Showing papers by "University of Miami published in 2002"

Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection.

Abstract: Background Treatment with peginterferon alfa-2a alone produces significantly higher sustained virologic responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus (HCV) infection. We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin, interferon alfa-2b plus ribavirin, and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. Methods A total of 1121 patients were randomly assigned to treatment and received at least one dose of study medication, consisting of 180 μg of peginterferon alfa-2a once weekly plus daily ribavirin (1000 or 1200 mg, depending on body weight), weekly peginterferon alfa-2a plus daily placebo, or 3 million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks. Results A significantly higher proportion of patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response (defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy) th...

The Ocular Hypertension Treatment Study: A Randomized Trial Determines That Topical Ocular Hypotensive Medication Delays or Prevents the Onset of Primary Open-Angle Glaucoma

Abstract: Background Primary open-angle glaucoma (POAG) is one of the leading causes of blindness in the United States and worldwide. Three to 6 million people in the United States are at increased risk for developing POAG because of elevated intraocular pressure (IOP), or ocular hypertension. There is no consensus on the efficacy of medical treatment in delaying or preventing the onset of POAG in individuals with elevated IOP. Therefore, we designed a randomized clinical trial, the Ocular Hypertension Treatment Study. Objective To determine the safety and efficacy of topical ocular hypotensive medication in delaying or preventing the onset of POAG. Methods A total of 1636 participants with no evidence of glaucomatous damage, aged 40 to 80 years, and with an IOP between 24 mm Hg and 32 mm Hg in one eye and between 21 mm Hg and 32 mm Hg in the other eye were randomized to either observation or treatment with commercially available topical ocular hypotensive medication. The goal in the medication group was to reduce the IOP by 20% or more and to reach an IOP of 24 mm Hg or less. Main Outcome Measures The primary outcome was the development of reproducible visual field abnormality or reproducible optic disc deterioration attributed to POAG. Abnormalities were determined by masked certified readers at the reading centers, and attribution to POAG was decided by the masked Endpoint Committee. Results During the course of the study, the mean ± SD reduction in IOP in the medication group was 22.5% ± 9.9%. The IOP declined by 4.0%± 11.6% in the observation group. At 60 months, the cumulative probability of developing POAG was 4.4% in the medication group and 9.5% in the observation group (hazard ratio, 0.40; 95% confidence interval, 0.27-0.59; P Conclusions Topical ocular hypotensive medication was effective in delaying or preventing the onset of POAG in individuals with elevated IOP. Although this does not imply that all patients with borderline or elevated IOP should receive medication, clinicians should consider initiating treatment for individuals with ocular hypertension who are at moderate or high risk for developing POAG.

Efficacy and Safety of Trastuzumab as a Single Agent in First-Line Treatment of HER2-Overexpressing Metastatic Breast Cancer

Abstract: PURPOSE: To evaluate the efficacy and safety of first-line, single-agent trastuzumab in women with HER2-overexpressing metastatic breast cancer. PATIENTS AND METHODS: One hundred fourteen women with HER2-overexpressing metastatic breast cancer were randomized to receive first-line treatment with trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg weekly, or a higher 8 mg/kg loading dose, followed by 4 mg/kg weekly. RESULTS: The objective response rate was 26% (95% confidence interval [CI], 18.2% to 34.4%), with seven complete and 23 partial responses. Response rates in 111 assessable patients with 3+ and 2+ HER2 overexpression by immunohistochemistry (IHC) were 35% (95% CI, 24.4% to 44.7%) and none (95% CI, 0% to 15.5%), respectively. The clinical benefit rates in assessable patients with 3+ and 2+ HER2 overexpression were 48% and 7%, respectively. The response rates in 108 assessable patients with and without HER2 gene amplification by fluorescence in situ hybridization (FISH) analysis were 34% (95% CI...

Environmental characterization of global sources of atmospheric soil dust identified with the nimbus 7 total ozone mapping spectrometer (toms) absorbing aerosol product

Abstract: [1] We use the Total Ozone Mapping Spectrometer (TOMS) sensor on the Nimbus 7 satellite to map the global distribution of major atmospheric dust sources with the goal of identifying common environmental characteristics The largest and most persistent sources are located in the Northern Hemisphere, mainly in a broad “dust belt” that extends from the west coast of North Africa, over the Middle East, Central and South Asia, to China There is remarkably little large-scale dust activity outside this region In particular, the Southern Hemisphere is devoid of major dust activity Dust sources, regardless of size or strength, can usually be associated with topographical lows located in arid regions with annual rainfall under 200–250 mm Although the source regions themselves are arid or hyperarid, the action of water is evident from the presence of ephemeral streams, rivers, lakes, and playas Most major sources have been intermittently flooded through the Quaternary as evidenced by deep alluvial deposits Many sources are associated with areas where human impacts are well documented, eg, the Caspian and Aral Seas, Tigris-Euphrates River Basin, southwestern North America, and the loess lands in China Nonetheless, the largest and most active sources are located in truly remote areas where there is little or no human activity Thus, on a global scale, dust mobilization appears to be dominated by natural sources Dust activity is extremely sensitive to many environmental parameters The identification of major sources will enable us to focus on critical regions and to characterize emission rates in response to environmental conditions With such knowledge we will be better able to improve global dust models and to assess the effects of climate change on emissions in the future It will also facilitate the interpretation of the paleoclimate record based on dust contained in ocean sediments and ice cores

Service Quality Delivery Through Web Sites: A Critical Review of Extant Knowledge

Abstract: Evidence exists that service quality delivery through Web sites is an essential strategy to success, possibly more important than low price and Web presence. To deliver superior service quality, managers of companies with Web presences must first understand how customers perceive and evaluate online customer service. Information on this topic is beginning to emerge from both academic and practitioner sources, but this information has not yet been examined as a whole. The goals of this article are to review and synthesize the literature about service quality delivery through Web sites, describe what is known about the topic, and develop an agenda for needed research.

The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma.

Abstract: Background The Ocular Hypertension Treatment Study (OHTS) has shown that topical ocular hypotensive medication is effective in delaying or preventing the onset of primary open-angle glaucoma (POAG) in individuals with elevated intraocular pressure (ocular hypertension) and no evidence of glaucomatous damage. Objective To describe baseline demographic and clinical factors that predict which participants in the OHTS developed POAG. Methods Baseline demographic and clinical data were collected prior to randomization except for corneal thickness measurements, which were performed during follow-up. Proportional hazards models were used to identify factors that predicted which participants in the OHTS developed POAG. Results In univariate analyses, baseline factors that predicted the development of POAG included older age, race (African American), sex (male), larger vertical cup-disc ratio, larger horizontal cup-disc ratio, higher intraocular pressure, greater Humphrey visual field pattern standard deviation, heart disease, and thinner central corneal measurement. In multivariate analyses, baseline factors that predicted the development of POAG included older age, larger vertical or horizontal cup-disc ratio, higher intraocular pressure, greater pattern standard deviation, and thinner central corneal measurement. Conclusions Baseline age, vertical and horizontal cup-disc ratio, pattern standard deviation, and intraocular pressure were good predictors for the onset of POAG in the OHTS. Central corneal thickness was found to be a powerful predictor for the development of POAG.

Late-Onset Sepsis in Very Low Birth Weight Neonates: The Experience of the NICHD Neonatal Research Network

Abstract: Objective. Late-onset sepsis (occurring after 3 days of age) is an important problem in very low birth weight (VLBW) infants. To determine the current incidence of late-onset sepsis, risk factors for disease, and the impact of late-onset sepsis on subsequent hospital course, we evaluated a cohort of 6956 VLBW (401–1500 g) neonates admitted to the clinical centers of the National Institute of Child Health and Human Development Neonatal Research Network over a 2-year period (1998–2000). Methods. The National Institute of Child Health and Human Development Neonatal Research Network maintains a prospective registry of all VLBW neonates admitted to participating centers within 14 days of birth. Expanded infection surveillance was added in 1998. Results. Of 6215 infants who survived beyond 3 days, 1313 (21%) had 1 or more episodes of blood culture-proven late-onset sepsis. The vast majority of infections (70%) were caused by Gram-positive organisms, with coagulase-negative staphylococci accounting for 48% of infections. Rate of infection was inversely related to birth weight and gestational age. Complications of prematurity associated with an increased rate of late-onset sepsis included patent ductus arteriosus, prolonged ventilation, prolonged intravascular access, bronchopulmonary dysplasia, and necrotizing enterocolitis. Infants who developed late-onset sepsis had a significantly prolonged hospital stay (mean length of stay: 79 vs 60 days). They were significantly more likely to die than those who were uninfected (18% vs 7%), especially if they were infected with Gram-negative organisms (36%) or fungi (32%). Conclusions. Late-onset sepsis remains an important risk factor for death among VLBW preterm infants and for prolonged hospital stay among VLBW survivors. Strategies to reduce late-onset sepsis and its medical, social, and economic toll need to be addressed urgently.

The Influence of Multiple Store Environment Cues on Perceived Merchandise Value and Patronage Intentions

Abstract: Research on how store environment cues influence consumers’ store choice decision criteria, such as perceived merchandise value and shopping experience costs, is sparse. Especially absent is research on the simultaneous impact of multiple store environment cues. The authors propose a comprehensive store choice model that includes (1) three types of store environment cues (social, design, and ambient) as exogenous constructs, (2) various store choice criteria (including shopping experience costs that heretofore have not been included in store choice models) as mediating constructs, and (3) store patronage intentions as the endogenous construct. They then empirically examine the extent to which environmental cues influence consumers’ assessments of a store on various store choice criteria and how those assessments, in turn, influence patronage intentions. The results of two different studies provide support for the model. The authors conclude by discussing the results to develop an agenda for addit...

Face detection in color images

Abstract: Human face detection plays an important role in applications such as video surveillance, human computer interface, face recognition, and face image database management. We propose a face detection algorithm for color images in the presence of varying lighting conditions as well as complex backgrounds. Based on a novel lighting compensation technique and a nonlinear color transformation, our method detects skin regions over the entire image and then generates face candidates based on the spatial arrangement of these skin patches. The algorithm constructs eye, mouth, and boundary maps for verifying each face candidate. Experimental results demonstrate successful face detection over a wide range of facial variations in color, position, scale, orientation, 3D pose, and expression in images from several photo collections (both indoors and outdoors).

Earnings Management and Investor Protection: An International Comparison

Abstract: This paper examines the pervasiveness of earnings management across 31 countries between 1990 and 1999. It documents systematic differences in earnings management across different clusters of countries. We propose an explanation for these differences based on the notion that insiders, in an attempt to protect their private control benefits, use earnings management to conceal firm performance from outsiders. Thus, earnings management is expected to decrease in investor protection because strong protection limits insiders' ability to acquire private control benefits, which reduces their incentives to mask firm performance. Our evidence is consistent with this prediction. The findings suggest a link between corporate governance and the quality of reported earnings, and complement prior finance research that treats the quality of corporate reporting as exogenous.

Results of a Prospective Study of Acute Liver Failure at 17 Tertiary Care Centers in the United States

Abstract: Acetaminophen overdose and idiosyncratic drug reactions have replaced viral hepatitis as the most frequent causes of acute liver failure. The cause of liver failure and coma grade at admission were...

2001 Consensus Guidelines for the Management of Women With Cervical Cytological Abnormalities

Abstract: ObjectiveTo provide evidence-based consensus guidelines for the management of women with cervical cytological abnormalities and cervical cancer precursors.ParticipantsA panel of 121 experts in the diagnosis and management of cervical cancer precursors, including representatives from 29 professional organizations, federal agencies, and national and international health organizations, were invited to participate in a consensus conference sponsored by the American Society for Colposcopy and Cervical Pathology (ASCCP).Evidence and Consensus ProcessGuidelines for the management of women with cervical cytological abnormalities were developed through a multistep process. Starting 6 months before the conference, working groups developed draft management guidelines based on formal literature reviews of English-language articles published in 1988-2001, as well as input from the professional community at large, obtained using interactive Internet-based bulletin boards. On September 6-8, 2001, the ASCCP Consensus Conference was held in Bethesda, Md. Guidelines with supporting evidence were presented and underwent discussion, revision, and voting.ConclusionsManagement of women with atypical squamous cells (ASC) depends on whether the Papanicolaou test is subcategorized as of undetermined significance (ASC-US) or as cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H). Women with ASC-US should be managed using a program of 2 repeat cytology tests, immediate colposcopy, or DNA testing for high-risk types of human papillomavirus (HPV). Testing for HPV DNA is the preferred approach when liquid-based cytology is used for screening. In most instances, women with ASC-H, low-grade squamous intraepithelial lesion, HSIL, and atypical glandular cells should be referred for immediate colposcopic evaluation.

Performance Matched Discretionary Accrual Measures

Abstract: Prior research shows that extant discretionary accrual models are misspecified when applied to firms with extreme performance. Nonetheless, use of such models in tests of earnings management and market efficiency is commonplace in the literature. We examine the specification and power of the test based on a performance-matched discretionary accrual measure and compare it with traditional discretionary accrual measures (e.g., Jones and Modified-Jones Models). Performance matching is on return on assets and industry and is designed to control for the effect of performance on measured discretionary accruals. The results suggest that our performance-matched discretionary accrual measure is a viable alternative to existing discretionary accrual models for use in earnings management research.

REVEL: A model for Recent plate velocities from space geodesy

Abstract: [1] We present a new global model for Recent plate velocities, REVEL, describing the relative velocities of 19 plates and continental blocks. The model is derived from publicly available space geodetic (primarily GPS) data for the period 1993–2000. We include an independent and rigorous estimate for GPS velocity uncertainties to assess plate rigidity and propagate these uncertainties to the velocity estimates. The velocity fields for North America, Eurasia, and Antarctica clearly show the effects of glacial isostatic adjustment, and Australia appears to depart from rigid plate behavior in a manner consistent with the mapped intraplate stress field. Two thirds of tested plate pairs agree with the NUVEL-1A geologic (3 Myr average) velocities within uncertainties. Three plate pairs (Caribbean–North America, Caribbean–South America, and North America–Pacific) exhibit significant differences between the geodetic and geologic model that may reflect systematic errors in NUVEL-1A due to the use of seafloor magnetic rate data that do not reflect the full plate rate because of tectonic complexities. Most other differences probably reflect real velocity changes over the last few million years. Several plate pairs (Arabia–Eurasia, Arabia–Nubia, Eurasia–India) move more slowly than the 3 Myr NUVEL-1A average, perhaps reflecting long-term deceleration associated with continental collision. Several other plate pairs, including Nazca–Pacific, Nazca–South America and Nubia–South America, are experiencing slowing that began ∼25 Ma, the beginning of the current phase of Andean crustal shortening.

Contract, cooperation, and performance in international joint ventures

Abstract: This study examines how contract, cooperation, and performance are associated with one another within international joint ventures (IJVs). We argue that contract and cooperation are not substitutes but complements in relation to IJV performance. An IJV contract provides an institutional framework guiding the course of cooperation, while cooperation overcomes the adaptive limits of contracts. Our analysis of 293 IJVs in a dynamic market demonstrates that previous cooperation bolsters contractual adaptability, which in turn nurtures current cooperation between the same partners. We find that contract completeness and cooperation drive IJV performance both independently and interactively. When contracts are more complete, cooperation contributes more to performance. Contract and cooperation differ in their quadratic effects such that the contribution of contract completeness to performance declines as completeness increases but the contribution of cooperation remains linear. Copyright © 2002 John Wiley & Sons, Ltd.

Practice Guidelines for the Diagnosis and Management of Group A Streptococcal Pharyngitis

Abstract: Alan L. Bisno, Michael A. Gerber, Jack M. Gwaltney, Jr., Edward L. Kaplan, and Richard H. Schwartz Department of Medicine, University of Miami School of Medicine and Veterans Affairs Medical Center, Miami, Florida; 2 Cincinnati Children’s Hospital Medical Center and University of Cincinnati School of Medicine, Ohio; University of Virginia School of Medicine, Charlottesville, Inova Fairfax Hospital for Children, Falls Church, Virginia; and Department of Pediatrics, University of Minnesota Medical School, Minneapolis

Climate Change Impacts on U.S. Coastal and Marine Ecosystems

Abstract: Increases in concentrations of greenhouse gases projected for the 21st century are expected to lead to increased mean global air and ocean temperatures. The National Assessment of Potential Consequences of Climate Variability and Change (NAST 2001) was based on a series of regional and sector assessments. This paper is a summary of the coastal and marine resources sector review of potential impacts on shorelines, estuaries, coastal wetlands, coral reefs, and ocean margin ecosystems. The assessment considered the impacts of several key drivers of climate change: sea level change; alterations in precipitation patterns and subsequent delivery of freshwater, nutrients, and sediment; increased ocean temperature; alterations in circulation patterns; changes in frequency and intensity of coastal storms; and increased levels of atmospheric CO2. Increasing rates of sea-level rise and intensity and frequency of coastal storms and hurricanes over the next decades will increase threats to shorelines, wetlands, and coastal development. Estuarine productivity will change in response to alteration in the timing and amount of freshwater, nutrients, and sediment delivery. Higher water temperatures and changes in freshwater delivery will alter estuarine stratification, residence time, and eutrophication. Increased ocean temperatures are expected to increase coral bleaching and higher CO2 levels may reduce coral calcification, making it more difficult for corals to recover from other disturbances, and inhibiting poleward shifts. Ocean warming is expected to cause poleward shifts in the ranges of many other organisms, including commercial species, and these shifts may have secondary effects on their predators and prey. Although these potential impacts of climate change and variability will vary from system to system, it is important to recognize that they will be superimposed

Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants.

Abstract: Background It is uncertain whether the rates and causes of early-onset sepsis (that occurring within 72 hours after birth) among very-low-birth-weight infants have changed in recent years, since antibiotics have begun to be used more widely during labor and delivery. Methods We studied 5447 very-low-birth-weight infants (those weighing between 401 and 1500 g) born at centers of the Neonatal Research Network of the National Institute of Child Health and Human Development between 1998 and 2000 who had at least one blood culture in the first three days of life and compared them with 7606 very-low-birth-weight infants born at centers in the network between 1991 and 1993. Results Early-onset sepsis (as confirmed by positive blood cultures) was present in 84 infants in the more recent birth cohort (1.5 percent). As compared with the earlier birth cohort, there was a marked reduction in group B streptococcal sepsis (from 5.9 to 1.7 per 1000 live births of infants weighing 401 to 1500 g, P<0.001) and an increase ...

An Investigation of Personal Learning in Mentoring Relationships: Content, Antecedents, and Consequences

Abstract: To examine antecedents and consequences of learning in the context of mentoring relationships, we developed a new measure of personal learning, relational job learning and personal skill development. The presence of a mentor and mentoring functions were found to be antecedents of personal learning. Job satisfaction, role ambiguity, intentions to leave a job (turnover intentions), and actual leaving (turnover) were found to be consequences of personal learning. This study also explored personal learning as a mediator between mentoring functions and organizational consequences. Implications for future research and practice are discussed.

Current status of hydrogen energy

Abstract: This paper examines the present status of hydrogen energy and looks at different approaches for technological advances. Some of the new developments in the progress of the recent directions of world hydrogen production and utilization are reported. The aim of this article is to inform the reader of hydrogen technology, economics, environmental impact, special system applications, hydrogen energy status around the world at the end of the 20 century as well as hydrogen organizations, associations, projects, periodicals and conferences.

Toward Improved Validation of Satellite Sea Surface Skin Temperature Measurements for Climate Research

Abstract: A poor validation strategy will compromise the quality of satellite-derived sea surface temperature (SST) products because confidence limits cannot be quantified. This paper addresses the question of how to provide the best operational strategy to validate satellite-derived skin sea surface temperature (SST skin) measurements. High quality in situ observations obtained using different state-of-the-art infrared radiometer systems are used to characterize the relationship between the SST skin, the subsurface SST at depth (SSTdepth), and the surface wind speed. Data are presented for different oceans and seasons. These data indicate that above a wind speed of approximatel y6ms 21 the relationship between the SSTskin and SSTdepth, is well characterized for both day- and nighttime conditions by a cool bias of 20.17 6 0.07 K rms. At lower wind speeds, stratification of the upperocean layers during the day may complicate the relationship, while at night a cooler skin is normally observed. Based on these observations, a long-term global satellite SST skin validation strategy is proposed. Emphasis is placed on the use of autonomous, ship-of-opportunity radiometer systems for areas characterized by prevailing low‐wind speed conditions. For areas characterized by higher wind speed regimes, well-calibrated, qualitycontrolled, ship and buoy SSTdepth observations, corrected for a cool skin bias, should also be used. It is foreseen that SSTdepth data will provide the majority of in situ validation data required for operational satellite SST validation. We test the strategy using SSTskin observations from the Along Track Scanning Radiometer, which are shown to be accurate to approximately 0.2 K in the tropical Pacific Ocean, and using measurements from the Advanced Very High Resolution Radiometer. We note that this strategy provides for robust retrospective calibration and validation of satellite SST data and a means to compare and compile in a meaningful and consistent fashion similar datasets. A better understanding of the spatial and temporal variability of thermal stratification of the upper-ocean layers during low‐wind speed conditions is fundamental to improvements in SST validation and development of multisensor satellite SST products.

Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the State of Florida Brain Bank.

Abstract: Alzheimer disease (AD) is the most common dementing illness in the elderly, but there is equivocal evidence regarding the frequency of other disorders such as Lewy body disease (LBD), vascular dementia (VaD), frontotemporal dementia (FTD), and hippocampal sclerosis (HS). This ambiguity may be related to factors such as the age and gender of subjects with dementia. Therefore, the objective of this study was to calculate the relative frequencies of AD, LBD, VaD, FTD, and HS among 382 subjects with dementia from the State of Florida Brain Bank and to study the effect of age and gender on these frequencies. AD was the most frequent pathologic finding (77%), followed by LBD (26%), VaD (18%), HS (13%), and FTD (5%). Mixed pathology was common: Concomitant AD was present in 66% of LBD patients, 77% of VaD patients, and 66% of HS patients. The relative frequency of VaD increased with age, whereas the relative frequencies of FTD and LBD declined with age. Males were overrepresented among those with LBD, whereas females were overrepresented among AD subjects with onset age over 70 years. These estimates of the a priori probabilities of dementing disorders have implications for clinicians and researchers.

Glutamate release and free radical production following brain injury: effects of posttraumatic hypothermia.

Abstract: Posttraumatic hypothermia reduces the extent of neuronal damage in remote cortical and subcortical structures following traumatic brain injury (TBI). We evaluated whether excessive extracellular release of glutamate and generation of hydroxyl radicals are associated with remote traumatic injury, and whether posttraumatic hypothermia modulates these processes. Lateral fluid percussion was used to induce TBI in rats. The salicylate-trapping method was used in conjunction with microdialysis and HPLC to detect hydroxyl radicals by measurement of the stable adducts 2,3- and 2,5-dihydroxybenzoic acid (DHBA). Extracellular glutamate was measured from the same samples. Following trauma, brain temperature was maintained for 3 h at either 37 or 30°C. Sham-trauma animals were treated in an identical manner. In the normothermic group, TBI induced significant elevations in 2,3-DHBA (3.3-fold, p < 0.01), 2,5-DHBA (2.5-fold, p < 0.01), and glutamate (2.8-fold, p < 0.01) compared with controls. The levels of 2,3-DHBA and glutamate remained high for approximately 1 h after trauma, whereas levels of 2,5-DHBA remained high for the entire sampling period (4 h). Linear regression analysis revealed a significant positive correlation between integrated 2,3-DHBA and glutamate concentrations (p < 0.05). Posttraumatic hypothermia resulted in suppression of both 2,3- and 2,5-DHBA elevations and glutamate release. The present data indicate that TBI is followed by prompt increases in both glutamate release and hydroxyl radical production from cortical regions adjacent to the impact site. The magnitude of glutamate release is correlated with the extent of the hydroxyl radical adduct, raising the possibility that the two responses are associated. Posttraumatic hypothermia blunts both responses, suggesting a mechanism by which hypothermia confers protection following TBI.

A controlled trial of rasagiline in early Parkinson disease: The tempo study

Abstract: CONTEXT Monotherapy with rasagiline mesylate may be useful in early Parkinson disease (PD). OBJECTIVE To evaluate the safety and efficacy of the selective monoamine oxidase type B inhibitor rasagiline. DESIGN Multicenter, 26-week, parallel-group, randomized, double-blind, placebo-controlled clinical trial. SETTING Academically based movement disorders clinics. PATIENTS Patients with early PD not requiring dopaminergic therapy (n = 404). INTERVENTION Research participants were randomized to rasagiline mesylate at dosages of 1 mg or 2 mg per day or matching placebo. A 1-week escalation period was followed by a 25-week maintenance period. MAIN OUTCOME MEASURE The primary prespecified measure of efficacy was the change in the total Unified Parkinson's Disease Rating Scal score between baseline and 26 weeks of treatment, comparing each active treatment group with the placebo group. RESULTS Monotherapy with rasagiline was effective in this 26-week study. The adjusted effect size for the total Unified Parkinson's Disease Rating Scale was -4.20 units comparing 1 mg of rasagiline and placebo (95% confidence interval, -5.66 to -2.73 units; P<.001) and -3.56 units comparing a 2-mg dosage and placebo (95% confidence interval, -5.04 to -2.08 units; P<.001). There were no meaningful differences in the frequency of adverse events or premature withdrawals among the treatment groups. CONCLUSIONS Rasagiline is effective as monotherapy for patients with early PD. The 2 dosages in this trial were both effective relative to placebo. Further study is warranted to evaluate the longer-term effects of rasagiline in PD.

Genome Sequence of Yersinia pestis KIM

Abstract: We present the complete genome sequence of Yersinia pestis KIM, the etiologic agent of bubonic and pneumonic plague. The strain KIM, biovar Mediaevalis, is associated with the second pandemic, including the Black Death. The 4.6-Mb genome encodes 4,198 open reading frames (ORFs). The origin, terminus, and most genes encoding DNA replication proteins are similar to those of Escherichia coli K-12. The KIM genome sequence was compared with that of Y. pestis CO92, biovar Orientalis, revealing homologous sequences but a remarkable amount of genome rearrangement for strains so closely related. The differences appear to result from multiple inversions of genome segments at insertion sequences, in a manner consistent with present knowledge of replication and recombination. There are few differences attributable to horizontal transfer. The KIM and E. coli K-12 genome proteins were also compared, exposing surprising amounts of locally colinear “backbone,” or synteny, that is not discernible at the nucleotide level. Nearly 54% of KIM ORFs are significantly similar to K-12 proteins, with conserved housekeeping functions. However, a number of E. coli pathways and transport systems and at least one global regulator were not found, reflecting differences in lifestyle between them. In KIM-specific islands, new genes encode candidate pathogenicity proteins, including iron transport systems, putative adhesins, toxins, and fimbriae.