Showing papers by "University of Rochester published in 2009"
TL;DR: In a test set of 168 CKiD patients at 1 yr of follow-up, this formula compared favorably with previously published estimating equations for children, and with height measured in cm, a bedside calculation provides a good approximation to the estimated GFR formula.
Abstract: The Schwartz formula was devised in the mid-1970s to estimate GFR in children. Recent data suggest that this formula currently overestimates GFR as measured by plasma disappearance of iohexol, likely a result of a change in methods used to measure creatinine. Here, we developed equations to estimate GFR using data from the baseline visits of 349 children (aged 1 to 16 yr) in the Chronic Kidney Disease in Children (CKiD) cohort. Median iohexol-GFR (iGFR) was 41.3 ml/min per 1.73 m(2) (interquartile range 32.0 to 51.7), and median serum creatinine was 1.3 mg/dl. We performed linear regression analyses assessing precision, goodness of fit, and accuracy to develop improvements in the GFR estimating formula, which was based on height, serum creatinine, cystatin C, blood urea nitrogen, and gender. The best equation was: GFR(ml/min per 1.73 m(2))=39.1[height (m)/Scr (mg/dl)](0.516) x [1.8/cystatin C (mg/L)](0.294)[30/BUN (mg/dl)](0.169)[1.099](male)[height (m)/1.4](0.188). This formula yielded 87.7% of estimated GFR within 30% of the iGFR, and 45.6% within 10%. In a test set of 168 CKiD patients at 1 yr of follow-up, this formula compared favorably with previously published estimating equations for children. Furthermore, with height measured in cm, a bedside calculation of 0.413*(height/serum creatinine), provides a good approximation to the estimated GFR formula. Additional studies of children with higher GFR are needed to validate these formulas for use in screening all children for CKD.
2,816 citations
Book•
02 Dec 2009TL;DR: In this paper, a detailed account of the electromechanical interactions that govern the behaviour of small particles when an electric or magnetic field is present is presented, with numerous real-world examples.
Abstract: Small particles in the size range from one micron to one millimetre are increasingly important in today's technological world. They serve as workhorses in many mechanisms and devices - from electrostatic copiers to fluidised beds. A more recent development involves the characterisation and manipulation of individual cells and DNA molecules. Particulates can also be a hazard, for example, particulate pollution. Because all particles have electrical and magnetic properties associated with their shape and the materials of which they are constituted, they experience forces and torques when subjected to electric and/or magnetic fields. This book offers a lucid account of the electromechanical interactions that govern the behaviour of particles when an electric or magnetic field is present. With numerous real-world examples, the book should interest a wide range of scientists and engineers.
2,468 citations
TL;DR: Brand experience is conceptualized as sensations, feelings, cognitions, and behavioral responses evoked by brand-related stimuli that are part of a brand's design and identity, packaging, communications, and environments as discussed by the authors.
Abstract: Brand experience is conceptualized as sensations, feelings, cognitions, and behavioral responses evoked by brand-related stimuli that are part of a brand's design and identity, packaging, communications, and environments. The authors distinguish several experience dimensions and construct a brand experience scale that includes four dimensions: sensory, affective, intellectual, and behavioral. In six studies, the authors show that the scale is reliable, valid, and distinct from other brand measures, including brand evaluations, brand involvement, brand attachment, customer delight, and brand personality. Moreover, brand experience affects consumer satisfaction and loyalty directly and indirectly through brand personality associations.
2,050 citations
TL;DR: Current understanding of the benefits and concerns surrounding the use of plastics are synthesized, and future priorities, challenges and opportunities are looked to.
Abstract: Plastics have transformed everyday life; usage is increasing and annual production is likely to exceed 300 million tonnes by 2010. In this concluding paper to the Theme Issue on Plastics, the Environment and Human Health, we synthesize current understanding of the benefits and concerns surrounding the use of plastics and look to future priorities, challenges and opportunities. It is evident that plastics bring many societal benefits and offer future technological and medical advances. However, concerns about usage and disposal are diverse and include accumulation of waste in landfills and in natural habitats, physical problems for wildlife resulting from ingestion or entanglement in plastic, the leaching of chemicals from plastic products and the potential for plastics to transfer chemicals to wildlife and humans. However, perhaps the most important overriding concern, which is implicit throughout this volume, is that our current usage is not sustainable. Around 4 per cent of world oil production is used as a feedstock to make plastics and a similar amount is used as energy in the process. Yet over a third of current production is used to make items of packaging, which are then rapidly discarded. Given our declining reserves of fossil fuels, and finite capacity for disposal of waste to landfill, this linear use of hydrocarbons, via packaging and other short-lived applications of plastic, is simply not sustainable. There are solutions, including material reduction, design for end-of-life recyclability, increased recycling capacity, development of bio-based feedstocks, strategies to reduce littering, the application of green chemistry life-cycle analyses and revised risk assessment approaches. Such measures will be most effective through the combined actions of the public, industry, scientists and policymakers. There is some urgency, as the quantity of plastics produced in the first 10 years of the current century is likely to approach the quantity produced in the entire century that preceded.
2,006 citations
TL;DR: Clinicians and patients should maximize the therapeutic effects of communication by explicitly orienting communication to achieve intermediate outcomes associated with improved health.
1,780 citations
TL;DR: Self-Determination Theory (SDT) assumes that inherent in human nature is the propensity to be curious about one's environment and interested in learning and developing one's knowledge.
Abstract: Self-determination theory (SDT) assumes that inherent in human nature is the propensity to be curious about one's environment and interested in learning and developing one's knowledge. All too ofte...
1,768 citations
TL;DR: RSV infection is associated with substantial morbidity in U.S. children in both inpatient and outpatient settings, suggesting that control strategies targeting only high-risk children will have a limited effect on the total disease burden of RSV infection.
Abstract: Background The primary role of respiratory syncytial virus (RSV) in causing infant hospitalizations is well recognized, but the total burden of RSV infection among young children remains poorly defined Methods We conducted prospective, population-based surveillance of acute respiratory infections among children under 5 years of age in three US counties We enrolled hospitalized children from 2000 through 2004 and children presenting as outpatients in emergency departments and pediatric offices from 2002 through 2004 RSV was detected by culture and reverse-transcriptase polymerase chain reaction Clinical information was obtained from parents and medical records We calculated population-based rates of hospitalization associated with RSV infection and estimated the rates of RSV-associated outpatient visits Results Among 5067 children enrolled in the study, 919 (18%) had RSV infections Overall, RSV was associated with 20% of hospitalizations, 18% of emergency department visits, and 15% of office visit
1,678 citations
TL;DR: The role of important factors such as solution ionic strength, pH, and particle surface chemistry that control nanoparticle dispersion was examined in this article, where the size and zeta potential of four TiO2 and three quantum dot samples dispersed in different solutions (including one physiological medium) were characterized.
Abstract: Characterizing the state of nanoparticles (such as size, surface charge, and degree of agglomeration) in aqueous suspensions and understanding the parameters that affect this state are imperative for toxicity investigations. In this study, the role of important factors such as solution ionic strength, pH, and particle surface chemistry that control nanoparticle dispersion was examined. The size and zeta potential of four TiO2 and three quantum dot samples dispersed in different solutions (including one physiological medium) were characterized. For 15 nm TiO2 dispersions, the increase of ionic strength from 0.001 M to 0.1 M led to a 50-fold increase in the hydrodynamic diameter, and the variation of pH resulted in significant change of particle surface charge and the hydrodynamic size. It was shown that both adsorbing multiply charged ions (e.g., pyrophosphate ions) onto the TiO2 nanoparticle surface and coating quantum dot nanocrystals with polymers (e.g., polyethylene glycol) suppressed agglomeration and stabilized the dispersions. DLVO theory was used to qualitatively understand nanoparticle dispersion stability. A methodology using different ultrasonication techniques (bath and probe) was developed to distinguish agglomerates from aggregates (strong bonds), and to estimate the extent of particle agglomeration. Probe ultrasonication performed better than bath ultrasonication in dispersing TiO2 agglomerates when the stabilizing agent sodium pyrophosphate was used. Commercially available Degussa P25 and in-house synthesized TiO2 nanoparticles were used to demonstrate identification of aggregated and agglomerated samples.
1,519 citations
TL;DR: Participation in a mindful communication program was associated with short-term and sustained improvements in well-being and attitudes associated with patient-centered care, and these findings warrant randomized trials involving a variety of practicing physicians.
Abstract: Context Primary care physicians report high levels of distress, which is linked to burnout, attrition, and poorer quality of care. Programs to reduce burnout before it results in impairment are rare; data on these programs are scarce. Objective To determine whether an intensive educational program in mindfulness, communication, and self-awareness is associated with improvement in primary care physicians' well-being, psychological distress, burnout, and capacity for relating to patients. Design, Setting, and Participants Before-and-after study of 70 primary care physicians in Rochester, New York, in a continuing medical education (CME) course in 2007-2008. The course included mindfulness meditation, self-awareness exercises, narratives about meaningful clinical experiences, appreciative interviews, didactic material, and discussion. An 8-week intensive phase (2.5 h/wk, 7-hour retreat) was followed by a 10-month maintenance phase (2.5 h/mo). Main Outcome Measures Mindfulness (2 subscales), burnout (3 subscales), empathy (3 subscales), psychosocial orientation, personality (5 factors), and mood (6 subscales) measured at baseline and at 2, 12, and 15 months. Results Over the course of the program and follow-up, participants demonstrated improvements in mindfulness (raw score, 45.2 to 54.1; raw score change [Δ], 8.9; 95% confidence interval [CI], 7.0 to 10.8); burnout (emotional exhaustion, 26.8 to 20.0; Δ = −6.8; 95% CI, −4.8 to −8.8; depersonalization, 8.4 to 5.9; Δ = −2.5; 95% CI, −1.4 to −3.6; and personal accomplishment, 40.2 to 42.6; Δ = 2.4; 95% CI, 1.2 to 3.6); empathy (116.6 to 121.2; Δ = 4.6; 95% CI, 2.2 to 7.0); physician belief scale (76.7 to 72.6; Δ = −4.1; 95% CI, −1.8 to −6.4); total mood disturbance (33.2 to 16.1; Δ = −17.1; 95% CI, −11 to −23.2), and personality (conscientiousness, 6.5 to 6.8; Δ = 0.3; 95% CI, 0.1 to 5 and emotional stability, 6.1 to 6.6; Δ = 0.5; 95% CI, 0.3 to 0.7). Improvements in mindfulness were correlated with improvements in total mood disturbance (r = −0.39, P Conclusions Participation in a mindful communication program was associated with short-term and sustained improvements in well-being and attitudes associated with patient-centered care. Because before-and-after designs limit inferences about intervention effects, these findings warrant randomized trials involving a variety of practicing physicians.
1,442 citations
TL;DR: It is demonstrated that miR-145 can direct the smooth muscle fate and that mi R-145 and miR -143 function to regulate the quiescent versus proliferative phenotype of smooth muscle cells.
Abstract: MicroRNAs (miRNAs) are regulators of myriad cellular events, but evidence for a single miRNA that can efficiently differentiate multipotent stem cells into a specific lineage or regulate direct reprogramming of cells into an alternative cell fate has been elusive. Here we show that miR-145 and miR-143 are co-transcribed in multipotent murine cardiac progenitors before becoming localized to smooth muscle cells, including neural crest stem-cell-derived vascular smooth muscle cells. miR-145 and miR-143 were direct transcriptional targets of serum response factor, myocardin and Nkx2-5 (NK2 transcription factor related, locus 5) and were downregulated in injured or atherosclerotic vessels containing proliferating, less differentiated smooth muscle cells. miR-145 was necessary for myocardin-induced reprogramming of adult fibroblasts into smooth muscle cells and sufficient to induce differentiation of multipotent neural crest stem cells into vascular smooth muscle. Furthermore, miR-145 and miR-143 cooperatively targeted a network of transcription factors, including Klf4 (Kruppel-like factor 4), myocardin and Elk-1 (ELK1, member of ETS oncogene family), to promote differentiation and repress proliferation of smooth muscle cells. These findings demonstrate that miR-145 can direct the smooth muscle fate and that miR-145 and miR-143 function to regulate the quiescent versus proliferative phenotype of smooth muscle cells.
1,404 citations
University of California, Davis1, Columbia University2, Spectrum Health3, George Washington University4, University of Utah5, University of Pennsylvania6, Johns Hopkins University7, University of Michigan8, University of Rochester9, Washington University in St. Louis10, Wayne State University11, University of Maryland, Baltimore12, University at Buffalo13, New York University14, Holy Cross Hospital15, State University of New York Upstate Medical University16, Medical College of Wisconsin17, University of Cincinnati18, Harvard University19, Saint Barnabas Medical Center20, Northwestern University21, Memorial Hospital of South Bend22, Calvert Memorial Hospital23
TL;DR: These validated prediction rules identified children at very low risk of clinically-important traumatic brain injuries (ciTBI) for whom CT might be unnecessary and missed neurosurgery in validation populations.
Loyola University Chicago1, Radiation Therapy Oncology Group2, Memorial Sloan Kettering Cancer Center3, Wayne State University4, University of Toronto5, Tom Baker Cancer Centre6, University of Rochester7, University of Arizona8, University of North Carolina at Chapel Hill9, University of California, Davis10, NorthShore University HealthSystem11, University Health Network12, Vanderbilt University13, Medical University of South Carolina14, Mayo Clinic15, Primary Children's Hospital16, University of Texas MD Anderson Cancer Center17
TL;DR: The primary endpoint was overall survival (OS) and an exploratory analysis, OS was improved for patients who underwent lobectomy, but not pneumonectomy, versus chemotherapy plus radiotherapy, compared with standard concurrent chemotherapy and definitive radiotherapy without resection.
TL;DR: It is reported here that protoplasmic astrocytes in human neocortex are 2.6-fold larger in diameter and extend 10-fold more GFAP (glial fibrillary acidic protein)-positive primary processes than their rodent counterparts, and it is posited that thisAstrocytic complexity has permitted the increased functional competence of the adult human brain.
Abstract: Defining the microanatomic differences between the human brain and that of other mammals is key to understanding its unique computational power. Although much effort has been devoted to comparative studies of neurons, astrocytes have received far less attention. We report here that protoplasmic astrocytes in human neocortex are 2.6-fold larger in diameter and extend 10-fold more GFAP (glial fibrillary acidic protein)-positive primary processes than their rodent counterparts. In cortical slices prepared from acutely resected surgical tissue, protoplasmic astrocytes propagate Ca2+ waves with a speed of 36 μm/s, approximately fourfold faster than rodent. Human astrocytes also transiently increase cystosolic Ca2+ in response to glutamatergic and purinergic receptor agonists. The human neocortex also harbors several anatomically defined subclasses of astrocytes not represented in rodents. These include a population of astrocytes that reside in layers 5–6 and extend long fibers characterized by regularly spaced varicosities. Another specialized type of astrocyte, the interlaminar astrocyte, abundantly populates the superficial cortical layers and extends long processes without varicosities to cortical layers 3 and 4. Human fibrous astrocytes resemble their rodent counterpart but are larger in diameter. Thus, human cortical astrocytes are both larger, and structurally both more complex and more diverse, than those of rodents. On this basis, we posit that this astrocytic complexity has permitted the increased functional competence of the adult human brain.
TL;DR: Adjuvant radiotherapy after radical prostatectomy for a man with pT3N0M0 prostate cancer significantly reduces the risk of metastasis and increases survival.
TL;DR: Head-to-head clinical trials comparing NP therapies are needed to help assess the relative clinical efficacy of treatments, ideally using HR-QOL and utility outcomes, and to facilitate future cost-effectiveness research in NP.
Abstract: A number of different diseases or injuries can damage the central or peripheral nervous system and produce neuropathic pain (NP), which seems to be more difficult to treat than many other types of chronic pain. As a group, patients with NP have greater medical co-morbidity burden than age- and sex-adjusted controls, which makes determining the humanistic and economic burden attributable to NP challenging. Health-related quality of life (HR-QOL) is substantially impaired among patients with NP. Patients describe pain-related interference in multiple HR-QOL and functional domains, as well as reduced ability to work and reduced mobility due to their pain. In addition, the spouses of NP patients have been shown to experience adverse social consequences related to NP. In randomized controlled trials, several medications have been shown to improve various measures of HR-QOL. Changes in HR-QOL appear to be tightly linked to pain relief, but not to the development of adverse effects. However, in cross-sectional studies, many patients continue to have moderate or severe pain and markedly impaired HR-QOL, despite taking medications prescribed for NP. The quality of NP treatment appears to be poor, with few patients receiving recommended medications in efficacious dosages. The substantial costs to society of NP derive from direct medical costs, loss of the ability to work, loss of caregivers' ability to work and possibly greater need for institutionalization or other living assistance. No single study has measured all of these costs to society for chronic NP. The cost effectiveness of various interventions for the treatment or prevention of different types of NP has been assessed in several different studies. The most-studied diseases are post-herpetic neuralgia and painful diabetic neuropathy, for which tricyclic antidepressants (both amitriptyline and desipramine) have been found to be either cost effective or dominant relative to other strategies. Increasing the use of cost-effective therapies such as tricyclic antidepressants for post-herpetic neuralgia and painful diabetic neuropathy may improve the HR-QOL of patients and decrease societal costs. Head-to-head clinical trials comparing NP therapies are needed to help assess the relative clinical efficacy of treatments, ideally using HR-QOL and utility outcomes. The full costs to society of NP, including productivity loss costs, have not been determined for chronic NP. Improved relative efficacy, utility and cost estimates would facilitate future cost-effectiveness research in NP.
TL;DR: A growing body of data suggests that ED crowding is associated both with objective clinical endpoints, such as mortality, as well as clinically important processes of care,such as time to treatment for patients with time-sensitive conditions such as pneumonia.
Abstract: Background: An Institute of Medicine (IOM) report defines six domains of quality of care: safety, patient-centeredness, timeliness, efficiency, effectiveness, and equity. The effect of emergency department (ED) crowding on these domains of quality has not been comprehensively evaluated.
Objectives: The objective was to review the medical literature addressing the effects of ED crowding on clinically oriented outcomes (COOs).
Methods: We reviewed the English-language literature for the years 1989–2007 for case series, cohort studies, and clinical trials addressing crowding’s effects on COOs. Keywords searched included “ED crowding,”“ED overcrowding,”“mortality,”“time to treatment,”“patient satisfaction,”“quality of care,” and others.
Results: A total of 369 articles were identified, of which 41 were kept for inclusion. Study quality was modest; most articles reflected observational work performed at a single institution. There were no randomized controlled trials. ED crowding is associated with an increased risk of in-hospital mortality, longer times to treatment for patients with pneumonia or acute pain, and a higher probability of leaving the ED against medical advice or without being seen. Crowding is not associated with delays in reperfusion for patients with ST-elevation myocardial infarction. Insufficient data were available to draw conclusions on crowding’s effects on patient satisfaction and other quality endpoints.
Conclusions: A growing body of data suggests that ED crowding is associated both with objective clinical endpoints, such as mortality, as well as clinically important processes of care, such as time to treatment for patients with time-sensitive conditions such as pneumonia. At least two domains of quality of care, safety and timeliness, are compromised by ED crowding.
TL;DR: A framework for conceptualizing the development of individual differences in reading ability is presented in this paper that synthesizes a great deal of the research literature and places special emphasis on reading ability.
Abstract: A framework for conceptualizing the development of individual differences in reading ability is presented that synthesizes a great deal of the research literature. The framework places special emph...
TL;DR: In this article, the formation of various heteronanostructures using the Frank-van der Merwe (FM), Volmer-Weber (VW), and Stranski-Krastanov (SK) growth modes is discussed.
TL;DR: In this paper, a theoretical model linking achievement goals and achievement emotions to academic performance was proposed, which was tested in a prospective study with undergraduates, using exam-specific assessments of both goals and emotions as predictors of exam performance in an introductory-level psychology course.
Abstract: The authors propose a theoretical model linking achievement goals and achievement emotions to academic performance. This model was tested in a prospective study with undergraduates (N = 213), using exam-specific assessments of both goals and emotions as predictors of exam performance in an introductory-level psychology course. The findings were consistent with the authors' hypotheses and supported all aspects of the proposed model. In multiple regression analysis, achievement goals (mastery, performance approach, and performance avoidance) were shown to predict discrete achievement emotions (enjoyment, boredom, anger, hope, pride, anxiety, hopelessness, and shame), achievement emotions were shown to predict performance attainment, and 7 of the 8 focal emotions were documented as mediators of the relations between achievement goals and performance attainment. All of these findings were shown to be robust when controlling for gender, social desirability, positive and negative trait affectivity, and scholastic ability. The results are discussed with regard to the underdeveloped literature on discrete achievement emotions and the need to integrate conceptual and applied work on achievement goals and achievement emotions.
TL;DR: A new route for dissipation attacks quantum entanglement, the essential resource for quantum information as well as the central feature in the Einstein-Podolsky-Rosen so-called paradox and in discussions of the fate of Schrödinger's cat.
Abstract: A new development in the dynamical behavior of elementary quantum systems is the surprising discovery that correlation between two quantum units of information called qubits can be degraded by environmental noise in a way not seen previously in studies of dissipation. This new route for dissipation attacks quantum entanglement, the essential resource for quantum information as well as the central feature in the Einstein-Podolsky-Rosen so-called paradox and in discussions of the fate of Schrodinger9s cat. The effect has been labeled ESD, which stands for early-stage disentanglement or, more frequently, entanglement sudden death. We review recent progress in studies focused on this phenomenon.
TL;DR: In patients with pulmonary arterial hypertension, tadalafil 40 mg was well tolerated and improved exercise capacity and quality of life measures and reduced clinical worsening.
Abstract: Background— Treatment options for pulmonary arterial hypertension target the prostacyclin, endothelin, or nitric oxide pathways. Tadalafil, a phosphodiesterase type-5 inhibitor, increases cGMP, the final mediator in the nitric oxide pathway. Methods and Results— In this 16-week, double-blind, placebo-controlled study, 405 patients with pulmonary arterial hypertension (idiopathic or associated), either treatment-naive or on background therapy with the endothelin receptor antagonist bosentan, were randomized to placebo or tadalafil 2.5, 10, 20, or 40 mg orally once daily. The primary end point was the change from baseline to week 16 in the distance walked in 6 minutes. Changes in World Health Organization functional class, clinical worsening, and health-related quality of life were also assessed. Patients completing the 16-week study could enter a long-term extension study. Tadalafil increased the distance walked in 6 minutes in a dose-dependent manner; only the 40-mg dose met the prespecified level of statistical significance ( P P =0.041), incidence of clinical worsening (68% relative risk reduction; P =0.038), and health-related quality of life. The changes in World Health Organization functional class were not statistically significant. The most common treatment-related adverse events reported with tadalafil were headache, myalgia, and flushing. Conclusions— In patients with pulmonary arterial hypertension, tadalafil 40 mg was well tolerated and improved exercise capacity and quality of life measures and reduced clinical worsening.
20 Jun 2009
TL;DR: This paper presents a systematic framework for recognizing realistic actions from videos “in the wild”, and uses motion statistics to acquire stable motion features and clean static features, and PageRank is used to mine the most informative static features.
Abstract: In this paper, we present a systematic framework for recognizing realistic actions from videos ldquoin the wildrdquo. Such unconstrained videos are abundant in personal collections as well as on the Web. Recognizing action from such videos has not been addressed extensively, primarily due to the tremendous variations that result from camera motion, background clutter, changes in object appearance, and scale, etc. The main challenge is how to extract reliable and informative features from the unconstrained videos. We extract both motion and static features from the videos. Since the raw features of both types are dense yet noisy, we propose strategies to prune these features. We use motion statistics to acquire stable motion features and clean static features. Furthermore, PageRank is used to mine the most informative static features. In order to further construct compact yet discriminative visual vocabularies, a divisive information-theoretic algorithm is employed to group semantically related features. Finally, AdaBoost is chosen to integrate all the heterogeneous yet complementary features for recognition. We have tested the framework on the KTH dataset and our own dataset consisting of 11 categories of actions collected from YouTube and personal videos, and have obtained impressive results for action recognition and action localization.
TL;DR: The present report highlights and integrates the growing connections between imbalances in GSH homeostasis and a multitude of human diseases and suggests the high GSH content makes cancer cells chemoresistant, which is a major factor that limits drug treatment.
Abstract: Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and as a result, disturbances in GSH homeostasis are implicated in the etiology and/or progression of a number of human diseases, including cancer, diseases of aging, cystic fibrosis, and cardiovascular, inflammatory, immune, metabolic, and neurodegenerative diseases. Owing to the pleiotropic effects of GSH on cell functions, it has been quite difficult to define the role of GSH in the onset and/or the expression of human diseases, although significant progress is being made. GSH levels, turnover rates, and/or oxidation state can be compromised by inherited or acquired defects in the enzymes, transporters, signaling molecules, or transcription factors that are involved in its homeostasis, or from exposure to reactive chemicals or metabolic intermediates. GSH deficiency or a decrease in the GSH/glutathione disulfide ratio manifests itself largely through an increased susceptibility to oxidative stress, and the resulting damage is thought to be involved in diseases, such as cancer, Parkinson's disease, and Alzheimer's disease. In addition, imbalances in GSH levels affect immune system function, and are thought to play a role in the aging process. Just as low intracellular GSH levels decrease cellular antioxidant capacity, elevated GSH levels generally increase antioxidant capacity and resistance to oxidative stress, and this is observed in many cancer cells. The higher GSH levels in some tumor cells are also typically associated with higher levels of GSH-related enzymes and transporters. Although neither the mechanism nor the implications of these changes are well defined, the high GSH content makes cancer cells chemoresistant, which is a major factor that limits drug treatment. The present report highlights and integrates the growing connections between imbalances in GSH homeostasis and a multitude of human diseases.
TL;DR: A consensus group of experts comprised of experts in pediatric and adult endocrinology, diabetes education, transplantation, metabolism, bariatric/metabolic surgery, and (for another perspective) hematology-oncology met in June 2009 to discuss issues.
Abstract: The mission of the American Diabetes Association is “to prevent and cure diabetes and to improve the lives of all people affected by diabetes.” Increasingly, scientific and medical articles (1) and commentaries (2) about diabetes interventions use the terms “remission” and “cure” as possible outcomes. Several approved or experimental treatments for type 1 and type 2 diabetes (e.g., pancreas or islet transplants, immunomodulation, bariatric/metabolic surgery) are of curative intent or have been portrayed in the media as a possible cure. However, defining remission or cure of diabetes is not as straightforward as it may seem. Unlike “dichotomous” diseases such as many malignancies, diabetes is defined by hyperglycemia, which exists on a continuum and may be impacted over a short time frame by everyday treatment or events (medications, diet, activity, intercurrent illness). The distinction between successful treatment and cure is blurred in the case of diabetes. Presumably improved or normalized glycemia must be part of the definition of remission or cure. Glycemic measures below diagnostic cut points for diabetes can occur with ongoing medications (e.g., antihyperglycemic drugs, immunosuppressive medications after a transplant), major efforts at lifestyle change, a history of bariatric/metabolic surgery, or ongoing procedures (such as repeated replacements of endoluminal devices). Do we use the terms remission or cure for all patients with normal glycemic measures, regardless of how this is achieved?
A consensus group comprised of experts in pediatric and adult endocrinology, diabetes education, transplantation, metabolism, bariatric/metabolic surgery, and (for another perspective) hematology-oncology met in June 2009 to discuss these issues. The group considered a wide variety of questions, including whether it is ever accurate to say that a chronic illness is cured; what the definitions of management, remission, or cure might be; whether goals of managing comorbid conditions revert to those of patients without diabetes if someone is …
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TL;DR: Current and future trends in usage, together with the many benefits that plastics bring to society are described, along with the environmental consequences resulting from the accumulation of waste plastic and the effects of plastic debris on wildlife.
Abstract: Within the last few decades, plastics have revolutionized our daily lives. Globally we use in excess of 260 million tonnes of plastic per annum, accounting for approximately 8 per cent of world oil production. In this Theme Issue of Philosophical Transactions of the Royal Society, we describe current and future trends in usage, together with the many benefits that plastics bring to society. At the same time, we examine the environmental consequences resulting from the accumulation of waste plastic, the effects of plastic debris on wildlife and concerns for human health that arise from the production, usage and disposal of plastics. Finally, we consider some possible solutions to these problems together with the research and policy priorities necessary for their implementation.
TL;DR: A continuous-flow LVAD provides effective hemodynamic support for at least 18 months in patients awaiting transplantation, with improved functional status and quality of life.
TL;DR: Liraglutide combined with metformin and a thiazolidinedione is a well-tolerated combination therapy for type 2 diabetes, providing significant improvements in glycemic control and C-peptide and homeostasis model assessment of β-cell function.
Abstract: OBJECTIVE To determine the efficacy and safety of liraglutide (a glucagon-like peptide-1 receptor agonist) when added to metformin and rosiglitazone in type 2 diabetes.
RESEARCH DESIGN AND METHODS This 26-week, double-blind, placebo-controlled, parallel-group trial randomized 533 subjects (1:1:1) to once-daily liraglutide (1.2 or 1.8 mg) or liraglutide placebo in combination with metformin (1 g twice daily) and rosiglitazone (4 mg twice daily). Subjects had type 2 diabetes, A1C 7–11% (previous oral antidiabetes drug [OAD] monotherapy ≥3 months) or 7–10% (previous OAD combination therapy ≥3 months), and BMI ≤45 kg/m2.
RESULTS Mean A1C values decreased significantly more in the liraglutide groups versus placebo (mean ± SE −1.5 ± 0.1% for both 1.2 and 1.8 mg liraglutide and −0.5 ± 0.1% for placebo). Fasting plasma glucose decreased by 40, 44, and 8 mg/dl for 1.2 and 1.8 mg and placebo, respectively, and 90-min postprandial glucose decreased by 47, 49, and 14 mg/dl, respectively ( P < 0.001 for all liraglutide groups vs. placebo). Dose-dependent weight loss occurred with 1.2 and 1.8 mg liraglutide (1.0 ± 0.3 and 2.0 ± 0.3 kg, respectively) ( P < 0.0001) compared with weight gain with placebo (0.6 ± 0.3 kg). Systolic blood pressure decreased by 6.7, 5.6, and 1.1 mmHg with 1.2 and 1.8 mg liraglutide and placebo, respectively. Significant increases in C-peptide and homeostasis model assessment of β-cell function and significant decreases in the proinsulin-to-insulin ratio occurred with liraglutide versus placebo. Minor hypoglycemia occurred more frequently with liraglutide, but there was no major hypoglycemia. Gastrointestinal adverse events were more common with liraglutide, but most occurred early and were transient.
CONCLUSIONS Liraglutide combined with metformin and a thiazolidinedione is a well-tolerated combination therapy for type 2 diabetes, providing significant improvements in glycemic control.
TL;DR: Strong evidence now shows that people with RA are at a high risk for developing several comorbid disorders, that these conditions may have atypical features and thus may be difficult to diagnose, and that persons with RA experience poorer outcomes after comorbridity compared with the general population.
Abstract: Epidemiology is the study of the distribution and determinants of disease in human populations. Over the past decade there has been considerable progress in our understanding of the fundamental descriptive epidemiology (levels of disease frequency: incidence and prevalence, comorbidity, mortality, trends over time, geographic distributions, and clinical characteristics) of the rheumatic diseases. This progress is reviewed for the following major rheumatic diseases: rheumatoid arthritis (RA), juvenile rheumatoid arthritis, psoriatic arthritis, osteoarthritis, systemic lupus erythematosus, giant cell arteritis, polymyalgia rheumatica, gout, Sjogren's syndrome, and ankylosing spondylitis. These findings demonstrate the dynamic nature of the incidence and prevalence of these conditions – a reflection of the impact of genetic and environmental factors. The past decade has also brought new insights regarding the comorbidity associated with rheumatic diseases. Strong evidence now shows that persons with RA are at a high risk for developing several comorbid disorders, that these conditions may have atypical features and thus may be difficult to diagnose, and that persons with RA experience poorer outcomes after comorbidity compared with the general population. Taken together, these findings underscore the complexity of the rheumatic diseases and highlight the key role of epidemiological research in understanding these intriguing conditions.
TL;DR: In this article, a uniform mid-infrared imaging and photometric survey of 36 young, nearby, star-forming clusters and groups using Spitzer IRAC and MIPS is presented.
Abstract: We present a uniform mid-infrared imaging and photometric survey of 36 young, nearby, star-forming clusters and groups using Spitzer IRAC and MIPS. We have confidently identified and classified 2548 young stellar objects (YSOs) using recently established mid-infrared color-based methods. We have devised and applied a new algorithm for the isolation of local surface density enhancements from point source distributions, enabling us to extract the overdense cores of the observed star-forming regions for further analysis. We have compiled several basic structural measurements of these cluster cores from the data, such as mean surface densities of sources, cluster core radii, and aspect ratios, in order to characterize the ranges for these quantities. We find that a typical cluster core is 0.39 pc in radius, has 26 members with infrared excess in a ratio of Class II to Class I sources of 3.7, is embedded in a A{sub K} = 0.8 mag cloud clump, and has a surface density of 60 pc{sup -2}. We examine the nearest neighbor distances among the YSOs in several ways, demonstrating similarity in the spacings between Class II and Class I sources but large member clusters appear more dense than smaller clusters. We demonstrate that near-uniform source spacingsmore » in cluster cores are common, suggesting that simple Jeans fragmentation of parsec-scale cloud clumps may be the dominant process governing star formation in nearby clusters and groups. Finally, we compare our results to other similar surveys in the literature and discuss potential biases in the data to guide further interpretation.« less
TL;DR: In young adults with AML, intensifying induction therapy with a high daily dose of daunorubicin improved the rate of complete remission and the duration of overall survival, as compared with the standard dose.
Abstract: Background In young adults with acute myeloid leukemia (AML), intensification of the anthracycline dose during induction therapy has improved the rate of complete remission but not of overall survival. We evaluated the use of cytarabine plus either standard-dose or high-dose daunorubicin as induction therapy, followed by intensive consolidation therapy, in inducing complete remission to improve overall survival. Methods In this phase 3 randomized trial, we assigned 657 patients between the ages of 17 and 60 years who had untreated AML to receive three once-daily doses of daunorubicin at either the standard dose (45 mg per square meter of body-surface area) or a high dose (90 mg per square meter), combined with seven daily doses of cytarabine (100 mg per square meter) by continuous intravenous infusion. Patients who had a complete remission were offered either allogeneic hematopoietic stem-cell transplantation or high-dose cytarabine, with or without a single dose of the monoclonal antibody gemtuzumab ozog...