Showing papers by "Emory University published in 2004"

In vivo cancer targeting and imaging with semiconductor quantum dots

Abstract: We describe the development of multifunctional nanoparticle probes based on semiconductor quantum dots (QDs) for cancer targeting and imaging in living animals. The structural design involves encapsulating luminescent QDs with an ABC triblock copolymer and linking this amphiphilic polymer to tumor-targeting ligands and drug-delivery functionalities. In vivo targeting studies of human prostate cancer growing in nude mice indicate that the QD probes accumulate at tumors both by the enhanced permeability and retention of tumor sites and by antibody binding to cancer-specific cell surface biomarkers. Using both subcutaneous injection of QD-tagged cancer cells and systemic injection of multifunctional QD probes, we have achieved sensitive and multicolor fluorescence imaging of cancer cells under in vivo conditions. We have also integrated a whole-body macro-illumination system with wavelength-resolved spectral imaging for efficient background removal and precise delineation of weak spectral signatures. These results raise new possibilities for ultrasensitive and multiplexed imaging of molecular targets in vivo.

NOX enzymes and the biology of reactive oxygen

Abstract: Professional phagocytes generate high levels of reactive oxygen species (ROS) using a superoxide-generating NADPH oxidase as part of their armoury of microbicidal mechanisms. The multicomponent phagocyte oxidase (Phox), which has been well characterized over the past three decades, includes the catalytic subunit gp91phox. Lower levels of ROS are seen in non-phagocytic cells, but are usually thought to be 'accidental' byproducts of aerobic metabolism. The discovery of a family of superoxide-generating homologues of gp91phox has led to the concept that ROS are 'intentionally' generated in these cells with distinctive cellular functions related to innate immunity, signal transduction and modification of the extracellular matrix.

Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression

Abstract: Skeletal muscle atrophy is a debilitating response to starvation and many systemic diseases including diabetes, cancer, and renal failure. We had proposed that a common set of transcriptional adaptations underlie the loss of muscle mass in these different states. To test this hypothesis, we used cDNA microarrays to compare the changes in content of specific mRNAs in muscles atrophying from different causes. We compared muscles from fasted mice, from rats with cancer cachexia, streptozotocin-induced diabetes mellitus, uremia induced by subtotal nephrectomy, and from pair-fed control rats. Although the content of >90% of mRNAs did not change, including those for the myofibrillar apparatus, we found a common set of genes (termed atrogins) that were induced or suppressed in muscles in these four catabolic states. Among the strongly induced genes were many involved in protein degradation, including polyubiquitins, Ub fusion proteins, the Ub ligases atrogin-1/MAFbx and MuRF-1, multiple but not all subunits of the 20S proteasome and its 19S regulator, and cathepsin L. Many genes required for ATP production and late steps in glycolysis were down-regulated, as were many transcripts for extracellular matrix proteins. Some genes not previously implicated in muscle atrophy were dramatically up-regulated (lipin, metallothionein, AMP deaminase, RNA helicase-related protein, TG interacting factor) and several growth-related mRNAs were down-regulated (P311, JUN, IGF-1-BP5). Thus, different types of muscle atrophy share a common transcriptional program that is activated in many systemic diseases.

Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection.

Abstract: ContextNeonatal infections are frequent complications of extremely low-birth-weight (ELBW) infants receiving intensive care.ObjectiveTo determine if neonatal infections in ELBW infants are associated with increased risks of adverse neurodevelopmental and growth sequelae in early childhood.Design, Setting, and ParticipantsInfants weighing 401 to 1000 g at birth (born in 1993-2001) were enrolled in a prospectively collected very low-birth-weight registry at academic medical centers participating in the National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental and growth outcomes were assessed at a comprehensive follow-up visit at 18 to 22 months of corrected gestational age and compared by infection group. Eighty percent of survivors completed the follow-up visit and 6093 infants were studied. Registry data were used to classify infants by type of infection: uninfected (n = 2161), clinical infection alone (n = 1538), sepsis (n = 1922), sepsis and necrotizing enterocolitis (n = 279), or meningitis with or without sepsis (n = 193).Main Outcome MeasuresCognitive and neuromotor development, neurologic status, vision and hearing, and growth (weight, length, and head circumference) were assessed at follow-up.ResultsThe majority of ELBW survivors (65%) had at least 1 infection during their hospitalization after birth. Compared with uninfected infants, those in each of the 4 infection groups were significantly more likely to have adverse neurodevelopmental outcomes at follow-up, including cerebral palsy (range of significant odds ratios [ORs], 1.4-1.7), low Bayley Scales of Infant Development II scores on the mental development index (ORs, 1.3-1.6) and psychomotor development index (ORs, 1.5-2.4), and vision impairment (ORs, 1.3-2.2). Infection in the neonatal period was also associated with impaired head growth, a known predictor of poor neurodevelopmental outcome.ConclusionsThis large cohort study suggests that neonatal infections among ELBW infants are associated with poor neurodevelopmental and growth outcomes in early childhood. Additional studies are needed to elucidate the pathogenesis of brain injury in infants with infection so that novel interventions to improve these outcomes can be explored.

Foundations of Human Sociality - Economic Experiments and Ethnographic: Evidence From Fifteen Small-Scale Societies

Abstract: 1. Introduction and Guide to the Volume 2. Overview and Synthesis 3. Measuring Social Norms and Preferences Using Experimental Games: A Guide for Social Sciences 4. Coalitional Effects on Reciprocal Fairness in the Ultimatum Game: A Case from the Ecuadorian Amazon 5. Comparative Experimental Evidence from Machiguenga, Mapuche, Huinca, and American Populations Shows Substantial Variation Among Social Groups in Bargaining and Public Goods Behavior 6. Dictators and Ultimatums in an Egalitarian Society of Hunter-Gatherers - the Hadza of Tanzania 7. Does Market Exposure Affect Economic Game Behavior? The Ultimatum Game and the Public Goods Game Among the Tsimane of Bolivia 8. Market Integration, Reciprocity, and Fairness in Rural Papua New Guinea: Results from a Two-Village Ultimatum Game Experiment 9. Ultimatum Game with an Ethnicity Manipulation: Results from Khovdiin Bulgan Sum, Mongolia 10. Kinship, Familiarity, and Trust: An Experimental Investigation 11. Community Structure, Mobility, and the Strength of Norms in an Africa Society: the Sangu of Tanzania 12. Market Integration and Fairness: Evidence from Ultimatum, Dictator, and Public Goods Experiments in East Africa 13. Economic Experiments to Examine Fairness and Cooperation among the Ache Indians of Paraguay 14. The Ultimatum Game, Fairness, and Cooperation among Big Game Hunters

The emergence of autobiographical memory: a social cultural developmental theory.

Abstract: The authors present a multicomponent dynamic developmental theory of human autobiographical memory that emerges gradually across the preschool years. The components that contribute to the process of emergence include basic memory abilities, language and narrative, adult memory talk, temporal understanding, and understanding of self and others. The authors review the empirical developmental evidence within each of these components to show how each contributes to the timing, quantity, and quality of personal memories from the early years of life. The authors then consider the relevance of the theory to explanations of childhood amnesia and how the theory accounts for and predicts the complex findings on adults' earliest memories, including individual, gender, and cultural differences.

The empirical status of empirically supported psychotherapies: assumptions, findings, and reporting in controlled clinical trials.

Abstract: This article provides a critical review of the assumptions and findings of studies used to establish psychotherapies as empirically supported. The attempt to identify empirically supported therapies (ESTs) imposes particular assumptions on the use of randomized controlled trial (RCT) methodology that appear to be valid for some disorders and treatments (notably exposure-based treatments of specific anxiety symptoms) but substantially violated for others. Meta-analytic studies support a more nuanced view of treatment efficacy than implied by a dichotomous judgment of supported versus unsupported. The authors recommend changes in reporting practices to maximize the clinical utility of RCTs, describe alternative methodologies that may be useful when the assumptions underlying EST methodology are violated, and suggest a shift from validating treatment packages to testing intervention strategies and theories of change that clinicians can integrate into empirically informed therapies.

The Collaborative Cross, a community resource for the genetic analysis of complex traits

Abstract: The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease.

The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore

Abstract: A sudden increase in permeability of the inner mitochondrial membrane, the so-called mitochondrial permeability transition, is a common feature of apoptosis and is mediated by the mitochondrial permeability transition pore (mtPTP). It is thought that the mtPTP is a protein complex formed by the voltage-dependent anion channel, members of the pro- and anti-apoptotic BAX-BCL2 protein family, cyclophilin D, and the adenine nucleotide (ADP/ATP) translocators (ANTs)1,2. The latter exchange mitochondrial ATP for cytosolic ADP and have been implicated in cell death. To investigate the role of the ANTs in the mtPTP, we genetically inactivated the two isoforms of ANT3,4,5 in mouse liver and analysed mtPTP activation in isolated mitochondria and the induction of cell death in hepatocytes. Mitochondria lacking ANT could still be induced to undergo permeability transition, resulting in release of cytochrome c. However, more Ca2+ than usual was required to activate the mtPTP, and the pore could no longer be regulated by ANT ligands. Moreover, hepatocytes without ANT remained competent to respond to various initiators of cell death. Therefore, ANTs are non-essential structural components of the mtPTP, although they do contribute to its regulation.

Measuring Marketing Productivity: Current Knowledge and Future Directions:

Abstract: For too long, marketers have not been held accountable for showing how marketing expenditures add to shareholder value. As time has gone by, this lack of accountability has undermined marketers’ credibility, threatened the standing of the marketing function within the firm, and even threatened marketing’s existence as a distinct capability within the firm. This article proposes a broad framework for assessing marketing productivity, cataloging what is already known, and suggesting areas for further research. The authors conclude that it is possible to show how marketing expenditures add to shareholder value. The effective dissemination of new methods of assessing marketing productivity to the business community will be a major step toward raising marketing’s vitality in the firm and, more important, toward raising the performance of the firm itself. The authors also suggest many areas in which further research is essential to making methods of evaluating marketing productivity increasingly valid,...

Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear.

Abstract: Background Traditional pharmacological approaches to treating psychiatric disorders focus on correcting presumed biochemical abnormalities. However, some disorders, particularly the anxiety-related disorders exemplified by specific phobia, have an emotional learning component to them that can be facilitated with psychotherapy. Objective To determine whether D-cycloserine (DCS), a partial agonist at theN-methyl-D-aspartate receptor that has previously been shown to improve extinction of fear in rodents, will also improve extinction of fear in human phobic patients undergoing behavioral exposure therapy. Design Randomized, double-blind, placebo-controlled trial examining DCS vs placebo treatment in combination with a precisely controlled exposure paradigm. Setting Participants were recruited from the general community to a research clinic. Participants Twenty-eight subjects with acrophobia diagnosed by the Structured Clinical Interview forDSM-IVwere enrolled. Interventions After we obtained pretreatment measures of fear, subjects were treated with 2 sessions of behavioral exposure therapy using virtual reality exposure to heights within a virtual glass elevator. Single doses of placebo or DCS were taken prior to each of the 2 sessions of virtual reality exposure therapy. Subjects, therapists, and assessors were blind to the treatment condition. Subjects returned at 1 week and 3 months posttreatment for measures to determine the presence and severity of acrophobia symptoms. Main Outcome Measures Included were measures of acrophobia within the virtual environment, measures of acrophobia in the real world, and general measures of overall improvement. An objective measure of fear, electrodermal skin fluctuation, was also included during the virtual exposure to heights. Symptoms were assessed by self-report and by independent assessors at approximately 1 week and 3 months posttreatment. Results Exposure therapy combined with DCS resulted in significantly larger reductions of acrophobia symptoms on all main outcome measures. Subjects receiving DCS had significantly more improvement compared with subjects receiving placebo within the virtual environment (1 week after treatment,P≤.001; 3 months later,P≤.05). Subjects receiving DCS also showed significantly greater decreases in posttreatment skin conductance fluctuations during the virtual exposure (P≤.05). Additionally, subjects receiving DCS had significantly greater improvement compared with subjects receiving placebo on general measures of real-world acrophobia symptoms (acrophobia avoidance [P≤.02], acrophobia anxiety [P≤.01], attitudes toward heights [P≤.04], clinical global improvement [P≤.01], and number of self-exposures to real-world heights [P≤.01]); the improvement was evident early in treatment and was maintained at 3 months. Conclusion These pilot data provide initial support for the use of acute dosing of DCS as an adjunct to exposure-based psychotherapy to accelerate the associative learning processes that contribute to correcting psychopathology.

Cultural group selection, coevolutionary processes and large-scale cooperation

Abstract: In constructing improved models of human behavior, both experimental and behavioral economists have increasingly turned to evolutionary theory for insights into human psychology and preferences. Unfortunately, the existing genetic evolutionary approaches can explain neither the degree of prosociality (altruism and altruistic punishment) observed in humans, nor the patterns of variation in these behaviors across different behavioral domains and social groups. Ongoing misunderstandings about why certain models work, what they predict, and what the place is of “group selection” in evolutionary theory have hampered the use of insights from biology and anthropology. This paper clarifies some of these issues and proposes an approach to the evolution of prosociality rooted in the interaction between cultural and genetic transmission. I explain how, in contrast to non-cultural species, the details of our evolved cultural learning capacities (e.g., imitative abilities) create the conditions for the cultural evolution of prosociality. By producing multiple behavioral equilibria, including group-beneficial equilibria, cultural evolution endogenously generates a mechanism of equilibrium selection that can favor prosociality. Finally, in the novel social environments left in the wake of these cultural evolutionary processes, natural selection is likely to favor prosocial genes that would not be expected in a purely genetic approach. © 2003 Published by Elsevier B.V.

Lumpectomy plus Tamoxifen with or without Irradiation in Women 70 Years of Age or Older with Early Breast Cancer

Abstract: BACKGROUND In women 70 years of age or older who have early breast cancer, it is unclear whether lumpectomy plus tamoxifen is as effective as lumpectomy followed by tamoxifen plus radiation therapy. METHODS Between July 1994 and February 1999, we randomly assigned 636 women who were 70 years of age or older and who had clinical stage I (T1N0M0 according to the tumor-node-metastasis classification), estrogen-receptor-positive breast carcinoma treated by lumpectomy to receive tamoxifen plus radiation therapy (317 women) or tamoxifen alone (319 women). Primary end points were the time to local or regional recurrence, the frequency of mastectomy for recurrence, breast-cancer-specific survival, the time to distant metastasis, and overall survival. RESULTS The only significant difference between the two groups was in the rate of local or regional recurrence at five years (1 percent in the group given tamoxifen plus irradiation and 4 percent in the group given tamoxifen alone, P<0.001). There were no significant differences between the two groups with regard to the rates of mastectomy for local recurrence, distant metastases, or five-year rates of overall survival (87 percent in the group given tamoxifen plus irradiation and 86 percent in the tamoxifen group, P=0.94). Assessment by physicians and patients of cosmetic results and adverse events uniformly rated tamoxifen plus irradiation inferior to tamoxifen alone. CONCLUSIONS Lumpectomy plus adjuvant therapy with tamoxifen alone is a realistic choice for the treatment of women 70 years of age or older who have early, estrogen-receptor-positive breast cancer.

Group Social Capital and Group Effectiveness: The Role of Informal Socializing Ties

Abstract: This study introduces the concept of group social capital, which is the configuration of group members' social relationships within a group and in the social structure of a broader organization, an...

Memory CD8 T-Cell Differentiation during Viral Infection

Abstract: Memory CD8 T cells are an important component of protective immunity against viral infections, and understanding their development will aid in the design of optimal vaccines. Recent work has shed light on the complex differentiation process that occurs during a CD8 T-cell response to viral infection

Demography and cultural evolution: How adaptive cultural processes can produce maladaptive losses: The Tasmanian case

Abstract: A combination of archeological and ethnohistorical evidence indicates that, over an approximately 8,000-year period, from the beginning of the Holocene until European explorers began arriving in the eighteenth century, the societies of Tasmania lost a series of valuable skills and technologies. These likely included bone tools, cold-weather clothing, hafted tools, nets, fishing spears, barbed spears, spear-throwers, and boomerangs. To address this puzzle, and the more general question of how human cognition and social interaction can generate both adaptive cultural evolution and maladaptive losses of culturally acquired skills, this paper constructs a formal model of cultural evolution rooted in the cognitive details of human social learning and inference. The analytical results specify the conditions for differing rates of adaptive cultural evolution, and reveal regimes that will produce maladaptive losses of particular kinds of skills and related technologies. More specifically, the results suggest that the relatively sudden reduction in the effective population size (the size of the interacting pool of social learners) that occurred with the rising ocean levels at the end of the last glacial epoch, which cut Tasmania off from the rest of Australia for the ensuing ten millennia, could have initiated a cultural evolutionary process that (1) kept stable or even improved relatively simple technological skills, and (2) produced an increasing deterioration of more complex skills leading to the complete disappearance of some technologies and practices. This pattern is consistent with the empirical record in Tasmania. Beyond this case, I speculate on the applicability of the model to understanding the variability in rates of adaptive cultural evolution.

Were there Regime Switches in U.S. Monetary Policy

Abstract: A multivariate model, identifying monetary policy and allowing for simultaneity and regime switching in coefficients and variances, is confronted with U.S. data since 1959. The best fit is with a model that allows time variation in structural disturbance variances only. Among models that also allow for changes in equation coefficients, the best fit is for a model that allows coefficients to change only in the monetary policy rule. That model allows switching among three main regimes and one rarely and briefly occurring regime. The three main regimes correspond roughly to periods when most observers believe that monetary policy actually differed, and the differences in policy behavior are substantively interesting, though statistically ill determined. The estimates imply monetary targeting was central in the early '80s but was also important sporadically in the '70s. The changes in regime were essential neither to the rise in inflation in the '70s nor to its decline in the '80s.

Sudden infant death syndrome and unclassified sudden infant deaths: a definitional and diagnostic approach.

Abstract: The definition of sudden infant death syndrome (SIDS) originally appeared in 1969 and was modified 2 decades later. During the following 15 years, an enormous amount of additional information has emerged, justifying additional refinement of the definition of SIDS to incorporate epidemiologic features, risk factors, pathologic features, and ancillary test findings. An expert panel of pediatric and forensic pathologists and pediatricians considered these issues and developed a new general definition of SIDS for administrative and vital statistics purposes. The new definition was then stratified to facilitate research into sudden infant death. Another category, defined as unclassified sudden infant deaths, was introduced for cases that do not meet the criteria for a diagnosis of SIDS and for which alternative diagnoses of natural or unnatural conditions were equivocal. It is anticipated that these new definitions will be modified in the future to accommodate new understanding of SIDS and sudden infant death.

Containing Pandemic Influenza with Antiviral Agents

Abstract: For the first wave of pandemic influenza or a bioterrorist influenza attack, antiviral agents would be one of the few options to contain the epidemic in the United States until adequate supplies of vaccine were available. The authors use stochastic epidemic simulations to investigate the effectiveness of targeted antiviral prophylaxis to contain influenza. In this strategy, close contacts of suspected index influenza cases take antiviral agents prophylactically. The authors compare targeted antiviral prophylaxis with vaccination strategies. They model an influenza pandemic or bioterrorist attack for an agent similar to influenza A virus (H2N2) that caused the Asian influenza pandemic of 1957-1958. In the absence of intervention, the model predicts an influenza illness attack rate of 33% of the population (95% confidence interval (CI): 30, 37) and an influenza death rate of 0.58 deaths/1,000 persons (95% Cl: 0.4, 0.8). With the use of targeted antiviral prophylaxis, if 80% of the exposed persons maintained prophylaxis for up to 8 weeks, the epidemic would be contained, and the model predicts a reduction to an illness attack rate of 2% (95% Cl: 0.2, 16) and a death rate of 0.04 deaths/1,000 persons (95% CI: 0.0003, 0.25). Such antiviral prophylaxis is nearly as effective as vaccinating 80% of the population. Vaccinating 80% of the children aged less than 19 years is almost as effective as vaccinating 80% of the population. Targeted antiviral prophylaxis has potential as an effective measure for containing influenza until adequate quantities of vaccine are available.

Measurement and standardization protocols for anthropometry used in the construction of a new international growth reference.

Abstract: Thorough training, continuous standardization, and close monitoring of the adherence to measurement procedures during data collection are essential for minimizing random error and bias in multicenter studies. Rigorous anthropometry and data collection protocols were used in the WHO Multicentre Growth Reference Study to ensure high data quality. After the initial training and standardization, study teams participated in standardization sessions every two months for a continuous assessment of the precision and accuracy of their measurements. Once a year the teams were restandardized against the WHO lead anthropometrist, who observed their measurement techniques and retrained any deviating observers. Robust and precise equipment was selected and adapted for field use. The anthropometrists worked in pairs, taking measurements independently, and repeating measurements that exceeded preset maximum allowable differences. Ongoing central and local monitoring identified anthropometrists deviating from standard procedures, and immediate corrective action was taken. The procedures described in this paper are a model for research settings.

Computed Tomographic Colonography (Virtual Colonoscopy) A Multicenter Comparison With Standard Colonoscopy for Detection of Colorectal Neoplasia

Abstract: ContextConventional colonoscopy is the best available method for detection of colorectal cancer; however, it is invasive and not without risk. Computed tomographic colonography (CTC), also known as virtual colonoscopy, has been reported to be reasonably accurate in the diagnosis of colorectal neoplasia in studies performed at expert centers.ObjectiveTo assess the accuracy of CTC in a large number of participants across multiple centers.Design, Setting, and ParticipantsA nonrandomized, evaluator-blinded, noninferiority study design of 615 participants aged 50 years or older who were referred for routine, clinically indicated colonoscopy in 9 major hospital centers between April 17, 2000, and October 3, 2001. The CTC was performed by using multislice scanners immediately before standard colonoscopy; findings at colonoscopy were reported before and after segmental unblinding to the CTC results.Main Outcome MeasuresThe sensitivity and specificity of CTC and conventional colonoscopy in detecting participants with lesions sized at least 6 mm. Secondary outcomes included detection of all lesions, detection of advanced lesions, possible technical confounders, participant preferences, and evidence for increasing accuracy with experience.ResultsA total of 827 lesions were detected in 308 of 600 participants who underwent both procedures; 104 participants had lesions sized at least 6 mm. The sensitivity of CTC for detecting participants with 1 or more lesions sized at least 6 mm was 39.0% (95% confidence interval [CI], 29.6%-48.4%) and for lesions sized at least 10 mm, it was 55.0% (95% CI, 39.9%-70.0%). These results were significantly lower than those for conventional colonoscopy, with sensitivities of 99.0% (95% CI, 97.1%->99.9%) and 100%, respectively. A total of 496 participants were without any lesion sized at least 6 mm. The specificity of CTC and conventional colonoscopy for detecting participants without any lesion sized at least 6 mm was 90.5% (95% CI, 87.9%-93.1%) and 100%, respectively, and without lesions sized at least 10 mm, 96.0% (95% CI, 94.3%-97.6%) and 100%, respectively. Computed tomographic colonography missed 2 of 8 cancers. The accuracy of CTC varied considerably between centers and did not improve as the study progressed. Participants expressed no clear preference for either technique.ConclusionsComputed tomographic colonography by these methods is not yet ready for widespread clinical application. Techniques and training need to be improved.

Comparison of MRI and CT for Detection of Acute Intracerebral Hemorrhage

Abstract: ContextNoncontrast computed tomography (CT) is the standard brain imaging study for the initial evaluation of patients with acute stroke symptoms. Multimodal magnetic resonance imaging (MRI) has been proposed as an alternative to CT in the emergency stroke setting. However, the accuracy of MRI relative to CT for the detection of hyperacute intracerebral hemorrhage has not been demonstrated.ObjectiveTo compare the accuracy of MRI and CT for detection of acute intracerebral hemorrhage in patients presenting with acute focal stroke symptoms.Design, Setting, and PatientsA prospective, multicenter study was performed at 2 stroke centers (UCLA Medical Center and Suburban Hospital, Bethesda, Md), between October 2000 and February 2003. Patients presenting with focal stroke symptoms within 6 hours of onset underwent brain MRI followed by noncontrast CT.Main Outcome MeasuresAcute intracerebral hemorrhage and any intracerebral hemorrhage diagnosed on gradient recalled echo (GRE) MRI and CT scans by a consensus of 4 blinded readers.ResultsThe study was stopped early, after 200 patients were enrolled, when it became apparent at the time of an unplanned interim analysis that MRI was detecting cases of hemorrhagic transformation not detected by CT. For the diagnosis of any hemorrhage, MRI was positive in 71 patients with CT positive in 29 (P<.001). For the diagnosis of acute hemorrhage, MRI and CT were equivalent (96% concordance). Acute hemorrhage was diagnosed in 25 patients on both MRI and CT. In 4 other patients, acute hemorrhage was present on MRI but not on the corresponding CT—each of these 4 cases was interpreted as hemorrhagic transformation of an ischemic infarct. In 3 patients, regions interpreted as acute hemorrhage on CT were interpreted as chronic hemorrhage on MRI. In 1 patient, subarachnoid hemorrhage was diagnosed on CT but not on MRI. In 49 patients, chronic hemorrhage, most often microbleeds, was visualized on MRI but not on CT.ConclusionMRI may be as accurate as CT for the detection of acute hemorrhage in patients presenting with acute focal stroke symptoms and is more accurate than CT for the detection of chronic intracerebral hemorrhage.

FoodNet Estimate of the Burden of Illness Caused by Nontyphoidal Salmonella Infections in the United States

Abstract: To determine the burden of Salmonella infections in the United States, Foodborne Diseases Active Surveillance Network (FoodNet) investigators conducted population-based active surveillance for culture-confirmed Salmonella infections during 1996‐1999 at FoodNet laboratories. In addition, all clinical microbiology FoodNet laboratories were surveyed to determine their practices for isolating Salmonella. Telephone interviews were also conducted among residents of the FoodNet sites to determine the proportion of persons with diarrheal illness who sought medical care and the proportion who submitted stool specimens for bacterial culture. Using our model, we estimated that there were 1.4 million nontyphoidal Salmonella infections in the United States, resulting in 168,000 physician office visits per year during 1996‐1999. Including both culture-confirmed infections and those not confirmed by culture, we estimated that Salmonella infections resulted in 15,000 hospitalizations and 400 deaths annually. These estimates indicate that salmonellosis presents a major ongoing burden to public health.