Showing papers by "University of Rochester published in 2000"

Self-determination theory and the facilitation of intrinsic motivation, social development, and well-being.

Abstract: Human beings can be proactive and engaged or, alternatively, passive and alienated, largely as a function of the social conditions in which they develop and function. Accordingly, research guided by self-determination theo~ has focused on the social-contextual conditions that facilitate versus forestall the natural processes of self-motivation and healthy psychological development. Specifically, factors have been examined that enhance versus undermine intrinsic motivation, self-regulation, and well-being. The findings have led to the postulate of three innate psychological needs--competence, autonomy, and relatednesswhich when satisfied yield enhanced self-motivation and mental health and when thwarted lead to diminished motivation and well-being. Also considered is the significance of these psychological needs and processes within domains such as health care, education, work, sport, religion, and psychotherapy. T he fullest representations of humanity show people to be curious, vital, and self-motivated. At their best, they are agentic and inspired, striving to learn; extend themselves; master new skills; and apply their talents responsibly. That most people show considerable effort, agency, and commitment in their lives appears, in fact, to be more normative than exceptional, suggesting some very positive and persistent features of human nature. Yet, it is also clear that the human spirit can be diminished or crushed and that individuals sometimes reject growth and responsibility. Regardless of social strata or cultural origin, examples of both children and adults who are apathetic, alienated, and irresponsible are abundant. Such non-optimal human functioning can be observed not only in our psychological clinics but also among the millions who, for hours a day, sit passively before their televisions, stare blankly from the back of their classrooms, or wait listlessly for the weekend as they go about their jobs. The persistent, proactive, and positive tendencies of human nature are clearly not invariantly apparent. The fact that human nature, phenotypically expressed, can be either active or passive, constructive or indolent, suggests more than mere dispositional differences and is a function of more than just biological endowments. It also bespeaks a wide range of reactions to social environments that is worthy of our most intense scientific investigation. Specifically, social contexts catalyze both within- and between-person differences in motivation and personal growth, resulting in people being more self-motivated, energized, and integrated in some situations, domains, and cultures than in others. Research on the conditions that foster versus undermine positive human potentials has both theoretical import and practical significance because it can contribute not only to formal knowledge of the causes of human behavior but also to the design of social environments that optimize people's development, performance, and well-being. Research guided by self-determination theory (SDT) has had an ongoing concern with precisely these

The "What" and "Why" of Goal Pursuits: Human Needs and the Self-Determination of Behavior

Abstract: Self-determination theory (SDT) maintains that an understanding of human motivation requires a consideration of innate psychological needs for competence, autonomy, and relatedness. We discuss the SDT concept of needs as it relates to previous need theories, emphasizing that needs specify the necessary conditions for psychological growth, integrity, and well-being. This concept of needs leads to the hypotheses that different regulatory processes underlying goal pursuits are differentially associated with effective functioning and well-being and also that different goal contents have different relations to the quality of behavior and mental health, specifically because different regulatory processes and different goal contents are associated with differing degrees of need satisfaction. Social contexts and individual differences that support satisfaction of the basic needs facilitate natural growth processes including intrinsically motivated behavior and integration of extrinsic motivations, whereas those that forestall autonomy, competence, or relatedness are associated with poorer motivation, performance, and well-being. We also discuss the relation of the psychological needs to cultural values, evolutionary processes, and other contemporary motivation theories.

The Construct of Resilience: A Critical Evaluation and Guidelines for Future Work

Abstract: This paper presents a critical appraisal of resilience, a construct connoting the maintenance of positive adaptation by individuals despite experiences of significant adversity. As empirical research on resilience has burgeoned in recent years, criticisms have been levied at work in this area. These critiques have generally focused on ambiguities in definitions and central terminology; heterogeneity in risks experienced and competence achieved by individuals viewed as resilient; instability of the phenomenon of resilience; and concerns regarding the usefulness of resilience as a theoretical construct. We address each identified criticism in turn, proposing solutions for those we view as legitimate and clarifying misunderstandings surrounding those we believe to be less valid. We conclude that work on resilience possesses substantial potential for augmenting the understanding of processes affecting at-risk individuals. Realization of the potential embodied by this construct, however, will remain constrained without continued scientific attention to some of the serious conceptual and methodological pitfalls that have been noted by skeptics and proponents alike.

Does Schooling Cause Growth

Abstract: A number of economists find that growth and schooling are highly correlated across countries. A model is examined in which the ability to build on the human capital of one's elders plays an important role in linking growth to schooling. The model is calibrated to quantify the strength of the effect of schooling on growth by using evidence from the labor literature on Mincerian returns to education. The upshot is that the impact of schooling on growth explains less than one-third of the empirical cross-country relationship. The ability of reverse causality to explain this empirical relationship is also investigated.

Daily Well-Being: The Role of Autonomy, Competence, and Relatedness

Abstract: Emotional well-being is most typically studied in trait or trait-like terms, yet a growing literature indicates that daily (within-person) fluctuations in emotional well-being may be equally important. The present research explored the hypothesis that daily variations may be understood in terms of the degree to which three basic needs—autonomy, competence, and relatedness—are satisfied in daily activity. Hierarchical linear models were used to examine this hypothesis across 2 weeks of daily activity and well-being reports controlling for trait-level individual differences. Results strongly supported the hypothesis. The authors also examined the social activities that contribute to satisfaction of relatedness needs. The best predictors were meaningful talk and feeling understood and appreciated by interaction partners. Finally, the authors found systematic day-of-the-week variations in emotional well-being and need satisfaction. These results are discussed in terms of the importance of daily activities and...

The construct of resilience: Implications for interventions and social policies

Abstract: The focus of this article is on the interface between research on resilience—a construct representing positive adaptation despite adversity —and the applications of this work to the development of interventions and social policies. Salient defining features of research on resilience are delineated, as are various advantages, limitations, and precautions linked with the application of the resilience framework to developing interventions. For future applied efforts within this tradition, a series of guiding principles are presented along with exemplars of existing programs based on the resilience paradigm. The article concludes with discussions of directions for future work in this area, with emphases on an enhanced interface between science and practice, and a broadened scope of resilience-based interventions in terms of the types of populations, and the types of adjustment domains, that are encompassed.

The effects of instructors' autonomy support and students' autonomous motivation on learning organic chemistry: A self-determination theory perspective

Abstract: This prospective study applied self-determination theory to investigate the effects of students' course-specific self-regulation and their perceptions of their instructors' autonomy support on adjustment and academic performance in a college-level organic chemistry course. The study revealed that: (1) students' reports of entering the course for relatively autonomous (vs. controlled) reasons predicted higher perceived competence and interest/enjoyment and lower anxiety and grade-focused performance goals during the course, and were related to whether or not the students dropped the course; and (2) students' perceptions of their instructors' autonomy support predicted increases in autonomous self-regulation, perceived competence, and interest/enjoyment, and decreases in anxiety over the semester. The change in autonomous self-regulation in turn predicted students' performance in the course. Further, instructor autonomy support also predicted course performance directly, although differences in the initial level of students' autonomous self-regulation moderated that effect, with autonomy support relating strongly to academic performance for students initially low in autonomous self-regulation but not for students initially high in autonomous self-regulation. © 2000 John Wiley & Sons, Inc. Sci Ed84:740–756, 2000.

Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus.

Abstract: The innate immune system contributes to the earliest phase of the host defense against foreign organisms and has both soluble and cellular pattern recognition receptors for microbial products. Two important members of this receptor group, CD14 and the Toll-like receptor (TLR) pattern recognition receptors, are essential for the innate immune response to components of Gram-negative and Gram-positive bacteria, mycobacteria, spirochetes and yeast. We now find that these receptors function in an antiviral response as well. The innate immune response to the fusion protein of an important respiratory pathogen of humans, respiratory syncytial virus (RSV), was mediated by TLR4 and CD14. RSV persisted longer in the lungs of infected TLR4-deficient mice compared to normal mice. Thus, a common receptor activation pathway can initiate innate immune responses to both bacterial and viral pathogens.

History Lessons Institutions, Factor Endowments, and Paths of Development in the New World

Abstract: The explanations offered for the contrasting records of long-run growth and development among the societies of North and South America most often focus on institutions. The traditional explanations for the sources of these differences in institutions, typically highlight the significance of national heritage or religion. We, in contrast, argue that a hemispheric perspective across the wide range of colonies established in the New World by the Europeans suggests that although there were many influences, factor endowments or initial conditions had profound and enduring effects on the long-run paths of institutional and economic development followed by the respective economies.

Striatonigrostriatal Pathways in Primates Form an Ascending Spiral from the Shell to the Dorsolateral Striatum

Abstract: Clinical manifestations in diseases affecting the dopamine system include deficits in emotional, cognitive, and motor function. Although the parallel organization of specific corticostriatal pathways is well documented, mechanisms by which dopamine might integrate information across different cortical/basal ganglia circuits are less well understood. We analyzed a collection of retrograde and anterograde tracing studies to understand how the striatonigrostriatal (SNS) subcircuit directs information flow between ventromedial (limbic), central (associative), and dorsolateral (motor) striatal regions. When viewed as a whole, the ventromedial striatum projects to a wide range of the dopamine cells and receives a relatively small dopamine input. In contrast, the dorsolateral striatum (DLS) receives input from a broad expanse of dopamine cells and has a confined input to the substantia nigra (SN). The central striatum (CS) receives input from and projects to a relatively wide range of the SN. The SNS projection from each striatal region contains three substantia nigra components: a dorsal group of nigrostriatal projecting cells, a central region containing both nigrostriatal projecting cells and its reciprocal striatonigral terminal fields, and a ventral region that receives a specific striatonigral projection but does not contain its reciprocal nigrostriatal projection. Examination of results from multiple tracing experiments simultaneously demonstrates an interface between different striatal regions via the midbrain dopamine cells that forms an ascending spiral between regions. The shell influences the core, the core influences the central striatum, and the central striatum influences the dorsolateral striatum. This anatomical arrangement creates a hierarchy of information flow and provides an anatomical basis for the limbic/cognitive/motor interface via the ventral midbrain.

A Theory of Shape by Space Carving

Abstract: In this paper we consider the problem of computing the 3D shape of an unknown, arbitrarily-shaped scene from multiple photographs taken at known but arbitrarily-distributed viewpoints. By studying the equivalence class of all 3D shapes that reproduce the input photographs, we prove the existence of a special member of this class, the photo hull, that (1) can be computed directly from photographs of the scene, and (2) subsumes all other members of this class. We then give a provably-correct algorithm, called Space Carving, for computing this shape and present experimental results on complex real-world scenes. The approach is designed to (1) capture photorealistic shapes that accurately model scene appearance from a wide range of viewpoints, and (2) account for the complex interactions between occlusion, parallax, shading, and their view-dependent effects on scene-appearance.

Capital-skill complementarity and inequality: A macroeconomic analysis

Abstract: The supply and price of skilled labor relative to unskilled labor have changed dramatically over the postwar period. The relative quantity of skilled labor has increased substantially, and the skill premium, which is the wage of skilled labor relative to that of unskilled labor, has grown significantly since 1980. Many studies have found that accounting for the increase in the skill premium on the basis of observable variables is difficult and have concluded implicitly that latent skill-biased technological change must be the main factor responsible. This paper examines that view systematically. We develop a framework that provides a simple, explicit economic mechanism for understanding skill-biased technological change in terms of observable variables, and we use the framework to evaluate the fraction of variation in the skill premium that can be accounted for by changes in observed factor quantities. We find that with capital-skill complementarity, changes in observed inputs alone can account for most of the variations in the skill premium over the last 30 years.

Chronic pain as an outcome of surgery. A review of predictive factors.

Abstract: ONE potential adverse outcome from surgery is chronic pain. Analysis of predictive and pathologic factors is important to develop rational strategies to prevent this problem. Additionally, the natural history of patients with and without persistent pain after surgery provides an opportunity to improve the understanding of the physiology and psychology of chronic pain. Ideally, studies of chronic postoperative pain should include (1) sufficient preoperative data (assessment of pain, physiologic and psychologic risk factors for chronic pain); (2) detailed descriptions of the operative approaches used (location and length of incisions, handling of nerves and muscles); (3) the intensity and character of acute postoperative pain and its management; and (4) follow-up at intervals to 1 yr or more. In addition, there would be information about postoperative interventions that may influence pain, such as radiation therapy or chemotherapy. At long-term follow-up visits, patient function, physical signs, and symptoms would be evaluated using a standardized algorithm, including quantitative and descriptive pain assessments. We found no studies that contain all of these data. For this review, we specifically sought population data that reflect the incidence of chronic postoperative pain or predictors (medical, physiologic, and psychologic) of chronic pain. We selected five groups of surgeries (limb amputations, breast surgery, gallbladder surgery, lung surgery, and inguinal hernia surgery). These surgeries were selected because the incidence of pain is known to be high, thus improving the probability of detecting predictive factors. They also represent a range of major surgical procedures.

Within-person variation in security of attachment: a self-determination theory perspective on attachment, need fulfillment, and well-being.

Abstract: Attachment research has traditionally focused on individual differences in global patterns of attachment to important others. The current research instead focuses primarily on within-person variability in attachments across relational partners. It was predicted that within-person variability would be substantial, even among primary attachment figures of mother, father, romantic partner, and best friend. The prediction was supported in three studies. Furthermore, in line with self-determination theory, multilevel modeling and regression analyses showed that, at the relationship level, individuals' experience of fulfillment of the basic needs for autonomy, competence, and relatedness positively predicted overall attachment security, model of self, and model of other. Relations of both attachment and need satisfaction to well-being were also explored.

Spectrum of Mutations in Long-QT Syndrome Genes KVLQT1, HERG, SCN5A, KCNE1, and KCNE2

Abstract: Background—Long-QT Syndrome (LQTS) is a cardiovascular disorder characterized by prolongation of the QT interval on ECG and presence of syncope, seizures, and sudden death. Five genes have been imp...

Inequality in quality : Addressing socioeconomic, racial, and ethnic disparities in health care

Abstract: Socioeconomic and racial/ethnic disparities in health care quality have been extensively documented. Recently, the elimination of disparities in health care has become the focus of a national initiative. Yet, there is little effort to monitor and address disparities in health care through organizational quality improvement. After reviewing literature on disparities in health care, we discuss the limitations in existing quality assessment for identifying and addressing these disparities. We propose 5 principles to address these disparities through modifications in quality performance measures: disparities represent a significant quality problem; current data collection efforts are inadequate to identify and address disparities; clinical performance measures should be stratified by race/ethnicity and socioeconomic position for public reporting; population-wide monitoring should incorporate adjustment for race/ethnicity and socioeconomic position; and strategies to adjust payment for race/ethnicity and socioeconomic position should be considered to reflect the known effects of both on morbidity. JAMA. 2000;283:2579-2584

Bacterial Quorum Sensing in Pathogenic Relationships

Abstract: Bacteria were for a long time believed to exist as individual cells that sought primarily to find nutrients and multiply The discovery of intercellular communication among bacteria has led to the realization that bacteria are capable of coordinated activity that was once believed to be restricted to multicellular organisms The capacity to behave collectively as a group has obvious advantages, for example, the ability to migrate to a more suitable environment/better nutrient supply and to adopt new modes of growth, such as sporulation or biofilm formation, which may afford protection from deleterious environments The “language” used for this intercellular communication is based on small, self-generated signal molecules called autoinducers Through the use of autoinducers, bacteria can regulate their behavior according to population density The phenomenon of quorum sensing, or cell-to-cell communication, relies on the principle that when a single bacterium releases autoinducers (AIs) into the environment, their concentration is too low to be detected However, when sufficient bacteria are present, autoinducer concentrations reach a threshold level that allows the bacteria to sense a critical cell mass and, in response, to activate or repress target genes Most of the bacteria thus far identified that utilize quorum-sensing systems are associated in some way with plants or animals The nature of these relationships can be either amicable, as characterized by symbiotic bacteria, or adversarial, as seen with pathogenic bacteria There are numerous bacteria that have components of a quorum-sensing system for which the phenotype regulated remains an enigma Similarly, there are bacteria known to regulate a specific phenotype via quorum sensing for which one or more of the regulatory components have thus far eluded identification In this review we give examples of pathogenic relationships, focusing on organisms for which many of the facets of their quorum-sensing systems have been elucidated

The Darker and Brighter Sides of Human Existence: Basic Psychological Needs as a Unifying Concept

Abstract: (2000). The Darker and Brighter Sides of Human Existence: Basic Psychological Needs as a Unifying Concept. Psychological Inquiry: Vol. 11, No. 4, pp. 319-338.

The lipid treatment assessment project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals.

Abstract: Methods: Adult patients with dyslipidemia, who had been receiving the same lipid-lowering therapy for at least 3 months, were assessed at investigation sites. Lipid levels were determined once in each patient at the time of enrollment. The primary end point was the success rate, defined as the proportion of patients who achieved their LDL-C target level as specified by NCEP guidelines. Results: A total of 4888 patients from 5 regions of the United States were studied. Of these, 23% had fewer than 2 risk factors for coronary heart disease (CHD) and no evidence of CHD (low-risk group), 47% had 2 or more risk factors and no evidence of CHD (high-risk group), and 30% had established CHD. Overall, only 38% of patients achieved NCEP-specified LDL-C target levels; success rates were 68% among low-risk patients, 37% among high-risk patents, and 18% among patients with CHD. Drug therapy was significantly (P#.001) more effective than nondrug therapy in all patient risk groups. However, many patients treated with lipid-lowering drugs did not achieve LDL-C target levels. Conclusions: Large proportions of dyslipidemic patients receiving lipid-lowering therapy are not achieving NCEP LDL-C target levels. These findings indicate that more aggressive treatment of dyslipidemia is needed to attain goals established by NCEP guidelines. Arch Intern Med. 2000;160:459-467

Efficacy of Implantable Cardioverter–Defibrillators for the Prevention of Sudden Death in Patients with Hypertrophic Cardiomyopathy

Abstract: Background Hypertrophic cardiomyopathy is a genetic disease associated with a risk of ventricular tachyarrhythmias and sudden death, especially in young patients. Methods We conducted a retrospective multicenter study of the efficacy of implantable cardioverter–defibrillators in preventing sudden death in 128 patients with hypertrophic cardiomyopathy who were judged to be at high risk for sudden death. Results At the time of the implantation of the defibrillator, the patients were 8 to 82 years old (mean [±SD], 40±16), and 69 patients (54 percent) were less than 41 years old. The average follow-up period was 3.1 years. Defibrillators were activated appropriately in 29 patients (23 percent), by providing defibrillation shocks or antitachycardia pacing, with the restoration of sinus rhythm; the average age at the time of the intervention was 41 years. The rate of appropriate defibrillator discharge was 7 percent per year. A total of 32 patients (25 percent) had episodes of inappropriate discharges. In the g...

The spliceosome deposits multiple proteins 20–24 nucleotides upstream of mRNA exon–exon junctions

Abstract: Eukaryotic mRNAs exist in vivo as ribonucleoprotein particles (mRNPs). The protein components of mRNPs have important functions in mRNA metabolism, including effects on subcellular localization, translational efficiency and mRNA half-life. There is accumulating evidence that pre-mRNA splicing can alter mRNP structure and thereby affect downstream mRNA metabolism. Here, we report that the spliceosome stably deposits several proteins on mRNAs, probably as a single complex of approximately 335 kDa. This complex protects 8 nucleotides of mRNA from complete RNase digestion at a conserved position 20-24 nucleotides upstream of exon-exon junctions. Splicing-dependent RNase protection of this region was observed in both HeLa cell nuclear extracts and Xenopus laevis oocyte nuclei. Immunoprecipitations revealed that five components of the complex are the splicing-associated factors SRm160, DEK and RNPS1, the mRNA-associated shuttling protein Y14 and the mRNA export factor REF. Possible functions for this complex in nucleocytoplasmic transport of spliced mRNA, as well as the nonsense-mediated mRNA decay pathway, are discussed.

Efficacy and Safety of the Oral Neuraminidase Inhibitor Oseltamivir in Treating Acute Influenza

Abstract: ContextPrevious studies have shown oseltamivir, a neuraminidase inhibitor, to be effective in preventing influenza and treating experimental influenza.ObjectiveTo evaluate the efficacy and safety of oseltamivir in the treatment of naturally acquired influenza infection.DesignRandomized, placebo-controlled, double-blind study conducted January through March 1998.SettingSixty primary care and university health centers throughout the United States.ParticipantsA total of 629 healthy nonimmunized adults aged 18 to 65 years with febrile respiratory illness of no more than 36 hours' duration with temperature of 38°C or more plus at least 1 respiratory symptom and 1 constitutional symptom.InterventionsIndividuals were randomized to 1 of 3 treatment groups with identical appearing pills: oral oseltamivir phosphate, 75 mg twice daily (n = 211) or 150 mg (n = 209) twice daily, or placebo (n = 209).Main Outcome MeasuresDuration and severity of illness in individuals infected with influenza.ResultsTwo individuals withdrew before receiving medication and were excluded from further analyses. A total of 374 individuals (59.6%) were infected with influenza. Their duration of illness was reduced by more than 30% with both oseltamivir, 75 mg twice daily (median, 71.5 hours; P<.001), and oseltamivir, 150 mg twice daily (median, 69.9 hours; P = .006), compared with placebo (median, 103.3 hours). Severity of illness was reduced by 38% (median score, 597 score-hours; P<.001) with oseltamivir, 75 mg twice daily, and by 35% (median score, 626 score-hours; P<.001) with oseltamivir, 150 mg twice daily, vs placebo (median score, 963 score-hours). Oseltamivir treatment reduced the duration of fever and oseltamivir recipients returned to usual activities 2 to 3 days earlier than placebo recipients (P≤.05). Secondary complications such as bronchitis and sinusitis occurred in 15% of placebo recipients compared with 7% of combined oseltamivir recipients (P = .03). Among all 629 subjects, oseltamivir reduced illness duration (76.3 hours and 74.3 hours for 75 mg and 150 mg, respectively, vs 97.0 hours for placebo; P = .004 for both comparisons) and illness severity (686 score-hours and 629 score-hours for 75 mg and 150 mg, respectively, vs 887 score-hours for placebo; P<.001 for both comparisons). Nausea and vomiting occurred more frequently in both oseltamivir groups (combined, 18.0% and 14.1%, respectively; P = .002) than in the placebo group (7.4% and 3.4%; P<.001).ConclusionsOur data suggest that oral oseltamivir treatment reduces the duration and severity of acute influenza in healthy adults and may decrease the incidence of secondary complications.

Pramipexole vs Levodopa as initial treatment for Parkinson disease: A randomized controlled trial

Abstract: CONTEXT Pramipexole and levodopa both ameliorate the motor symptoms of early Parkinson disease (PD), but no controlled studies have compared long-term outcomes after initiating dopaminergic therapy with pramipexole vs levodopa. OBJECTIVE To compare the development of dopaminergic motor complications after initial treatment of early PD with pramipexole vs levodopa. DESIGN Multicenter, parallel-group, double-blind, randomized controlled trial. SETTING Academic movement disorders clinics at 22 sites in the United States and Canada. PATIENTS Three hundred one patients with early PD who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997. INTERVENTIONS Subjects were randomly assigned to receive pramipexole, 0.5 mg 3 times per day, with levodopa placebo (n = 151); or carbidopa/levodopa, 25/100 mg 3 times per day, with pramipexole placebo (n = 150). For patients with residual disability, the dosage was escalated during the first 10 weeks. From week 11 to month 23.5, investigators were permitted to add open-label levodopa to treat continuing or emerging disability. MAIN OUTCOME MEASURES Time to the first occurrence of any of 3 dopaminergic complications: wearing off, dyskinesias, or on-off motor fluctuations; changes in scores on the Unified Parkinson's Disease Rating Scale (UPDRS), assessed at baseline and follow-up evaluations; and, in a subgroup of 82 subjects evaluated at baseline and 23.5 months, ratio of specific to nondisplaceable striatal iodine 123 2-beta-carboxymethoxy-3-beta-(4-iodophenyl)tropane (beta-CIT) uptake on single photon emission computed tomography imaging of the dopamine transporter. RESULTS Initial pramipexole treatment resulted in significantly less development of wearing off, dyskinesias, or on-off motor fluctuations (28%) compared with levodopa (51%) (hazard ratio, 0.45; 95% confidence interval [CI], 0. 30-0.66; P<.001). The mean improvement in total UPDRS score from baseline to 23.5 months was greater in the levodopa group than in the pramipexole group (9.2 vs 4.5 points; P<.001). Somnolence was more common in pramipexole-treated patients than in levodopa-treated patients (32.4% vs 17.3%; P =.003), and the difference was seen during the escalation phase of treatment. In the subgroup study, patients treated initially with pramipexole (n = 39) showed a mean (SD) decline of 20.0% (14.2%) in striatal beta-CIT uptake compared with a 24.8% (14.4%) decline in subjects treated initially with levodopa (n = 39; P =.15). CONCLUSIONS Fewer patients receiving initial treatment for PD with pramipexole developed dopaminergic motor complications than with levodopa therapy. Despite supplementation with open-label levodopa in both groups, the levodopa-treated group had a greater improvement in total UPDRS compared with the pramipexole group. JAMA. 2000;284:1931-1938.

Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy.

Abstract: Myotonic dystrophy (DM1) is an autosomal dominant neuromuscular disorder associated with a (CTG)n expansion in the 3′-untranslated region of the DM1 protein kinase (DMPK) gene. To explain disease pathogenesis, the RNA dominance model proposes that the DM1 mutation produces a gain-of-function at the RNA level in which CUG repeats form RNA hairpins that sequester nuclear factors required for proper muscle development and maintenance. Here, we identify the triplet repeat expansion (EXP) RNA-binding proteins as candidate sequestered factors. As predicted by the RNA dominance model, binding of the EXP proteins is specific for dsCUG RNAs and proportional to the size of the triplet repeat expansion. Remarkably, the EXP proteins are homologous to the Drosophila muscleblind proteins required for terminal differentiation of muscle and photoreceptor cells. EXP expression is also activated during mammalian myoblast differentiation, but the EXP proteins accumulate in nuclear foci in DM1 cells. We propose that DM1 disease is caused by aberrant recruitment of the EXP proteins to the DMPK transcript (CUG)n expansion.

Trends and Disparities in Coronary Heart Disease, Stroke, and Other Cardiovascular Diseases in the United States Findings of the National Conference on Cardiovascular Disease Prevention

Abstract: A workshop was held September 27 through 29, 1999, to address issues relating to national trends in mortality and morbidity from cardiovascular diseases; the apparent slowing of declines in mortality from cardiovascular diseases; levels and trends in risk factors for cardiovascular diseases; disparities in cardiovascular diseases by race/ethnicity, socioeconomic status, and geography; trends in cardiovascular disease preventive and treatment services; and strategies for efforts to reduce cardiovascular diseases overall and to reduce disparities among subpopulations. The conference concluded that coronary heart disease mortality is still declining in the United States as a whole, although perhaps at a slower rate than in the 1980s; that stroke mortality rates have declined little, if at all, since 1990; and that there are striking differences in cardiovascular death rates by race/ethnicity, socioeconomic status, and geography. Trends in risk factors are consistent with a slowing of the decline in mortality; there has been little recent progress in risk factors such as smoking, physical inactivity, and hypertension control. There are increasing levels of obesity and type 2 diabetes, with major differences among subpopulations. There is considerable activity in population-wide prevention, primary prevention for higher risk people, and secondary prevention, but wide disparities exist among groups on the basis of socioeconomic status and geography, pointing to major gaps in efforts to use available, proven approaches to control cardiovascular diseases. Recommendations for strategies to attain the year 2010 health objectives were made.

Roles of PLC-β2 and -β3 and PI3Kγ in Chemoattractant-Mediated Signal Transduction

Abstract: The roles of phosphoinositide 3-kinase (PI3K) and phospholipase C (PLC) in chemoattractant-elicited responses were studied in mice lacking these key enzymes. PI3Kgamma was required for chemoattractant-induced production of phosphatidylinositol 3,4,5-trisphosphate [PtdIns (3,4,5)P3] and has an important role in chemoattractant-induced superoxide production and chemotaxis in mouse neutrophils and in production of T cell-independent antigen-specific antibodies composed of the immunoglobulin lambda light chain (TI-IglambdaL). The study of the mice lacking PLC-beta2 and -beta3 revealed that the PLC pathways have an important role in chemoattractant-mediated production of superoxide and regulation of protein kinases, but not chemotaxis. The PLC pathways also appear to inhibit the chemotactic activity induced by certain chemoattractants and to suppress TI-IglambdaL production.

Multidimensional femtosecond correlation spectroscopies of electronic and vibrational excitations.

Abstract: Femtosecond visible and infrared analogues of multiple-pulse nuclear magnetic resonance techniques provide novel snapshot probes into the structure and electronic and vibrational dynamics of complex molecular assemblies such as photosynthetic antennae, proteins, and hydrogen-bonded liquids. A classical-oscillator description of these spectroscopies in terms of interacting quasiparticles (rather than transitions among global eigenstates) is developed and sets the stage for designing new pulse sequences and inverting the multidimensional signals to yield molecular structures. Considerable computational advantages and a clear physical insight into the origin of the response and the relevant coherence sizes are provided by a real-space analysis of the underlying coherence-transfer pathways in Liouville space.