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Showing papers by "University of Pittsburgh published in 2009"


Journal ArticleDOI
01 Nov 2009-Thyroid
TL;DR: Evidence-based recommendations are developed to inform clinical decision-making in the management of thyroid nodules and differentiated thyroid cancer and represent, in the authors' opinion, contemporary optimal care for patients with these disorders.
Abstract: Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Gr...

10,501 citations


Journal ArticleDOI
TL;DR: An outlook is presented on what will be required to drive this young photovoltaic technology towards the next major milestone, a 10% power conversion efficiency, considered by many to represent the efficiency at which OPV can be adopted in wide-spread applications.
Abstract: Solution-processed bulk-heterojunction solar cells have gained serious attention during the last few years and are becoming established as one of the future photovoltaic technologies for low-cost power production. This article reviews the highlights of the last few years, and summarizes today's state-of-the-art performance. An outlook is given on relevant future materials and technologies that have the potential to guide this young photovoltaic technology towards the magic 10% regime. A cost model supplements the technical discussions, with practical aspects any photovoltaic technology needs to fulfil, and answers to the question as to whether low module costs can compensate lower lifetimes and performances.

3,084 citations


Journal ArticleDOI
12 Jun 2009-Science
TL;DR: Studying a mouse model of PDA that is refractory to the clinically used drug gemcitabine, it is found that the tumors in this model were poorly perfused and poorly vascularized, properties that are shared with human PDA.
Abstract: Pancreatic ductal adenocarcinoma (PDA) is among the most lethal human cancers in part because it is insensitive to many chemotherapeutic drugs. Studying a mouse model of PDA that is refractory to the clinically used drug gemcitabine, we found that the tumors in this model were poorly perfused and poorly vascularized, properties that are shared with human PDA. We tested whether the delivery and efficacy of gemcitabine in the mice could be improved by coadministration of IPI-926, a drug that depletes tumor-associated stromal tissue by inhibition of the Hedgehog cellular signaling pathway. The combination therapy produced a transient increase in intratumoral vascular density and intratumoral concentration of gemcitabine, leading to transient stabilization of disease. Thus, inefficient drug delivery may be an important contributor to chemoresistance in pancreatic cancer.

2,831 citations


Journal ArticleDOI
TL;DR: The Adult OSA Task Force of the American Academy of Sleep Medicine (AASM) was assembled to produce a clinical guideline from a review of existing practice parameters and available literature as discussed by the authors.
Abstract: Background Obstructive sleep apnea (OSA) is a common chronic disorder that often requires lifelong care. Available practice parameters provide evidence-based recommendations for addressing aspects of care. Objective This guideline is designed to assist primary care providers as well as sleep medicine specialists, surgeons, and dentists who care for patients with OSA by providing a comprehensive strategy for the evaluation, management and long-term care of adult patients with OSA. Methods The Adult OSA Task Force of the American Academy of Sleep Medicine (AASM) was assembled to produce a clinical guideline from a review of existing practice parameters and available literature. All existing evidence-based AASM practice parameters relevant to the evaluation and management of OSA in adults were incorporated into this guideline. For areas not covered by the practice parameters, the task force performed a literature review and made consensus recommendations using a modified nominal group technique. Recommendations Questions regarding OSA should be incorporated into routine health evaluations. Suspicion of OSA should trigger a comprehensive sleep evaluation. The diagnostic strategy includes a sleep-oriented history and physical examination, objective testing, and education of the patient. The presence or absence and severity of OSA must be determined before initiating treatment in order to identify those patients at risk of developing the complications of sleep apnea, guide selection of appropriate treatment, and to provide a baseline to establish the effectiveness of subsequent treatment. Once the diagnosis is established, the patient should be included in deciding an appropriate treatment strategy that may include positive airway pressure devices, oral appliances, behavioral treatments, surgery, and/or adjunctive treatments. OSA should be approached as a chronic disease requiring long-term, multidisciplinary management. For each treatment option, appropriate outcome measures and long-term follow-up are described.

2,089 citations


Book
04 Oct 2009
TL;DR: In this article, the authors present a review of vector calculus and functions of a complex variable and Fraunhoffer diffraction by a circular hole, and a miscellany of bidirectional reflectances and related quantities.
Abstract: Acknowledgements 1. Introduction 2. Electromagnetic wave propagation 3. The absorption of light 4. Specular reflection 5. Single particle scattering: perfect spheres 6. Single particle scattering: irregular particles 7. Propagation in a nonuniform medium: the equation of radiative transfer 8. The bidirectional reflectance of a semi-infinite medium 9. The opposition effect 10. A miscellany of bidirectional reflectances and related quantities 11. Integrated reflectances and planetary photometry 12. Photometric effects of large scale roughness 13. Polarization 14. Reflectance spectroscopy 15. Thermal emission and emittance spectroscopy 16. Simultaneous transport of energy by radiation and conduction Appendix A. A brief review of vector calculus Appendix B. Functions of a complex variable Appendix C. The wave equation in spherical coordinates Appendix D. Fraunhoffer diffraction by a circular hole Appendix E. Table of symbols Bibliography Index.

1,951 citations


Journal ArticleDOI
TL;DR: Overall, there was no significant difference in the rates of death and major cardiovascular events between patients undergoing prompt revascularization and those undergoing medical therapy or between strategies of insulin sensitization and insulin provision.
Abstract: At 5 years, rates of survival did not differ significantly between the revascularization group (88.3%) and the medical ­ therapy group (87.8%, P = 0.97) or between the in­ sulin ­ sensitization group (88.2%) and the insulin ­ provision group (87.9%, P = 0.89). The rates of freedom from major cardiovascular events also did not differ signifi­ cantly among the groups: 77.2% in the revascularization group and 75.9% in the medical ­ treatment group (P = 0.70) and 77.7% in the insulin ­ sensitization group and 75.4% in the insulin ­ provision group (P = 0.13). In the PCI stratum, there was no sig­ nificant difference in primary end points between the revascularization group and the medical ­ therapy group. In the CABG stratum, the rate of major cardiovascular events was significantly lower in the revascularization group (22.4%) than in the medical ­ therapy group (30.5%, P = 0.01; P = 0.002 for interaction between stratum and study group). Adverse events and serious adverse events were generally similar among the groups, although severe hypoglycemia was more frequent in the insulin ­ provision group (9.2%) than in the insulin ­ sensitization group (5.9%, P = 0.003). Conclusions Overall, there was no significant difference in the rates of death and major cardio­ vascular events between patients undergoing prompt revascularization and those undergoing medical therapy or between strategies of insulin sensitization and in­ sulin provision. (ClinicalTrials.gov number, NCT00006305.)

1,743 citations


Journal ArticleDOI
TL;DR: New definitions for asthma control, severity, and exacerbations are developed, based on current treatment principles and clinical and research relevance, to provide a basis for a multicomponent assessment of asthma by clinicians, researchers, and other relevant groups in the design, conduct, and evaluation of clinical trials, and in clinical practice.
Abstract: Background: The assessment of asthma control is pivotal to the evaluation of treatment response in individuals and in clinical trials. Previously, asthma control, severity, and exacerbations were defined and assessed in many different ways.Purpose: The Task Force was established to provide recommendations about standardization of outcomes relating to asthma control, severity, and exacerbations in clinical trials and clinical practice, for adults and children aged 6 years or older.Methods: A narrative literature review was conducted to evaluate the measurement properties and strengths/weaknesses of outcome measures relevant to asthma control and exacerbations. The review focused on diary variables, physiologic measurements, composite scores, biomarkers, quality of life questionnaires, and indirect measures.Results: The Task Force developed new definitions for asthma control, severity, and exacerbations, based on current treatment principles and clinical and research relevance. In view of current knowledge ...

1,642 citations


Journal ArticleDOI
TL;DR: Treatment of mild gestational diabetes mellitus did not significantly reduce the frequency of a composite outcome that included stillbirth or perinatal death and several neonatal complications, but it did reduce the risks of fetal overgrowth, shoulder dystocia, cesarean delivery, and hypertensive disorders.
Abstract: Background It is uncertain whether treatment of mild gestational diabetes mellitus improves pregnancy outcomes. Methods Women who were in the 24th to 31st week of gestation and who met the criteria for mild gestational diabetes mellitus (i.e., an abnormal result on an oral glucose-tolerance test but a fasting glucose level below 95 mg per deciliter [5.3 mmol per liter]) were randomly assigned to usual prenatal care (control group) or dietary intervention, self-monitoring of blood glucose, and insulin therapy, if necessary (treatment group). The primary outcome was a composite of stillbirth or perinatal death and neonatal complications, including hyperbilirubinemia, hypoglycemia, hyperinsulinemia, and birth trauma. Results A total of 958 women were randomly assigned to a study group — 485 to the treatment group and 473 to the control group. We observed no significant difference between groups in the frequency of the composite outcome (32.4% and 37.0% in the treatment and control groups, respectively; P=0.1...

1,587 citations


Journal ArticleDOI
17 Jun 2009-JAMA
TL;DR: This meta-analysis yielded no evidence that the serotonin transporter genotype alone or in interaction with stressful life events is associated with an elevated risk of depression in men alone, women alone, or in both sexes combined.
Abstract: Context Substantial resources are being devoted to identify candidate genes for complex mental and behavioral disorders through inclusion of environmental exposures following the report of an interaction between the serotonin transporter linked polymorphic region (5-HTTLPR) and stressful life events on an increased risk of major depression. Objective To conduct a meta-analysis of the interaction between the serotonin transporter gene and stressful life events on depression using both published data and individual-level original data. Data Sources Search of PubMed, EMBASE, and PsycINFO databases through March 2009 yielded 26 studies of which 14 met criteria for the meta-analysis. Study Selection Criteria for studies for the meta-analyses included published data on the association between 5-HTTLPR genotype (SS, SL, or LL), number of stressful life events (0, 1, 2, ≥3) or equivalent, and a categorical measure of depression defined by the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) or the International Statistical Classification of Diseases, 10th Revision (ICD-10) or use of a cut point to define depression from standardized rating scales. To maximize our ability to use a common framework for variable definition, we also requested original data from all studies published prior to 2008 that met inclusion criteria. Of the 14 studies included in the meta-analysis, 10 were also included in a second sex-specific meta-analysis of original individual-level data. Data Extraction Logistic regression was used to estimate the effects of the number of short alleles at 5-HTTLPR, the number of stressful life events, and their interaction on depression. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated separately for each study and then weighted averages of the individual estimates were obtained using random-effects meta-analysis. Both sex-combined and sex-specific meta-analyses were conducted. Of a total of 14 250 participants, 1769 were classified as having depression; 12 481 as not having depression. Results In the meta-analysis of published data, the number of stressful life events was significantly associated with depression (OR, 1.41; 95% CI,1.25-1.57). No association was found between 5-HTTLPR genotype and depression in any of the individual studies nor in the weighted average (OR, 1.05; 95% CI, 0.98-1.13) and no interaction effect between genotype and stressful life events on depression was observed (OR, 1.01; 95% CI, 0.94-1.10). Comparable results were found in the sex-specific meta-analysis of individual-level data. Conclusion This meta-analysis yielded no evidence that the serotonin transporter genotype alone or in interaction with stressful life events is associated with an elevated risk of depression in men alone, women alone, or in both sexes combined.

1,486 citations


Journal ArticleDOI
TL;DR: Recommendations from the ACE and the ADA generally endorsed tight glycemic control in critical care units and for patients in general medical and surgical units, where RCT evidence regarding treatment targets was lacking, glycemic goals similar to those advised for outpatients were advocated.
Abstract: People with diabetes are more likely to be hospitalized and to have longer durations of hospital stay than those without diabetes. A recent survey estimated that 22% of all hospital inpatient days were incurred by people with diabetes and that hospital inpatient care accounted for half of the 174 billion USD total U.S. medical expenditures for this disease (1). These findings are due, in part, to the continued expansion of the worldwide epidemic of type 2 diabetes. In the U.S. alone, there are ∼1.6 million new cases of diabetes each year, with an over all prevalence of 23.6 million people (7.8% of the population, with one-fourth of the cases remaining undiagnosed). An additional 57 million American adults are at high risk for type 2 diabetes (2). Although the costs of illness-related stress hyperglycemia are not known, they are likely to be considerable in light of the poor prognosis of such patients (3–6). There is substantial observational evidence linking hyperglycemia in hospitalized patients (with or without diabetes) to poor outcomes. Cohort studies as well as a few early randomized controlled trials (RCTs) have suggested that intensive treatment of hyperglycemia improved hospital outcomes (5–8). In 2004, this evidence led the American College of Endocrinology (ACE) and the American Association of Clinical Endocrinologists (AACE), in collaboration with the American Diabetes Association (ADA) and other medical organizations, to develop recommendations for treatment of inpatient hyperglycemia (9). In 2005, the ADA added recommendations for treatment of hyperglycemia in the hospitalto itsannual Standards of Medical Care (10). Recommendations from the ACE and the ADA generally endorsed tight glycemic control in critical care units. For patients in general medical and surgical units, where RCT evidence regarding treatment targets was lacking, glycemic goals similar to those advised for outpatients were advocated (9, …

1,471 citations


Journal ArticleDOI
TL;DR: Laparoscopic liver surgery is a safe and effective approach to the management of surgical liver disease in the hands of trained surgeons with experience in hepatobiliary and laparoscopic surgery, and national and international societies should become involved in the goal of establishing training standards and credentialing.
Abstract: Objective:To summarize the current world position on laparoscopic liver surgery.Summary Background Data:Multiple series have reported on the safety and efficacy of laparoscopic liver surgery. Small and medium sized procedures have become commonplace in many centers, while major laparoscopic liver re

Journal ArticleDOI
TL;DR: An overview of the composition and structure of selected ECM scaffolding materials, the effects of manufacturing methods upon the structural properties and resulting mechanical behavior of the scaffold materials, and the in vivo degradation and remodeling of ECm scaffolds with an emphasis on tissue function is provided.

Journal ArticleDOI
28 May 2009-Nature
TL;DR: Several new susceptibility genes encoding neuronal cell-adhesion molecules, including NLGN1 and ASTN2, were enriched with CNVs in ASD cases compared to controls, and duplications 55 kilobases upstream of complementary DNA AK123120 indicate that these two important gene networks expressed within the central nervous system may contribute to the genetic susceptibility of ASD.
Abstract: Several lines of evidence point to genetic involvement in autism spectrum disorders (ASDs), neurodevelopmental and neuropsychiatric disorders characterized by impaired verbal communication and social interaction. The clinical and genetic complexities of the condition make it difficult to identify susceptibility factors, but two related studies now present robust evidence for a genetic involvement. The first, a genome-wide association study, identifies six single-nucleotide polymorphisms strongly associated with autism. These variants lie between two genes encoding neuronal cell-adhesion molecules (cadherins 9 and 10), suggesting possible involvement in ASD pathogenesis. The second study used copy number variation screens to identify genetic variants in two major gene pathways in children with ASDs. The changes are in the ubiquitin pathway, which has previously been associated with neurological disease, and in genes for neuronal cell-adhesion molecules.

Journal ArticleDOI
TL;DR: The overall risk of death and other adverse outcomes after bariatric surgery was low and varied considerably according to patient characteristics, andExtreme values of body-mass index were significantly associated with an increased risk of the composite end point, whereas age, sex, race, ethnic group, and other coexisting conditions were not.
Abstract: BACKGROUND To improve decision making in the treatment of extreme obesity, the risks of bariatric surgical procedures require further characterization. METHODS We performed a prospective, multicenter, observational study of 30-day outcomes in consecutive patients undergoing bariatric surgical procedures at 10 clinical sites in the United States from 2005 through 2007. A composite end point of 30-day major adverse outcomes (including death; venous thromboembolism; percutaneous, endoscopic, or operative reintervention; and failure to be discharged from the hospital) was evaluated among patients undergoing first-time bariatric surgery. RESULTS There were 4776 patients who had a first-time bariatric procedure (mean age, 44.5 years; 21.1% men; 10.9% nonwhite; median body-mass index [the weight in kilograms divided by the square of the height in meters], 46.5). More than half had at least two coexisting conditions. A Roux-en-Y gastric bypass was performed in 3412 patients (with 87.2% of the procedures performed laparoscopically), and laparoscopic adjustable gastric banding was performed in 1198 patients; 166 patients underwent other procedures and were not included in the analysis. The 30-day rate of death among patients who underwent a Roux-en-Y gastric bypass or laparoscopic adjustable gastric banding was 0.3%; a total of 4.3% of patients had at least one major adverse outcome. A history of deep-vein thrombosis or pulmonary embolus, a diagnosis of obstructive sleep apnea, and impaired functional status were each independently associated with an increased risk of the composite end point. Extreme values of body-mass index were significantly associated with an increased risk of the composite end point, whereas age, sex, race, ethnic group, and other coexisting conditions were not. CONCLUSIONS The overall risk of death and other adverse outcomes after bariatric surgery was low and varied considerably according to patient characteristics. In helping patients make appropriate choices, short-term safety should be considered in conjunction with both the long-term effects of bariatric surgery and the risks associated with being extremely obese. (ClinicalTrials.gov number, NCT00433810.)

Journal ArticleDOI
TL;DR: The biology of latent tuberculosis is discussed as part of a broad range of responses that occur following infection with Mycobacterium tuberculosis, which result in the formation of physiologically distinct granulomatous lesions that provide microenvironments with differential ability to support or suppress the persistence of viable bacteria.
Abstract: Immunological tests provide evidence of latent tuberculosis in one third of the global population, which corresponds to more than two billion individuals. Latent tuberculosis is defined by the absence of clinical symptoms but carries a risk of subsequent progression to clinical disease, particularly in the context of co-infection with HIV. In this Review we discuss the biology of latent tuberculosis as part of a broad range of responses that occur following infection with Mycobacterium tuberculosis, which result in the formation of physiologically distinct granulomatous lesions that provide microenvironments with differential ability to support or suppress the persistence of viable bacteria. We then show how this model can be used to develop a rational programme to discover effective drugs for the eradication of M. tuberculosis infection.

Journal ArticleDOI
TL;DR: Research defining the signal transduction pathways induced by IL-17R family cytokines has lagged behind that of other cytokine families, but studies in the past 2 years have begun to delineate unusual functional motifs and new proximal signalling mediators used by the IL- 17R family to mediate downstream events.
Abstract: Interleukin-17A (IL-17A), the hallmark cytokine of the newly defined T helper 17 (T(H)17) cell subset, has important roles in protecting the host against extracellular pathogens, but also promotes inflammatory pathology in autoimmune disease. IL-17A and its receptor (IL-17RA) are the founding members of a newly described family of cytokines and receptors that have unique structural features which distinguish them from other cytokine families. Research defining the signal transduction pathways induced by IL-17R family cytokines has lagged behind that of other cytokine families, but studies in the past 2 years have begun to delineate unusual functional motifs and new proximal signalling mediators used by the IL-17R family to mediate downstream events.

Journal ArticleDOI
TL;DR: The findings reflect the current status of the cancer vaccine field, highlight the possibility that additional organized efforts and funding would accelerate the development of therapeutically effective cancer vaccines, and accentuate the need for prioritization.
Abstract: The purpose of the National Cancer Institute pilot project to prioritize cancer antigens was to develop a well-vetted, priority-ranked list of cancer vaccine target antigens based on predefined and preweighted objective criteria. An additional aim was for the National Cancer Institute to test a new approach for prioritizing translational research opportunities based on an analytic hierarchy process for dealing with complex decisions. Antigen prioritization involved developing a list of "ideal" cancer antigen criteria/characteristics, assigning relative weights to those criteria using pairwise comparisons, selecting 75 representative antigens for comparison and ranking, assembling information on the predefined criteria for the selected antigens, and ranking the antigens based on the predefined, preweighted criteria. Using the pairwise approach, the result of criteria weighting, in descending order, was as follows: (a) therapeutic function, (b) immunogenicity, (c) role of the antigen in oncogenicity, (d) specificity, (e) expression level and percent of antigen-positive cells, (f) stem cell expression, (g) number of patients with antigen-positive cancers, (h) number of antigenic epitopes, and (i) cellular location of antigen expression. None of the 75 antigens had all of the characteristics of the ideal cancer antigen. However, 46 were immunogenic in clinical trials and 20 of them had suggestive clinical efficacy in the "therapeutic function" category. These findings reflect the current status of the cancer vaccine field, highlight the possibility that additional organized efforts and funding would accelerate the development of therapeutically effective cancer vaccines, and accentuate the need for prioritization.

Journal ArticleDOI
TL;DR: In a cohort of 6,441 volunteers followed over an average of 8.2 years, Naresh Punjabi and colleagues find sleep-disordered breathing to be independently associated with mortality and identify predictive characteristics.
Abstract: Background: Sleep-disordered breathing is a common condition associated with adverse health outcomes including hypertension and cardiovascular disease. The overall objective of this study was to determine whether sleep-disordered breathing and its sequelae of intermittent hypoxemia and recurrent arousals are associated with mortality in a community sample of adults aged 40 years or older. Methods and Findings: We prospectively examined whether sleep-disordered breathing was associated with an increased risk of death from any cause in 6,441 men and women participating in the Sleep Heart Health Study. Sleep-disordered breathing was assessed with the apnea–hypopnea index (AHI) based on an in-home polysomnogram. Survival analysis and proportional hazards regression models were used to calculate hazard ratios for mortality after adjusting for age, sex, race, smoking status, body mass index, and prevalent medical conditions. The average follow-up period for the cohort was 8.2 y during which 1,047 participants (587 men and 460 women) died. Compared to those without sleep-disordered breathing (AHI: ,5 events/h), the fully adjusted hazard ratios for all-cause mortality in those with mild (AHI: 5.0–14.9 events/h), moderate (AHI: 15.0–29.9 events/h), and severe (AHI: $30.0 events/h) sleep-disordered breathing were 0.93 (95% CI: 0.80– 1.08), 1.17 (95% CI: 0.97–1.42), and 1.46 (95% CI: 1.14–1.86), respectively. Stratified analyses by sex and age showed that the increased risk of death associated with severe sleep-disordered breathing was statistically significant in men aged 40–70 y (hazard ratio: 2.09; 95% CI: 1.31–3.33). Measures of sleep-related intermittent hypoxemia, but not sleep fragmentation, were independently associated with all-cause mortality. Coronary artery disease–related mortality associated with sleepdisordered breathing showed a pattern of association similar to all-cause mortality. Conclusions: Sleep-disordered breathing is associated with all-cause mortality and specifically that due to coronary artery disease, particularly in men aged 40–70 y with severe sleep-disordered breathing. Please see later in the article for the Editors’ Summary.

Journal ArticleDOI
01 Jun 2009-Emotion
TL;DR: Change in resilience mediated the relation between positive emotions and increased life satisfaction, suggesting that happy people become more satisfied not simply because they feel better but because they develop resources for living well.
Abstract: Happiness—a composite of life satisfaction, coping resources, and positive emotions—predicts desirable life outcomes in many domains. The broaden-and-build theory suggests that this is because positive emotions help people build lasting resources. To test this hypothesis, the authors measured emotions daily for 1 month in a sample of students (N 86) and assessed life satisfaction and trait resilience at the beginning and end of the month. Positive emotions predicted increases in both resilience and life satisfaction. Negative emotions had weak or null effects and did not interfere with the benefits of positive emotions. Positive emotions also mediated the relation between baseline and final resilience, but life satisfaction did not. This suggests that it is in-the-moment positive emotions, and not more general positive evaluations of one’s life, that form the link between happiness and desirable life outcomes. Change in resilience mediated the relation between positive emotions and increased life satisfaction, suggesting that happy people become more satisfied not simply because they feel better but because they develop resources for living well.

Journal ArticleDOI
TL;DR: The practical implementation of various signal processing techniques for removing physiological, instrumental, and motion-artifact noise from optical data are described within the context of the MATLAB-based graphical user interface program, HomER, which is developed and distributed to facilitate the processing of optical functional brain data.
Abstract: Near-infrared spectroscopy (NIRS) is a noninvasive neuroimaging tool for studying evoked hemodynamic changes within the brain. By this technique, changes in the optical absorption of light are recorded over time and are used to estimate the functionally evoked changes in cerebral oxyhemoglobin and deoxyhemoglobin concentrations that result from local cerebral vascular and oxygen metabolic effects during brain activity. Over the past three decades this technology has continued to grow, and today NIRS studies have found many niche applications in the fields of psychology, physiology, and cerebral pathology. The growing popularity of this technique is in part associated with a lower cost and increased portability of NIRS equipment when compared with other imaging modalities, such as functional magnetic resonance imaging and positron emission tomography. With this increasing number of applications, new techniques for the processing, analysis, and interpretation of NIRS data are continually being developed. We review some of the time-series and functional analysis techniques that are currently used in NIRS studies, we describe the practical implementation of various signal processing techniques for removing physiological, instrumental, and motion-artifact noise from optical data, and we discuss the unique aspects of NIRS analysis in comparison with other brain imaging modalities. These methods are described within the context of the MATLAB-based graphical user interface program, HomER, which we have developed and distributed to facilitate the processing of optical functional brain data.

Journal ArticleDOI
TL;DR: Loss of leg MT in older adults is greater than muscle CSA loss, which suggests a decrease in MQ, and aging is associated with an increase in IMF regardless of changes in weight or SF.

Journal ArticleDOI
TL;DR: An extended deterrence theory model is presented that combines work from criminology, social psychology, and information systems and suggests that user awareness of security countermeasures directly influences the perceived certainty and severity of organizational sanctions associated with IS misuse, which leads to reduced IS misuse intention.
Abstract: Intentional insider misuse of information systems resources (i.e., IS misuse) represents a significant threat to organizations. For example, industry statistics suggest that between 50%--75% of security incidents originate from within an organization. Because of the large number of misuse incidents, it has become important to understand how to reduce such behavior. General deterrence theory suggests that certain controls can serve as deterrent mechanisms by increasing the perceived threat of punishment for IS misuse. This paper presents an extended deterrence theory model that combines work from criminology, social psychology, and information systems. The model posits that user awareness of security countermeasures directly influences the perceived certainty and severity of organizational sanctions associated with IS misuse, which leads to reduced IS misuse intention. The model is then tested on 269 computer users from eight different companies. The results suggest that three practices deter IS misuse: user awareness of security policies; security education, training, and awareness (SETA) programs; and computer monitoring. The results also suggest that perceived severity of sanctions is more effective in reducing IS misuse than certainty of sanctions. Further, there is evidence that the impact of sanction perceptions vary based on one's level of morality. Implications for the research and practice of IS security are discussed.

Journal ArticleDOI
TL;DR: Type or intensity of 14 months of treatment for ADHD in childhood does not predict functioning 6 to 8 years later, and early ADHD symptom trajectory regardless of treatment type is prognostic, implying that children with behavioral and sociodemographic advantage, with the best response to any treatment, will have the best long-term prognosis.
Abstract: Objectives To determine any long-term effects, 6 and 8 years after childhood enrollment, of the randomly assigned 14-month treatments in the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA; N = 436); to test whether attention-deficit/hyperactivity disorder (ADHD) symptom trajectory through 3 years predicts outcome in subsequent years; and to examine functioning level of the MTA adolescents relative to their non-ADHD peers (local normative comparison group; N = 261). Method Mixed-effects regression models with planned contrasts at 6 and 8 years tested a wide range of symptom and impairment variables assessed by parent, teacher, and youth report. Results In nearly every analysis, the originally randomized treatment groups did not differ significantly on repeated measures or newly analyzed variables (e.g., grades earned in school, arrests, psychiatric hospitalizations, other clinically relevant outcomes). Medication use decreased by 62% after the 14-month controlled trial, but adjusting for this did not change the results. ADHD symptom trajectory in the first 3 years predicted 55% of the outcomes. The MTA participants fared worse than the local normative comparison group on 91% of the variables tested. Conclusions Type or intensity of 14 months of treatment for ADHD in childhood (at age 7.0–9.9 years) does not predict functioning 6 to 8 years later. Rather, early ADHD symptom trajectory regardless of treatment type is prognostic. This finding implies that children with behavioral and sociodemographic advantage, with the best response to any treatment, will have the best long-term prognosis. As a group, however, despite initial symptom improvement during treatment that is largely maintained after treatment, children with combined-type ADHD exhibit significant impairment in adolescence. Innovative treatment approaches targeting specific areas of adolescent impairment are needed.

Journal ArticleDOI
TL;DR: In experienced hands, laparoscopic liver resections are safe with acceptable morbidity and mortality for both minor and major hepatic resection, albeit in a selected group of patients.
Abstract: Objective To provide a review of the world literature on laparoscopic liver resection. Summary background data Initially described for peripheral, benign tumors resected by nonanatomic wedge resections, minimally invasive liver resections are now being performed more frequently, even for larger, malignant tumors located in challenging locations. Although a few small review articles have been reported, a comprehensive review on laparoscopic liver resection has not been published. Methods We conducted a literature search using Pubmed, screening all English publications on laparoscopic liver resections. All data were analyzed and apparent case duplications in updated series were excluded from the total number of patients. Tumor type, operative characteristics, perioperative morbidity, and oncologic outcomes were tabulated. Results A total of 127 published articles of original series on laparoscopic liver resection were identified, and accounted for 2,804 reported minimally invasive liver resections. Fifty percent were for malignant tumors, 45% were for benign lesions, 1.7% were for live donor hepatectomies, and the rest were indeterminate. Of the resections, 75% were performed totally laparoscopically, 17% were hand-assisted, and 2% were laparoscopic-assisted open hepatic resection (hybrid) technique, with the remainder being other techniques or conversions to open hepatectomies. The most common laparoscopic liver resection was a wedge resection or segmentectomy (45%) followed by anatomic left lateral sectionectomy (20%), right hepatectomy (9%), and left hepatectomy (7%). Conversion from laparoscopy to open laparotomy and from laparoscopy to hand-assisted approach occurred in 4.1% and 0.7% of reported cases, respectively. Overall mortality was 9 of 2,804 patients (0.3%), and morbidity was 10.5%, with no intraoperative deaths reported. The most common cause of postoperative death was liver failure. Postoperative bile leak was observed in 1.5% of cases. For cancer resections, negative surgical margins were achieved in 82% to 100% of reported series. The 5-year overall and disease-free survival rates after laparoscopic liver resection for hepatocellular carcinoma were 50% to 75% and 31% to 38.2%, respectively. The 3-year overall and disease-free survival rates after laparoscopic liver resection for colorectal metastasis to the liver were 80% to 87% and 51%, respectively. Conclusion In experienced hands, laparoscopic liver resections are safe with acceptable morbidity and mortality for both minor and major hepatic resections. Oncologically, 3- and 5-year survival rates reported for hepatocellular carcinoma and colorectal cancer metastases are comparable to open hepatic resection, albeit in a selected group of patients.

Journal ArticleDOI
16 Jul 2009-Nature
TL;DR: Analysis of the 363 megabase nuclear genome of the blood fluke, the first sequenced flatworm, and a representative of the Lophotrochozoa offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and theDevelopment of tissues into organs.
Abstract: Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.

Journal ArticleDOI
TL;DR: In this article, Kowalski et al. combined the CfA3 supernovae Type Ia (SNIa) sample with samples from the literature to calculate improved constraints on the dark energy equation of state parameter, w.r.t.
Abstract: We combine the CfA3 supernovae Type Ia (SN Ia) sample with samples from the literature to calculate improved constraints on the dark energy equation of state parameter, w. The CfA3 sample is added to the Union set of Kowalski et al. to form the Constitution set and, combined with a BAO prior, produces 1 + w = 0.013+0.066 –0.068 (0.11 syst), consistent with the cosmological constant. The CfA3 addition makes the cosmologically useful sample of nearby SN Ia between 2.6 and 2.9 times larger than before, reducing the statistical uncertainty to the point where systematics play the largest role. We use four light-curve fitters to test for systematic differences: SALT, SALT2, MLCS2k2 (RV = 3.1), and MLCS2k2 (RV = 1.7). SALT produces high-redshift Hubble residuals with systematic trends versus color and larger scatter than MLCS2k2. MLCS2k2 overestimates the intrinsic luminosity of SN Ia with 0.7 < Δ < 1.2. MLCS2k2 with RV = 3.1 overestimates host-galaxy extinction while RV 1.7 does not. Our investigation is consistent with no Hubble bubble. We also find that, after light-curve correction, SN Ia in Scd/Sd/Irr hosts are intrinsically fainter than those in E/S0 hosts by 2σ, suggesting that they may come from different populations. We also find that SN Ia in Scd/Sd/Irr hosts have low scatter (0.1 mag) and reddening. Current systematic errors can be reduced by improving SN Ia photometric accuracy, by including the CfA3 sample to retrain light-curve fitters, by combining optical SN Ia photometry with near-infrared photometry to understand host-galaxy extinction, and by determining if different environments give rise to different intrinsic SN Ia luminosity after correction for light-curve shape and color.

Journal ArticleDOI
TL;DR: Therapeutic hypothermia is a highly promising treatment, but the potential side effects need to be properly managed particularly if prolonged treatment periods are required.
Abstract: tance, impaired drug clearance, and mild coagulopathy. Targeted interventions are required to effectively manage these side effects. Hypothermia does not decrease myocardial contractility or induce hypotension if hypovolemia is corrected, and preliminary evidence suggests that it can be safely used in patients with cardiac shock. Cardiac output will decrease due to hypothermiainduced bradycardia, but given that metabolic rate also decreases the balance between supply and demand, is usually maintained or improved. In contrast to deep hypothermia (<30°C), moderate hypothermia does not induce arrhythmias; indeed, the evidence suggests that arrhythmias can be prevented and/or more easily treated under hypothermic conditions. Conclusions: Therapeutic hypothermia is a highly promising treatment, but the potential side effects need to be properly managed particularly if prolonged treatment periods are required. Understanding the underlying mechanisms, awareness of physiological changes associated with cooling, and prevention of potential side effects are all key factors for its effective clinical usage. (Crit Care Med 2009; 37[Suppl.]:S186 –S202)

Journal ArticleDOI
28 May 2009-Nature
TL;DR: The results implicate neuronal cell-adhesion molecules in the pathogenesis of ASDs, and represent, to the authors' knowledge, the first demonstration of genome-wide significant association of common variants with susceptibility to ASDs.
Abstract: Several lines of evidence point to genetic involvement in autism spectrum disorders (ASDs), neurodevelopmental and neuropsychiatric disorders characterized by impaired verbal communication and social interaction. The clinical and genetic complexities of the condition make it difficult to identify susceptibility factors, but two related studies now present robust evidence for a genetic involvement. The first, a genome-wide association study, identifies six single-nucleotide polymorphisms strongly associated with autism. These variants lie between two genes encoding neuronal cell-adhesion molecules (cadherins 9 and 10), suggesting possible involvement in ASD pathogenesis. The second study used copy number variation screens to identify genetic variants in two major gene pathways in children with ASDs. The changes are in the ubiquitin pathway, which has previously been associated with neurological disease, and in genes for neuronal cell-adhesion molecules.

Proceedings ArticleDOI
20 Jun 2009
TL;DR: The results indicate that it is feasible to use PCM technology in place of DRAM in the main memory for better energy efficiency and the design choices of implementing PCM to achieve the best tradeoff between energy and performance.
Abstract: Using nonvolatile memories in memory hierarchy has been investigated to reduce its energy consumption because nonvolatile memories consume zero leakage power in memory cells One of the difficulties is, however, that the endurance of most nonvolatile memory technologies is much shorter than the conventional SRAM and DRAM technology This has limited its usage to only the low levels of a memory hierarchy, eg, disks, that is far from the CPUIn this paper, we study the use of a new type of nonvolatile memories -- the Phase Change Memory (PCM) as the main memory for a 3D stacked chip The main challenges we face are the limited PCM endurance, longer access latencies, and higher dynamic power compared to the conventional DRAM technology We propose techniques to extend the endurance of the PCM to an average of 13 (for MLC PCM cell) to 22 (for SLC PCM) years We also study the design choices of implementing PCM to achieve the best tradeoff between energy and performance Our design reduced the total energy of an already low-power DRAM main memory of the same capacity by 65%, and energy-delay2 product by 60% These results indicate that it is feasible to use PCM technology in place of DRAM in the main memory for better energy efficiency

Journal ArticleDOI
TL;DR: The International Nanofluid Property Benchmark Exercise (INPBE) as mentioned in this paper was held in 1998, where the thermal conductivity of identical samples of colloidally stable dispersions of nanoparticles or "nanofluids" was measured by over 30 organizations worldwide, using a variety of experimental approaches, including the transient hot wire method, steady state methods, and optical methods.
Abstract: This article reports on the International Nanofluid Property Benchmark Exercise, or INPBE, in which the thermal conductivity of identical samples of colloidally stable dispersions of nanoparticles or “nanofluids,” was measured by over 30 organizations worldwide, using a variety of experimental approaches, including the transient hot wire method, steady-state methods, and optical methods. The nanofluids tested in the exercise were comprised of aqueous and nonaqueous basefluids, metal and metal oxide particles, near-spherical and elongated particles, at low and high particle concentrations. The data analysis reveals that the data from most organizations lie within a relatively narrow band (±10% or less) about the sample average with only few outliers. The thermal conductivity of the nanofluids was found to increase with particle concentration and aspect ratio, as expected from classical theory. There are (small) systematic differences in the absolute values of the nanofluid thermal conductivity among the various experimental approaches; however, such differences tend to disappear when the data are normalized to the measured thermal conductivity of the basefluid. The effective medium theory developed for dispersed particles by Maxwell in 1881 and recently generalized by Nan et al. [J. Appl. Phys. 81, 6692 (1997)], was found to be in good agreement with the experimental data, suggesting that no anomalous enhancement of thermal conductivity was achieved in the nanofluids tested in this exercise.