bluuebunny/crossref_metadata_2025 huggingface dataset:
Liposome‐Encapsulated Hemoglobin Reduces the Size of Cerebral Infarction in Rats: Effect of Oxygen Affinity
Authors: Fukumoto Dai , Kawaguchi Akira T. , Haida Munetaka , Yamano Mariko , Ogata Yoshitaka , Tsukada Hideo
Published: January 2009

Liposome‐encapsulated hemoglobin (LEH) with a low oxygen affinity (l‐LEH, P50 = 45 mm Hg) was found to be protective in the rodent and primate models of ischemic stroke. This study investigated the role of LEH with a high O2 affinity (h‐LEH, P50 = 10 mm Hg) in its protective effect on brain ischemia. The extent of cerebral infarction was determined 24 h after photochemically induced thrombosis of the middle cerebral artery from the integrated area of infarction detected by triphenyltetrazolium chloride staining in rats receiving various doses of h‐LEH as well as l‐LEH. Both h‐LEH and l‐LEH significantly reduced the extent of cortical infarction. h‐LEH remained protective at a lower concentration (minimal effective dose [MED]: 0.08 mL/kg) than l‐LEH (MED: 2 mL/kg) in the cortex. h‐LEH reduced the infarction extent in basal ganglia as well (MED: 0.4 mL/kg), whereas l‐LEH provided no significant protection. h‐LEH provided better protection than l‐LEH. The protective effect of both high‐ and low‐affinity LEH may suggest the importance of its small particle size (230 nm) as compared to red blood cells. The superiority of h‐LEH over l‐LEH supports an optimal O2 delivery to the ischemic penumbra as the mechanism of action in protecting against brain ischemia and reperfusion.
In Vivo Distribution of Liposome‐Encapsulated Hemoglobin Determined by Positron Emission Tomography
Authors: Urakami Takeo , Kawaguchi Akira T. , Akai Shuji , Hatanaka Kentaro , Koide Hiroyuki , Shimizu Kosuke , Asai Tomohiro , Fukumoto Dai , Harada Norihiro , Tsukada Hideo , Oku Naoto
Published: January 2009

Positron emission tomography (PET) is a noninvasive imaging technology that enables the determination of biodistribution of positron emitter‐labeled compounds. Lipidic nanoparticles are useful for drug delivery system (DDS), including the artificial oxygen carriers. However, there has been no appropriate method to label preformulated DDS drugs by positron emitters. We have developed a rapid and efficient labeling method for lipid nanoparticles and applied it to determine the movement of liposome‐encapsulated hemoglobin (LEH). Distribution of LEH in the rat brain under ischemia was examined by a small animal PET with an enhanced resolution. While the blood flow was almost absent in the ischemic region observed by [15O]H2O imaging, distribution of 18F‐labeled LEH in the region was gradually increased during 60‐min dynamic PET scanning. The results suggest that LEH deliver oxygen even into the ischemic brain from the periphery toward the core of ischemia. The real‐time observation of flow pattern, deposition, and excretion of LEH in the ischemic rodent brain was possible by the new methods of positron emitter labeling and PET system with a high resolution.
S‐Nitrosylated Pegylated Hemoglobin Reduces the Size of Cerebral Infarction in Rats
Authors: Kawaguchi Akira T. , Nakai Kunihiko , Fukumoto Dai , Yamano Mariko , Haida Munetaka , Tsukada Hideo
Published: January 2009

Cell‐free hemoglobin‐based oxygen carriers have well‐documented safety and efficacy problems such as nitric oxide (NO) scavenging and extravasation that preclude clinical use. To counteract these effects, we developed S‐nitrosylated pegylated hemoglobin (SNO‐PEG‐Hb, P50 = 12 mm Hg) and tested it in a brain ischemia and reperfusion model. Neurological function and extent of cerebral infarction was determined 24 h after photochemically induced thrombosis of the middle cerebral artery in the rat. Infarction extent was determined from the integrated area in the cortex and basal ganglia detected by triphenyltetrazolium chloride staining in rats receiving various doses of SNO‐PEG‐Hb (2, 0.4, and 0.08 mL/kg) and compared with rats receiving pegylated hemoglobin without S‐nitrosylation (PEG‐Hb) or saline of the same dosage. Results indicated that successive dilution revealed SNO‐PEG‐Hb but not PEG‐Hb to be effective in reducing the size of cortical infarction but not neurological function at a dose of 0.4 mL/kg. In conclusion, SNO‐PEG‐Hb in a dose of 0.4 mL/kg (Hb 24 mg/kg) showed to be most effective in reducing the size of cortical infarction, however, without functional improvement.
Responsiveness and Clinical Utility of the Geriatric Self‐Efficacy Index for Urinary Incontinence
Authors: Tannenbaum Cara , Brouillette Judith , Michaud Julie , Korner‐Bitensky Nicol , Dumoulin Chantale , Corcos Jacques , Tu Le Mai , Lemieux Marie‐Claude , Ouellet Stephane , Valiquette Luc
Published: January 2009

OBJECTIVES: To report on the responsiveness testing and clinical utility of the 12‐item Geriatric Self‐Efficacy Index for Urinary Incontinence (GSE‐UI).

DESIGN: Prospective cohort study.

SETTING: Six urinary incontinence (UI) outpatient clinics in Quebec, Canada.

PARTICIPANTS: Community‐dwelling incontinent adults aged 65 and older.

MEASUREMENTS: The abridged 12‐item GSE‐UI, measuring older adults' level of confidence for preventing urine loss, was administered to all new consecutive incontinent patients 1 week before their initial clinic visit, at baseline, and 3 months posttreatment. At follow‐up, a positive rating of improvement in UI was ascertained from patients and their physicians using the Patient's and Clinician's Global Impression of Improvement scales, respectively. Responsiveness of the GSE‐UI was calculated using Guyatt's change index. Its clinical utility was determined using receiver operating curves.

RESULTS: Eighty‐nine of 228 eligible patients (39.0%) participated (mean age 72.6+5.8, range 65–90). At 3‐month follow‐up, 22.5% of patients were very much better, and 41.6% were a little or much better. Guyatt's change index was 2.6 for patients who changed by a clinically meaningful amount and 1.5 for patients having experienced any level of improvement. An improvement of 14 points on the 12‐item GSE‐UI had a sensitivity of 75.1% and a specificity of 78.2% for detecting clinically meaningful changes in UI status. Mean GSE‐UI scores varied according to improvement status (P<.001) and correlated with changes in quality‐of‐life scores (r=0.7, P<.001) and reductions in UI episodes (r=0.4, P=.004).

CONCLUSION: The GSE‐UI is responsive and clinically useful.
The Co‐Occurrence of Chronic Diseases and Geriatric Syndromes: The Health and Retirement Study
Authors: Lee Pearl G. , Cigolle Christine , Blaum Caroline
Published: January 2009

OBJECTIVES: To analyze the co‐occurrence, in adults aged 65 and older, of five conditions that are highly prevalent, lead to substantial morbidity, and have evidence‐based guidelines for management and well‐developed measures of medical care quality.

DESIGN: Secondary data analysis of the 2004 wave of the Health and Retirement Study (HRS).

SETTING: Nationally representative health interview survey.

PARTICIPANTS: Respondents in the 2004 wave of the HRS aged 65 and older.

MEASUREMENTS: Self‐reported presence of five index conditions (three chronic diseases (coronary artery disease, congestive heart failure, and diabetes mellitus) and two geriatric syndromes (urinary incontinence and injurious falls)) and demographic information (age, sex, race, living situation, net worth, and education).

RESULTS: Eleven thousand one hundred thirteen adults, representing 37.1 million Americans aged 65 and older, were interviewed. Forty‐five percent were aged 76 and older, 58% were female, 8% were African American, and 4% resided in a nursing home. Respondents with more conditions were older and more likely to be female, single, and residing in a nursing home (all P<.001). Fifty‐six percent had at least one of the five index conditions, and 23% had two or more. Of respondents with one condition, 20% to 55% (depending on the index condition) had two or more additional conditions.

CONCLUSION: Five common conditions (3 chronic diseases, 2 geriatric syndromes) often co‐occur in older adults, suggesting that coordinated management of comorbid conditions, both diseases and geriatric syndromes, is important. Care guidelines and quality indicators, rather than considering one condition at a time, should be developed to address comprehensive and coordinated management of co‐occurring diseases and geriatric syndromes.
Carbon monoxide concentration in donated blood: relation to cigarette smoking and other sources
Authors: Åberg Anna‐Maja , Sojka Birgitta Nilsson , Winsö Ola , Abrahamsson Pernilla , Johansson Göran , Larsson Jan Erik
Published: January 2009

BACKGROUND: Carbon monoxide (CO) is normally present in the human body due to endogenous production of CO. CO can also be inhaled by exposure to external sources such as cigarette smoke, car exhaust, and fire. The purpose of this study was to investigate CO concentrations in blood from 410 blood donors at the blood center in Umeå, Sweden. To further evaluate the effects of cigarette smoking on CO concentrations, the elimination time for CO was examined in six volunteer smokers after a smoked cigarette.

STUDY DESIGN AND METHODS: Blood samples from whole blood donors were obtained during the blood center's routine operation. In connection with blood donations, demographic and behavioral data were collected from the donors. The CO concentration was determined using gas chromatography.

RESULTS: The majority of blood donors had approximately the same CO concentration (mean, 84.5 µmol/L). In 6 percent of the samples, the concentrations were higher than 130 µmol per L. The highest CO concentration was 561 µmol per L. The main source for these high CO concentrations appeared to be cigarette smoking. In the volunteer smokers, the elimination time after a smoked cigarette varied significantly, with elimination half‐lives from 4.7 to 8.4 hours.

CONCLUSION: These results show that blood bank red blood cell bags may have CO concentrations above the physiologic level. The time interval between cigarette smoking and blood donation seems to be a particularly important factor for elevated CO concentrations.
Two novel Jknull alleles derived from 222C>A in Exon 5 and 896G>A in Exon 9 of the JK gene
Authors: Liu Hsueng‐Mei , Lin Jeong‐Shi , Chen Pei‐Shan , Lyou Jau‐Yi , Chen Ying‐Ju , Tzeng Cheng‐Hwai
Published: January 2009

BACKGROUND: Polynesian Jknull is well known for its mutation as Intron 5 g>a at the 3′ splice acceptor site. After sequencing analysis, however, it was noticed that only three of eight samples with the Jknull phenotype carried typical homozygous Polynesian Jknull mutation. Five others were noted to be unreported heterozygous Polynesian Jknull mutation. An investigation was then conducted to characterize the underlying mechanism leading to this particular Jknull genotype.

STUDY DESIGN AND METHODS: Genomic DNA covering 5′‐untranslated region exons and intervening introns of the JK gene was amplified by polymerase chain reaction, and the fragments were directly sequenced. The sequencing results were compared with those published in literature and related biologic Web sites.

RESULTS: In all five samples with a heterozygous Polynesian Jknull mutation, additional mutations were identified. Two samples carried missense mutations: 222C>A (Asn74Lys) in Exon 5 and 499A>G (Met167Val) in Exon 7. Three others had missense mutation 896G>A (Gly299Glu) in Exon 9. These substituted amino acids were located either near or at transmembrane domains, respectively. In addition, two polymorphic nucleotides at positions −103 (a>g) and −119(c>a) from the 3′ end of Intron 1 were also Polynesian mutation–related.

CONCLUSIONS: In contrast to the typical homozygous Polynesian Jknull mutation, two novel heterozygous Jknull alleles were noted to be associated with the Jknull phenotype. One carried missense mutation 222C>A in Exon 5, and the other had 896G>A missense mutation in Exon 9. These findings may have implications in designing a molecular screening assay for people with the Jknull phenotype.
Real‐World Personal Conversations Using a Hands‐Free Embedded Wireless Device While Driving: Effect on Airbag‐Deployment Crash Rates
Authors: Young Richard A. , Schreiner Christopher
Published: January 2009

A wireless device embedded in the vehicle allowed the user to engage in a personal hands‐free conversation (HFC), and automatically placed an emergency notification call to an OnStar call center if the vehicle was involved in a crash in which its airbag deployed. A database stored the exact counts, start timestamps, and billed durations of all HFC and airbag notification calls. In 30 months of naturalistic driving, there were 91 million HFC calls from an average of 323,994 drivers per month who made calls. There were 14 airbag deployments in 276 million driver‐minutes of HFC conversation for an exposed incidence rate of 5.08 airbag crashes per 100 million driver‐minutes. There were 2,023 airbag deployments in an estimated 24.7 billion driver‐minutes of no HFC conversation for a not‐exposed incidence rate of 8.18 airbag crashes per 100 million driver‐minutes. The crash incidence rate ratio (IRR) is the ratio of these two rates or 0.62 (95% C.I. 0.37 to 1.05). Sensitivity analyses controlled for the impact on the crash IRR of estimated time spent driving per day and calls by passengers. Counting all crashes as much as 20 minutes later than a call as related to that call gave similar results. We conclude that for personal conversations using a hands‐free embedded device the risk of an airbag crash is somewhere in a range from a moderately lower risk to a risk near that of driving without a recent personal conversation. These results are not consistent with the large increase in crash risk reported in epidemiological studies using the case‐crossover method.
High‐Water Marks: High Risk Appetites? Convex Compensation, Long Horizons, and Portfolio Choice
Authors: PANAGEAS STAVROS , WESTERFIELD MARK M.
Published: January 2009

We study the portfolio choice of hedge fund managers who are compensated by high‐water mark contracts. We find that even risk‐neutral managers do not place unbounded weights on risky assets, despite option‐like contracts. Instead, they place a constant fraction of funds in a mean‐variance efficient portfolio and the rest in the riskless asset, acting as would constant relative risk aversion (CRRA) investors. This result is a direct consequence of the in(de)finite horizon of the contract. We show that the risk‐seeking incentives of option‐like contracts rely on combining finite horizons and convex compensation schemes rather than on convexity alone.
Share Repurchases and Pay‐Performance Sensitivity of Employee Compensation Contracts
Authors: BABENKO ILONA
Published: January 2009

I show that share repurchases increase pay‐performance sensitivity of employee compensation and lead to greater employee effort and higher stock prices. Consistent with the model, I find that after repurchases, employees and managers receive fewer stock option and equity grants, and that the market reacts favorably to repurchase announcements when employees have many unvested stock options. Managers are more likely to initiate share repurchases when employees hold a large stake in the firm. Moreover, since employees are forced to bear more risk in firms that repurchase shares, they exercise their stock options earlier and receive higher compensation.
Financing Innovation and Growth: Cash Flow, External Equity, and the 1990s R&D Boom
Authors: BROWN JAMES R. , FAZZARI STEVEN M. , PETERSEN BRUCE C.
Published: January 2009

The financing of R&D provides a potentially important channel to link finance and economic growth, but there is no direct evidence that financial effects are large enough to impact aggregate R&D. U.S. firms finance R&D from volatile sources: cash flow and stock issues. We estimate dynamic R&D models for high‐tech firms and find significant effects of cash flow and external equity for young, but not mature, firms. The financial coefficients for young firms are large enough that finance supply shifts can explain most of the dramatic 1990s R&D boom, which implies a significant connection between finance, innovation, and growth.
CEO Compensation and Board Structure
Authors: CHHAOCHHARIA VIDHI , GRINSTEIN YANIV
Published: January 2009

In response to corporate scandals in 2001 and 2002, major U.S. stock exchanges issued new board requirements to enhance board oversight. We find a significant decrease in CEO compensation for firms that were more affected by these requirements, compared with firms that were less affected, taking into account unobservable firm effects, time‐varying industry effects, size, and performance. The decrease in compensation is particularly pronounced in the subset of affected firms with no outside blockholder on the board and in affected firms with low concentration of institutional investors. Our results suggest that the new board requirements affected CEO compensation decisions.
Do Entrenched Managers Pay Their Workers More?
Authors: CRONQVIST HENRIK , HEYMAN FREDRIK , NILSSON MATTIAS , SVALERYD HELENA , VLACHOS JONAS
Published: January 2009

Analyzing a panel that matches public firms with worker‐level data, we find that managerial entrenchment affects workers' pay. CEOs with more control pay their workers more, but financial incentives through cash flow rights ownership mitigate such behavior. Entrenched CEOs pay more to employees closer to them in the corporate hierarchy, geographically closer to the headquarters, and associated with conflict‐inclined unions. The evidence is consistent with entrenched CEOs paying more to enjoy private benefits such as lower effort wage bargaining and improved social relations with employees. Our results show that managerial ownership and corporate governance can play an important role for employee compensation.
Market Sidedness: Insights into Motives for Trade Initiation
Authors: SARKAR ASANI , SCHWARTZ ROBERT A.
Published: January 2009

We infer motives for trade initiation from market sidedness. We define trading as more two‐sided (one‐sided) if the correlation between the number of buyer‐ and seller‐initiated trades increases (decreases), and assess changes in sidedness (relative to a control sample) around events that identify trade initiators. Consistent with asymmetric information, trading is more one‐sided before merger news. Consistent with belief heterogeneity, trading is more two‐sided before earnings and macro announcements with greater dispersion in analyst forecasts, and after news with larger announcement surprises. We examine the codeterminacy of sidedness, bid‐ask spread, volatility, number of trades, and order imbalance.
Private Benefits of Control, Ownership, and the Cross‐listing Decision
Authors: DOIDGE CRAIG , KAROLYI G. ANDREW , LINS KARL V. , MILLER DARIUS P. , STULZ RENÉ M.
Published: January 2009

This paper investigates how a foreign firm's decision to cross‐list on a U.S. stock exchange is related to the consumption of private benefits of control by its controlling shareholders. Theory has proposed that when private benefits are high, controlling shareholders are less likely to choose to cross‐list in the United States because of constraints on the consumption of private benefits resulting from such listings. Using several proxies for private benefits related to the control and cash flow ownership rights of controlling shareholders, we find support for this hypothesis with a sample of more than 4,000 firms from 31 countries.
Right Ventricular Outflow Tract Septal Pacing: Long‐Term Follow‐Up of Ventricular Lead Performance
Authors: MEDI CAROLINE , MOND HARRY G.
Published: January 2009

Background: The detrimental effects of right ventricular apical pacing on left ventricular function has driven interest in selective site pacing, predominantly on the right ventricular outflow tract (RVOT) septum. There is currently no information on long‐term ventricular lead electrical performance from this site.

Methods: A total of 100 patients with ventricular lead placement on the RVOT septum undergoing pacemaker implantation for bradycardia indications were analyzed retrospectively. Lead positioning was confirmed with the use of fluoroscopy. Long‐term (1 year) follow‐up was obtained in 92 patients. Information on stimulation threshold, R‐wave sensing, lead impedance, and lead complications were collected.

Results: Lead performance at the RVOT septal position was stable in the long term. Ventricular electrical parameters were acceptable with stable long‐term stimulation thresholds, sensing, and impedance for all lead types. One‐year results demonstrated mean stimulation threshold of 0.71 ± 0.25 V, mean R wave of 12.4 ± 6.05 mV, and mean impedance values of 520 ± 127 Ω. There were no cases of high pacing thresholds or inadequate sensing.

Conclusions: This study confirms satisfactory long‐term performance with leads placed on the RVOT septum, comparable to traditional pacing sites. It is now time to undertake studies to examine the long‐term hemodynamic effects of RVOT septal pacing.
Reversal of Atrial Remodeling after Cardioversion of Persistent Atrial Fibrillation Measured with Magnetocardiography
Authors: LEHTO MIKA , JURKKO RAIJA , PARIKKA HANNU , MÄNTYNEN VILLE , VÄÄNÄNEN HEIKKI , MONTONEN JUHA , VOIPIO‐PULKKI LIISA‐MARIA , TOIVONEN LAURI , LAINE MIKA
Published: January 2009

Background: Atrial fibrillation (AF) causes electrical, functional, and structural changes in the atria. We examined electrophysiologic remodeling caused by AF and its reversal noninvasively by applying a new atrial signal analysis based on magnetocardiography (MCG).

Methods: In 26 patients with persistent AF, MCG, signal‐averaged electrocardiography (SAECG), and echocardiography were performed immediately after electrical cardioversion (CV), and repeated after 1 month in 15 patients who remained in sinus rhythm (SR). Twenty‐four matched subjects without history of AF served as controls. P‐wave duration (Pd) and dispersion (standard deviation of Pd values in individual channels) and root mean square amplitudes of the P wave over the last 40 ms portions (RMS40) were determined.

Results: In MCG Pd was longer (122.8 ± 18.2 ms vs 101.5 ± 14.6 ms, P < 0.01) and RMS40 was higher (60.4 ± 28.2 vs 46.9 ± 19.1 fT) in AF patients immediately after CV as compared to the controls. In SAECG Pd dispersion was increased in AF patients. Mitral A‐wave velocity and left atrial (LA) contraction were decreased and LA diameter was increased (all P < 0.01). After 1 month, Pd in MCG still remained longer and LA diameter greater (both P < 0.05), while RMS40 in MCG, Pd dispersion in SAECG, mitral A‐wave velocity, and LA contraction were recovered.

Conclusions: Magnetocardiographically detected atrial electrophysiologic alterations in persistent AF diminish rapidly although incompletely during maintained SR after CV. This might be related to the known early high and late lower, but still existent tendency to AF relapses.
Insights into the Effects of Contraction Dyssynchrony on Global Left Ventricular Mechano‐Energetic Function
Authors: JOHNSON LAUREN , SIMON MARC A. , PINSKY MICHAEL R. , SHROFF SANJEEV G.
Published: January 2009

Background: The effects of dyssynchrony on global left ventricular (LV) mechanics have been well documented; however, its impact on LV energetics has received less attention.

Objective: To assess the effects of LV contraction dyssynchrony on global LV mechano‐energetic function in a pacing‐induced acute model of dyssynchrony.

Methods: Using blood‐perfused isolated rabbit heart preparations (n = 11), LV pressure, coronary flow, and arteriovenous oxygen content difference were recorded for isovolumic contractions under right atrial (RA) pacing (control) and simultaneous RA and right ventricular outflow tract (RVOT) pacing (dyssynchrony). LV mechanical function was quantified by the end‐systolic pressure‐volume relationship (ESPVR). Myocardial oxygen consumption‐pressure‐volume area (MVO2‐PVA) relationship quantified LV energetic function. Internal PVA for MVO2 RVOT was calculated based on the MVO2‐PVA relationship for RA pacing. Thus, lost PVA (internal PVA–PVARVOT) represents the mechanical energy not observable at the global level.

Results: Compared to RA pacing, RVOT pacing depressed LV mechanics as indicated by a rightward shift of ESPVR (i.e., increase in Vd from 0.58 ± 0.10 to 0.67 ± 0.10 mL, P < 0.05). Despite depressed mechanics, RVOT pacing was associated with greater MVO2 such that the MVO2‐PVA relationship intercept was markedly increased from 0.025 ± 0.003 to 0.029 ± 0.003 mL•O2/beat/100gLV (P < 0.05). Excess MVO2 (i.e., MVO2 RVOT– MVO2 RA) significantly correlated with lost PVA (R2= 0.54, P < 0.001).

Conclusion: A potential mechanism explaining the observed increase in MVO2 with dyssynchrony may be that the measured PVA at the global level underestimates the internal PVA at the cellular level, which is likely to be the true determinant of MVO2.
Profound Hypotension Due to Slow Atrioventricular Nodal Pathway Conduction during Atrial Tachycardia
Authors: NAZARIAN SAMAN , DONG JUN , TOMASELLI GORDON F. , MARINE JOSEPH E.
Published: January 2009

Paroxysmal supraventricular tachycardia (SVT) may have a variety of hemodynamic effects depending on rate, patient volume status, and presence of structural heart disease or left bundle branch block. We report a case of a patient with atrial tachycardia and dual atrioventricular (AV) nodal physiology who developed profound hypotension during transition from fast to slow AV nodal pathway conduction, despite similar tachycardia cycle length. This case illustrates the potential importance of AV timing in determining the hemodynamic effect of SVT.
Use of Coronary Venous Angioplasty to Facilitate Optimal Placement of Left Ventricular Lead during CRT
Authors: OSMAN FAIZEL , KUNDU SUMAN , TUAN JUIN , PATHMANATHAN RAVI K.
Published: January 2009

Cardiac resynchronization therapy (CRT) has become an accepted treatment for selected patients with drug‐resistant heart failure. In some cases CRT implantation can be difficult, particularly optimal left ventricular stimulation through proper lead placement. Difficulties can arise from venous stenosis, atypical and tortuous coronary sinus anatomy, presence of venous valves, postoperative deformation, and absence of vessels in the target location. Various methods adapted from percutaneous coronary artery intervention can be applied to resolve these problems and ensure a good lead position.
A Multilevel Model for Continuous Time Population Estimation
Authors: Sutherland Jason M. , Castelluccio Pete , Schwarz Carl James
Published: January 2009

Summary Statistical methods have been developed and applied to estimating populations that are difficult or too costly to enumerate. Known as multilist methods in epidemiological settings, individuals are matched across lists and estimation of population size proceeds by modeling counts in incomplete multidimensional contingency tables (based on patterns of presence/absence on lists). As multilist methods typically assume that lists are compiled instantaneously, there are few options available for estimating the unknown size of a closed population based on continuously (longitudinally) compiled lists. However, in epidemiological settings, continuous time lists are a routine byproduct of administrative functions. Existing methods are based on time‐to‐event analyses with a second step of estimating population size. We propose an alternative approach to address the twofold epidemiological problem of estimating population size and of identifying patient factors related to duration (in days) between visits to a health care facility. A Bayesian framework is proposed to model interval lengths because, for many patients, the data are sparse; many patients were observed only once or twice. The proposed method is applied to the motivating data to illustrate the methods' applicability. Then, a small simulation study explores the performance of the estimator under a variety of conditions. Finally, a small discussion section suggests opportunities for continued methodological development for continuous time population estimation.
Comparison of Hierarchical Bayesian Models for Overdispersed Count Data using DIC and Bayes' Factors
Authors: Millar Russell B.
Published: January 2009

Summary When replicate count data are overdispersed, it is common practice to incorporate this extra‐Poisson variability by including latent parameters at the observation level. For example, the negative binomial and Poisson‐lognormal (PLN) models are obtained by using gamma and lognormal latent parameters, respectively. Several recent publications have employed the deviance information criterion (DIC) to choose between these two models, with the deviance defined using the Poisson likelihood that is obtained from conditioning on these latent parameters. The results herein show that this use of DIC is inappropriate. Instead, DIC was seen to perform well if calculated using likelihood that was marginalized at the group level by integrating out the observation‐level latent parameters. This group‐level marginalization is explicit in the case of the negative binomial, but requires numerical integration for the PLN model. Similarly, DIC performed well to judge whether zero inflation was required when calculated using the group‐marginalized form of the zero‐inflated likelihood. In the context of comparing multilevel hierarchical models, the top‐level DIC was obtained using likelihood that was further marginalized by additional integration over the group‐level latent parameters, and the marginal densities of the models were calculated for the purpose of providing Bayes' factors. The computational viability and interpretability of these different measures is considered.
Incorporating Genotype Uncertainty into Mark–Recapture‐Type Models For Estimating Abundance Using DNA Samples
Authors: Wright Janine A. , Barker Richard J. , Schofield Matthew R. , Frantz Alain C. , Byrom Andrea E. , Gleeson Dianne M.
Published: January 2009

SummarySampling DNA noninvasively has advantages for identifying animals for uses such as mark–recapture modeling that require unique identification of animals in samples. Although it is possible to generate large amounts of data from noninvasive sources of DNA, a challenge is overcoming genotyping errors that can lead to incorrect identification of individuals. A major source of error is allelic dropout, which is failure of DNA amplification at one or more loci. This has the effect of heterozygous individuals being scored as homozygotes at those loci as only one allele is detected. If errors go undetected and the genotypes are naively used in mark–recapture models, significant overestimates of population size can occur. To avoid this it is common to reject low‐quality samples but this may lead to the elimination of large amounts of data. It is preferable to retain these low‐quality samples as they still contain usable information in the form of partial genotypes. Rather than trying to minimize error or discarding error‐prone samples we model dropout in our analysis. We describe a method based on data augmentation that allows us to model data from samples that include uncertain genotypes. Application is illustrated using data from the European badger (Meles meles).
Covariate Adjusted Correlation Analysis with Application to FMR1 Premutation Female Carrier Data
Authors: Şentürk Damla , Nguyen Danh V. , Tassone Flora , Hagerman Randi J. , Carroll Raymond J. , Hagerman Paul J.
Published: January 2009

Summary Motivated by molecular data on female premutation carriers of the fragile X mental retardation 1 (FMR1) gene, we present a new method of covariate adjusted correlation analysis to examine the association of messenger RNA (mRNA) and number of CGG repeat expansion in the FMR1 gene. The association between the molecular variables in female carriers needs to adjust for activation ratio (ActRatio), a measure which accounts for the protective effects of one normal X chromosome in females carriers. However, there are inherent uncertainties in the exact effects of ActRatio on the molecular measures of interest. To account for these uncertainties, we develop a flexible adjustment that accommodates both additive and multiplicative effects of ActRatio nonparametrically. The proposed adjusted correlation uses local conditional correlations, which are local method of moments estimators, to estimate the Pearson correlation between two variables adjusted for a third observable covariate. The local method of moments estimators are averaged to arrive at the final covariate adjusted correlation estimator, which is shown to be consistent. We also develop a test to check the nonparametric joint additive and multiplicative adjustment form. Simulation studies illustrate the efficacy of the proposed method. (Application to FMR1 premutation data on 165 female carriers indicates that the association between mRNA and CGG repeat after adjusting for ActRatio is stronger.) Finally, the results provide independent support for a specific jointly additive and multiplicative adjustment form for ActRatio previously proposed in the literature.
Flexible Designs for Genomewide Association Studies
Authors: Scherag André , Hebebrand Johannes , Schäfer Helmut , Müller Hans‐Helge
Published: January 2009

Summary Genomewide association studies attempting to unravel the genetic etiology of complex traits have recently gained attention. Frequently, these studies employ a sequential genotyping strategy: A large panel of markers is examined in a subsample of subjects, and the most promising markers are genotyped in the remaining subjects. In this article, we introduce a novel method for such designs enabling investigators to, for example, modify marker densities and sample proportions while strongly controlling the family‐wise type I error rate. Loss of efficiency is avoided by redistributing conditional type I error rates of discarded markers. Our approach can be combined with cost optimal designs and entails a greater flexibility than all previously suggested designs. Among other features, it allows for marker selections based upon biological criteria instead of statistical criteria alone, or the option to modify the sample size at any time during the course of the project. For practical applicability, we develop a new algorithm, subsequently evaluate it by simulations, and illustrate it using a real data set.
Adaptive Randomization for Multiarm Comparative Clinical Trials Based on Joint Efficacy/Toxicity Outcomes
Authors: Ji Yuan , Bekele B. Nebiyou
Published: January 2009

Summary We present an outcome‐adaptive randomization (AR) scheme for comparative clinical trials in which the primary endpoint is a joint efficacy/toxicity outcome. Under the proposed scheme, the randomization probabilities are unbalanced adaptively in favor of treatments with superior joint outcomes characterized by higher efficacy and lower toxicity. This type of scheme is advantageous from the patients' perspective because on average, more patients are randomized to superior treatments. We extend the approximate Bayesian time‐to‐event model in Cheung and Thall (2002, Biometrics 58, 89–97) to model the joint efficacy/toxicity outcomes and perform posterior computation based on a latent variable approach. Consequently, this allows us to incorporate essential information about patients with incomplete follow‐up. Based on the computed posterior probabilities, we propose an AR scheme that favors the treatments with larger joint probabilities of efficacy and no toxicity. We illustrate our methodology with a leukemia trial that compares three treatments in terms of their 52‐week molecular remission rates and 52‐week toxicity rates.
Flexible Regression Model Selection for Survival Probabilities: With Application to AIDS
Authors: DiRienzo A. Gregory
Published: January 2009

SummaryClinicians are often interested in the effect of covariates on survival probabilities at prespecified study times. Because different factors can be associated with the risk of short‐ and long‐term failure, a flexible modeling strategy is pursued. Given a set of multiple candidate working models, an objective methodology is proposed that aims to construct consistent and asymptotically normal estimators of regression coefficients and average prediction error for each working model, that are free from the nuisance censoring variable. It requires the conditional distribution of censoring given covariates to be modeled. The model selection strategy uses stepup or stepdown multiple hypothesis testing procedures that control either the proportion of false positives or generalized familywise error rate when comparing models based on estimates of average prediction error. The context can actually be cast as a missing data problem, where augmented inverse probability weighted complete case estimators of regression coefficients and prediction error can be used (Tsiatis, 2006, Semiparametric Theory and Missing Data). A simulation study and an interesting analysis of a recent AIDS trial are provided.
Implantable cardioverter defibrillator in maintenance hemodialysis patients with ventricular tachyarrhythmias: A single‐center experience
Authors: ITO Itaru , KONO Koichi , SHINBO Goro , TADOKORO Kazuyoshi , ABE Chikara , TAKEMURA Naoki , IEMURA Tomomi , MATSUHASHI Noritaka , NAKANO Nobuyuki , OTA Satoshi , ISHIMITSU Toshihiko , MATSUOKA Hiroaki
Published: January 2009

Patients with hemodialysis (HD) are at risk of death due to cardiac arrhythmias, worsening congestive heart failure (CHF), and noncardiac causes. This study reviews our experience with the use of implantable cardioverter defibrillators (ICDs) in patients with ventricular tachycardia who are under maintenance HD. We retrospectively reviewed 71 consecutive patients who underwent an ICD implantation in our hospital. There were 11 patients under maintenance HD and 60 patients without HD. The group of patients with HD (HD group) was compared with the patients without HD (control group). The mean follow‐up period was 30±9 vs. 39±4 months in the HD group vs. the control group, respectively. Among these patients, 6 in the HD group and 26 in the control group received appropriate ICD therapies. There was no difference in appropriate ICD therapy, time to the first therapy, and electrical storm between the 2 groups. In the HD group, 1 patient underwent surgical removal of the ICD system due to infective endocarditis. There were 5 deaths in the HD group (4 from CHF) and 8 deaths in the control group (4 from CHF). There were no sudden cardiac deaths or arrhythmic deaths in both groups of patients during the follow‐up period. However, the overall death rate was significantly higher in the HD group (P<0.01). In HD patients, ICD therapy prevented arrhythmic death, but their rate of nonarrhythmic adverse outcomes was high. This risk‐benefit association should be considered before implantation of the device.
A pilot study of genetic polymorphisms and hemodialysis vascular access thrombosis
Authors: BROPHY Donald F. , BUKAVECKAS Bonny L. , FERREIRA‐GONZALEZ Andrea , ARCHER Kellie J. , MARTIN Erika J. , GEHR Todd W.B.
Published: January 2009

Vascular access thrombosis (VAT) remains a significant problem worldwide. This study determined the association between VAT and 7 candidate gene polymorphisms (factor V Leiden 1691G>A, factor II 20210G>A, methylenetetrahydrofolate reductase 677C>T, angiotensin converting enzyme 287 base pair (bp) insertion/deletion, transforming growth factor‐β1 869T>C and 915G>C, NOS3 −786T>C and intron 4 27 bp tandem repeat, and endotoxin receptor CD14 −159C>T). This was a retrospective case‐control pilot study conducted in 101 hemodialysis patients at a large tertiary‐care, University health‐science center. Sixty cases that experienced frequent VAT and 41 controls that had not experienced VAT in at least 3 years were evaluated for demographics and genotyping. These data were summarized, and univariable and multivariable regression models were constructed. Univariate VAT predictors included the NOS3 420 bp allele (P=0.03) and the presence of a central venous dialysis catheter (P<0.01). Aspirin use was protective against VAT (P=0.02). In the multivariate analysis, the dialysis access type remained a significant predictor of thrombosis (P<0.01), while aspirin use retained its protective status (P=0.01). Statin use was associated with the cases (P=0.02); however, the NOS3 420 bp allele failed to improve the model. These data confirm that central venous dialysis catheter access is associated with thrombosis, while aspirin use appears protective. The NOS3 420 bp allele may have an association with thrombosis; however, further epidemiologic data evaluating large dialysis registries are needed to confirm our observation.
The anticoagulant activity of enoxaparin sodium during on‐line hemodiafiltration and conventional hemodialysis
Authors: SOMBOLOS Kostas I. , FRAGIA Theodora K. , GIONANLIS Lazaros C. , VENETI Panagiota E. , BAMICHAS Gerasimos I. , FRAGIDIS Stelios K. , GEORGOULIS Ioannis E. , NATSE Taïsir A.
Published: January 2009

To study and compare the anticoagulant activity of enoxaparin sodium during on‐line hemodiafiltration (OL‐HDF) and conventional hemodialysis (C‐HD). Enoxaparin was administered as an anticoagulant to 21 hemodialysis patients at the beginning of a single 4‐hour OL‐HDF session as an intravenous bolus dose of 80 mg/kg. On‐line hemodiafiltration was performed using a high‐flux polyester polymer alloy dialyzer and a total of 18 L replacement fluid (session A). One week later, the study was repeated in the same patients during a single 4‐hour session of C‐HD using a low‐flux polysulfone dialyzer (session B). Blood samples for the measurement of Hb, blood urea and nitrogen (BUN), activated partial thromboplastin time (APTT), and anti‐Xa levels were taken before each study session and 5‐minute postdialysis. In 13 more patients, the same study was performed during OL‐HDF using a high‐flux polysulfone dialyzer (session C). No differences were found between sessions A, B, and C when predialysis values for Hb, BUN, APTT, and anti‐Xa were compared. The mean postdialysis APTT and anti‐Xa values were 32.5±3.8 seconds and 0.19±0.11 IU/mL, respectively, in session A, 39.0±5.0 seconds and 0.71±0.17 IU/mL in session B, and 33.8±3.1 seconds and 0.35±17 IU/mL in session C (A vs. B, P<0.0001, for both parameters, A vs. C, P<0.003 for anti‐XA, and B vs. C, P<0.005, for both parameters). The anticoagulant activity of enoxaparin sodium is decreased significantly during a 4‐hour OL‐HDF session compared with to a similar session of C‐HD. The degree of the reduction seems to depend on the dialyzer's membrane.
The Paradox of Democracy in the New Racial Domain
Authors: Harrison Faye V
Published: January 2009

Joseph Jones is contributing editor for the AAA's RACE Project column in Anthropology News.
Call for Papers, 108th Annual Meeting, American Anthropological Association: The End/s of Anthropology.
Authors: Jackson John L , Thomas Deborah
Published: January 2009

“The End/s of Anthropology,” John L Jackson, Jr and Deborah Thomas

“General Rules for Participation”

“Travel to Philly on a Tight Budget”
Triage of women with equivocal or low‐grade cervical cytology results: a meta‐analysis of the HPV test positivity rate
Authors: Arbyn Marc , Martin‐Hirsch Pierre , Buntinx Frank , Van Ranst Marc , Paraskevaidis Evangelos , Dillner Joakim
Published: January 2009

Introduction

Methods

Results

Discussion

Conclusion

Consistent evidence underlines the utility of human papillomavirus (HPV) DNA testing in the management of women with equivocal cervical cytological abnormalities, but not in case of low‐grade lesions. We performed a meta‐analysis including studies where the high‐risk probe of the Hybrid Capture‐II is used to triage these two cytological categories. The triage test‐positivity rate reflects the colposcopy referral workload.Data were pooled on the HPV test positivity rate in women with atypical squamous cells of undetermined significance (ASCUS/ASC‐US) or low‐grade squamous intraepithelial lesions (LSIL), derived from different cytological classification systems. The meta‐analysis was restricted to studies, published between 1991 and 2007. A random‐effect model was applied for meta‐analytical pooling and the influence of covariates on the HPV positivity rate was analyzed by meta‐regression. The variation by age was assessed within individual studies since age strata were not defined uniformly. On an average, 43% (95% CI: 40–46%) of women with ASCUS/ASC‐US were high‐risk HPV positive (range 23–74%). In women with LSIL, the pooled positivity rate was 76% (95% CI: 71–81%; range 55–89%). In spite of considerable inter‐study heterogeneity, the difference in HPV positivity between the two triage groups was large and highly significant: 32% (95% CI: 27–38%). HPV rates dropped tremendously as age and cutoffs of test positivity increased. Other factors (cytological classification system, country, continent, collection method and year of publication) had no statistically significant impact, except in LSIL triage where HPV positivity was significantly lower in European compared to American studies. Women with LSIL, especially younger women, have high HPV positivity rates suggesting limited utility of reflex HPV triaging these cases. Research is needed to identify more specific methods to triage women with low‐grade squamous cervical lesions.
The role of caveolae and caveolin 1 in calcium handling in pacing and contraction of mouse intestine
Authors: Daniel Edwin E. , Eteraf Tahereh , Sommer Bettina , Cho Woo Jung , Elyazbi Ahmed
Published: January 2009

In mouse intestine, caveolae and caveolin‐1 (Cav‐1) are present in smooth muscle (responsible for executing contractions) and in interstitial cells of Cajal (ICC; responsible for pacing contractions). We found that a number of calcium handling/dependent molecules are associated with caveolae, including L‐type Ca2+channels, Na+‐Ca2+exchanger type 1 (NCX1), plasma membrane Ca2+pumps and neural nitric oxide synthase (nNOS), and that caveolae are close to the peripheral endo‐sarcoplasmic reticulum (ER‐SR). Also we found that this assemblage may account for recycling of calcium from caveolar domains to SR through L‐type Ca+channels to sustain pacing and contractions. Here we test this hypothesis further comparing pacing and contractions under various conditions in longitudinal muscle of Cav‐1 knockout mice (lacking caveolae) and in their genetic controls. We used a procedure in which pacing frequencies (indicative of functioning of ICC) and contraction amplitudes (indicative of functioning of smooth muscle) were studied in calcium‐free media with 100 mM ethylene glycol tetra‐acetic acid (EGTA). The absence of caveolae in ICC inhibited the ability of ICC to maintain frequencies of contraction in the calcium‐free medium by reducing recycling of calcium from caveolar plasma membrane to SR when the calcium stores were initially full. This recycling to ICC involved primarily L‐type Ca2+channels;i.e.pacing frequencies were enhanced by opening and inhibited by closing these channels. However, when these stores were depleted by block of the sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA) pump or calcium release was activated by carbachol, the absence of Cav‐1 or caveolae had little or no effect. The absence of caveolae had little impact on contraction amplitudes, indicative of recycling of calcium to SR in smooth muscle. However, the absence of caveolae slowed the rate of loss of calcium from SR under some conditions in both ICC and smooth muscle, which may reflect the loss of proximity to store operated Ca channels. We found evidence that these channels were associated with Cav‐1. These changes were all consistent with the hypothesis that a reduction of the extracellular calcium associated with caveolae in ICC of the myenteric plexus, the state of L‐type Ca2+channels or an increase in the distance between caveolae and SR affected calcium handling.