Showing papers by "University of Rochester published in 2006"

Principles of nano-optics

Abstract: 1. Introduction 2. Theoretical foundations 3. Propagation and focusing of optical fields 4. Spatial resolution and position accuracy 5. Nanoscale optical microscopy 6. Near-field optical probes 7. Probe-sample distance control 8. Light emission and optical interaction in nanoscale environments 9. Quantum emitters 10. Dipole emission near planar interfaces 11. Photonic crystals and resonators 12. Surface plasmons 13. Forces in confined fields 14. Fluctuation-induced phenomena 15. Theoretical methods in nano-optics Appendices Index.

The motivational pull of video games: A self-determination theory approach

Abstract: Four studies apply self-determination theory (SDT; Ryan & Deci, 2000) in investigating motivation for computer game play, and the effects of game play on well-being. Studies 1–3 examine individuals playing 1, 2 and 4 games, respectively and show that perceived in-game autonomy and competence are associated with game enjoyment, preferences, and changes in well-being pre- to post-play. Competence and autonomy perceptions are also related to the intuitive nature of game controls, and the sense of presence or immersion in participants’ game play experiences. Study 4 surveys an on-line community with experience in multi-player games. Results show that SDT’s theorized needs for autonomy, competence, and relatedness independently predict enjoyment and future game play. The SDT model is also compared with Yee’s (2005) motivation taxonomy of game play motivations. Results are discussed in terms of the relatively unexplored landscape of human motivation within virtual worlds.

Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic Events

Abstract: Background Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events. Methods We randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes. Results The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin (relative risk, 0.93; 95 percent confidence interval, 0.83 to 1.05; P = 0.22). The respective rate of the principal secondary efficacy end point, which included hospitalizations for ischemic events, was 16.7 percent and 17.9 percent (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.995; P = 0.04), and the rate of severe bleeding was 1.7 percent and 1.3 percent (relative risk, 1.25; 95 percent confidence interval, 0.97 to 1.61 percent; P = 0.09). The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo (relative risk, 1.2; 95 percent confidence interval, 0.91 to 1.59; P = 0.20) and the rate of death from cardiovascular causes also was higher with clopidogrel (3.9 percent vs. 2.2 percent, P = 0.01). In the subgroup with clinically evident atherothrombosis, the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo (relative risk, 0.88; 95 percent confidence interval, 0.77 to 0.998; P = 0.046). Conclusions In this trial, there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors. Overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes. (ClinicalTrials.gov number, NCT00050817.)

Towards A Positive Theory of the Determination of Accounting Standards

Abstract: This article provides the beginning of a positive theory of accounting by exploring those factors influencing management's attitudes on accounting standards that are likely to affect a firm's cashflows and in turn are affected by accounting standards. These factors are taxes, regulation, management compensation plans, bookkeeping costs and political costs, and they are combined into a model that predicts that large firms that experience reduced earnings due to changed accounting standards favor the change. All other firms oppose the change if the additional bookkeeping costs justify the cost of lobbying. This prediction was tested using the corporate submissions to the FASB's Discussion Memorandum on General Price Level Adjustments. The empirical results are consistent with the theory.

Principles of Nano-Optics by Lukas Novotny

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Positive Accounting Theory: A Ten Year Perspective

Abstract: This paper reviews and critiques the positive accounting literature following the publication of Watts and Zimmerman (1978, 1979), The 1978 paper helped generate the positive accounting literature that offers an explanation of accounting practice, suggests the importance of contracting costs, and has led to the discovery of some previously unknown empirical regularities. The 1979 paper produced a methodological debate that has not been very productive. This paper attempts to remove some common misconceptions about methodology that surfaced in that debate. It also suggests ways to improve positive research in accounting choice. The most important of these improvements is tighter links between the theory and the empirical tests. A second suggested improvement is the development of models that recognize the endogeneity among the variables in the regressions. A third improvement is reduction in measurement errors in both the dependent and independent variables in the regressions.

The Toxicology of Mercury and Its Chemical Compounds

Abstract: This review covers the toxicology of mercury and its compounds. Special attention is paid to those forms of mercury of current public health concern. Human exposure to the vapor of metallic mercury dates back to antiquity but continues today in occupational settings and from dental amalgam. Health risks from methylmercury in edible tissues of fish have been the subject of several large epidemiological investigations and continue to be the subject of intense debate. Ethylmercury in the form of a preservative, thimerosal, added to certain vaccines, is the most recent form of mercury that has become a public health concern. The review leads to general discussion of evolutionary aspects of mercury, protective and toxic mechanisms, and ends on a note that mercury is still an "element of mystery."

Cancer Stem Cells

Abstract: This review describes cancer stem cells, a topic of considerable biologic and clinical interest in oncology.

Neural correlations, population coding and computation

Abstract: How the brain encodes information in population activity, and how it combines and manipulates that activity as it carries out computations, are questions that lie at the heart of systems neuroscience. During the past decade, with the advent of multi-electrode recording and improved theoretical models, these questions have begun to yield answers. However, a complete understanding of neuronal variability, and, in particular, how it affects population codes, is missing. This is because variability in the brain is typically correlated, and although the exact effects of these correlations are not known, it is known that they can be large. Here, we review studies that address the interaction between neuronal noise and population codes, and discuss their implications for population coding in general.

Intrinsic Versus Extrinsic Goal Contents in Self-Determination Theory: Another Look at the Quality of Academic Motivation

Abstract: Examination of motivational dynamics in academic contexts within self-determination theory has centered primarily around both the motives (initially intrinsic vs. extrinsic, later autonomous vs. controlled) that regulate learners' study behavior and the contexts that promote or hinder these regulations. Less attention has been paid to the goal contents (intrinsic vs. extrinsic) that learners hold and to the different goal contents that are communicated in schools to increase the perceived relevance of the learning. Recent field experiments are reviewed showing that intrinsic goal framing (relative to extrinsic goal framing and no-goal framing) produces deeper engagement in learning activities, better conceptual learning, and higher persistence at learning activities. These effects occur for both intrinsically and extrinsically oriented individuals. Results are discussed in terms of self-determination theory's concept of basic psychological needs for autonomy, competence, and relatedness.

Bayesian inference with probabilistic population codes.

Abstract: Recent psychophysical experiments indicate that humans perform near-optimal Bayesian inference in a wide variety of tasks, ranging from cue integration to decision making to motor control. This implies that neurons both represent probability distributions and combine those distributions according to a close approximation to Bayes' rule. At first sight, it would seem that the high variability in the responses of cortical neurons would make it difficult to implement such optimal statistical inference in cortical circuits. We argue that, in fact, this variability implies that populations of neurons automatically represent probability distributions over the stimulus, a type of code we call probabilistic population codes. Moreover, we demonstrate that the Poisson-like variability observed in cortex reduces a broad class of Bayesian inference to simple linear combinations of populations of neural activity. These results hold for arbitrary probability distributions over the stimulus, for tuning curves of arbitrary shape and for realistic neuronal variability.

Self-regulation and the problem of human autonomy: does psychology need choice, self-determination, and will?

Abstract: The term autonomy literally refers to regulation by the self. Its opposite, heteronomy, refers to controlled regulation, or regulation that occurs without self-endorsement. At a time when philosophers and economists are increasingly detailing the nature of autonomy and recognizing its social and practical significance, many psychologists are questioning the reality and import of autonomy and closely related phenomena such as will, choice, and freedom. Using the framework of self-determination theory (Ryan & Deci, 2000), we review research concerning the benefits of autonomous versus controlled regulation for goal performance, persistence, affective experience, quality of relationships, and well-being across domains and cultures. We also address some of the controversies and terminological issues surrounding the construct of autonomy, including critiques of autonomy by biological reductionists, cultural relativists, and behaviorists. We conclude that there is a universal and cross-developmental value to autonomous regulation when the construct is understood in an exacting way.

Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion.

Abstract: Background Severe, often refractory anemia is characteristic of the myelodysplastic syndrome associated with chromosome 5q31 deletion. We investigated whether lenalidomide (CC5013) could reduce the transfusion requirement and suppress the abnormal 5q31− clone in patients with this disorder. Methods One hundred forty-eight patients received 10 mg of lenalidomide for 21 days every 4 weeks or daily. Hematologic, bone marrow, and cytogenetic changes were assessed after 24 weeks of treatment by an intention-to-treat analysis. Results Among the 148 patients, 112 had a reduced need for transfusions (76%; 95% confidence interval [CI], 68 to 82) and 99 patients (67%; 95% CI, 59 to 74) no longer required transfusions, regardless of the karyotype complexity. The response to lenalidomide was rapid (median time to response, 4.6 weeks; range, 1 to 49) and sustained; the median duration of transfusion independence had not been reached after a median of 104 weeks of follow-up. The maximum hemoglobin concentration reached...

Adolescent development in interpersonal and societal contexts.

Abstract: In this chapter we review theoretical and empirical advances in research on adolescent development in interpersonal and societal contexts. First, we identify several trends in current research, including the current emphasis on ecological models and the focus on diversity in and relational models of adolescent development. Next, we discuss recent research on interpersonal relationships, with an eye toward identifying major research themes and findings. Research on adolescents' relationships with parents, siblings, other relatives, peers, and romantic partners, and adolescents' involvement in community and society is reviewed. Future directions in research on adolescent development are discussed.

Asthma Control Test: Reliability, validity, and responsiveness in patients not previously followed by asthma specialists

Abstract: Background The development of the Asthma Control Test (ACT), a short, simple, patient-based tool for identifying patients with poorly controlled asthma, was recently described in patients under the routine care of an asthma specialist. Objectives We sought to evaluate the reliability and validity of the ACT in a longitudinal study of asthmatic patients new to the care of an asthma specialist. Methods Patients (n = 313) completed the ACT and the Asthma Control Questionnaire (ACQ) at 2 physician visits (4-12 weeks apart). Pulmonary function was measured, and asthma specialists rated asthma control. Results Internal consistency reliability of the ACT was 0.85 (baseline) and 0.79 (follow-up). Test-retest reliability was 0.77. Criterion validity was demonstrated by significant correlations between baseline ACT scores and baseline specialists' ratings of asthma control ( r = 0.52, P r = −0.89, P P r = 0.44, P r = −0.69, P 1 values ( r = 0.29, P Conclusions The ACT is reliable, valid, and responsive to changes in asthma control over time in patients new to the care of asthma specialists. A cutoff score of 19 or less identifies patients with poorly controlled asthma. Clinical implications In a clinical setting the ACT should be a useful tool to help physicians identify patients with uncontrolled asthma and facilitate their ability to follow patients' progress with treatment.

Astrocyte-mediated control of cerebral blood flow.

Abstract: Local increase in blood flow during neural activity forms the basis for functional brain imaging, but its mechanism remains poorly defined. Here we show that cortical astrocytes in vivo possess a powerful mechanism for rapid vasodilation. We imaged the activity of astrocytes labeled with the calcium (Ca(2+))-sensitive indicator rhod-2 in somatosensory cortex of adult mice. Photolysis of caged Ca(2+) in astrocytic endfeet ensheathing the vessel wall was associated with an 18% increase in arterial cross-section area that corresponded to a 37% increase in blood flow. Vasodilation occurred with a latency of only 1-2 s, and both indomethacin and the cyclooxygenase-1 inhibitor SC-560 blocked the photolysis-induced hyperemia. These observations implicate astrocytes in the control of local microcirculation and suggest that one of their physiological roles is to mediate vasodilation in response to increased neural activity.

Translocation of inhaled ultrafine manganese oxide particles to the central nervous system.

Abstract: An important step in assessing the toxicology of particles is to determine their fate after inhalation. Of particular interest to us are airborne ultrafine particles (UFPs; < 100 nm), which are abundant in ambient urban air and are of the same size as engineered nanoparticles. Translocation to extrapulmonary sites after respiratory tract deposition represents an important mechanism for these particles to cause direct effects in secondary target organs (Oberdorster et al. 2005). The extent to which this process occurs depends on several factors including particle solubility, particle or aggregate size, the site of deposition, and the integrity of the epithelial lining. UFPs deposit efficiently in all regions of the respiratory tract, depending on their size; specifically, as particle size decreases toward the smallest UFPs, nasopharyngeal deposition increases (International Committee on Radiological Protection 1994). Studies in rats have shown translocation of soluble manganese compounds from the nose along olfactory neuronal pathways to the olfactory bulb (Dorman et al. 2004; Henriksson and Tjalve 2000; Tjalve et al. 1996; Tjalve and Henriksson 1999) after inhalation or intranasal instillation exposures. Likewise, the few studies that have examined the fate of UFPs deposited on the nasal mucosa identified translocation along the neuronal olfactory route as a pathway to the olfactory bulb of the central nervous system (CNS). These include early studies in non-human primates, which demonstrated the translocation of solid nanosized particles (30 nm poliovirus; 50 nm silver-coated gold colloids) along the axons of olfactory nerves into the olfactory bulb (Bodian and Howe 1941a, 1941b; DeLorenzo 1970). We have also shown that inhaled elemental carbon particles (13C; 35 nm, count median diameter) accumulate in rat olfactory bulb after whole-body inhalation (Oberdorster et al. 2004). Regarding penetration into deeper brain regions, Tjalve et al. (1995) demonstrated that soluble ionic Mn instilled into the olfactory chamber of pike has the ability to pass synaptic junctions and migrate from the olfactory tract to more distal regions, including the hypothalamus. Dorman et al. (2004) found Mn in the striatum and cerebellum of rats after subchronic inhalation exposure to a soluble Mn salt (sulfate); however, this was attributed to uptake from the blood. Thus, contributions to brain Mn levels from the blood need to be considered and may also be an issue for inhaled solid UFPs. The effects of translocated particles in the brain are also important to determine. For example, preliminary information has emerged from populations of welders that some of them may develop parkinsonism 17 years earlier than the general population (Racette et al. 2001). Welding produces high amounts of fumes containing Mn UFPs (Zimmer et al. 2002). Several recent epidemiologic studies describe occupational exposure ranges of approximately 0.01–5 mg/m3 Mn in fumes from various welding processes and materials (Korczynski 2000; Li et al. 2004; Sinczuk-Walczak et al. 2001). Conflicting data emerge from animal studies, however, regarding effects of inhaled Mn compounds in the brain. Henriksson and Tjalve (2000) reported changes in glial fibrillary acidic protein (GFAP) and S-100b, markers of astrocyte activation, in several brain regions from rats exposed intranasally to Mn chloride. However, Dorman et al. (2004) did not find any evidence of changes in GFAP levels in the brain after exposure to Mn sulfate or phosphate. Potential contributing factors to the lack of concurrence in results include differences in the solubilities of the Mn salts used, the doses, and the contribution of olfactory epithelial damage. In the present study, we sought to address the hypothesis that a major translocation route for inhaled poorly soluble Mn oxide UFPs from deposits in the nose is to the olfactory bulb in the CNS. We characterized the size, oxidation state, and in vitro solubility of gas-phase–generated Mn oxide particles and also compared the translocation kinetics to the olfactory bulb of Mn oxide and MnCl2 that were applied to the nasal epithelium of rats via instillation. We then measured the accumulation of Mn in lung, liver, and olfactory bulb after repeated inhalation exposures with both nares patent or with one naris occluded. We show that Mn oxide UFPs are translocated to and retained in the olfactory bulb (ipsilateral to the patent naris only) and present evidence of exposure-induced effects in that region of the brain. These studies demonstrate the importance of UFPs size and of solubility in olfactory translocation processes.

Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease.

Abstract: Background Second-generation (atypical) antipsychotic drugs are widely used to treat psychosis, aggression, and agitation in patients with Alzheimer’s disease, but their benefits are uncertain and concerns about safety have emerged. We assessed the effectiveness of atypical antipsychotic drugs in outpatients with Alzheimer’s disease. Methods In this 42-site, double-blind, placebo-controlled trial, 421 outpatients with Alzheimer’s disease and psychosis, aggression, or agitation were randomly assigned to receive olanzapine (mean dose, 5.5 mg per day), quetiapine (mean dose, 56.5 mg per day), risperidone (mean dose, 1.0 mg per day), or placebo. Doses were adjusted as needed, and patients were followed for up to 36 weeks. The main outcomes were the time from initial treatment to the discontinuation of treatment for any reason and the number of patients with at least minimal improvement on the Clinical Global Impression of Change (CGIC) scale at 12 weeks. Results There were no significant differences among treatments with regard to the time to the discontinuation of treatment for any reason: olanzapine (median, 8.1 weeks), quetiapine (median, 5.3 weeks), risperidone (median, 7.4 weeks), and placebo (median, 8.0 weeks) (P = 0.52). The median time to the discontinuation of treatment due to a lack of efficacy favored olanzapine (22.1 weeks) and risperidone (26.7 weeks) as compared with quetiapine (9.1 weeks) and placebo (9.0 weeks) (P = 0.002). The time to the discontinuation of treatment due to adverse events or intolerability favored placebo. Overall, 24% of patients who received olanzapine, 16% of patients who received quetiapine, 18% of patients who received risperidone, and 5% of patients who received placebo discontinued their assigned treatment owing to intolerability (P = 0.009). No significant differences were noted among the groups with regard to improvement on the CGIC scale. Improvement was observed in 32% of patients assigned to olanzapine, 26% of patients assigned to quetiapine, 29% of patients assigned to risperidone, and 21% of patients assigned to placebo (P = 0.22). Conclusions Adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation in patients with Alzheimer’s disease. (ClinicalTrials.gov number, NCT00015548.)

Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology

Abstract: Increased production of mitochondrial reactive oxygen species (ROS) by hyperglycemia is recognized as a major cause of the clinical complications associated with diabetes and obesity [Brownlee, M. (2001) Nature 414, 813–820]. We observed that dynamic changes in mitochondrial morphology are associated with high glucose-induced overproduction of ROS. Mitochondria undergo rapid fragmentation with a concomitant increase in ROS formation after exposure to high glucose concentrations. Neither ROS increase nor mitochondrial fragmentation was observed after incubation of cells with the nonmetabolizable stereoisomer l-glucose. However, inhibition of mitochondrial pyruvate uptake that blocked ROS increase did not prevent mitochondrial fragmentation in high glucose conditions. Importantly, we found that mitochondrial fragmentation mediated by the fission process is a necessary component for high glucose-induced respiration increase and ROS overproduction. Extended exposure to high glucose conditions, which may mimic untreated diabetic conditions, provoked a periodic and prolonged increase in ROS production concomitant with mitochondrial morphology change. Inhibition of mitochondrial fission prevented periodic fluctuation of ROS production during high glucose exposure. These results indicate that the dynamic change of mitochondrial morphology in high glucose conditions contributes to ROS overproduction and that mitochondrial fission/fusion machinery can be a previously unrecognized target to control acute and chronic production of ROS in hyperglycemia-associated disorders.

Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients.

Abstract: BACKGROUND Hospitalization for febrile neutropenia (FN) in cancer patients is associated with considerable morbidity, mortality, and cost. The study was undertaken to better define mortality, length of stay (LOS), cost, and risk factors associated with mortality and prolonged hospitalization in cancer patients with FN. METHODS The longitudinal discharge database derived from 115 US medical centers was used to study all adult cancer patients hospitalized with FN between 1995 and 2000, comprising a total of 41,779 patients. Primary outcomes included mortality, LOS, and cost per episode. RESULTS Overall, in-hospital mortality was 9.5%. Patients without any major comorbidities had a 2.6% risk of mortality, whereas 1 major comorbidity was associated with a 10.3% and more than 1 major comorbidity with a ≥21.4% risk of mortality, respectively. Mean (median) length of stay was 11.5 (6) days, and the mean (median) cost was $19,110 ($8,376) per episode of FN. Patients hospitalized for ≥10 days (35% of all patients) accounted for 78% of overall cost. Independent major risk factors for inpatient mortality included invasive fungal infections, Gram-negative sepsis, pneumonia and other lung disease, cerebrovascular, renal, and liver disease. Main predictors for LOS ≥10 days included leukemia, invasive fungal infections, other types of infection, and several comorbid conditions. CONCLUSION Factors associated with increased mortality, LOS, and cost in hospitalized adult cancer patients with FN include patient characteristics, type of malignancy, comorbidities, and infectious complications. These factors may be useful in identifying patients at increased risk of serious medical complications and mortality for more aggressive supportive care measures. Cancer 2006. © 2006 American Cancer Society.

Deep Brain Stimulation

Abstract: Deep brain stimulation (DBS) has provided remarkable benefits for people with a variety of neurologic conditions. Stimulation of the ventral intermediate nucleus of the thalamus can dramatically relieve tremor associated with essential tremor or Parkinson disease (PD). Similarly, stimulation of the subthalamic nucleus or the internal segment of the globus pallidus can substantially reduce bradykinesia, rigidity, tremor, and gait difficulties in people with PD. Multiple groups are attempting to extend this mode of treatment to other conditions. Yet, the precise mechanism of action of DBS remains uncertain. Such studies have importance that extends beyond clinical therapeutics. Investigations of the mechanisms of action of DBS have the potential to clarify fundamental issues such as the functional anatomy of selected brain circuits and the relationship between activity in those circuits and behavior. Although we review relevant clinical issues, we emphasize the importance of current and future investigations on these topics.

Gender Differences in Caregiver Stressors, Social Resources, and Health: An Updated Meta-Analysis

Abstract: This meta-analysis integrates results from 229 studies on gender differences in caregiver psychological and physical health, caregiving stressors, and social resources. Contrary to common perceptions, gender differences in caregiving variables were small to very small. Women had higher levels of burden and depression, and lower levels of subjective well-being and physical health. They reported that their care recipient had more behavioral problems; they provided more caregiving hours, helped with more caregiving tasks, and assisted with more personal care. Women and men did not differ in the use of informal and formal support. Statistically controlling for gender differences in stressors and resources reduced the size of gender differences in depression and physical health to levels that have been observed in noncaregiving samples. The results support stress-and-coping theories on gender differences in caregiving.

The Hierarchical Model of Approach-Avoidance Motivation

Abstract: Approach motivation is the energization of behavior by, or the direction of behavior toward, positive stimuli (objects, events, possibilities), whereas avoidance motivation is the energization of behavior by, or the direction of behavior away from, negative stimuli (objects, events, possibilities). In this article, I provide a brief overview of this distinction between approach and avoidance motivation. In addition, I provide a brief overview of a model of motivation in which this approach-avoidance distinction plays an integral role—the hierarchical model of approach-avoidance motivation.

Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial.

Abstract: ContextDespite a stage-shift to earlier cancer stages and lower tumor volumes for prostate cancer, pathologically advanced disease is detected at radical prostatectomy in 38% to 52% of patients. However, the optimal management of these patients after radical prostatectomy is unknown.ObjectiveTo determine whether adjuvant radiotherapy improves metastasis-free survival in patients with stage pT3 N0 M0 prostate cancer.Design, Setting, and PatientsRandomized, prospective, multi-institutional, US clinical trial with enrollment between August 15, 1988, and January 1, 1997 (with database frozen for statistical analysis on September 21, 2005). Patients were 425 men with pathologically advanced prostate cancer who had undergone radical prostatectomy.InterventionMen were randomly assigned to receive 60 to 64 Gy of external beam radiotherapy delivered to the prostatic fossa (n = 214) or usual care plus observation (n = 211).Main Outcome MeasuresPrimary outcome was metastasis-free survival, defined as time to first occurrence of metastatic disease or death due to any cause. Secondary outcomes included prostate-specific antigen (PSA) relapse, recurrence-free survival, overall survival, freedom from hormonal therapy, and postoperative complications.ResultsAmong the 425 men, median follow-up was 10.6 years (interquartile range, 9.2-12.7 years). For metastasis-free survival, 76 (35.5%) of 214 men in the adjuvant radiotherapy group were diagnosed with metastatic disease or died (median metastasis-free estimate, 14.7 years), compared with 91 (43.1%) of 211 (median metastasis-free estimate, 13.2 years) of those in the observation group (hazard ratio [HR], 0.75; 95% CI, 0.55-1.02; P = .06). There were no significant between-group differences for overall survival (71 deaths, median survival of 14.7 years for radiotherapy vs 83 deaths, median survival of 13.8 years for observation; HR, 0.80; 95% CI, 0.58-1.09; P = .16). PSA relapse (median PSA relapse–free survival, 10.3 years for radiotherapy vs 3.1 years for observation; HR, 0.43; 95% CI, 0.31-0.58; P<.001) and disease recurrence (median recurrence-free survival, 13.8 years for radiotherapy vs 9.9 years for observation; HR, 0.62; 95% CI, 0.46-0.82; P = .001) were both significantly reduced with radiotherapy. Adverse effects were more common with radiotherapy vs observation (23.8% vs 11.9%), including rectal complications (3.3% vs 0%), urethral strictures (17.8% vs 9.5%), and total urinary incontinence (6.5% vs 2.8%).ConclusionsIn men who had undergone radical prostatectomy for pathologically advanced prostate cancer, adjuvant radiotherapy resulted in significantly reduced risk of PSA relapse and disease recurrence, although the improvements in metastasis-free survival and overall survival were not statistically significant.Trial Registrationclinicaltrials.gov Identifier: NCT00394511

Effect of Introduction of the Pneumococcal Conjugate Vaccine on Drug-Resistant Streptococcus pneumoniae

Abstract: BACKGROUND Five of seven serotypes in the pneumococcal conjugate vaccine, introduced for infants in the United States in 2000, are responsible for most penicillin-resistant infections. We examined the effect of this vaccine on invasive disease caused by resistant strains. METHODS We used laboratory-based data from Active Bacterial Core surveillance to measure disease caused by antibiotic-nonsusceptible pneumococci from 1996 through 2004. Cases of invasive disease, defined as disease caused by pneumococci isolated from a normally sterile site, were identified in eight surveillance areas. Isolates underwent serotyping and susceptibility testing. RESULTS Rates of invasive disease caused by penicillin-nonsusceptible strains and strains not susceptible to multiple antibiotics peaked in 1999 and decreased by 2004, from 6.3 to 2.7 cases per 100,000 (a decline of 57 percent; 95 percent confidence interval, 55 to 58 percent) and from 4.1 to 1.7 cases per 100,000 (a decline of 59 percent; 95 percent confidence interval, 58 to 60 percent), respectively. Among children under two years of age, disease caused by penicillin-nonsusceptible strains decreased from 70.3 to 13.1 cases per 100,000 (a decline of 81 percent; 95 percent confidence interval, 80 to 82 percent). Among persons 65 years of age or older, disease caused by penicillin-nonsusceptible strains decreased from 16.4 to 8.4 cases per 100,000 (a decline of 49 percent). Rates of resistant disease caused by vaccine serotypes fell 87 percent. An increase was seen in disease caused by serotype 19A, a serotype not included in the vaccine (from 2.0 to 8.3 per 100,000 among children under two years of age). CONCLUSIONS The rate of antibiotic-resistant invasive pneumococcal infections decreased in young children and older persons after the introduction of the conjugate vaccine. There was an increase in infections caused by serotypes not included in the vaccine.

Molecular diagnosis of Burkitt's lymphoma.

Abstract: Background The distinction between Burkitt’s lymphoma and diffuse large-B-cell lymphoma is crucial because these two types of lymphoma require different treatments. We examined whether gene-expression profiling could reliably distinguish Burkitt’s lymphoma from diffuse large-B-cell lymphoma. Methods Tumor-biopsy specimens from 303 patients with aggressive lymphomas were profiled for gene expression and were also classified according to morphology, immunohistochemistry, and detection of the t(8;14) c-myc translocation. Results A classifier based on gene expression correctly identified all 25 pathologically verified cases of classic Burkitt’s lymphoma. Burkitt’s lymphoma was readily distinguished from diffuse large-B-cell lymphoma by the high level of expression of c-myc target genes, the expression of a subgroup of germinal-center B-cell genes, and the low level of expression of major-histocompatibility-complex class I genes and nuclear factor-κB target genes. Eight specimens with a pathological diagnosis of diffuse large-B-cell lymphoma had the typical gene-expression profile of Burkitt’s lymphoma, suggesting they represent cases of Burkitt’s lymphoma that are difficult to diagnose by current methods. Among 28 of the patients with a molecular diagnosis of Burkitt’s lymphoma, the overall survival was superior among those who had received intensive chemotherapy regimens instead of lower-dose regimens. Conclusions Gene-expression profiling is an accurate, quantitative method for distinguishing Burkitt’s lymphoma from diffuse large-B-cell lymphoma.

Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy

Abstract: Summary Background Appropriate timing of androgen deprivation treatment (ADT) for prostate cancer is controversial. Our aim was to determine whether immediate ADT extends survival in men with node-positive prostate cancer who have undergone radical prostatectomy and pelvic lymphadenectomy compared with those who received ADT only once disease progressed. Methods Eligible patients from 36 institutes in the USA were randomly assigned in 1988–93 to receive immediate ADT (n=47) or to be observed (n=51), with ADT to be given on detection of distant metastases or symptomatic recurrences. Patients were followed up every 3 months for the first year and every 6 months thereafter. The primary endpoint was progression-free survival; secondary endpoints were overall and disease-specific survival. Analysis was by intention to treat. To ensure that the treatment groups were comparable, we did a retrospective central pathology review of slides and regraded the Gleason scores for available samples. This trial predates the requirement for clinical trial registration. Findings At median follow-up of 11·9 years (range 9·7–14·5 for surviving patients), men assigned immediate ADT had a significant improvement in overall survival (hazard ratio 1·84 [95% CI 1·01–3·35], p=0·04), prostate-cancer-specific survival (4·09 [1·76–9·49], p=0·0004), and progression-free survival (3·42 [1·96–5·98], p Interpretation Early ADT benefits patients with nodal metastases who have undergone prostatectomy and lymphadenectomy, compared with those who receive deferred treatment. The beneficial effects of early ADT, rather than an imbalance in risk factors, are likely to explain the differences in outcomes between treatments.

Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma: a metaanalysis.

Abstract: BACKGROUND Lymphatic mapping with sentinel lymph node biopsy has the potential for reducing the morbidity associated with breast carcinoma staging. It has become a widely used technology despite limited data from controlled clinical trials. METHODS A systematic review of the world's literature of sentinel lymph node (SLN) biopsy in patients with early-stage breast carcinoma was undertaken by using electronic and hand searching techniques. Only studies that incorporated full axillary lymph node dissection (ALND), regardless of SLN results, were included. Individual study results along with weighted summary measures were estimated using the Mantel–Haenszel method. The correlations of outcomes with the study size, the proportion of positive lymph nodes, the technique used, and the study quality were evaluated. RESULTS Between 1970 and 2003, 69 trials were reported that met eligibility criteria. Of the 8059 patients who were studied, 7765 patients (96%) had successfully mapped SLNs. The proportion of patients who had successfully mapped SLNs ranged from 41% to 100%, with > 50% of studies reporting a rate 10%. Significant inverse correlations were observed between the FNR and both the number of patients studied (r = − 0.42; P < 0.01) and the proportion of patients who had successfully mapped SLNs nodes (r = − 0.32; P = 0.009). CONCLUSIONS Lymphatic mapping with SLN biopsy is used widely to reduce the complications associated with ALND in patients with low-risk breast carcinoma. This systematic review revealed a wide variation in test performance. Cancer 2006. © 2005 American Cancer Society.

Bose–Einstein condensation of quasi-equilibrium magnons at room temperature under pumping

Abstract: Bose–Einstein condensation (BEC), a form of matter first postulated in 1924, has famously been demonstrated in dilute atomic gases at ultra-low temperatures. Much effort is now being devoted to exploring solid-state systems in which BEC can occur. In theory semiconductor microcavities, where photons are confined and coupled to electronic excitations leading to the creation of polaritons, could allow BEC at standard cryogenic temperatures. Kasprzak et al. now present experiments in which polaritons are excited in such a microcavity. Above a critical polariton density, spontaneous onset of a macroscopic quantum phase occurs, indicating a solid-state BEC. BEC should also be possible at higher temperatures if coupling of light with solid excitations is sufficiently strong. Demokritov et al. have achieved just that, BEC at room temperature in a gas of magnons, which are a type of magnetic excitation. Bose–Einstein condensation, the formation of a collective quantum state of identical particles, called bosons, is observed at room temperature in a gas of magnons, which are a type of magnetic excitation. Bose–Einstein condensation1,2 is one of the most fascinating phenomena predicted by quantum mechanics. It involves the formation of a collective quantum state composed of identical particles with integer angular momentum (bosons), if the particle density exceeds a critical value. To achieve Bose–Einstein condensation, one can either decrease the temperature or increase the density of bosons. It has been predicted3,4 that a quasi-equilibrium system of bosons could undergo Bose–Einstein condensation even at relatively high temperatures, if the flow rate of energy pumped into the system exceeds a critical value. Here we report the observation of Bose–Einstein condensation in a gas of magnons at room temperature. Magnons are the quanta of magnetic excitations in a magnetically ordered ensemble of magnetic moments. In thermal equilibrium, they can be described by Bose–Einstein statistics with zero chemical potential and a temperature-dependent density. In the experiments presented here, we show that by using a technique of microwave pumping it is possible to excite additional magnons and to create a gas of quasi-equilibrium magnons with a non-zero chemical potential. With increasing pumping intensity, the chemical potential reaches the energy of the lowest magnon state, and a Bose condensate of magnons is formed.