bluuebunny/crossref_metadata_2025 huggingface dataset:
Absence of Significant Interactive Effects of High‐Dosed‐Cycloserine and Ethanol in Healthy Human Subjects: Preliminary Insights Into Ethanol Actions at the GlycineBSite of NMDA Glutamate Receptors
Authors: Trevisan Louis , Petrakis Ismene L. , Pittman Brian , Gueorguieva Ralitza , D’Souza D. Cyril , Perry Edward , Limoncelli Diana , Krystal John H.
Published: November 2007

Background: Ethanol reducesN‐methyl‐d‐aspartate (NMDA) glutamate receptor function via multiple cellular targets. It is not yet clear whether direct ethanol antagonism of the glycineBco‐agonist site of NMDA receptors is relevant to this effect. The purpose of this study was to evaluate whether ethanol effects at the glycineBco‐agonist site was clinically relevant by evaluating some aspects of the psychopharmacologic interactions between the glycineBpartial agonist,d‐cycloserine (DCS), and ethanol in healthy human subjects.

Methods: All subjects completed 4 test days under double‐blind conditions in which DCS or placebo was administered orally prior to ethanol or an ethanol‐tainted placebo drink. Two groups of healthy subjects were studied. A first group of subjects (n = 25) were pretreated orally with DCS 500 mg or placebo 4 hours prior to ethanol (0.8 g/kg, p.o. or placebo) administration. A second group of subjects (n = 20) were pretreated with DCS 1000 mg or placebo prior to ethanol administration. Outcomes included subjective and cognitive responses to the experimental interventions.

Results: Predictable ethanol responses were observed in both groups of subjects, although the response to ethanol and the breath alcohol levels, but not plasma alcohol levels, were slightly but significantly lower in the group that received the higher DCS dose. DCS produced mild sedative effects that were greater for the lower than the higher dose. It also produced a mild impairment of verbal fluency without impairing attention. No statistically significant interactions between ethanol and DCS emerged in analyses. However, the combination of ethanol and DCS produced significantly greater impairment than both ethanol or DCS administered alone on a test of verbal fluency and aspects of memory function.

Implications: DCS and ethanol both produced sedative and cognitive effects, consistent with their ability to reduce NMDA receptor function. However, the absence of interactive effects observed in this study raises questions about the clinical significance of the glycineBsite as a target for ethanol in the brain at levels of ethanol intoxication associated with social drinking. However, it should be noted that this conclusion is limited to the dependent measures evaluated and the doses of ethanol and DCS studied.
Chronic Alcohol Feeding Impairs mTOR(Ser2448) Phosphorylation in Rat Hearts
Authors: Vary Thomas C. , Deiter Gina , Lantry Rachel
Published: November 2007

Background:  Chronic alcohol administration impairs protein synthesis ultimately causing a loss of proteins in cardiac muscle. Inhibition of protein synthesis resides in the process of mRNA translation. The present set of experiments were designed to examine the potential regulatory effect of chronic alcohol consumption on mammalian target of rapamycin (mTOR), a serine/threonine kinase important in controlling signaling cascades in the mRNA translation initiation pathway in rat hearts.

Methods:  Rats were fed a diet containing ethanol for 20 to 26 weeks. Pair‐fed rats served as controls. Rates of protein synthesis were measured following intravenous infusion of [3H]‐l‐phenylalanine (150 mM, 30 μCi/ml; 1 ml/100 g body weight). The phosphorylation state of mTOR, eukaryotic initiation factor 4G (eIF4G), protein kinase B (PKB) and S6K1 in heart were measured using immunoblot techniques with phospho‐specific antibodies.

Results:  Protein synthesis was reduced by 35% in animals consuming a diet containing ethanol. The fall in protein synthesis was accompanied by diminished S6K1(Thr389) and eIF4G (Ser1108) phosphorylation, both downstream effectors of mTOR signaling. These changes in phosphorylation of S6K1 and eIF4G were not associated with differences in the distribution of mTOR between TORC1 and TORC2. Instead, phosphorylation of mTOR on Ser2448 but not on Ser2481 was significantly reduced following feeding rats an ethanol containing diet. Decreased phosphorylation of mTOR(Ser2448) was not associated with a corresponding lessening of tumor suppressor complex 2 phosphorylation or expression of regulated in development and DNA damage 1, both upstream regulators of mTOR. Likewise, phosphorylation of PKB on either Ser473 or Thr308 was unaffected by long‐term alcohol consumption.

Conclusions:  Chronic ethanol consumption does not alter the distribution of mTOR between TORC1 and TORC2, but instead diminishes mTOR phosphorylation on Ser2448 independent of changes in tumor suppressor complex 2 and PKB phosphorylation. Furthermore, the data suggest that protein synthesis in rats fed a diet containing ethanol is limited by mTOR‐dependent reduction in phosphorylation of S6K1(Thr389) and eIF4G(Ser1108) secondary to reduced phosphorylation of mTOR(Ser2448).
A Complex Relationship Between Co‐occurring Social Anxiety and Alcohol Use Disorders: What Effect Does Treating Social Anxiety Have on Drinking?
Authors: Thomas Suzanne E. , Randall Patrick K. , Book Sarah W. , Randall Carrie L.
Published: November 2007

Background:  Individuals with social anxiety disorder and co‐occurring alcohol problems report using alcohol to cope with anxiety symptoms. Interventions that reduce both social anxiety and drinking are needed. Paroxetine, an FDA‐approved medication to treat social anxiety disorder, reduces anxiety in individuals with co‐occurring alcohol problems.

Objectives:  To examine whether effective treatment of social anxiety with paroxetine reduces drinking in dual‐diagnosed individuals who endorse using alcohol to cope.

Methods:  A 16‐week, double‐blind, randomized controlled trial of paroxetine was conducted. Participants (placebo n = 22; paroxetine n = 20) met DSM‐IV diagnostic criteria for social anxiety disorder and alcohol abuse or dependence. Participants were seeking treatment for social anxiety, not for the alcohol problem. Alcohol use outcomes were measured with conventional quantity/frequency measures and novel measures of drinking to cope.

Results:  Paroxetine improved social anxiety more than placebo. Paroxetine reduced self‐reported reliance on alcohol for self‐medication purposes, but was not different than placebo in changing quantity and frequency drinking or the proportion of drinking days that were identified as coping‐related. Exploratory analyses revealed that for the placebo group, drinking during the trial was correlated with social anxiety severity, whereas for the paroxetine‐treated group, drinking was uncoupled from social anxiety severity.

Conclusions:  Successfully treating social anxiety symptoms with paroxetine does not reduce drinking in dual‐diagnosed individuals who are not seeking treatment for alcohol problems. Paroxetine does, however, reduce reliance on alcohol to engage in social situations, and may change the reasons why one drinks (such that drinking occurs for other reasons besides coping with anxiety). These results have implications for staging of social anxiety and alcohol treatment in individuals with the co‐occurring disorders presenting to a mental health or primary care provider.
Person and Environment Predictors of Blood Alcohol Concentrations: A Multi‐Level Study of College Parties
Authors: Clapp John D. , Min Jong Won , Shillington Audrey M. , Reed Mark B. , Ketchie Croff Julie
Published: November 2007

Aims:  This study builds upon previous research by assessing the relationship of breath blood alcohol concentrations (BrAC) to environmental and individual characteristics.

Design:  We conducted a multi‐level study of college parties. Our design included observational measures of party environments, a brief self‐administered questionnaire, and the collection of breath samples from partygoers.

Setting:  Data were collected in private residences of students living in a neighborhood adjacent to a large public university located in the Southwestern United States.

Participants:  A total of 1,304 individuals attending 66 parties participated in the study.

Measures:  Observational measures of party characteristics were made by 2 trained research assistants at each party. Four to 5 trained interviewers administered a brief field survey to partygoers at each party. In addition, the trained interviewers collected breath samples using handheld breathalyzer devices.

Findings:  Hierarchical linear modeling analyses revealed significant variation at the party and individual levels. At the individual level, motivations to socialize were significantly associated with lower BrAC, while drinking games and providing the sample after 11:00 pm were associated with higher BrACs. At the party level, large parties were significantly associated with lower BrACs while reports of many intoxicated partygoers were associated with higher BrACs. Finally, we identified a significant gender by theme party interaction, indicating women had higher BrACs at theme parties relative to nontheme parties; however, BrACs for men were similar regardless of the type of party attended.

Conclusions:  Alcohol consumption among young adults in natural settings is a function of both person and environmental factors.
Evaluation of the Effect of Ethanol’s Toxic Metabolite Acetaldehyde on the Gastrointestinal Oligopeptide Transporter, PEPT1: In Vitro and in Vivo Studies
Authors: Fisher Scott J. , Lee Insong J. , Swaan Peter W. , Eddington Natalie D.
Published: November 2007

Background: The effects of alcohol consumption and its subsequent metabolism on drug transport, absorption and pharmacokinetics are poorly understood. This study examines the effects of the ethanol metabolite, acetaldehyde, on the clinically relevant drug transporter, PEPT1. The metabolism of ethanol and the following acetaldehyde formation is thought to modulate the uptake capacity of PEPT1 within the gastrointestinal tract for a variety of clinically important peptidomimetic drug compounds.

Methods: Glycylsarcosine ([3H]‐GlySar), a nonhydrolysable PEPT1 specific substrate was used in our studies. In vitro uptake studies were performed in the Caco‐2 and Chinese hamster ovary (CHO)‐hPEPT1 cell models, measuring cellular uptake of labeled compound against increasing levels of unlabeled compound in the presence of acetaldehyde. In vivo absorption of [3H]‐GlySar was measured in male Sprague–Dawley rats that were treated with oral dose of ethanol/disulfiram (5 g/kg / 100 mg/kg) for 6 days. These results were compared to control rats treated with saline, ethanol alone or disulfiram alone.

Results: In vitro uptake of [3H]‐GlySar in CHO‐hPEPT1 cells treated with 1 mM acetaldehyde was significantly decreased (p < 0.05) as compared to untreated controls. The uptake of [3H]‐GlySar in Caco‐2 cell monolayers treated with 1 mM acetaldehyde was also significantly decreased as compared to the untreated control cells. In vivo absorption of [3H]‐GlySar in ethanol treated rats, as measured by AUC0–12 hourswere decreased by approximately 50% versus the control rat group.

Conclusion: The effects of acetaldehyde due to consumption of ethanol on the uptake and bioavailability of therapeutic drug compounds transported by the PEPT1 oligopeptide transporter have not been documented. In the present studies, we demonstrate that acetaldehyde significantly modulates PEPT1 function and, thereby, affects drug bioavailability. To our best knowledge, this is the first report on the effects of an ethanol metabolite on substrate absorption in the gastrointestinal tract, rather than interactions in the liver, which is an under‐represented area of research in alcohol pathophysiology.
How Would Terminally Ill Patients Have Others Make Decisions for Them in the Event of Decisional Incapacity? A Longitudinal Study
Authors: Sulmasy Daniel P. , Hughes Mark T. , Thompson Richard E. , Astrow Alan B. , Terry Peter B. , Kub Joan , Nolan Marie T.
Published: November 2007

OBJECTIVES:To determine the role terminally ill patients would opt to have their loved ones and physicians play in healthcare decisions should they lose decision‐making capacity and how this changes over time.

DESIGN:Serial interviews.

SETTING:The study institutions were The Johns Hopkins Medical Institutions in Baltimore, Maryland, and St. Vincent's Hospital, in New York.

PARTICIPANTS:One hundred forty‐seven patients with cancer, amyotrophic lateral sclerosis, or heart failure, at baseline and 3 and 6 months.

RESULTS:Patients' baseline decision control preferences varied widely, but most opted for shared decision‐making, leaning slightly toward independence from their loved ones. This did not change significantly at 3 or 6 months. Fifty‐seven percent opted for the same degree of decision control at 3 months as at baseline. In a generalized estimating equation model adjusted for time, more‐independent decision‐making was associated with college education (P=.046) and being female (P=.01), whereas more‐reliant decision‐making was associated with age (P<.001). Patients leaned toward more reliance upon physicians to make best‐interest determinations at diagnosis but opted for physicians to decide based upon their own independent wishes (substituted judgment) over time, especially if college educated.

CONCLUSION:Terminally ill patients vary in how much they wish their own preferences to control decisions made on their behalf, but most would opt for shared decision‐making with loved ones and physicians. Control preferences are stable over time with respect to loved ones, but as they live longer with their illnesses, patients prefer somewhat less reliance upon physicians.
Prediction of Mortality in Community‐Living Frail Elderly People with Long‐Term Care Needs
Authors: Carey Elise C. , Covinsky Kenneth E. , Lui Li‐Yung , Eng Catherine , Sands Laura P. , Walter Louise C.
Published: November 2007

OBJECTIVES: To develop and validate a prognostic index for mortality in community‐living, frail elderly people.

DESIGN: Cohort study of Program of All‐Inclusive Care for the Elderly (PACE) participants enrolled between 1988 and 1996.

SETTING: Eleven PACE sites, a community‐based long‐term care program that cares for frail, chronically ill elderly people who meet criteria for nursing home placement.

PARTICIPANTS: Three thousand eight hundred ninety‐nine PACE enrollees. The index was developed in 2,232 participants and validated in 1,667.

MEASUREMENTS: Time to death was predicted using risk factors obtained from a geriatric assessment performed by the PACE interdisciplinary team at the time of enrollment. Risk factors included demographic characteristics, comorbid conditions, and functional status.

RESULTS: The development cohort had a mean age of 79 (68% female, 40% white). The validation cohort had a mean age of 79 (76% female, 65% white). In the development cohort, eight independent risk factors of mortality were identified and weighted, using Cox regression, to create a risk score: male sex, 2 points; age (75–79, 2 points; 80–84, 2 points; ≥85, 3 points); dependence in toileting, 1 point; dependence in dressing (partial dependence, 1 point; full dependence, 3 points); malignant neoplasm, 2 points; congestive heart failure, 3 points; chronic obstructive pulmonary disease, 1 point; and renal insufficiency, 3 points. In the development cohort, respective 1‐ and 3‐year mortality rates were 6% and 21% in the lowest‐risk group (0–3 points), 12% and 36% in the middle‐risk group (4–5 points), and 21% and 54% in the highest‐risk group (>5 points). In the validation cohort, respective 1‐ and 3‐year mortality rates were 7% and 18% in the lowest‐risk group, 11% and 36% in the middle‐risk group, and 22% and 55% in the highest‐risk group. The area under the receiver operating characteristic curve for the point score was 0.66 and 0.69 in the development and validation cohorts, respectively.

CONCLUSION: A multidimensional prognostic index was developed and validated using age, sex, functional status, and comorbidities that effectively stratifies frail, community‐living elderly people into groups at varying risk of mortality.
Weight, Mortality, Years of Healthy Life, and Active Life Expectancy in Older Adults
Authors: Diehr Paula , O'Meara Ellen S. , Fitzpatrick Annette , Newman Anne B. , Kuller Lewis , Burke Gregory
Published: November 2007

OBJECTIVES:To determine whether weight categories predict subsequent mortality and morbidity in older adults.

DESIGN:Multistate life tables, using data from the Cardiovascular Health Study, a longitudinal population‐based cohort of older adults.

SETTING:Data were provided by community‐dwelling seniors in four U.S. counties: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania.

PARTICIPANTS:Five thousand eight hundred eighty‐eight adults aged 65 and older at baseline.

MEASUREMENTS:The age‐ and sex‐specific probabilities of transition from one health state to another and from one weight category to another were estimated. From these probabilities, future life expectancy, years of healthy life, active life expectancy, and the number of years spent in each weight and health category after age 65 were estimated.

RESULTS:Women who are healthy and of normal weight at age 65 have a life expectancy of 22.1 years. Of that, they spend, on average, 9.6 years as overweight or obese and 5.3 years in fair or poor health. For both men and women, being underweight at age 65 was associated with worse outcomes than being normal weight, whereas being overweight or obese was rarely associated with worse outcomes than being normal weight and was sometimes associated with significantly better outcomes.

CONCLUSION:Similar to middle‐aged populations, older adults are likely to be or to become overweight or obese, but higher weight is not associated with worse health in this age group. Thus, the number of older adults at a “healthy” weight may be much higher than currently believed.
Interventions for Preventing Falls in Acute‐ and Chronic‐Care Hospitals: A Systematic Review and Meta‐Analysis
Authors: Coussement Joke , De Paepe Leen , Schwendimann René , Denhaerynck Kris , Dejaeger Eddy , Milisen Koen
Published: November 2007

OBJECTIVES: To determine the characteristics and the effectiveness of hospital fall prevention programs.

DESIGN: Systematic literature search of multiple databases (Medline, Cinahl, Precinahl, Invert, the Cochrane Library) and of the reference list of each identified publication.

SETTING: Inclusion of prospective controlled‐design studies reporting the effectiveness of fall prevention programs in hospitals.

PARTICIPANTS: Two reviewers.

MEASUREMENTS: The methodological qualities of the studies were assessed based on 10 criteria. For the meta‐analysis, the relative risk of a fall per occupied bed day (RRfall) and the relative risk of being a faller (RRfaller) were calculated.

RESULTS: Eight studies met the inclusion criteria, of which four studies tested multifactorial interventions. Although these studies took place in hospitals, most were conducted on long‐stay (mean length of stay (LOS) >1.5 years) and rehabilitation units (mean LOS 36.9 days). For analysis of the number of falls, one unifactorial and two multifactorial studies showed a significant reduction of 30% to 49% in the intervention group, with the greatest effect obtained in the unifactorial study that assessed a pharmacological intervention. The pooled RRfall for the four multifactorial studies became nonsignificant after adjustment for clustering (RRfall=0.82, 95% confidence interval (CI)=0.65–1.03). No studies reported a significant reduction, either single or pooled, in the number of fallers in the intervention group (pooled RRfaller‐0.87, 95% CI=0.70–1.08).

CONCLUSION: This meta‐analysis found no conclusive evidence that hospital fall prevention programs can reduce the number of falls or fallers, although more studies are needed to confirm the tendency observed in the analysis of individual studies that targeting a patient's most important risk factors for falls actively helps in reducing the number of falls. These interventions seem to be useful only on long‐stay care units.
Long‐Term Effects of Childhood Abuse on the Quality of Life and Health of Older People: Results from the Depression and Early Prevention of Suicide in General Practice Project
Authors: Draper Brian , Pfaff Jon J. , Pirkis Jane , Snowdon John , Lautenschlager Nicola T. , Wilson Ian , Almeida Osvaldo P. ,   for the Depression and Early Prevention of Suicide in General Practice Study Group
Published: November 2007

OBJECTIVES: To determine whether childhood physical and sexual abuse are associated with poor mental and physical health outcomes in older age.

DESIGN: Cross‐sectional, postal questionnaire survey.

SETTING: Medical clinics of 383 general practitioners (GPs) in Australia.

PARTICIPANTS: More than 21,000 older adults (aged ≥60) currently under the care of GPs participating in the Depression and Early Prevention of Suicide in General Practice (DEPS‐GP) Study. Participants were divided into two groups according to whether they acknowledged experiencing childhood physical or sexual abuse.

MEASUREMENTS: Main outcome measures targeted participants' current physical health (Medical Outcomes Study 12‐item Short Form Survey, Version 2 and Common Medical Morbidities Inventory) and mental health (Patient Health Questionnaire‐9 and Hospital Anxiety and Depression Scale).

RESULTS: One thousand four hundred fifty‐eight (6.7%) and 1,429 participants (6.5%) reported childhood physical and sexual abuse, respectively. Multivariate models of the associations with childhood abuse indicated that participants who had experienced either childhood sexual or physical abuse had a greater risk of poor physical (odds ratio (OR)=1.35, 95% confidence interval (CI)=1.21–1.50) and mental (OR=1.89, 95% CI=1.63–2.19) health, after adjustments. Older adults who reported both childhood sexual and physical abuse also had a higher risk of poor physical (OR=1.60, 95% CI=1.33–1.92) and mental (OR=2.40, 95% CI=1.97–2.94) health.

CONCLUSION: The effects of childhood abuse appear to last a lifetime. Further research is required to improve understanding of the pathways that lead to such deleterious outcomes and ways to minimize its late‐life effects.
Minimum infectious dose of hepatitis B virus in chimpanzees and difference in the dynamics of viremia between genotype A and genotype C
Authors: Komiya Yutaka , Katayama Keiko , Yugi Hisao , Mizui Masaaki , Matsukura Harumichi , Tomoguri Tetsushi , Miyakawa Yuzo , Tabuchi Ayako , Tanaka Junko , Yoshizawa Hiroshi
Published: November 2007

BACKGROUND: In planning optimal hepatitis B virus (HBV) blood screening strategies, the minimum infectious dose and early dynamics of HBV need to be determined for defining the window period for HBV DNA as well as for hepatitis B surface antigen (HBsAg).

STUDY DESIGN AND METHODS: Pairs of chimpanzees were inoculated with preacute‐phase inocula containing HBV of genotype A or genotype C to determine the minimum infectious dose, and two pairs of chimps infected with the lowest infectious dose of genotypes A and C were followed for HBV markers.

RESULTS: The minimum 50 percent chimpanzee infectious dose (CID50) was estimated to be approximately 10 copies for genotype A and for genotype C. In the two chimps inoculated with the lowest infectious dose, the HBV DNA window was 55 to 76 days for genotype  A and 35 to 50 days for genotype C, respectively. The HBsAg window was 69 to 97 days for genotype A and 50 to 64 days for genotype C, respectively. The doubling times of HBV DNA were 3.4 days (95% confidence interval [CI], 2.6‐4.9 days) for genotype A and 1.9 days (95% CI, 1.6‐2.3 days) for genotype C. When comparing the replication velocity of HBV DNA between the two genotypes, the doubling time of genotype C was significantly shorter than that of HBV genotype A (p < 0.01).

CONCLUSION: Although the CID50 of approximately 10 copies was similar for the two HBV genotypes, the doubling time and pre‐HBV nucleic acid amplification technology (<100 copies/mL) window period in chimps infected with the lowest infectious dose seemed to be shorter for genotype C than for genotype A.
Potential and limitation of UVC irradiation for the inactivation of pathogens in platelet concentrates
Authors: Terpstra Fokke G. , Van 't Wout Angélique B. , Schuitemaker Hanneke , Van Engelenburg Frank A.C. , Dekkers David W.C. , Verhaar Robin , De Korte Dirk , Verhoeven Arthur J.
Published: November 2007

BACKGROUND: Pathogen contamination, causing transfusion‐transmitted diseases, is an ongoing concern in transfusion of cellular blood products. In this explorative study, the pathogen‐inactivating capacity of UVC irradiation in platelet (PLT) concentrates was investigated. The dose dependencies of inactivation of several viruses and bacteria were compared with the effect on PLT quality.

STUDY DESIGN AND METHODS: The potential of UVC irradiation was studied with a range of lipid‐enveloped (LE) and non–lipid‐enveloped viruses (NLE) and bacteria. LE viruses were bovine viral diarrhea virus (BVDV), human immunodeficiency virus (HIV), pseudorabies virus (PRV), transmissible gastroenteritis virus (TGEV), and vesicular stomatitis virus (VSV). NLE viruses were canine parvovirus (CPV) and simian virus 40 (SV40). Bacteria were Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, and Bacillus cereus. After spiking and irradiation, samples were tested for residual infectivity and reduction factors (RFs) were calculated. Furthermore, the effect of UVC irradiation on PLT quality was determined by measuring in vitro quality variables.

RESULTS: A UVC dose of 500 J per m2 resulted in acceptable PLT quality (as measured by pH, lactate production, CD62P expression, and exposure of phosphatidylserine) and high RFs (>4 log) for CPV, TGEV, VSV, S. epidermidis, S. aureus, and E. coli. Intermediate RFs (approx. 3 log) were observed for BVDV, PRV, and B. cereus. Low RFs (approx. 1 log) were found for HIV and SV40. No differences in virus reduction were observed between cell‐free and cell‐associated virus.

CONCLUSION: UVC irradiation is a promising pathogen‐reducing technique in PLT concentrates, inactivating bacteria, and a broad range of viruses (with the exception of HIV) under conditions that have limited effects on PLT quality. Further optimization of the UVC procedure, however, is necessary to deal with blood‐borne viruses like HIV.
Establishing a cord blood banking and transplantation program in Mexico: a single institution experience
Authors: Novelo‐Garza Barbara , Limon‐Flores Alejandro , Guerra‐Marquez Angel , Luna‐Bautista Fernando , Juan‐Shum Luis , Montero Ines , Sanchez‐Valle Elizabeth , Vélez‐Ruelas Maria Antonieta , Mayani Hector
Published: November 2007

BACKGROUND: Over the past decade, umbilical cord blood (UCB) banking and transplantation have increased significantly worldwide. The experience in developing countries, however, is still limited. In January 2005 the Mexican Institute of Social Security (IMSS) initiated its UCB banking and transplantation program. This study reports on the experience generated at this institution during the first 2 years of activities.

STUDY DESIGN AND METHODS: A public UCB bank was established at La Raza Medical Center, IMSS, in Mexico City. Good manufacturing practices and standard operating procedures were used to address donor selection, as well as UCB collection, processing, and cryopreservation. Based mainly on human leukocyte antigen (HLA) and total nucleated cell (TNC) content, specific UCB units were thawed, processed, and released for transplantation.

RESULTS: Based on stringent selection criteria, 360 UCB units were collected from January 2005 to December 2006. A total of 201 (56%) units (minimum volume, 50 mL without anticoagulant) were processed and stored. Median values for specific parameters were as follows: volume, 89.9 mL; viability, 94.8%; TNCs, 0.91 × 109; CD34+ cells, 3.13 × 106; and colony‐forming cells, 1.20 × 106. During this period, 10 units had been released for transplantation to seven patients (six children and one adult). Engraftment was observed in five patients; four of them were still in remission (114‐293 days after transplant). In spite of showing sustained engraftment, one patient died on Day +88. Two patients showed no engraftment and died 29 to 30 days after transplant.

CONCLUSION: The results obtained during this initial period are encouraging and indicate that the UCB banking and transplantation program at IMSS will help to improve already existing hematopoietic cell transplant programs in Mexico. The experience generated at IMSS may be helpful to other institutions, particularly those in developing countries.
Neonatal alloimmune thrombocytopenia associated with maternal‐fetal incompatibility for blood group B
Authors: Curtis Brian R. , Fick Andrea , Lochowicz Andrew J. , McFarland Janice G. , Ball Robert H. , Peterson Julie , Aster Richard H.
Published: November 2007

BACKGROUND: Blood group A and B antigens are expressed only weakly on platelets (PLTs) of most individuals but are very strongly expressed on PLTs from approximately 1 percent of normal subjects (Type II high expressers). The implications of this trait for transfusion medicine are undefined.

STUDY DESIGN AND METHODS: A family was studied in which two Group B infants were born with neonatal thrombocytopenia, whereas a third infant whose blood group was A2 had a normal PLT count at birth.

RESULTS: Serologic studies demonstrated a maternal antibody that reacted strongly with PLTs from the father and the two group B children in flow cytometry and with GPIIb/IIIa from their PLTs in solid‐phase assays. No PLT‐specific antibodies were detected in maternal serum sample, but it contained a high‐titer immunoglobulin G antibody specific for blood group B. All PLT‐reactive antibody in the mother's serum was removed by absorption with pooled, washed group A and B red cells (RBCs). Studies with monoclonal anti‐B and measurement of serum B‐glycosyltransferase activity showed that the father and both group B children were Type II high expressers of blood group B.

CONCLUSIONS: The findings indicate that high‐titer blood group antibodies acquired from the mother can cause thrombocytopenia in infants possessing the Type II high‐expresser phenotype despite competition for antibody binding by blood group antigens expressed on RBCs and other tissues.
Clinical cardiac involvement in thrombotic thrombocytopenic purpura: a systematic review
Authors: Hawkins Beau M. , Abu‐Fadel Mazen , Vesely Sara K. , George James N.
Published: November 2007

BACKGROUND: Autopsy studies consistently demonstrate cardiac involvement in thrombotic thrombocytopenic purpura (TTP), but clinical evidence for cardiac abnormalities is rarely reported.

STUDY DESIGN AND METHODS: This systematic review addresses the apparent discrepancy between autopsy and clinical data. English language articles were identified by keywords for both TTP and for cardiac symptoms, testing, or events. Patients were analyzed if they were more than 10 years old with idiopathic TTP.

RESULTS: Thirty articles were identified that described 111 eligible patients: 20 case reports described 27 patients, 9 retrospective cohort studies described 74 patients, and 1 prospective cohort study described 10 patients. Cardiac events included infarction (26 patients), congestive failure (17), arrhythmias (10), cardiogenic shock (6), and sudden cardiac death (8). Mortality was assessed in 101 patients: 55 died, and 48 autopsies were described. All demonstrated cardiac microvascular thrombi, hemorrhage, and/or necrosis. Follow‐up information was reported in only 6 of the 16 patients who survived a cardiac event (follow‐up duration, 10 days‐2 years; median, 7 weeks).

CONCLUSIONS: The frequency and sequelae of clinical cardiac abnormalities in TTP cannot be accurately assessed because most patients were described in reports of few selected patients; many patients were reported before the availability of effective treatment for TTP and sensitive tests for cardiac involvement. Continuing case reports and cohort studies, however, suggest that cardiac abnormalities may be important and often unrecognized causes of mortality and morbidity in patients with TTP. Prospective studies are needed to determine if cardiac therapy can improve survival and long‐term outcomes of patients with TTP.
Unemployment and Inflation Consequences of Unexpected Election Results
Authors: BERLEMANN MICHAEL , MARKWARDT GUNTHER
Published: November 2007

The empirical evidence toward rational partisan theory of business cycles is mixed and thus inconclusive. This is due to the enormous heterogeneity of the existing empirical studies. Only a few of these test explicitly for the central theoretical innovation that post‐electoral blips in economic activity depend on the degree of the electoral surprise. Using polling data we present empirical evidence in favor of rational partisan theory for a panel of OECD countries.
The Value of Interest Rate Stabilization Policies When Agents Are Learning
Authors: DUFFY JOHN , XIAO WEI
Published: November 2007

We examine the expectational stability (E‐stability) of rational expectations equilibrium in the “New Keynesian” model where monetary policy is optimally derived and interest rate stabilization is added to the central bank's traditional objectives of inflation and output stabilization. We consider both the case where the central bank lacks a commitment technology and the case of full commitment. We show that for both cases, optimal policy rules yield rational expectations equilibria that are E‐stable for a wide range of empirically plausible parameter values. These findings stand in contrast to Evans and Honkapohja's findings for optimal monetary policy rules in environments where interest rate stabilization is not a central bank objective.
Collegial Influence and Judicial Voting Change: The Effect of Membership Change on U.S. Supreme Court Justices
Authors: Meinke Scott R. , Scott Kevin M.
Published: November 2007

Understanding the source of voting changes by appellate judges provides an important window into the factors that shape the votes of the judges more generally. We argue that membership changes, by altering the collegial context in which judges make their choices, affect the information environment, long-term collegial considerations, and short-term strategic calculations. As a result, membership change should lead to greater uncertainty and more frequent voting changes among continuing justices in the term following a replacement. We test this proposition by looking at vote change by justices of the U.S. Supreme Court in two separate analyses: justices' votes on search-and-seizure cases since Mapp v. Ohio (1961) and on the progeny of Miranda v. Arizona (1966). Our results support the argument that the collegial context helps explain changes in voting choices. Our analysis suggests that collegial considerations are an important component of judges' behavior and merit further evaluation in a cross-national context.
Government as Catalyst: Can It Work Again with Wireless Internet Access?
Authors: Jain Abhijit , Mandviwalla Munir , Banker Rajiv D.
Published: November 2007

As the Internet becomes an indispensable component of the global economy, Internet access is an increasingly important prerequisite to exploiting social, economic and educational opportunities. Municipal wireless networks (MWNs), which are wireless Internet access networks created with active local leadership and involvement, are seen as a potential solution. In this case study we describe the development of the Philadelphia MWN including goals, stakeholder expectations, policy, applications, technology, management models, funding, and implementation. The case provides insights on how communities can act as catalysts and use information technology to promote social and economic change. We found that MWNs involve competing private and public sector stakeholders, and it is important to clearly identify the main application of the MWN. We also found that focusing on the digital divide affords both opportunities and risks, and there are powerful external forces that impact MWNs and the underlying technology.
Write the Rules and Win: Understanding Citizen Participation Game Dynamics
Authors: Stewart Kennedy
Published: November 2007

In attempting to move beyond normative‐based theories and simple descriptive accounts of extra‐electoral citizen participation, this article explores the biases that are inherent in citizen participation mechanisms and proposes a model to estimate when and why different participation mechanisms might be used during “citizen participation games.” Mechanism bias is explored using a matrix designed to gauge how different mechanisms afford different degrees of agenda‐setting and decision‐making control to citizens and state officials. Attention then turns to leadership capacity to explain the mechanisms through which teams of citizens and government officials might play their participatory games. A second matrix suggests that the choice of mechanism may vary considerably depending on whether rookie leaders are matched against other rookies, novices, or expert opponents. Though the model suggests that mechanisms affording less control to citizens are more common, it also implies that in the future, citizen players may demand mechanisms affording them more control as their leaders gain experience.
“There Was No Plan”: An Interview with Rajiv Chandrasekaran
Authors: Kosar Kevin
Published: November 2007

The George W. Bush administration’s doctrines of preemption and democratization through military action have been much debated. Discussants have included former members of the military, students of international relations and diplomacy, philosophers, and legal theorists, to name a few. Not surprisingly, the focus of these expostulations has been on the utility of hard and soft power, the international ripple effects of military action and state toppling, and the legal and moral propriety of preemption.

For the most part, public administrators have little participated in these debates. This is regrettable, for the central question nestled within any debate over public policy is the question of plausibility. Can this policy be executed successfully?

The governance challenges in postconflict states are profound. Who should rule? How should the state be reconstructed? What administrative structures should be erected? Who should staff government offices and bureaucracies, and what principles should guide them? If preemption and democratization are to succeed, then these questions must be answered.

Rajiv Chandrasekaran is an assistant managing editor of the Washington Post. His book Imperial Life in the Emerald City: Inside Iraq’s Green Zone (Alfred A. Knopf, 2006) is an examination of the Coalition Provisional Authority that governed Iraq from April 2003 through June 2004. Mr. Chandrasekaran has served as the journalist in residence for the International Reporting Project at the Johns Hopkins School for Advanced International Studies and as a public policy scholar at the Woodrow Wilson International Center in Washington, D.C. In March 2007, Mr. Chandrasekaran was interviewed by Kevin Kosar on behalf of the Public Administration Review.
Cardiac Arrest and Left Ventricular Fibrosis in a Finnish Family with the Lamin A/C Mutation
Authors: HOOKANA EEVA , JUNTTILA M. JUHANI , SÄRKIOJA TERTTU , SORMUNEN RAIJA , NIEMELÄ MATTI , RAATIKAINEN M.J. PEKKA , UUSIMAA PAAVO , LIZOTTE ERIC , PEUHKURINEN KEIJO , BRUGADA RAMON , HUIKURI HEIKKI V.
Published: November 2007

Introduction: We screened the candidate genes from a Finnish family in which the mother was resuscitated from ventricular fibrillation and the daughter died suddenly without any prior cardiac symptoms.

Methods and Results: In addition to screening of potential structural gene mutations, phenotyping of the proband and medico‐legal autopsy of the victim of the sudden death, including histopathological examinations, were performed. Genetic screening revealed an R541C mutation in the lamin A/C gene both in the proband and her daughter. None of the 16 first‐ or second‐degree relatives, or 96 unrelated healthy subjects, carried the same mutation. In the proband, the size and the global function of the left ventricle (LV) were normal, but a local hypokinesia and thinning of inferoposterior area of the LV were seen in 2D echocardiography and magnetic resonance imaging. Coronary angiogram and the results of the electrophysiological study were normal. Autopsy of the victim of sudden death showed localized thinning and fibrosis in the inferoposterior area of the LV, with only minimal fibrosis in the right ventricle and no abnormalities in the interventricular septum.

Conclusion: These observations indicate that a fatal or near‐fatal cardiac arrhythmia can be the first clinical manifestation of a “de novo” mutation R541C of the lamin A/C gene. Replacement of cardiac myocytes by fibrosis seems to be the predominant pathologic‐anatomic finding.
Catheter Ablation of Peri‐AV Nodal Atrial Tachycardia from the Noncoronary Cusp of the Aortic Valve
Authors: DAS SAUMYA , NEUZIL PETR , ALBERT CHRISTINE M. , D'AVILA ANDRE , MANSOUR MOUSSA , MELA THEOFANIE , ELLINOR PATRICK T. , SINGH JAGMEET , PATTON KRISTEN , RUSKIN JEREMY N. , REDDY VIVEK Y.
Published: November 2007

Introduction: Atrial tachycardias (AT) originating from the anteroseptal region of the aortic root, near the atrioventricular node can be challenging to eliminate safely by catheter ablation. In this study, we examine the characteristics of anteroseptal ATs in a cohort of patients at our centers, and demonstrate the long‐term efficacy and safety of targeting the arrhythmias from within the base of the noncoronary aortic valve cusp (NCC).

Methods & Results: From among a cohort of 54 patients with symptomatic focal AT undergoing invasive electrophysiological evaluation, the point of earliest right atrial (RA) activation was at the peri‐AV nodal region in 10 patients, just postero‐superior to the His‐bundle. Before further mapping, RA lesions placed in two patients were unsuccessful in eliminating the arrhythmia. Because of its proximity to the interatrial septum, the base of the NCC was mapped using a retrograde aortic approach, and revealed a point of early activation without the presence of a His potential. The arrhythmia terminated with <10 seconds of radiofrequency or cryothermal energy delivery and was successfully eliminated in 7 of 10 patients. Transient termination or acceleration of the AT was noted in the other three patients, prompting successful ablation from a left atrial septal position or a reattempt from a para‐Hisian RA position. All patients have been arrhythmia free during follow‐up (41 ± 12 months).

Conclusions: Catheter ablation from within the base of the NCC represents a safe and effective means to eliminate focal AT arising from the peri‐AV nodal region.
Cellular Mechanism and Arrhythmogenic Potential of T‐Wave Alternans in the Brugada Syndrome
Authors: FISH JEFFREY M. , ANTZELEVITCH CHARLES
Published: November 2007

Introduction: T‐wave alternans (TWA) is characterized by beat to beat alteration in the amplitude, polarity and/or morphology of the electrocardiographic T wave. TWA has been reported in patients with the Brugada syndrome (BS) and is thought to be associated with an increased risk for development of VT/VF. The cellular mechanisms involved are not well‐defined and are the subject of this investigation.

Methods: In an experimental model of BS composed of an arterially perfused canine right ventricular wedge preparation pretreated with verapamil (1–7 μM), an agent with sodium and calcium channel blocking activity, we simultaneously recorded transmembrane action potentials from two epicardial and one endocardial site, together with a pseudo‐ECG. At select frequencies, verapamil induced alternans of both the T‐wave amplitude and QT interval. The alternans resulted from either loss of the epicardial action potential dome on alternate beats or concealed phase 2 reentry within the epicardium on alternate beats. Loss of the epicardial action potential dome significantly increased transmural dispersion of repolarization (TDR) when compared with control (18.0 ± 7.8 ms vs. 82.1 ± 16.8 ms, P < 0.001, n = 8). During alternans, TDR was greater in beats displaying a more negative T wave (55.1 ± 45.2 ms vs. 89.8 ± 39.3 ms, P < 0.001, n = 22 data points from 8 preparations).

Conclusions: Our data indicate that TWA in an experimental model of the Brugada syndrome is due to alternating loss of the epicardial AP dome and/or concealed phase 2 reentry, both serving to increase TDR and create the substrate for the development VT/VF.
The Effects of Regulatory Focus on Braking Speed1
Authors: Werth Lioba , Förster Jens
Published: November 2007

According to regulatory focus theory (Higgins, 1997), promotion focus is concerned with accomplishments and aspirations leading to strategic eagerness; whereas prevention focus is concerned with safety and responsibilities leading to strategic vigilance. In this study, we investigate how regulatory focus theory can predict braking behavior in driving. In Study 1, participants' assessed regulatory focus strength as measured by chronic personality differences in regulatory focus predicted braking speed, in that chronic prevention‐oriented participants initiated braking earlier, as compared to promotion‐oriented people. In Study 2, we experimentally induced regulatory focus and showed that induced prevention focus enhanced braking speed (i.e., faster), as compared to induced promotion focus.
Financial Debt and Suicide in Hong Kong SAR1
Authors: Yip Paul S. F. , Yang Kris C. T. , Ip Brian Y. T. , Law Y. W. , Watson Ray
Published: November 2007

The presence of indebtedness is known to be a risk factor that can trigger stressed persons to contemplate suicide. This study compares the profiles of suicides with and without debt problems based on 2002 Coroner's Court death files. The category of men aged 25–39 has seen a 70% increase in suicide rate since 1997, and the number using carbon monoxide poisoning has increased from 1% of the total deaths in 1997 to about 26% of the total deaths in 2002. Suicides associated with debt problems seem to involve fewer mental and physical problems with formal job attachment than do suicides without debt problems. Gambling is a significant contributing factor to unmanageable indebtedness.
Test‐Taker Reactions to the Selection Process: Effects of Outcome Favorability, Explanations, and Voice on Fairness Perceptions
Authors: Rolland Florence , Steiner Dirk D.
Published: November 2007

This study examined the effects of providing an explanation and voice on fairness perceptions and reactions of test takers under favorable and unfavorable selection decisions. Participants took either a cognitive ability test or an overt integrity test in a simulated selection situation. Then, the voice manipulation was introduced. Participants were informed of the hiring decision with or without an explanation. Results showed that type of test had effects on procedural fairness perceptions such that these reactions were more positive when a cognitive ability test was used. The results of voice and explanation manipulations on fairness perceptions indicated that providing an explanation had a positive effect on perceptions but, surprisingly, face‐validity perceptions were less favorable when participants had voice opportunity.