Showing papers by "University of Pittsburgh published in 2003"

Geant4—a simulation toolkit

Abstract: G eant 4 is a toolkit for simulating the passage of particles through matter. It includes a complete range of functionality including tracking, geometry, physics models and hits. The physics processes offered cover a comprehensive range, including electromagnetic, hadronic and optical processes, a large set of long-lived particles, materials and elements, over a wide energy range starting, in some cases, from 250 eV and extending in others to the TeV energy range. It has been designed and constructed to expose the physics models utilised, to handle complex geometries, and to enable its easy adaptation for optimal use in different sets of applications. The toolkit is the result of a worldwide collaboration of physicists and software engineers. It has been created exploiting software engineering and object-oriented technology and implemented in the C++ programming language. It has been used in applications in particle physics, nuclear physics, accelerator design, space engineering and medical physics.

2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference

Abstract: Objective: In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) convened a "Consensus Conference", the goals of which were to provide a conceptual and a practical framework to define the systemic inflammatory response to infection, which is a progressive inju- rious process that falls under the gen- eralized term 'sepsis' and includes sepsis-associated organ dysfunction as well. The general definitions intro- duced as a result of that conference have been widely used in practice, and have served as the foundation for in- clusion criteria for numerous clinical trials of therapeutic interventions. Nevertheless, there has been an impe- tus from experts in the field to modify these definitions to reflect our current understanding of the pathophysiology of these syndromes. Design: Several North American and European inten- sive care societies agreed to revisit the definitions for sepsis and related con- ditions. This conference was spon- sored by the Society of Critical Care Medicine (SCCM), The European So-

2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference

Abstract: In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) convened a "Consensus Conference," the goals of which were to "provide a conceptual and a practical framework to define the systemic inflammatory response to infection, which is a progressive injurious process that falls under the generalized term 'sepsis' and includes sepsis-associated organ dysfunction as well. The general definitions introduced as a result of that conference have been widely used in practice, and have served as the foundation for inclusion criteria for numerous clinical trials of therapeutic interventions. Nevertheless, there has been an impetus from experts in the field to modify these definitions to reflect our current understanding of the pathophysiology of these syndromes. Several North American and European intensive care societies agreed to revisit the definitions for sepsis and related conditions. This conference was sponsored by the Society of Critical Care Medicine (SCCM), The European Society of Intensive Care Medicine (ESICM), The American College of Chest Physicians (ACCP), the American Thoracic Society (ATS), and the Surgical Infection Society (SIS). 29 participants attended the conference from Europe and North America. In advance of the conference, subgroups were formed to evaluate the following areas: signs and symptoms of sepsis, cell markers, cytokines, microbiologic data, and coagulation parameters.. The present manuscript serves as the final report of the 2001 International Sepsis Definitions Conference. 1. Current concepts of sepsis, severe sepsis and septic shock remain useful to clinicians and researchers. 2. These definitions do not allow precise staging or prognostication of the host response to infection. 3. While SIRS remains a useful concept, the diagnostic criteria for SIRS published in 1992 are overly sensitive and non-specific. 4. An expanded list of signs and symptoms of sepsis may better reflect the clinical response to infection. 6. PIRO, a hypothetical model for staging sepsis is presented, which, in the future, may better characterize the syndrome on the basis of predisposing factors and premorbid conditions, the nature of the underlying infection, the characteristics of the host response, and the extent of the resultant organ dysfunction.

The neural basis of economic decision-making in the Ultimatum Game.

Abstract: The nascent field of neuroeconomics seeks to ground economic decisionmaking in the biological substrate of the brain. We used functional magnetic resonance imaging of Ultimatum Game players to investigate neural substrates of cognitive and emotional processes involved in economic decision-making. In this game, two players split a sum of money;one player proposes a division and the other can accept or reject this. We scanned players as they responded to fair and unfair proposals. Unfair offers elicited activity in brain areas related to both emotion (anterior insula) and cognition (dorsolateral prefrontal cortex). Further, significantly heightened activity in anterior insula for rejected unfair offers suggests an important role for emotions in decision-making.

Efficacy of Gefitinib, an Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase, in Symptomatic Patients with Non-Small Cell Lung Cancer: A Randomized Trial

Abstract: ContextMore persons in the United States die from non–small cell lung cancer (NSCLC) than from breast, colorectal, and prostate cancer combined. In preclinical testing, oral gefitinib inhibited the growth of NSCLC tumors that express the epidermal growth factor receptor (EGFR), a mediator of cell signaling, and phase 1 trials have demonstrated that a fraction of patients with NSCLC progressing after chemotherapy experience both a decrease in lung cancer symptoms and radiographic tumor shrinkages with gefitinib.ObjectiveTo assess differences in symptomatic and radiographic response among patients with NSCLC receiving 250-mg and 500-mg daily doses of gefitinib.Design, Setting, and PatientsDouble-blind, randomized phase 2 trial conducted from November 2000 to April 2001 in 30 US academic and community oncology centers. Patients (N = 221) had either stage IIIB or IV NSCLC for which they had received at least 2 chemotherapy regimens.InterventionDaily oral gefitinib, either 500 mg (administered as two 250-mg gefitinib tablets) or 250 mg (administered as one 250-mg gefitinib tablet and 1 matching placebo).Main Outcome MeasuresImprovement of NSCLC symptoms (2-point or greater increase in score on the summed lung cancer subscale of the Functional Assessment of Cancer Therapy-Lung [FACT-L] instrument) and tumor regression (>50% decrease in lesion size on imaging studies).ResultsOf 221 patients enrolled, 216 received gefitinib as randomized. Symptoms of NSCLC improved in 43% (95% confidence interval [CI], 33%-53%) of patients receiving 250 mg of gefitinib and in 35% (95% CI, 26%-45%) of patients receiving 500 mg. These benefits were observed within 3 weeks in 75% of patients. Partial radiographic responses occurred in 12% (95% CI, 6%-20%) of individuals receiving 250 mg of gefitinib and in 9% (95% CI, 4%-16%) of those receiving 500 mg. Symptoms improved in 96% of patients with partial radiographic responses. The overall survival at 1 year was 25%. There were no significant differences between the 250-mg and 500-mg doses in rates of symptom improvement (P = .26), radiographic tumor regression (P = .51), and projected 1-year survival (P = .54). The 500-mg dose was associated more frequently with transient acne-like rash (P = .04) and diarrhea (P = .006).ConclusionsGefitinib, a well-tolerated oral EGFR-tyrosine kinase inhibitor, improved disease-related symptoms and induced radiographic tumor regressions in patients with NSCLC persisting after chemotherapy.

Neoadjuvant Chemotherapy plus Cystectomy Compared with Cystectomy Alone for Locally Advanced Bladder Cancer

Abstract: BACKGROUND Despite aggressive local therapy, patients with locally advanced bladder cancer are at significant risk for metastases. We evaluated the ability of neoadjuvant chemotherapy to improve the outcome in patients with locally advanced bladder cancer who were treated with radical cystectomy. METHODS Patients were enrolled if they had muscle-invasive bladder cancer (stage T2 to T4a) and were to be treated with radical cystectomy. They were stratified according to age (less than 65 years vs. 65 years or older) and stage (superficial muscle invasion vs. more extensive disease) and were randomly assigned to radical cystectomy alone or three cycles of methotrexate, vinblastine, doxorubicin, and cisplatin followed by radical cystectomy. RESULTS We enrolled 317 patients over an 11-year period, 10 of whom were found to be ineligible; thus, 154 were assigned to receive surgery alone and 153 to receive combination therapy. According to an intention-to-treat analysis, the median survival among patients assigned to surgery alone was 46 months, as compared with 77 months among patients assigned to combination therapy (P=0.06 by a two-sided stratified log-rank test). In both groups, improved survival was associated with the absence of residual cancer in the cystectomy specimen. Significantly more patients in the combination-therapy group had no residual disease than patients in the cystectomy group (38 percent vs. 15 percent, P<0.001). CONCLUSIONS As compared with radical cystectomy alone, the use of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin followed by radical cystectomy increases the likelihood of eliminating residual cancer in the cystectomy specimen and is associated with improved survival among patients with locally advanced bladder cancer.

Immunology of tuberculosis.

Abstract: The resurgence of tuberculosis worldwide has intensified research efforts directed at examining the host defense and pathogenic mechanisms operative in Mycobacterium tuberculosis infection. This review summarizes our current understanding of the host immune response, with emphasis on the roles of macrophages, T cells, and the cytokine/chemokine network in engendering protective immunity. Specifically, we summarize studies addressing the ability of the organism to survive within macrophages by controlling phagolysosome fusion. The recent studies on Toll-like receptors and the impact on the innate response to M. tuberculosis are discussed. We also focus on the induction, specificity, and effector functions of CD4(+) and CD8(+) T cells, and the roles of cytokines and chemokines in the induction and effector functions of the immune response. Presentation of mycobacterial antigens by MHC class I, class II, and CD1 as well as the implications of these molecules sampling various compartments of the cell for presentation to T cells are discussed. Increased attention to this disease and the integration of animal models and human studies have afforded us a greater understanding of tuberculosis and the steps necessary to combat this infection. The pace of this research must be maintained if we are to realize an effective vaccine in the next decades.

Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group

Abstract: The monoclonal gammopathies are a group of disorders associated with monoclonal proliferation of plasma cells. The characterization of specific entities is an area of difficulty in clinical practice. The International Myeloma Working Group has reviewed the criteria for diagnosis and classification with the aim of producing simple, easily used definitions based on routinely available investigations. In monoclonal gammopathy of undetermined significance (MGUS) or monoclonal gammopathy, unattributed/unassociated (MG[u]), the monoclonal protein is < 30 g/l and the bone marrow clonal cells < 10% with no evidence of multiple myeloma, other B-cell proliferative disorders or amyloidosis. In asymptomatic (smouldering) myeloma the M-protein is greater than or equal to 30 g/l and/or bone marrow clonal cells greater than or equal to 10% but no related organ or tissue impairment (ROTI)(end-organ damage), which is typically manifested by increased calcium, renal insufficiency, anaemia, or bone lesions (CRAB) attributed to the plasma cell proliferative process. Symptomatic myeloma requires evidence of ROTI. Non-secretory myeloma is characterized by the absence of an M-protein in the serum and urine, bone marrow plasmacytosis and ROTI. Solitary plasmacytoma of bone, extramedullary plasmacytoma and multiple solitary plasmacytomas (+/- recurrent) are also defined as distinct entities. The use of these criteria will facilitate comparison of therapeutic trial data. Evaluation of currently available prognostic factors may allow better definition of prognosis in multiple myeloma.

SHEA guideline for preventing nosocomial transmission of multidrug-resistant strains of Staphylococcus aureus and enterococcus.

Abstract: patients with MRSA or VRE usually acquire it via spread. The CDC has long-recommended contact precautions for patients colonized or infected with such pathogens. Most facilities have required this as policy, but have not actively identified colonized patients with sur veillance cultures, leaving most colonized patients undetected and unisolated. Many studies have shown control of endemic and/or epidemic MRSA and VRE infections using surveillance cultures and contact precautions, demonstrating consistency of evidence, high strength of association, reversibility, a dose gradient, and specificity for control with this approach. Adjunctive control measures are also discussed. CONCLUSION: Active surveillance cultures are essential to identify the reservoir for spread of MRSA and VRE infections and make control possible using the CDC’s long-recommended contact precautions (Infect Control Hosp Epidemiol 2003;24:362-386).

Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects.

Abstract: Previously we described a reliable method based on immunodepletion for isolating mesenchymal stem cells (MSCs) from murine bone marrow and showed that, after intracranial transplantation, the cells migrated throughout forebrain and cerebellum and adopted neural cell fates. Here we systemically administered MSCs purified by immunodepletion from male bleomycin (BLM)-resistant BALB/c mice into female BLM-sensitive C57BL/6 recipients and quantified engraftment levels in lung by real-time PCR. Male DNA accounted for 2.21 × 10-5% of the total lung DNA in control-treated mice but was increased 23-fold (P = 0.05) in animals exposed to BLM before MSC transplantation. Fluorescence in situ hybridization revealed that engrafted male cells were localized to areas of BLM-induced injury and exhibited an epithelium-like morphology. Moreover, purification of type II epithelial cells from the lungs of transplant recipients resulted in a 3-fold enrichment of male, donor-derived cells as compared with whole lung tissue. MSC administration immediately after exposure to BLM also significantly reduced the degree of BLM-induced inflammation and collagen deposition within lung tissue. Collectively, these studies demonstrate that murine MSCs home to lung in response to injury, adopt an epithelium-like phenotype, and reduce inflammation and collagen deposition in lung tissue of mice challenged with BLM.

Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate

Abstract: We used transneuronal transport of neurotropic viruses to examine the topographic organization of circuits linking the cerebellar cortex with the arm area of the primary motor cortex (M1) and with area 46 in dorsolateral prefrontal cortex of monkeys. Retrograde transneuronal transport of the CVS-11 (challenge virus strain 11) strain of rabies virus in cerebello-thalamocortical pathways revealed that the arm area of M1 receives input from Purkinje cells located primarily in lobules IV-VI of the cerebellar cortex. In contrast, transneuronal transport of rabies from area 46 revealed that it receives input from Purkinje cells located primarily in Crus II of the ansiform lobule. Thus, both M1 and area 46 are the targets of output from the cerebellar cortex. However, the output to each area of the cerebral cortex originates from Purkinje cells in different regions of the cerebellar cortex. Anterograde transneuronal transport of the H129 strain of herpes simplex virus type 1 (HSV1) revealed that neurons in the arm area of M1 project via the pons to granule cells primarily in lobules IV-VI, whereas neurons in area 46 project to granule cells primarily in Crus II. Together, the findings from rabies and HSV1 experiments indicate that the regions of the cerebellar cortex that receive input from M1 are the same as those that project to M1. Similarly, the regions of the cerebellar cortex that receive input from area 46 are the same as those that project to area 46. Thus, our observations suggest that multiple closed-loop circuits represent a fundamental architectural feature of cerebrocerebellar interactions.

Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.

Abstract: Background Women who have had a spontaneous preterm delivery are at greatly increased risk for preterm delivery in subsequent pregnancies. The results of several small trials have suggested that 17 alpha-hydroxyprogesterone caproate (17P) may reduce the risk of preterm delivery. Methods We conducted a double-blind, placebo-controlled trial involving pregnant women with a documented history of spontaneous preterm delivery. Women were enrolled at 19 clinical centers at 16 to 20 weeks of gestation and randomly assigned by a central data center, in a 2:1 ratio, to receive either weekly injections of 250 mg of 17P or weekly injections of an inert oil placebo; injections were continued until delivery or to 36 weeks of gestation. The primary outcome was preterm delivery before 37 weeks of gestation. Analysis was performed according to the intention-to-treat principle. Results Base-line characteristics of the 310 women in the progesterone group and the 153 women in the placebo group were similar. Treatment with 1...

National Standards for Diabetes Self-Management Education

Abstract: Diabetes self-management education (DSME) is a critical element of care for all people with diabetes and is necessary in order to improve patient outcomes. The National Standards for DSME are designed to define quality diabetes self-management education and to assist diabetes educators in a variety of settings to provide evidence-based education. Because of the dynamic nature of health care and diabetes-related research, these Standards are reviewed and revised approximately every 5 years by key organizations and federal agencies within the diabetes education community. A Task Force was jointly convened by the American Association of Diabetes Educators and the American Diabetes Association in the summer of 2006. Additional organizations that were represented included the American Dietetic Association, the Veteran's Health Administration, the Centers for Disease Control and Prevention, the Indian Health Service, and the American Pharmaceutical Association. Members of the Task Force included a person with diabetes; several health services researchers/behaviorists, registered nurses, and registered dietitians; and a pharmacist. The Task Force was charged with reviewing the current DSME standards for their appropriateness, relevance, and scientific basis. The Standards were then reviewed and revised based on the available evidence and expert consensus. The committee convened on 31 March 2006 and 9 September 2006, and the Standards were approved 25 March 2007. Diabetes self-management education (DSME) is the ongoing process of facilitating the knowledge, skill, and ability necessary for diabetes self-care. This process incorporates the needs, goals, and life experiences of the person with diabetes and is guided by evidence-based standards. The overall objectives of DSME are to support informed decision-making, self-care behaviors, problem-solving and active collaboration with the health care team and to improve clinical outcomes, health status, and quality of life. Before the review of the individual Standards, the Task Force identified overriding principles based on existing evidence that would …

Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women's Health Initiative randomized trial.

Abstract: Context In the Women's Health Initiative trial of estrogen-plus-progestin therapy, women assigned to active treatment had fewer fractures. Objective To test the hypothesis that the relative risk reduction of estrogen plus progestin on fractures differs according to risk factors for fractures. Design, setting, and participants Randomized controlled trial (September 1993-July 2002) in which 16 608 postmenopausal women aged 50 to 79 years with an intact uterus at baseline were recruited at 40 US clinical centers and followed up for an average of 5.6 years. Intervention Women were randomly assigned to receive conjugated equine estrogen, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). Main outcome measures All confirmed osteoporotic fracture events that occurred from enrollment to discontinuation of the trial (July 7, 2002); bone mineral density (BMD), measured in a subset of women (n = 1024) at baseline and years 1 and 3; and a global index, developed to summarize the balance of risks and benefits to test whether the risk-benefit profile differed across tertiles of fracture risk. Results Seven hundred thirty-three women (8.6%) in the estrogen-plus-progestin group and 896 women (11.1%) in the placebo group experienced a fracture (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.69-0.83). The effect did not differ in women stratified by age, body mass index, smoking status, history of falls, personal and family history of fracture, total calcium intake, past use of hormone therapy, BMD, or summary fracture risk score. Total hip BMD increased 3.7% after 3 years of treatment with estrogen plus progestin compared with 0.14% in the placebo group (P Conclusions This study demonstrates that estrogen plus progestin increases BMD and reduces the risk of fracture in healthy postmenopausal women. The decreased risk of fracture attributed to estrogen plus progestin appeared to be present in all subgroups of women examined. When considering the effects of hormone therapy on other important disease outcomes in a global model, there was no net benefit, even in women considered to be at high risk of fracture.

The Galaxy Luminosity Function and Luminosity Density at Redshift z = 0.1*

Abstract: Using a catalog of 147,986 galaxy redshifts and fluxes from the Sloan Digital Sky Survey (SDSS), we measure the galaxy luminosity density at z = 0.1 in five optical bandpasses corresponding to the SDSS bandpasses shifted to match their rest-frame shape at z = 0.1. We denote the bands 0.1u, 0.1g, 0.1r, 0.1i, 0.1z with λeff = (3216, 4240, 5595, 6792, 8111 A), respectively. To estimate the luminosity function, we use a maximum likelihood method that allows for a general form for the shape of the luminosity function, fits for simple luminosity and number evolution, incorporates the flux uncertainties, and accounts for the flux limits of the survey. We find luminosity densities at z = 0.1 expressed in absolute AB magnitudes in a Mpc3 to be (-14.10 ± 0.15, -15.18 ± 0.03, -15.90 ± 0.03, -16.24 ± 0.03, -16.56 ± 0.02) in (0.1u, 0.1g, 0.1r, 0.1i, 0.1z), respectively, for a cosmological model with Ω0 = 0.3, ΩΛ = 0.7, and h = 1 and using SDSS Petrosian magnitudes. Similar results are obtained using Sersic model magnitudes, suggesting that flux from outside the Petrosian apertures is not a major correction. In the 0.1r band, the best-fit Schechter function to our results has * = (1.49 ± 0.04) × 10-2 h3 Mpc-3, M* - 5 log10 h = -20.44 ± 0.01, and α = -1.05 ± 0.01. In solar luminosities, the luminosity density in 0.1r is (1.84 ± 0.04) × 108 h L0.1r,☉ Mpc-3. Our results in the 0.1g band are consistent with other estimates of the luminosity density, from the Two-Degree Field Galaxy Redshift Survey and the Millennium Galaxy Catalog. They represent a substantial change (~0.5 mag) from earlier SDSS luminosity density results based on commissioning data, almost entirely because of the inclusion of evolution in the luminosity function model.

Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone.

Abstract: Background Ewing's sarcoma and primitive neuroectodermal tumor of bone are closely related, highly malignant tumors of children, adolescents, and young adults. A new drug combination, ifosfamide and etoposide, was highly effective in patients with Ewing's sarcoma or primitive neuroectodermal tumor of bone who had a relapse after standard therapy. We designed a study to test whether the addition of these drugs to a standard regimen would improve the survival of patients with newly diagnosed disease. Methods Patients 30 years old or younger with Ewing's sarcoma, primitive neuroectodermal tumor of bone, or primitive sarcoma of bone were eligible. The patients were randomly assigned to receive 49 weeks of standard chemotherapy with doxorubicin, vincristine, cyclophosphamide, and dactinomycin or experimental therapy with these four drugs alternating with courses of ifosfamide and etoposide. Results A total of 518 patients met the eligibility requirements. Of 120 patients with metastatic disease, 62 were random...

Adult chronic rhinosinusitis: Definitions, diagnosis, epidemiology, and pathophysiology

Abstract: Chronic rhinosinusitis Chronic rhinosinusitis (CRS) is a term that has been used to describe a number of entities characterized by chronic symptoms of nasal and sinus inflammation or infection. There has been a lack of consensus regarding definitions and treatments because CRS may be a spectrum of diseases with a range of appropriate treatments. The absence of widely accepted definitions for CRS has resulted in a paucity of research directed at understanding its pathophysiology and has hampered efforts to improve treatment. A Task Force was convened by the Sinus and Allergy Health Partnership to summarize much of the current and important information available regarding the prevalence, economic impact, pathophysiology, common inflammatory mediators, and the role of infectious microbes such as bacteria and fungi in CRS. The goal is to establish a standard and usable definition. Through this thorough review of the literature and the expert input from Task Force members, a definition was developed that serves to create a consistent baseline so that many of the currently debated or unanswered questions may be addressed. The new and more-specific Task Force definition is that “ Chronic rhinosinusitis is a group of disorders characterized by inflammation of the mucosa of the nose and paranasal sinuses of at least 12 weeks duration.” Recommended criteria for making the diagnosis of CRS for both clinical care and research were also outlined.

Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus.

Abstract: Since the introduction of Laparoscopic Roux-en-Y gastric bypass (LRYGBP) in the early 1990s, several investigators have demonstrated that LRYGBP is as effective as open roux-en-Y gastric bypass (RYGBP) in achieving significant long-term weight loss (60–80% percent of excess body weight loss [%EWL]) in morbidly obese patients while significantly reducing perioperative morbidity and recovery time.1–5 In 2000, our group reported (n = 275 patients) a mean excess weight loss of 77% (mean body mass index [BMI] reduced from 48 to 27 kg/m2) at 30 months and a major morbidity and mortality rate of 3.3% and 0.4%, respectively.2 Quality of life was significantly improved and all obesity comorbidities, with the exception of depression, were significantly improved or resolved. Although that study did not focus specifically on type 2 diabetes mellitus (T2DM), we did find that 82% of T2DM patients (n = 18) achieved clinical resolution (withdrawal of all antidiabetic medication) whereas the remaining 18% had significant improvement. Other investigators have also demonstrated that not only Roux-en-Y gastric bypass but other bariatric operations may result in significant clinical improvement in T2DM after weight loss.2,5–13 However, little is known concerning the effect of weight loss surgery on the degree of glycemic control that is achieved and its impact on antidiabetic medication requirement. Furthermore, factors that may be associated with postoperative resolution versus improvement in diabetes have not been fully elucidated. The goal of this study then was to evaluate the effect of LRYGBP on morbidly obese patients with T2DM and their related comorbidites and diabetes-specific complications. Our hypothesis was that LRYGBP would result in sustained weight loss that would correspond to significant improvement in glycemic control, leading to clinical resolution or improvement in T2DM and related comorbidites and complications. We specifically evaluated postoperative outcomes, including surgical complications and weight loss as well as changes in fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1C), diabetic medication requirement, and changes in comorbidity and diabetes complications.

Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission

Abstract: The mesolimbic dopamine system is centrally involved in reward and goal-directed behavior, and it has been implicated in multiple psychiatric disorders. Understanding the mechanism by which dopamine participates in these activities requires comprehension of the dynamics of dopamine release. Here we report dissociable regulation of dopamine neuron discharge by two separate afferent systems in rats; inhibition of pallidal afferents selectively increased the population activity of dopamine neurons, whereas activation of pedunculopontine inputs increased burst firing. Only the increase in population activity increased ventral striatal dopamine efflux. After blockade of dopamine reuptake, however, enhanced bursting increased dopamine efflux three times more than did enhanced population activity. These results provide insight into multiple regulatory systems that modulate dopamine system function: burst firing induces massive synaptic dopamine release, which is rapidly removed by reuptake before escaping the synaptic cleft, whereas increased population activity modulates tonic extrasynaptic dopamine levels that are less influenced by reuptake.

Learning extraction patterns for subjective expressions

Abstract: This paper presents a bootstrapping process that learns linguistically rich extraction patterns for subjective (opinionated) expressions. High-precision classifiers label unannotated data to automatically create a large training set, which is then given to an extraction pattern learning algorithm. The learned patterns are then used to identify more subjective sentences. The bootstrapping process learns many subjective patterns and increases recall while maintaining high precision.

Objectifying Content Validity: Conducting a Content Validity Study in Social Work Research

Abstract: Social scientists frequently study complex constructs. Despite the plethora of measures for these constructs, researchers may need to create their own measure for a particular study. When a measure is created, psychometric testing is required, and the first step is to study the content validity of the measure. The purpose of this article is to demonstrate how to conduct a content validity study, including how to elicit the most from a panel of experts by collecting specific data. Instructions on how to calculate a content validity index, factorial validity index, and an interrater reliability index and guide for interpreting these indices are included. Implications regarding the value of conducting a content validity study for practitioners and researchers are discussed. Key words: constructs; content validity; measure; psychometric testing ********** Researchers in the social sciences study complex constructs for which valid and reliable measures are needed. The measures should be brief, clear, and easy to administer. Measures that are too long or difficult to read may result in a lowered response rate or inaccurate responses. In addition, the measure must be appropriate for use in the targeted population. For example, measures designed for use with heterogeneous populations may not be appropriate for a specific population with certain characteristics. A plethora of measures exist with known psychometric properties, but researchers may need to develop a new measure for a particular construct because no measure exists that operationalizes the construct as the researcher conceptualized it. In these circumstances, a content validity study should be conducted. VALIDITY Traditionally, three types of validity may be demonstrated: content, criterion, and construct validity. Content Validity Content validity refers to the extent to which the items on a measure assess the same content or how well the content material was sampled in the measure. Content validity can be characterized as face validity or logical validity. Face validity indicates that the measure appears to be valid, "on its face." Logical validity indicates a more rigorous process, such as using a panel of experts to evaluate the content validity of a measure. Nunnally and Bernstein (1994) did not distinguish among different types of content validity; but presented alternative ways of assessing content validity. They suggested evaluating content validity by demonstrating internal consistency through correlating the scores from the measure with another measure of the same construct and by showing change in posttest scores over pretest scores. Criterion Validity Criterion validity is demonstrated by finding a statistically significant relationship between a measure and a criterion (Nunnally & Bernstein, 1994). Criterion validity is considered the "gold standard," and usually a correlation is used to assess the statistical relationship. For example, the Graduate Record Examination (GRE) has been found to predict graduate school success (as measured by the first-year grade-point average) for certain disciplines (Rubio, Rubin, & Brennan, 2003). Three types of criterion validity are postdictive, concurrent, and predictive. If the criterion has occurred, the validity is postdictive. The validity is concurrent if the criterion exists at the same time as the construct measured. The GRE example demonstrates predictive validity, because graduate school success (criterion) occurs after taking the GRE (measure). According to Nunnally and Bernstein, a correlation of .30 indicates adequate criterion validity. Construct Validity Anastasi and Urbina (1997) described construct validity as "the extent to which the test may be said to measure a theoretical construct or trait" (p. 126). Three kinds of construct validity are factorial, known groups; and convergent and discriminant (or divergent) validity. …

Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

Abstract: Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. Background: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. Methods: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case- control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two- sided. Results: Breast cancer risk increased with increasing BMI (P-trend = .002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m(2) increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin- bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. Conclusion: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.

Production of α1,3-Galactosyltransferase-Deficient Pigs

Abstract: The enzyme alpha1,3-galactosyltransferase (alpha1,3GT or GGTA1) synthesizes alpha1,3-galactose (alpha1,3Gal) epitopes (Galalpha1,3Galbeta1,4GlcNAc-R), which are the major xenoantigens causing hyperacute rejection in pig-to-human xenotransplantation. Complete removal of alpha1,3Gal from pig organs is the critical step toward the success of xenotransplantation. We reported earlier the targeted disruption of one allele of the alpha1,3GT gene in cloned pigs. A selection procedure based on a bacterial toxin was used to select for cells in which the second allele of the gene was knocked out. Sequencing analysis demonstrated that knockout of the second allele of the alpha1,3GT gene was caused by a T-to-G single point mutation at the second base of exon 9, which resulted in inactivation of the alpha1,3GT protein. Four healthy alpha1,3GT double-knockout female piglets were produced by three consecutive rounds of cloning. The piglets carrying a point mutation in the alpha1,3GT gene hold significant value, as they would allow production of alpha1,3Gal-deficient pigs free of antibiotic-resistance genes and thus have the potential to make a safer product for human use.