Showing papers by "Vanderbilt University published in 2004"
TL;DR: The objective is to describe the performance of design-science research in Information Systems via a concise conceptual framework and clear guidelines for understanding, executing, and evaluating the research.
Abstract: Two paradigms characterize much of the research in the Information Systems discipline: behavioral science and design science The behavioral-science paradigm seeks to develop and verify theories that explain or predict human or organizational behavior The design-science paradigm seeks to extend the boundaries of human and organizational capabilities by creating new and innovative artifacts Both paradigms are foundational to the IS discipline, positioned as it is at the confluence of people, organizations, and technology Our objective is to describe the performance of design-science research in Information Systems via a concise conceptual framework and clear guidelines for understanding, executing, and evaluating the research In the design-science paradigm, knowledge and understanding of a problem domain and its solution are achieved in the building and application of the designed artifact Three recent exemplars in the research literature are used to demonstrate the application of these guidelines We conclude with an analysis of the challenges of performing high-quality design-science research in the context of the broader IS community
10,264 citations
TL;DR: The addition of bevacizumab to fluorouracil-based combination chemotherapy results in statistically significant and clinically meaningful improvement in survival among patients with metastatic colorectal cancer.
Abstract: background Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promising preclinical and clinical activity against metastatic colorectal cancer, particularly in combination with chemotherapy. methods Of 813 patients with previously untreated metastatic colorectal cancer, we randomly assigned 402 to receive irinotecan, bolus fluorouracil, and leucovorin (IFL) plus bevacizumab (5 mg per kilogram of body weight every two weeks) and 411 to receive IFL plus placebo. The primary end point was overall survival. Secondary end points were progression-free survival, the response rate, the duration of the response, safety, and the quality of life. results The median duration of survival was 20.3 months in the group given IFL plus bevacizumab, as compared with 15.6 months in the group given IFL plus placebo, corresponding to a hazard ratio for death of 0.66 (P<0.001). The median duration of progressionfree survival was 10.6 months in the group given IFL plus bevacizumab, as compared with 6.2 months in the group given IFL plus placebo (hazard ratio for disease progression, 0.54; P<0.001); the corresponding rates of response were 44.8 percent and 34.8 percent (P=0.004). The median duration of the response was 10.4 months in the group given IFL plus bevacizumab, as compared with 7.1 months in the group given IFL plus placebo (hazard ratio for progression, 0.62; P=0.001). Grade 3 hypertension was more common during treatment with IFL plus bevacizumab than with IFL plus placebo (11.0 percent vs. 2.3 percent) but was easily managed. conclusions The addition of bevacizumab to fluorouracil-based combination chemotherapy results in statistically significant and clinically meaningful improvement in survival among patients with metastatic colorectal cancer.
10,161 citations
TL;DR: Evidence is provided that psychological stress--both perceived stress and chronicity of stress--is significantly associated with higher oxidative stress, lower telomerase activity, and shorter telomere length, in peripheral blood mononuclear cells from healthy premenopausal women.
Abstract: Numerous studies demonstrate links between chronic stress and indices of poor health, including risk factors for cardiovascular disease and poorer immune function. Nevertheless, the exact mechanisms of how stress gets “under the skin” remain elusive. We investigated the hypothesis that stress impacts health by modulating the rate of cellular aging. Here we provide evidence that psychological stress— both perceived stress and chronicity of stress—is significantly associated with higher oxidative stress, lower telomerase activity, and shorter telomere length, which are known determinants of cell senescence and longevity, in peripheral blood mononuclear cells from healthy premenopausal women. Women with the highest levels of perceived stress have telomeres shorter on average by the equivalent of at least one decade of additional aging compared to low stress women. These findings have implications for understanding how, at the cellular level, stress may promote earlier onset of age-related diseases.
2,706 citations
New York University1, Radiation Therapy Oncology Group2, Johns Hopkins University3, Wayne State University4, Medical College of Wisconsin5, National Institutes of Health6, University of South Florida7, Vanderbilt University8, SUNY Downstate Medical Center9, University of Pennsylvania10, University of California, San Francisco11
TL;DR: Among high-risk patients with resected head and neck cancer, concurrent postoperative chemotherapy and radiotherapy significantly improve the rates of local and regional control and disease-free survival, however, the combined treatment is associated with a substantial increase in adverse effects.
Abstract: After a median follow-up of 45.9 months, the rate of local and regional control was significantly higher in the combined-therapy group than in the group given radiotherapy alone (hazard ratio for local or regional recurrence, 0.61; 95 percent confidence interval, 0.41 to 0.91; P=0.01). The estimated two-year rate of local and regional control was 82 percent in the combined-therapy group, as compared with 72 percent in the radiotherapy group. Disease-free survival was significantly longer in the combined-therapy group than in the radiotherapy group (hazard ratio for disease or death, 0.78; 95 percent confidence interval, 0.61 to 0.99; P=0.04), but overall survival was not (hazard ratio for death, 0.84; 95 percent confidence interval, 0.65 to 1.09; P=0.19). The incidence of acute adverse effects of grade 3 or greater was 34 percent in the radiotherapy group and 77 percent in the combined-therapy group (P<0.001). Four patients who received combined therapy died as a direct result of the treatment. conclusions Among high-risk patients with resected head and neck cancer, concurrent postoperative chemotherapy and radiotherapy significantly improve the rates of local and regional control and disease-free survival. However, the combined treatment is associated with a substantial increase in adverse effects.
2,665 citations
03 Nov 2004
TL;DR: The FTSP achieves its robustness by utilizing periodic flooding of synchronization messages, and implicit dynamic topology update and comprehensive error compensation including clock skew estimation, which is markedly better than that of the existing RBS and TPSN algorithms.
Abstract: Wireless sensor network applications, similarly to other distributed systems, often require a scalable time synchronization service enabling data consistency and coordination. This paper describes the Flooding Time Synchronization Protocol (FTSP), especially tailored for applications requiring stringent precision on resource limited wireless platforms. The proposed time synchronization protocol uses low communication bandwidth and it is robust against node and link failures. The FTSP achieves its robustness by utilizing periodic flooding of synchronization messages, and implicit dynamic topology update. The unique high precision performance is reached by utilizing MAC-layer time-stamping and comprehensive error compensation including clock skew estimation. The sources of delays and uncertainties in message transmission are analyzed in detail and techniques are presented to mitigate their effects. The FTSP was implemented on the Berkeley Mica2 platform and evaluated in a 60-node, multi-hop setup. The average per-hop synchronization error was in the one microsecond range, which is markedly better than that of the existing RBS and TPSN algorithms.
2,267 citations
TL;DR: It is revealed that fibroblasts have a more profound influence on the development and progression of carcinomas than was previously appreciated and this has important therapeutic implications.
Abstract: It is widely accepted that the development of carcinoma--the most common form of human cancer--is due to the accumulation of somatic mutations in epithelial cells. The behaviour of carcinomas is also influenced by the tumour microenvironment, which includes extracellular matrix, blood vasculature, inflammatory cells and fibroblasts. Recent studies reveal that fibroblasts have a more profound influence on the development and progression of carcinomas than was previously appreciated. These new findings have important therapeutic implications.
2,215 citations
TL;DR: It is demonstrated that peripheral tissues express self-sustained, rather than damped, circadian oscillations and the existence of organ-specific synchronizers of circadian rhythms at the cell and tissue level is suggested.
Abstract: Mammalian circadian rhythms are regulated by the suprachiasmatic nucleus (SCN), and current dogma holds that the SCN is required for the expression of circadian rhythms in peripheral tissues. Using a PERIOD2::LUCIFERASE fusion protein as a real-time reporter of circadian dynamics in mice, we report that, contrary to previous work, peripheral tissues are capable of self-sustained circadian oscillations for >20 cycles in isolation. In addition, peripheral organs expressed tissue-specific differences in circadian period and phase. Surprisingly, lesions of the SCN in mPer2Luciferase knockin mice did not abolish circadian rhythms in peripheral tissues, but instead caused phase desynchrony among the tissues of individual animals and from animal to animal. These results demonstrate that peripheral tissues express self-sustained, rather than damped, circadian oscillations and suggest the existence of organ-specific synchronizers of circadian rhythms at the cell and tissue level.
2,010 citations
University of Amsterdam1, Columbia University2, Rush University Medical Center3, Cornell University4, University of Washington5, National Institutes of Health6, Leiden University7, Imperial College London8, Vanderbilt University9, SUNY Downstate Medical Center10, Ohio State University11, St. Vincent's Health System12, University of North Carolina at Chapel Hill13, National University of Malaysia14, University of Paris15, University of Malaya16, Okayama University17, Federal University of São Paulo18, University of Tsukuba19
TL;DR: The main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies.
Abstract: The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving or = 50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions]. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.
2,004 citations
TL;DR: Bvacizumab in combination with carboplatin and paclitaxel improved overall response and time to progression in patients with advanced or recurrent non-small-cell lung cancer.
Abstract: Purpose To investigate the efficacy and safety of bevacizumab plus carboplatin and paclitaxel in patients with advanced or recurrent non-small-cell lung cancer. Patients and Methods In a phase II trial, 99 patients were randomly assigned to bevacizumab 7.5 (n = 32) or 15 mg/kg (n = 35) plus carboplatin (area under the curve = 6) and paclitaxel (200 mg/m2) every 3 weeks or carboplatin and paclitaxel alone (n = 32). Primary efficacy end points were time to disease progression and best confirmed response rate. On disease progression, patients in the control arm had the option to receive single-agent bevacizumab 15 mg/kg every 3 weeks. Results Compared with the control arm, treatment with carboplatin and paclitaxel plus bevacizumab (15 mg/kg) resulted in a higher response rate (31.5% v 18.8%), longer median time to progression (7.4 v 4.2 months) and a modest increase in survival (17.7 v 14.9 months). Of the 19 control patients that crossed over to single-agent bevacizumab, five experienced stable disease, and...
1,890 citations
TL;DR: The single most common cause of the withdrawal or restriction of the use of marketed drugs has been QT-interval prolongation associated with polymorphic ventricular tachycardia, or torsade de pointes, a condition that can be fatal.
Abstract: The single most common cause of the withdrawal or restriction of the use of marketed drugs has been QT-interval prolongation associated with polymorphic ventricular tachycardia, or torsade de pointes, a condition that can be fatal. This review summarizes the current knowledge about molecular and clinical predictors of drug-induced QT-interval prolongation and torsade de pointes and discusses how new molecular predictors of drug action might be incorporated into drug-development programs and clinical practice. A general approach to drugs suspected of causing this problem is presented.
1,696 citations
University of Amsterdam1, Columbia University2, Rush University Medical Center3, Cornell University4, University of Washington5, National Institutes of Health6, Leiden University7, Imperial College London8, Vanderbilt University9, SUNY Downstate Medical Center10, Ohio State University11, St. Vincent's Health System12, University of North Carolina at Chapel Hill13, National University of Malaysia14, University of Paris15, University of Malaya16, Okayama University17, Federal University of São Paulo18, University of Tsukuba19
TL;DR: The main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies.
TL;DR: Pulmonary arterial hypertension has a multifactorial pathobiology and recent genetic and pathophysiologic studies have emphasized the relevance of several mediators in this condition, including prostacyclin, nitric oxide, ET-1, angiopoietin- 1, serotonin, cytokines, chemokines, and members of the transforming-growth-factor-beta superfamily.
TL;DR: It is suggested that lower crustal foundering occurred within the North China craton during the Late Jurassic, and thus provides constraints on the timing of lithosphere removal beneath the NorthChina craton.
Abstract: Foundering of mafic lower continental crust into underlying convecting mantle has been proposed as one means to explain the unusually evolved chemical composition of Earth's continental crust, yet direct evidence of this process has been scarce. Here we report that Late Jurassic high-magnesium andesites, dacites and adakites (siliceous lavas with high strontium and low heavy-rare-earth element and yttrium contents) from the North China craton have chemical and petrographic features consistent with their origin as partial melts of eclogite that subsequently interacted with mantle peridotite. Similar features observed in adakites and some Archaean sodium-rich granitoids of the tonalite-trondhjemite-granodiorite series have been interpreted to result from interaction of slab melts with the mantle wedge. Unlike their arc-related counterparts, however, the Chinese magmas carry inherited Archaean zircons and have neodymium and strontium isotopic compositions overlapping those of eclogite xenoliths derived from the lower crust of the North China craton. Such features cannot be produced by crustal assimilation of slab melts, given the high Mg#, nickel and chromium contents of the lavas. We infer that the Chinese lavas derive from ancient mafic lower crust that foundered into the convecting mantle and subsequently melted and interacted with peridotite. We suggest that lower crustal foundering occurred within the North China craton during the Late Jurassic, and thus provides constraints on the timing of lithosphere removal beneath the North China craton.
TL;DR: Functional magnetic resonance imaging is used to suggest that activity in the posterior parietal cortex is tightly correlated with the limited amount of scene information that can be stored in visual short-term memory, and suggests that the posterior PAR cortex is a key neural locus of the authors' impoverished mental representation of the visual world.
Abstract: At any instant, our visual system allows us to perceive a rich and detailed visual world. Yet our internal, explicit representation of this visual world is extremely sparse: we can only hold in mind a minute fraction of the visual scene. These mental representations are stored in visual short-term memory (VSTM). Even though VSTM is essential for the execution of a wide array of perceptual and cognitive functions, and is supported by an extensive network of brain regions, its storage capacity is severely limited. With the use of functional magnetic resonance imaging, we show here that this capacity limit is neurally reflected in one node of this network: activity in the posterior parietal cortex is tightly correlated with the limited amount of scene information that can be stored in VSTM. These results suggest that the posterior parietal cortex is a key neural locus of our impoverished mental representation of the visual world.
TL;DR: TGF-β signaling in fibroblasts modulates the growth and oncogenic potential of adjacent epithelia in selected tissues and is associated with intraepithelial neoplasia in prostate and invasive squamous cell carcinoma of the forestomach.
Abstract: Stromal cells can have a significant impact on the carcinogenic process in adjacent epithelia. The role of transforming growth factor-beta (TGF-beta) signaling in such epithelial-mesenchymal interactions was determined by conditional inactivation of the TGF-beta type II receptor gene in mouse fibroblasts (Tgfbr2fspKO). The loss of TGF-beta responsiveness in fibroblasts resulted in intraepithelial neoplasia in prostate and invasive squamous cell carcinoma of the forestomach, both associated with an increased abundance of stromal cells. Activation of paracrine hepatocyte growth factor (HGF) signaling was identified as one possible mechanism for stimulation of epithelial proliferation. Thus, TGF-beta signaling in fibroblasts modulates the growth and oncogenic potential of adjacent epithelia in selected tissues.
TL;DR: This article found that teachers who were provided with mentors from the same subject field and who participated in collective induction activities, such as planning and collaboration with other teachers, were less likely to leave the teaching occupation after their first year of teaching.
Abstract: In recent years there has been an increase in the number of programs offering support, guidance, and orientation for beginning teachers during the transition into their first teaching job. This study examines whether such programs—collectively known as induction—have a positive effect on the retention of beginning teachers. The data used in the analysis are from the nationally representative 1999–2000 Schools and Staffing Survey. The results indicate that beginning teachers who were provided with mentors from the same subject field and who participated in collective induction activities, such as planning and collaboration with other teachers, were less likely to move to other schools and less likely to leave the teaching occupation after their first year of teaching.
TL;DR: It is shown that although acute injury, acute inflammation, or transient parietal cell loss within the stomach do not lead to BMDC recruitment, chronic infection of C57BL/6 mice with Helicobacter induces repopulation of the stomach with BMDCs, suggesting that epithelial cancers can originate from marrow-derived sources and thus have broad implications for the multistep model of cancer progression.
Abstract: Epithelial cancers are believed to originate from transformation of tissue stem cells. However, bone marrow-derived cells (BMDCs), which are frequently recruited to sites of tissue injury and inflammation, might also represent a potential source of malignancy. We show that although acute injury, acute inflammation, or transient parietal cell loss within the stomach do not lead to BMDC recruitment, chronic infection of C57BL/6 mice with Helicobacter, a known carcinogen, induces repopulation of the stomach with BMDCs. Subsequently, these cells progress through metaplasia and dysplasia to intraepithelial cancer. These findings suggest that epithelial cancers can originate from marrow-derived sources and thus have broad implications for the multistep model of cancer progression.
Journal Article•
Tufts University1, Wake Forest University2, Oregon Health & Science University3, Indiana University4, Albany College of Pharmacy and Health Sciences5, Rush University Medical Center6, Vanderbilt University7, East Carolina University8, University of Illinois at Chicago9, Beaumont Hospital10, Johns Hopkins University11, Cleveland Clinic12, University of Wisconsin-Madison13, University of Texas at Austin14, University of Pittsburgh15, Virginia Commonwealth University16, Texas Tech University Health Sciences Center17, National Institutes of Health18, University of Virginia19
TL;DR: The purpose of the Executive Summary is to provide a "stand-alone" summary of the background, scope, methods, and key recommendations, as well as the complete text of the guideline statements.
TL;DR: This perspective article seeks to clarify which cells fall under the NKT-cell umbrella, and which might be best considered as separate.
Abstract: Recent years have seen so-called natural killer T (NKT) cells emerge as important regulators of the immune response. The existence of NKT-cell subsets, and other types of T cell that resemble NKT cells, is an ongoing source of confusion in the literature. This perspective article seeks to clarify which cells fall under the NKT-cell umbrella, and which might be best considered as separate.
TL;DR: Evidence is provided that Gr+CD11b+ cells of immune origin induced by tumors directly contribute to tumor growth and vascularization by producing MMP9 and differentiating into ECs.
Vanderbilt University1, University of Southern California2, University of Texas MD Anderson Cancer Center3, University of Wisconsin-Madison4, University of California, Los Angeles5, National Center for Genome Resources6, Portland VA Medical Center7, University of Colorado Boulder8, University of Pennsylvania9, Hannover Medical School10, Johns Hopkins University11, Oregon Health & Science University12, Cornell University13, University of Michigan14, University of Tennessee Health Science Center15, Washington University in St. Louis16, University of Toronto17, University of Memphis18, Medical Research Council19, University of Massachusetts Medical School20, Hebrew University of Jerusalem21, Université de Montréal22, Purdue University23, University of California, Davis24, Academy of Sciences of the Czech Republic25, University at Buffalo26, Emory University27, University of Cincinnati28, University of Texas Southwestern Medical Center29, New York University30, University of Groningen31, Rutgers University32, Stanford University33, Max Planck Society34, National Institutes of Health35, University of Alabama at Birmingham36, International Livestock Research Institute37, Heidelberg University38, Medical College of Wisconsin39, Icahn School of Medicine at Mount Sinai40, Oak Ridge National Laboratory41, Charité42, University of Antwerp43, RWTH Aachen University44, Paul Sabatier University45, University of California, San Francisco46, McGill University47, Pasteur Institute48, University of Western Australia49, Yale University50, University of Oxford51, Case Western Reserve University52, Roswell Park Cancer Institute53, University of Kentucky54, University of Helsinki55, University of Nebraska–Lincoln56, Harvard University57, Merck & Co.58, King's College London59, Northwestern University60, Shriners Hospitals for Children61, Thomas Jefferson University62, Novartis63, University of North Carolina at Chapel Hill64, Southern Illinois University Carbondale65, University of Rochester66
TL;DR: The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way the authors approach human health and disease.
Abstract: The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease.
TL;DR: It is shown that mitochondria lacking ANT could still be induced to undergo permeability transition, resulting in release of cytochrome c.
Abstract: A sudden increase in permeability of the inner mitochondrial membrane, the so-called mitochondrial permeability transition, is a common feature of apoptosis and is mediated by the mitochondrial permeability transition pore (mtPTP). It is thought that the mtPTP is a protein complex formed by the voltage-dependent anion channel, members of the pro- and anti-apoptotic BAX-BCL2 protein family, cyclophilin D, and the adenine nucleotide (ADP/ATP) translocators (ANTs)1,2. The latter exchange mitochondrial ATP for cytosolic ADP and have been implicated in cell death. To investigate the role of the ANTs in the mtPTP, we genetically inactivated the two isoforms of ANT3,4,5 in mouse liver and analysed mtPTP activation in isolated mitochondria and the induction of cell death in hepatocytes. Mitochondria lacking ANT could still be induced to undergo permeability transition, resulting in release of cytochrome c. However, more Ca2+ than usual was required to activate the mtPTP, and the pore could no longer be regulated by ANT ligands. Moreover, hepatocytes without ANT remained competent to respond to various initiators of cell death. Therefore, ANTs are non-essential structural components of the mtPTP, although they do contribute to its regulation.
Ohio State University1, University of Alabama at Birmingham2, University of Texas Southwestern Medical Center3, National Institutes of Health4, George Washington University5, University of Utah6, University of Chicago7, University of Pittsburgh8, Wake Forest University9, Thomas Jefferson University10, Wayne State University11, Columbia University12, University of Cincinnati13, Brown University14, Northwestern University15, University of Miami16, University of Tennessee Health Science Center17, University of Texas at San Antonio18, University of North Carolina at Chapel Hill19, University of Texas at Austin20, Case Western Reserve University21, Vanderbilt University22
TL;DR: The proportion of women who attempt vaginal delivery after prior cesarean delivery has decreased largely because of concern about safety, and the absolute and relative risks associated with a trial of labor in women with a history of cesAREan delivery are uncertain.
Abstract: background The proportion of women who attempt vaginal delivery after prior cesarean delivery has decreased largely because of concern about safety The absolute and relative risks associated with a trial of labor in women with a history of cesarean delivery, as compared with elective repeated cesarean delivery without labor, are uncertain
TL;DR: This article found that teachers who were provided with mentors from the same subject field and who participated in collective induction activities, such as planning and collaboration with other teachers, were less likely to leave the teaching occupation after their first year of teaching.
Abstract: In recent years there has been an increase in the number of programs offering support, guidance, and orientation for beginning teachers during the transition into their first teaching job. This study examines whether such programs—collectively known as induction—have a positive effect on the retention of beginning teachers. The data used in the analysis are from the nationally representative 1999–2000 Schools and Staffing Survey. The results indicate that beginning teachers who were provided with mentors from the same subject field and who participated in collective induction activities, such as planning and collaboration with other teachers, were less likely to move to other schools and less likely to leave the teaching occupation after their first year of teaching.
TL;DR: A review of the literature on business incubators and business incubation can be found in this paper, focusing on the primary research orientations, i.e. studies centering on incubator development, incubator configurations, incubatee development, and incubator-incubation impacts.
Abstract: This article systematically reviews the literature on business incubators and business incubation. Focusing on the primary research orientations—i.e. studies centering on incubator development, incubator configurations, incubatee development, incubator-incubation impacts, and theorizing about incubators-incubation—problems with extant research are analyzed and opportunities for future research are identified. From our review, it is clear that research has just begun to scratch the surface of the incubator-incubation phenomenon. While much attention has been devoted to the description of incubator facilities, less attention has been focused on the incubatees, the innovations they seek to diffuse, and the incubation outcomes that have been achieved. As interest in the incubator-incubation concept continues to grow, new research efforts should focus not only on these under-researched units of analysis, but also on the incubation process itself.
TL;DR: SNPs in MDR1 in relation to population frequencies, drug levels, and phenotypes are outlined and issues relating to M DR1 haplotypes, environmental factors, and study design, as potential confounding factors of the observed MDR 1 polymorphism effect in vivo, are discussed.
Abstract: Drug transporters are increasingly recognized to be important to drug disposition and response. P-glycoprotein, the encoded product of the human MDR1 (ABCB1) gene, is of particular clinical relevance in that this transporter has broad substrate specificity, including a variety of structurally divergent drugs in clinical use today. Moreover, expression of this efflux transporter in certain tissue compartments such as the gastrointestinal tract and brain capillary endothelial cells limits oral absorption and central nervous system entry of many drugs. Recently, a number of single-nucleotide polymorphisms (SNPs) in MDR1 have been identified. An increasing number of studies have also implicated certain commonly occurring SNPs in MDR1 in problems including altered drug levels and host susceptibility to diseases such as Parkinson's disease, inflammatory bowel disease, refractory seizures, and CD4 cell recovery during human immunodeficiency virus therapy. However, in many such cases, the reported effects of MDR1 SNPs have been inconsistent and, in some cases, conflicting. In this review SNPs in MDR1 in relation to population frequencies, drug levels, and phenotypes are outlined. In addition, issues relating to MDR1 haplotypes, environmental factors, and study design, as potential confounding factors of the observed MDR1 polymorphism effect in vivo, are also discussed.
TL;DR: Human metapneumovirus infection is a leading cause of respiratory tract infection in the first years of life, with a spectrum of disease similar to that of respiratory syncytial virus.
Abstract: Background We sought to determine the role of human metapneumovirus in lower respiratory tract illness in previously healthy infants and children. Methods We tested nasal-wash specimens, obtained over a 25-year period from otherwise healthy children presenting with acute respiratory tract illness, for human metapneumovirus. Results A viral cause other than human metapneumovirus was determined for 279 of 687 visits for acute lower respiratory tract illness (41 percent) by 463 children in a population of 2009 infants and children prospectively seen from 1976 to 2001. There were 408 visits for lower respiratory tract illness by 321 children for which no cause was identified. Of these 321 children, specimens from 248 were available. Forty-nine of these 248 specimens (20 percent) contained human metapneumovirus RNA or viable virus. Thus, 20 percent of all previously virus-negative lower respiratory tract illnesses were attributable to human metapneumovirus, which means that 12 percent of all lower respiratory ...
TL;DR: Evidence for screening in susceptible patient groups and the approach to diagnosing PAH when it is suspected are reviewed, and specific recommendations for applying this evidence to clinical practice are provided.
TL;DR: The pharmacology and signaling of the nine known prostaglandin GPCRs are discussed and the specific roles that these receptors play in inflammation and immune modulation are highlighted.
TL;DR: The Brief Resilient Coping Scale is introduced, a 4-item measure designed to capture tendencies to cope with stress in a highly adaptive manner and may be useful for identifying individuals in need of interventions designed to enhance resilient coping skills.
Abstract: This article introduces the Brief Resilient Coping Scale (BRCS), a 4-item measure designed to capture tendencies to cope with stress in a highly adaptive manner. Two samples of individuals with rheumatoid arthritis (ns = 90 and 140) provide evidence for the reliability and validity of the BRCS. The BRCS has adequate internal consistency and test-retest reliability. Convergent validity of the scale is demonstrated by predictable correlations with measures of personal coping resources (e.g., optimism, helplessness, self-efficacy), pain coping behaviors, and psychological well-being. Resilient coping, as assessed by the BRCS, also buffers the effects of high levels of arthritis-related and non-arthritis-related stressors on depressive symptoms. The sensitivity of the BRCS to changes associated with a cognitive-behavioral intervention is also demonstrated. The BCRS may be useful for identifying individuals in need of interventions designed to enhance resilient coping skills.