), age 15 (mid‐adolescence), and age 26 (adulthood). Both cross‐sectional and longitudinal associations between smoking and headache status were examined using logistic regression.

Results.— During mid‐adolescence, the likelihood of frequent headaches doubled for smokers relative to nonsmokers (OR: 2.16, 95% CI: 1.39‐3.35). Smoking did not increase the risk of developing headaches in adulthood, however. In contrast, individuals who suffered from frequent headaches during mid‐adolescence were 2 times more likely to smoke in adulthood than those without headache (OR: 2.20, 95% CI: 1.3‐3.7), after controlling for sex and family socioeconomic status. Attempts to quit smoking were significantly more difficult for migraine sufferers with a history of headache than for those with tension‐type headache.

Conclusions.— Frequent headaches during mid‐adolescence appear to increase the risk of daily smoking in adolescence and adulthood. These individuals also have a more difficult time quitting than their headache‐free peers.
Patients With Chronic Tension‐Type Headache Demonstrate Increased Mechano‐Sensitivity of the Supra‐Orbital Nerve
Authors: Fernández‐de‐las‐Peñas César , Coppieters Michel W. , Cuadrado María Luz , Pareja Juan A.
Published: March 2008

Objective.— This study aimed to establish whether increased sensitivity to mechanical stimuli is present in neural tissues in chronic tension‐type headache (CTTH).

Background.— Muscle hyperalgesia is a common finding in CTTH. No previous studies have investigated the sensitivity of peripheral nerves in patients with CTTH.

Design.— A blinded controlled study.

Methods.— Pressure pain thresholds (PPT) and pain intensity following palpation of the supra‐orbital nerve (V1) were compared between 20 patients with CTTH and 20 healthy matched subjects. A pressure algometer and numerical pain rate scale were used to quantify PPT and pain to palpation. A headache diary was kept for 4 weeks to substantiate the diagnosis and record the pain history.

Results.— The analysis of variance demonstrated significantly lower PPT for patients (0.86 ± 0.13 kg/cm2) than controls (1.50 ± 0.19 kg/cm2) (P < .001). Pain to palpation was also higher for patients (2.73 ± 1.58) than controls (0.15 ± 0.28) (P < .001).Within the CTTH group, intensity, frequency, and duration of the headaches were negatively correlated with PPT (rs ≤ −0.75; P < .001), and positively correlated with pain to palpation (rs ≥ 0.72; P < .001).

Conclusions.— These findings reveal that mechanical hypersensitivity is not limited to muscles but also occurs in cranial nerves, and that the level of sensitization, either due to peripheral or central processes, is related to the severity of the primary headache.
Triptans vs Other Drugs for Acute Migraine. Are There Differences in Efficacy? A Comment
Authors: Tfelt‐Hansen Peer
Published: March 2008

The introduction of triptans in migraine treatment was apparently a revolution. Comparative randomized clinical trials (RCTs) with triptan and other drugs do not give a clear‐cut picture.

Oral triptans are superior to oral ergotamine most likely because the bioavailability oral of ergotamine is extremely low (<1%).

Compared with NSAIDs, in most cases aspirin, triptans were not superior and in several RCTs triptans caused more adverse events than aspirin plus metoclopramide.

Guidelines for treatment of migraine should be evidence‐based. It is suggested that based on current evidence, effervescent aspirin should be the first‐line drug for the treatment of migraine. Aspirin is also much cheaper than the triptans.
Triptans: Actions and Reactions
Authors: Nahas Stephanie J. , Silberstein Stephen D.
Published: March 2008

Subcutaneous sumatriptan is superior to placebo in achieving headache relief. Some commonly reported adverse events are paresthesias, tingling, and transient worsening of headache. Why do patients develop these symptoms? Our unique case may shed light on its actions.
Are Bank Holding Companies a Source of Strength to Their Banking Subsidiaries?
Authors: ASHCRAFT ADAM B.
Published: March 2008

I document evidence that a bank affiliated with a multi‐bank holding company (MBHC) is significantly safer than either a stand‐alone bank or a bank affiliated with a one‐bank holding company. Not only does MBHC affiliation reduce the probability of future financial distress, but distressed affiliated banks are also more likely to receive capital injections, recover more quickly, and are less likely to fail over the next year. Moreover, the measured benefits of affiliation are much larger than those that existed before recent reforms of bank holding company regulation, suggesting that much of the observed benefit can be attributed to regulation and not the market.
Relative Prices as Aggregate Supply Shocks with Trend Inflation
Authors: DEMERY DAVID , DUCK NIGEL W.
Published: March 2008

Ball and Mankiw (1995) use a static menu‐cost model to explain the historical behavior of the first and higher moments of commodity price changes in U.S. producer prices. We show that when appropriately modified for a world of positive trend inflation and forward‐looking behavior by firms, the menu‐cost model predicts a much weaker (possibly zero) correlation between the mean and the skewness of price changes than that found in the data.
Hyperbolic Discounting and the Phillips Curve
Authors: GRAHAM LIAM , SNOWER DENNIS J.
Published: March 2008

Using a standard dynamic general equilibrium model, we show that the interaction of staggered nominal contracts with hyperbolic discounting leads to inflation having significant long‐run effects on real variables.
Model Uncertainty and Delegation: A Case for Friedman's k‐Percent Money Growth Rule?
Authors: KILPONEN JUHA , LEITEMO KAI
Published: March 2008

Model uncertainty affects the monetary policy delegation problem. If there is uncertainty with regards to the determination of the delegated objective variables, the central bank will want robustness against potential model misspecifications. We show that with plausible degree of model uncertainty, delegation of the Friedman rule of increasing the money stock by k percent to the central bank will outperform commitment to the social loss function (flexible inflation targeting). The reason is that the price paid for robustness under flexible inflation targeting outweighs the inefficiency of money growth targeting. Imperfect control of money growth does not change this conclusion.
Reverse Auctions with Multiple Reinforcement Learning Agents*
Authors: Bandyopadhyay Subhajyoti , Rees Jackie , Barron John M.
Published: March 2008

Reverse auctions in business‐to‐business (B2B) exchanges provide numerous benefits to participants. Arguably the most notable benefit is that of lowered prices driven by increased competition in such auctions. The competition between sellers in reverse auctions has been analyzed using a game‐theoretic framework and equilibria have been established for several scenarios. One finding of note is that, in a setting in which sellers can meet total demand with the highest‐bidding seller being able to sell only a fraction of the total capacity, the sellers resort to a mixed‐strategy equilibrium. Although price randomization in industrial bidding is an accepted norm, one might argue that in reality managers do not utilize advanced game theory calculations in placing bids. More likely, managers adopt simple learning strategies. In this situation, it remains an open question as to whether the bid prices converge to the theoretical equilibrium over time. To address this question, we model reverse‐auction bidding behavior by artificial agents as both two‐player and n‐player games in a simulation environment. The agents begin the game with a minimal understanding of the environment but over time analyze wins and losses for use in determining future bids. To test for convergence, the agents explore the price space and exploit prices where profits are higher, given varying cost and capacity scenarios. In the two‐player case, the agents do indeed converge toward the theoretical equilibrium. The n‐player case provides results that reinforce our understanding of the theoretical equilibria. These results are promising enough to further consider the use of artificial learning mechanisms in reverse auctions and other electronic market transactions, especially as more sophisticated mechanisms are developed to tackle real‐life complexities. We also develop the analytical results when one agent does not behave strategically while the other agent does and show that our simulations for this environment also result in convergence toward the theoretical equilibrium. Because the nature of the best response in the new setting is very different (pure strategy as opposed to mixed), it indicates the robustness of the devised algorithm. The use of artificial agents can also overcome the limitations in rationality demonstrated by human managers. The results thus have interesting implications for designing artificial agents in automating bid responses for large numbers of bids where human intervention might not always be possible.
Determinants of Interoutsourcing: An Analytical Approach
Authors: Jiang Bin , Talluri Srinivas , Calantone Roger
Published: March 2008

Interoutsourcing is a round‐way process in which the vendor is its customer's customer and the customer is its vendor's vendor. While interoutsourcing is emerging as a prominent outsourcing strategy in many industries, there are no rigorous analytical studies focusing on this mechanism. In this article, we analytically demonstrate the efficacy of interoutsourcing by comparing it with normal outsourcing. Our results show that, compared with normal outsourcing, interoutsourcing acts as a self‐enforcer of vendor firms' behaviors toward increasing outsourcing service value. However, in situations where there is a mismatch of outsourcing activities, a high degree of incentive that is based on outsourcing service value, and a high cost of capital, interoutsourcing is not preferred to normal outsourcing. We discuss these results in detail and provide managerial implications for firms involved in interoutsourcing decisions.
Search for Alternatives and Collaboration with Incumbents: Two‐Sided Sourcing Behavior in Business Markets*
Authors: Kim Stephen Keysuk , Yamada Tetsuya , Kim Hyunchul
Published: March 2008

Sourcing strategies in business markets have been considered separately and the practice of two‐sided sourcing behavior—engaging in search for alternative suppliers and collaboration with an incumbent supplier—has not been examined. To fill that gap, we first identify boundary conditions under which the poor performance of an incumbent supplier intensifies an original equipment manufacturer's (OEM) search and collaboration. Then, we examine how an OEM's two‐sided sourcing behavior influences one of the critical elements of sourcing performance: the responsiveness of the incumbent supplier. Our proposed hypotheses were tested with data from a national survey of 539 OEM purchasing managers in the Japanese electronics industry. The analysis results indicate three main findings. First, two environmental conditions—pace of technological change and volume uncertainty—have contrasting influences on the link between incumbent supplier performance and an OEM's search and collaboration. While uncertainty from the upstream channel (pace of technological change) enhances an OEM's search and collaboration, uncertainty from the downstream channel (volume uncertainty) lowers an OEM's search and collaboration. Second, an OEM's dependence on its incumbent supplier has differential effects: an OEM reduces search as its dependence on incumbent supplier increases, while it enhances collaboration as its dependence on incumbent supplier increases. Third, while search alone has a negative effect on responsiveness of an incumbent supplier, engaging in two‐sided sourcing behavior (i.e., combining search with collaboration) has a positive effect on responsiveness of the incumbent supplier.
A Rewarming Maneuver Demonstrates the Contribution of Blood Flow to Electrode Cooling During Internally Irrigated RF Ablation
Authors: COOPER JOSHUA M. , SAPP JOHN L. , ROBINSON DAVID , EPSTEIN LAURENCE M. , STEVENSON WILLIAM G.
Published: March 2008

Introduction:Titration of radiofrequency (RF) ablation energy to avoid steam pops while maximizing lesion size is difficult because of disparities between electrode and tissue temperature. We hypothesized that the variable contribution of local blood flow to electrode cooling contributes to electrode‐tissue temperature disparity, even with an irrigated RF catheter.

Methods and Results: Forty RF lesions were made in the atria of live swine with an internally irrigated cooled RF catheter. Prior to RF delivery, the catheter tip was cooled and then allowed to rewarm to body temperature by stopping irrigant flow. The rewarming time (RT) was noted. The catheter was again cooled and RF energy delivered, with power titrated to achieve electrode temperature of 40°C, which was previously defined as the approximate upper limit of safety. Lesion formation and steam pops were observed with intracardiac echocardiography. The RT ranged from 10 to 47 seconds. Nine steam pops were seen. The mean RT for lesions with pops was faster than those without (20 vs. 33 seconds, P = 0.003). The 20 lesions with faster RT required more power to achieve target temperature than the 20 lesions with slower RT (P = 0.01). Eight of nine steam pops occurred in the group with faster RT.

Conclusions: RT quantifies convective heating by blood prior to RF. Faster RT predicts greater cooling by blood during irrigated RF, a greater power requirement to reach target electrode temperature, and a higher risk of steam pops during fixed‐temperature ablation. RT therefore can demonstrate the variation in blood cooling with each lesion and can be used to tailor energy delivery to maximize efficacy and safety.
Temporal Stability of the Location of the Esophagus in Patients Undergoing a Repeat Left Atrial Ablation Procedure for Atrial Fibrillation or Flutter
Authors: KENNEDY ROBERT , GOOD ERIC , ORAL HAKAN , HUETHER ELIZABETH , BOGUN FRANK , PELOSI FRANK , MORADY FRED , CHUGH AMAN
Published: March 2008

Background:
The esophagus may be mobile during a left atrial (LA) ablation procedure for atrial fibrillation (AF).

Objective:
The goal of the study was to determine whether the location of the esophagus is stable in patients undergoing a repeat LA ablation procedure.

Methods:
Forty‐two patients underwent repeat LA ablation a mean of 7 ± 2 months after the initial procedure. Cinefluoroscopic images of the esophagus during a barium swallow were recorded and the course of the esophagus was tagged on the 3D map. The position of the esophagus at the index and repeat procedure were compared.

Results:
At the index procedure, the esophagus was located near the left pulmonary veins (PVs) in 20 (48%), right PVs in 13 (31%), and at the mid LA in 9 (21%) patients. During the repeat procedure, the esophagus was found to be near the left PVs in 22 (52%), right PVs in 11 (26%), and at the mid LA in 9 patients (21%). In 35 of the 42 patients (83%), there was no change in the esophageal location, and in the remaining seven patients (17%), its position had shifted by ≥1 cm (range 1.0–4.0 cm).

Conclusions:
In more than 80% of patients presenting for a repeat LA ablation procedure, the esophagus is in the same position relative to the PVs as during the initial procedure. Therefore, if radiofrequency ablation at a particular location was limited by the position of the esophagus, safe ablation at that site is unlikely to be feasible during a repeat procedure.
Real‐Time Three‐Dimensional Echocardiography Permits Quantification of Left Ventricular Mechanical Dyssynchrony and Predicts Acute Response to Cardiac Resynchronization Therapy
Authors: MARSAN NINA AJMONE , BLEEKER GABE B. , YPENBURG CLAUDIA , GHIO STEFANO , VAN DE VEIRE NICO R. , HOLMAN EDUARD R. , VAN DER WALL ERNST E. , TAVAZZI L. , SCHALIJ MARTIN J. , BAX JEROEN J.
Published: March 2008

Objective: To evaluate the value of real‐time three‐dimensional echocardiography (RT3DE) to predict acute response to cardiac resynchronization therapy (CRT).

Methods: Sixty consecutive heart failure patients scheduled for CRT were included. RT3DE was performed before and within 48 hours after pacemaker implantation to calculate both left ventricular (LV) volumes and LV dyssynchrony. LV dyssynchrony was defined as the standard deviation of the time taken to reach the minimum systolic volume for 16 LV segments (referred to as the systolic dyssynchrony index, SDI). Patients were subsequently divided into acute responders or nonresponders, based on a reduction ≥ 15% in LV end‐systolic volume immediately after CRT.

Results: Four patients (7%) were excluded from further analysis because of either suboptimal apical acquisitions or significant translation artifacts. Out of the remaining 56 patients, 35 patients (63%) were classified as acute responders. Baseline characteristics were similar between responders and nonresponders, except for the SDI, which was larger in responders. Moreover, responders demonstrated a significant reduction of SDI immediately after CRT (from 9.7 ± 4.1% to 3.6 ± 1.8%, P < 0.0001), whereas SDI did not change in nonresponders (3.4 ± 1.8% vs 3.1 ± 1.1%, NS). ROC curve analysis revealed that a cut‐off value for SDI of 5.6% yielded a sensitivity of 88% with a specificity of 86% to predict acute echocardiographic response to CRT (AUC 0.96).

Conclusion: RT3DE is highly predictive for acute response to CRT (sensitivity 88% and specificity 86%). In addition, RT3DE allows assessment of changes in LV volumes and LV ejection fraction before and after CRT implantation.
Prevalence and Characteristics of Continuous Electrical Activity in Patients with Paroxysmal and Persistent Atrial Fibrillation
Authors: TADA HIROSHI , YOSHIDA KENTARO , CHUGH AMAN , BOONYAPISIT WARANGKNA , CRAWFORD THOMAS , SARRAZIN JEAN‐FRANCOIS , KUHNE MICHAEL , CHALFOUN NAGIB , WELLS DARRYL , DEY SUJOYA , VEERAREDDY SRIKAR , BILLAKANTY SREE , WONG WAI SHUN , KALRA DINESH , KFAHAGI AYMAN , GOOD ERIC , JONGNARANGSIN KRIT , PELOSI FRANK , BOGUN FRANK , MORADY FRED , ORAL HAKAN
Published: March 2008

Background:
Complex fractionated atrial electrograms (CFAEs) may play a role in the genesis of atrial fibrillation (AF). One type of CFAE is continuous electrical activity (CEA). The prevalence and characteristics of CEA in patients with paroxysmal and persistent AF are unclear.

Methods and Results:
In 44 patients (age = 59 ± 8 years) with paroxysmal (25) or persistent (19) AF, bipolar electrograms were systematically recorded for ≥5 seconds at 24 left atrial (LA) sites, including 8 antral sites, and 2 sites within the coronary sinus (CS). CEA was defined as continuous depolarization for >1 second with no isoelectric interval. CEA was recorded at the LA septum (79%), antrum (66%), posterior (68%) and anterior walls (67%), roof (66%), base of the LA appendage (61%), inferior wall (61%), posterior mitral annulus (48%), CS (41%), and in the LA appendage (14%). Antral CEA was equally prevalent in patients with paroxysmal (63%) and persistent AF (70%, P = 0.12). In patients with paroxysmal AF, the prevalence of CEA was similar among antral and nonantral LA sites, except for the LA appendage. However, in patients with persistent AF, CEA was more prevalent at the nonantral (80%) than antral sites (70%, P = 0.03). CEA at nonantral sites except the CS was more prevalent in persistent than in paroxysmal AF (80% vs 57%, P < 0.001). The mean duration of intermittent episodes of CEA was longer in persistent than in paroxysmal AF (P < 0.001).

Conclusions:
The higher prevalence and duration of CEA at nonantral sites in persistent than in paroxysmal AF is consistent with a greater contribution of LA reentrant mechanisms in persistent AF. However, the high prevalence of CEA at nonantral sites in paroxysmal atrial fibrillation (PAF) suggests that CEA alone is a nonspecific marker of appropriate target sites for ablation of AF. The characteristics of CEA that most accurately identify drivers of AF remain to be determined.
Coronary Sinus Focus Acting as a Trigger for Atrial Fibrillation in a Patient with Orthotopic Heart Transplantation
Authors: KANJ MOHAMED , DI BIASE LUIGI , WAZNI OUSSAMA , NATALE ANDREA
Published: March 2008

We report the case of a 46‐year‐old man who presented for evaluation and ablation of paroxysmal atrial fibrillation, which he developed one year prior to presentation and that was refractory to antiarrhythmic drugs. His past medical and surgical history was significant for orthotopic heart transplantation (OHTX) and idiopathic nonfamilial dilated cardiomyopathy.

We present the first case of post OHTX where the coronary sinus was acting as a trigger and driver for atrial fibrillation. This illustrates an unusual role of nonpulmonary vein foci in the etiology of atrial fibrillation in patients status post OHTX.
Residual‐Based Diagnostics for Structural Equation Models
Authors: Sánchez B. N. , Houseman E. A. , Ryan L. M.
Published: March 2008

Summary Classical diagnostics for structural equation models are based on aggregate forms of the data and are ill suited for checking distributional or linearity assumptions. We extend recently developed goodness‐of‐fit tests for correlated data based on subject‐specific residuals to structural equation models with latent variables. The proposed tests lend themselves to graphical displays and are designed to detect misspecified distributional or linearity assumptions. To complement graphical displays, test statistics are defined; the null distributions of the test statistics are approximated using computationally efficient simulation techniques. The properties of the proposed tests are examined via simulation studies. We illustrate the methods using data from a study of in utero lead exposure.
Fatigue Behavior of Alumina–Zirconia Multilayered Ceramics
Authors: Bermejo Raúl , Torres Yadir , Anglada Marc , Llanes Luis
Published: March 2008

The influence of sustained and cyclic loading on the crack growth behavior of a multilayered alumina–zirconia composite exhibiting high internal compressive stresses is investigated. The study was conducted on precracked notched samples and focused on evaluating the static and cyclic fatigue resistance to crack extension beyond the first arresting interface (threshold) as well as the mechanisms involved during stable crack growth through the layered structure for each loading condition studied. Although it is found that the layered composite is prone to subcritical crack growth, the effectiveness of operative toughening mechanisms, i.e., compressive residual stresses as well as crack bifurcation and delamination at interfaces, is observed to be independent of the loading conditions. As a consequence, fatigue degradation of the multilayered ceramics studied is restricted to the intrinsic environmental‐assisted cracking of the individual layers, pointing them out as toughened composites practically immune to variable stresses and much less static and cyclic fatigue sensitive than other structural ceramics.
Internationalizing the Broselow Tape: How Reliable Is Weight Estimation in Indian Children
Authors: Ramarajan Naresh , Krishnamoorthi Rajesh , Strehlow Matthew , Quinn James , Mahadevan Swaminatha V.
Published: March 2008

Objectives:  The Broselow pediatric emergency weight estimation tape is an accurate method of estimating children’s weights based on height–weight correlations and determining standardized medication dosages and equipment sizes using color‐coded zones. The study objective was to determine the accuracy of the Broselow tape in the Indian pediatric population.

Methods:  The authors conducted a 6‐week prospective cross‐sectional study of 548 children at a government pediatric hospital in Chennai, India, in three weight‐based groups: <10 kg (n = 175), 10–18 kg (n = 197), and >18 kg (n = 176). Measured weight was compared to Broselow‐predicted weight, and the percentage difference was calculated. Accuracy was defined as agreement on Broselow color‐coded zones, as well as agreement within 10% between the measured and Broselow‐predicted weights. A cross‐validated correction factor was also derived.

Results:  The mean percentage differences were −2.4, −11.3, and −12.9% for each weight‐based group. The Broselow color‐coded zone agreement was 70.8% in children weighing less than 10 kg, but only 56.3% in the 10‐ to 18‐kg group and 37.5% in the >18‐kg group. Agreement within 10% was 52.6% for the <10‐kg group, but only 44.7% for the 10‐ to 18‐kg group and 33.5% for the >18‐kg group. Application of a 10% weight‐correction factor improved the percentages to 77.1% for the 10‐ to 18‐kg group and 63.0% for the >18‐kg group.

Conclusions:  The Broselow tape overestimates weight by more than 10% in Indian children >10 kg. Weight overestimation increases the risk of medical errors due to incorrect dosing or equipment selection. Applying a 10% weight‐correction factor may be advisable.
A Decision Rule for Predicting Bacterial Meningitis in Children with Cerebrospinal Fluid Pleocytosis When Gram Stain Is Negative or Unavailable
Authors: Bonsu Bema K. , Ortega Henry W. , Marcon Mario J. , Harper Marvin B.
Published: March 2008

Objectives:  Among children with cerebrospinal fluid (CSF) pleocytosis, the task of separating aseptic from bacterial meningitis is hampered when the CSF Gram stain result is unavailable, delayed, or negative. In this study, the authors derive and validate a clinical decision rule for use in this setting.

Methods:  This was a review of peripheral blood and CSF test results from 78 children (<19 years) presenting to Children’s Hospital Columbus from 1998 to 2002. For those with a CSF leukocyte count of >7/μL, a rule was created for separating bacterial from viral meningitis that was based on routine laboratory tests, but excluded Gram stain. The rule was validated in 158 subjects seen at the same site (Columbus, 2002–2004) and in 871 subjects selected from a separate site (Boston, 1993–1999).

Results:  One point each (maximum, 6 points) was assigned for leukocytes >597/μL, neutrophils >74%, glucose <38 mg/dL, and protein >97 mg/dL in CSF and for leukocytes >17,000/mL and bands to neutrophils >11% in peripheral blood. Areas under receiver‐operator‐characteristic curves (AROCs) for the resultant score were 0.98 for the derivation set and 0.90 and 0.97, respectively, for validation sets from Columbus and Boston. Sensitivity and specificity pairs for the Boston data set were 100 and 44%, respectively, at a score of 0 and 97 and 81% at a score of 1. Likelihood ratios (LRs) increased from 0 at a score of 0 to 40 at a score of ≥4.

Conclusions:  Among children with CSF pleocytosis, a prediction score based on common tests of CSF and peripheral blood and intended for children with unavailable, negative, or delayed CSF Gram stain results has value for diagnosing bacterial meningitis.
Gender Disparity in Analgesic Treatment of Emergency Department Patients with Acute Abdominal Pain
Authors: Chen Esther H. , Shofer Frances S. , Dean Anthony J. , Hollander Judd E. , Baxt William G. , Robey Jennifer L. , Sease Keara L. , Mills Angela M.
Published: March 2008

Objectives:  Oligoanalgesia for acute abdominal pain historically has been attributed to the provider’s fear of masking serious underlying pathology. The authors assessed whether a gender disparity exists in the administration of analgesia for acute abdominal pain.

Methods:  This was a prospective cohort study of consecutive nonpregnant adults with acute nontraumatic abdominal pain of less than 72 hours’ duration who presented to an urban emergency department (ED) from April 5, 2004, to January 4, 2005. The main outcome measures were analgesia administration and time to analgesic treatment. Standard comparative statistics were used.

Results:  Of the 981 patients enrolled (mean age ± standard deviation [SD] 41 ± 17 years; 65% female), 62% received any analgesic treatment. Men and women had similar mean pain scores, but women were less likely to receive any analgesia (60% vs. 67%, difference 7%, 95% confidence interval [CI] = 1.1% to 13.6%) and less likely to receive opiates (45% vs. 56%, difference 11%, 95% CI = 4.1% to 17.1%). These differences persisted when gender‐specific diagnoses were excluded (47% vs. 56%, difference 9%, 95% CI = 2.5% to 16.2%). After controlling for age, race, triage class, and pain score, women were still 13% to 25% less likely than men to receive opioid analgesia. There was no gender difference in the receipt of nonopioid analgesia. Women waited longer to receive their analgesia (median time 65 minutes vs. 49 minutes, difference 16 minutes, 95% CI = 3.5 to 33 minutes).

Conclusions:  Gender bias is a possible explanation for oligoanalgesia in women who present to the ED with acute abdominal pain. Standardized protocols for analgesic administration may ameliorate this discrepancy.
Compliance with Recommended Cancer Screening among Emergency Department Patients: A Multicenter Survey
Authors: Ginde Adit A. , Millen Jennifer C. , Love Jennifer S. , Pang Jessica M. , Camargo Carlos A
Published: March 2008

Objectives:  The objectives were to measure compliance with, and possible sociodemographic disparities for, cancer screening among emergency department (ED) patients.

Methods:  This was a cross‐sectional survey in three academic EDs in Boston. The authors enrolled consecutive adult patients during two 24‐hour periods at each site. Self‐reported compliance with standard recommendations for cervical, breast, testicular, and prostate cancer screening were measured. The chi‐square test was used test to evaluate associations between demographic variables and cancer screening compliance.

Results:  The authors enrolled 387 patients (81% of those eligible). The participants had a mean (±standard deviation) age of 44 (±18) years and were 52% female, 16% Hispanic, and 65% white. Sixty‐seven percent (95% confidence interval [CI] = 60% to 73%) of all women reported Pap smear examinations in the past 3 years, 92% (95% CI = 85% to 96%) of women aged ≥40 years reported clinical breast examinations, and 88% (95% CI = 81% to 94%) of women aged ≥40 years reported mammography. Fifty‐one percent (95% CI = 40% to 61%) of men aged 18–39 years reported testicular self‐examinations, and among men aged ≥40 years, 79% (95% CI = 69% to 87%) reported digital rectal examinations (DREs) and 51% (95% CI = 40% to 61%) reported prostate‐specific antigen (PSA) testing. Racial and ethnic minorities reported slightly lower rates of clinical breast examinations and testicular self‐examinations.

Conclusions:  Most women and a majority of men in our ED‐based study were compliant with recommended measures of cervical, breast, testicular, and prostate cancer screening. No large sociodemographic disparities in our patient population were identified. Based on these data, and the many other pressing public health needs of our ED population, the authors would be reluctant to promote ED‐based cancer screening initiatives at this time.
H2S‐induced pancreatic acinar cell apoptosis is mediated via JNK and p38 MAP kinase
Authors: Adhikari Sharmila , Bhatia Madhav
Published: March 2008

Treatment of pancreatic acinar cells by hydrogen sulphide has been shown to induce apoptosis. However, a potential role of mitogen‐activated protein kinases (MAPKs) in this apoptotic pathway remains unknown. The present study examined the role of MAPKs in H2S‐induced apoptosis in mouse pancreatic acinar cells. Pancreatic acinar cells were treated with 10 μM NaHS (a donor of H2S) for 3 hrs. For the evaluation of the role of MAPKs, PD98059, SP600125 and SB203580 were used as MAPKs inhibitors for ERK1/2, JNK1/2 and p38 MAPK, respectively. We observed activation of ERK1/2, JNK1/2 and p38 when pancreatic acini were exposed to H2S. Moreover, H2S‐induced ERK1/2, JNK1/2 and p38 activation were blocked by pre‐treatment with their corresponding inhibitor in a dose‐dependent manner. H2S‐induced apoptosis led to an increase in caspase 3 activity and this activity was attenuated when caspase 3 inhibitor were used. Also, the cleavage of caspase 3 correlated with that of poly‐(ADP‐ribose)‐polymerase (PARP) cleavage. H2S treatment induced the release of cytochrome c, smac from mitochondria into the cytoplasm, translocation of Bax into mitochondria and decreased the protein level of Bcl‐2. Inhibition of ERK1/2 using PD98059 caused further enhancement of apoptosis as evidenced by annexin V staining, while SP600125 and SB203580 abrogated H2S‐induced apoptosis. Taken together, the data suggest that activation of ERKs promotes cell survival, whereas activation of JNKs and p38 MAP kinase leads to H2S‐induced apoptosis.
C‐terminal 37 residues of LRP promote the amyloidogenic processing of APP independent of FE65
Authors: Lakshmana Madepalli K. , Chen Eunice , Yoon Il‐Sang , Kang David E.
Published: March 2008

The major defining pathological hallmark of Alzheimer's disease (AD) is the accumulation of amyloid β protein (Aβ), a small peptide derived from β‐ and γ‐secretase cleavages of the amyloid precursor protein (APP). Recent studies have shown that the Low‐density lipoprotein receptor‐related protein (LRP) plays a pivotal role in the trafficking of APP and generation of Aβ. In particular, we recently showed that the soluble cytoplasmic tail of LRP (LRP‐ST) without a membrane tether was sufficient to promote Aβ generation. In this study, we demonstrate that the last 37 residues of LRP cytoplasmic tail (LRP‐C37) lacking the NPxY motifs and FE65 binding mediate the core pro‐amyloidogenic activity of LRP‐ST. Moreover, we show that the conserved dileucine motif within the LRP‐C37 region is a key determinant of its Aβ promoting activity. Finally, results from a yeast two‐hybrid screen using LRP‐C37 region as bait reveal four new LRP‐binding proteins implicated in intracellular signalling and membrane protein trafficking. Our findings indicate that the LRP‐C37 sequence represents a new protein‐binding domain that may be useful as a therapeutic target and tool to lower Aβ generation in AD.