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Showing papers by "Tulane University published in 2008"


Journal ArticleDOI
TL;DR: A revised Perdew-Burke-Ernzerhof generalized gradient approximation is introduced that improves equilibrium properties of densely packed solids and their surfaces.
Abstract: Popular modern generalized gradient approximations are biased toward the description of free-atom energies. Restoration of the first-principles gradient expansion for exchange over a wide range of density gradients eliminates this bias. We introduce a revised Perdew-Burke-Ernzerhof generalized gradient approximation that improves equilibrium properties of densely packed solids and their surfaces.

7,797 citations


Journal ArticleDOI
TL;DR: Overweight and obesity are important clinical and public health burdens worldwide and national programs for the prevention and treatment of overweight, obesity and related comorbidities and mortalities should be a public health priority.
Abstract: Objectives: To estimate the overall prevalence and absolute burden of overweight and obesity in the world and in various regions in 2005 and to project the global burden in 2030. Design: Pooling analysis Data Sources: We identified sex- and age-specific prevalence of overweight and obesity in representative population samples from 106 countries, which cover approximately 88% of the world population, using MEDLINE and other computerized databases, supplemented by a manual search of references from retrieved articles. Methods: Sex- and age-specific prevalence of overweight and obesity were applied to the 2005 population to estimate the numbers of overweight and obese individuals in each country, each world region and the entire world. In addition, the prevalence, with and without adjusting for secular trends, were applied to the 2030 population projections to forecast the number of overweight and obese individuals in 2030. Results: Overall, 23.2% (95% confidence interval 22.8-23.5%) of the world's adult population in 2005 was overweight (24.0% in men (23.4-24.5%) and 22.4% in women (21.9-22.9%)), and 9.8% (9.6-10.0%) was obese (7.7% in men (7.4-7.9%) and 11.9% in women (11.6-12.2%)). The estimated total numbers of overweight and obese adults in 2005 were 937 million (922-951 million) and 396 million (388-405 million), respectively. By 2030, the respective number of overweight and obese adults was projected to be 1.35 billion and 573 million individuals without adjusting for secular trends. If recent secular trends continue unabated, the absolute numbers were projected to total 2.16 billion overweight and 1.12 billion obese individuals. Conclusions: Overweight and obesity are important clinical and public health burdens worldwide. National programs for the prevention and treatment of overweight, obesity and related comorbidities and mortalities should be a public health priority.

2,774 citations


Journal ArticleDOI
TL;DR: In this paper, the effects of androgen treatment of hypogonadal men on multiple target organs and the recent studies show short-term beneficial effects of testosterone in older men that are similar to those in younger men.
Abstract: Demographic data clearly demonstrate that the percentage of the population in the older age group is increasing. Androgen deficiency in the aging male has become a topic of increasing interest and debate throughout the world. Cross-sectional and longitudinal data indicate that the testosterone falls progressively with age and that a significant percentage of men over the age of 60 years have serum testosterone levels that are below the lower limits of young adult (age 20–30 years) men (1–4). The principal questions raised by these observations are whether older hypogonadal men will benefit from testosterone treatment and what will be the risks associated with such intervention. The past decade has brought evidence of benefit of androgen treatment of hypogonadal men on multiple target organs and the recent studies show short-term beneficial effects of testosterone in older men that are similar to those in younger men. This has been comprehensively reviewed and summarized by the Institute of Medicine in ‘Testosterone and Aging: Clinical Research Directions’ (5). Long-term data on the effects of testosterone treatment in the older population are limited mainly to effects on body composition and bone mass (6–11). Key questions of the effects of testosterone on patient reported outcomes and functional benefits that may retard physical or mental frailty of the elderly or improve the quality of life are not yet available. Specific risk data on the prostate and cardiovascular systems are needed.

968 citations


Journal ArticleDOI
01 Jun 2008-Methods
TL;DR: Methods for the isolation, expansion and differentiation of ASCs are presented and described in detail and can be applied to adipose tissues from other species with minimal modifications.

965 citations


Journal ArticleDOI
TL;DR: Genetic variation at the MYH9 locus substantially explains the increased burden of FSGS and hypertensive ESKD among African Americans.
Abstract: The increased burden of chronic kidney and end-stage kidney diseases (ESKD) in populations of African ancestry has been largely unexplained. To identify genetic variants predisposing to idiopathic and HIV-1–associated focal segmental glomerulosclerosis (FSGS), we carried out an admixture-mapping linkage-disequilibrium genome scan on 190 African American individuals with FSGS and 222 controls. We identified a chromosome 22 region with a genome-wide logarithm of the odds (lod) score of 9.2 and a peak lod of 12.4 centered on MYH9, a functional candidate gene expressed in kidney podocytes. Multiple MYH9 SNPs and haplotypes were recessively associated with FSGS, most strongly a haplotype spanning exons 14 through 23 (OR ¼ 5.0, 95% CI ¼ 3.5–7.1; P ¼ 4 � 10 � 23 , n ¼ 852). This association extended to hypertensive ESKD (OR ¼ 2.2, 95% CI ¼ 1.5–3.4; n ¼ 433), but not type 2 diabetic ESKD (n ¼ 476). Genetic variation at the MYH9 locus substantially explains the increased burden of FSGS and hypertensive ESKD among African Americans.

679 citations


Journal ArticleDOI
TL;DR: Patients in all 3 treatments improved substantially on PTSD and depression, the primary measures, and improved on other indices of adjustment, but there were significant group differences in symptom reduction during the course of treatment whereby the CPT-C condition reported greater improvement in PTSD than the WA condition.
Abstract: The purpose of this experiment was to conduct a dismantling study of cognitive processing therapy in which the full protocol was compared with its constituent components—cognitive therapy only (CPT-C) and written accounts (WA)—for the treatment of posttraumatic stress disorder (PTSD) and comorbid symptoms. The intent-to-treat (ITT) sample included 150 adult women with PTSD who were randomized into 1 of the 3 conditions. Each condition consisted of 2 hr of therapy per week for 6 weeks; blind assessments were conducted before treatment, 2 weeks following the last session, and 6 months following treatment. Measures of PTSD and depression were collected weekly to examine the course of recovery during treatment as well as before and after treatment. Secondary measures assessed anxiety, anger, shame, guilt, and dysfunctional cognitions. Independent ratings of adherence and competence were also conducted. Analyses with the ITT sample and with study completers indicate that patients in all 3 treatments improved substantially on PTSD and depression, the primary measures, and improved on other indices of adjustment. However, there were significant group differences in symptom reduction during the course of treatment whereby the CPT-C condition reported greater improvement in PTSD than the WA condition.

678 citations


Journal ArticleDOI
TL;DR: In this article, the evolution of superconductivity and the phase diagram of the ternary Fe-based compounds were studied and a superconducting phase was discovered in the $0.3lxl1.0$ range, which exhibits an incommensurate antiferromagnetic order.
Abstract: We report our study of the evolution of superconductivity and the phase diagram of the ternary $\text{Fe}{({\text{Se}}_{1\ensuremath{-}x}{\text{Te}}_{x})}_{0.82}$ $(0\ensuremath{\le}x\ensuremath{\le}1.0)$ system. We discovered a superconducting phase with ${T}_{c,\text{max}}=14\text{ }\text{K}$ in the $0.3lxl1.0$ range. This superconducting phase is suppressed when the sample composition approaches the end member ${\text{FeTe}}_{0.82}$, which exhibits an incommensurate antiferromagnetic order. We discuss the relationship between the superconductivity and magnetism of this material system in terms of recent results from neutron-scattering measurements. Our results and analyses suggest that superconductivity in this class of Fe-based compounds is associated with magnetic fluctuations and therefore may be unconventional in nature.

591 citations


Journal ArticleDOI
TL;DR: In this article, the effects of TMT functional diversity on firm performance were investigated in the context of 207 U.S. firms in 11 industries and found that the effect of functional diversity was positively associated with the proportion of top management team members with offices in the same location.
Abstract: Prior findings on the association between top management team (TMT) functional diversity and firm performance have been inconsistent. We consider the moderating effects of internal context (colocation of TMT members) and external context (environmental uncertainty) on the TMT diversity-firm performance relationship. Additionally, we consider both dominant and intrapersonal functional diversity. In our results from 207 U.S. firms in 11 industries, the effects of TMT functional diversity on firm performance become more positive as the proportion of TMT members with offices in the same location increases. The effects of intrapersonal functional diversity also become more positive as environmental uncertainty increases.

538 citations


Journal ArticleDOI
TL;DR: Terrlipressin is an effective treatment to improve renal function in HRS type 1 and transplantation-free survival was similar between study groups; HRS reversal significantly improved survival at day 180.

534 citations


Posted Content
TL;DR: In this paper, the authors investigated the relation between stock liquidity and firm performance and found that firms with liquid stocks have better performance as measured by the firm market-to-book ratio.
Abstract: This paper investigates the relation between stock liquidity and firm performance. The study documents that firms with liquid stocks have better performance as measured by the firm market-to-book ratio. This result is robust to the inclusion of industry or firm fixed effects, a control for idiosyncratic risk, a control for endogenous liquidity using two stage least squares, and the use of alternative measures of liquidity. To identify the causal effect of liquidity on firm performance, we study an exogenous shock to liquidity --- the decimalization of stock trading --- and document that the increase in liquidity around decimalization improves firm performance. The causes of liquidity’s beneficial effect are investigated: Liquidity increases the information content of market prices and of performance sensitive managerial compensation. Finally, momentum trading, analyst coverage, investor overreaction, and the effect of liquidity on discount rates or expected returns do not appear to drive the results.

480 citations


Journal ArticleDOI
TL;DR: The findings suggest the possible importance of small neighbourhood food stores and their fresh produce availability in affecting fruit and vegetable intake, particularly for urban neighbourhoods with a greater concentration of small food stores.
Abstract: Objective: Previous studies on the relationship of dietary intake to the neighbourhood food environment have focused on access to supermarkets, quantified by geographic distance or store concentration measures. However, in-store food availability may also be an important determinant, particularly for urban neighbourhoods with a greater concentration of small food stores. This study synthesises both types of information - store access and in-store availability - to determine their potential relationship to fruit and vegetable consumption. Design: Residents in four census tracts were surveyed in 2001 about their fruit and vegetable intake. Household distances to food stores in these and surrounding tracts were obtained using geographical information system mapping techniques. In-store fruit and vegetable availability was measured by linear shelf space. Multivariate linear regression models were used to measure the association of these neighbourhood availability measures with consumption. Setting: Four contiguous census tracts in central-city New Orleans. Subjects: A random sample of 102 households. Results: Greater fresh vegetable availability within 100m of a residence was a positive predictor of vegetable intake; each additional metre of shelf space was associated with 0.35 servings per day of increased intake. Fresh fruit availability was not associated with intake, although having a small food store within this same distance was a marginal predictor of fruit consumption. Conclusions: The findings suggest the possible importance of small neighbourhood food stores and their fresh produce availability in affecting fruit and vegetable intake.

Journal ArticleDOI
TL;DR: It is shown that RDS is an effective technique, when designed and implemented appropriately, to sample most-at-risk populations for HIV biological and behavioral surveys.
Abstract: To determine operational and analytical characteristics of respondent-driven sampling (RDS) in international settings and to explore factors that may affect recruitment of most-at-risk populations using RDS, we reviewed HIV biological and behavioral surveillance studies that used this method outside of the United States. We identified 123 eligible studies, 59 from Europe, 40 from Asia and the Pacific, 14 from Latin America, seven from Africa and three from Oceania. Studies collectively recruited 32,298 participants between 2003 and 2007; 53% of studies were conducted among injecting drug users, which generally had faster recruitment compared with studies among sex workers. All but 13 studies reached > or = 90% of their intended sample size, and six studies failed to reach equilibrium for key variables. This review has shown that RDS is an effective technique, when designed and implemented appropriately, to sample most-at-risk populations for HIV biological and behavioral surveys.

Journal ArticleDOI
TL;DR: A novel TLR‐driven stress and immune modulating response for hMSCs that is critical to consider in the design of stem cell‐based therapies is defined.
Abstract: Adult human bone marrow-derived mesenchymal stem cells (hMSCs) are under study as therapeutic delivery agents that assist in the repair of damaged tissues. To achieve the desired clinical outcomes for this strategy requires a better understanding of the mechanisms that drive the recruitment, migration, and engraftment of hMSCs to the targeted tissues. It is known that hMSCs are recruited to sites of stress or inflammation to fulfill their repair function. It is recognized that toll-like receptors (TLRs) mediate stress responses of other bone marrow-derived cells. This study explored the role of TLRs in mediating stress responses of hMSCs. Accordingly, the presence of TLRs in hMSCs was initially established by reverse transcription-polymerase chain reaction assays. Flow cytometry and fluorescence immunocytochemical analyses confirmed these findings. The stimulation of hMSCs with TLR agonists led to the activation of downstream signaling pathways, including nuclear factor kappaB, AKT, and MAPK. Consequently, activation of these pathways triggered the induction and secretion of cytokines, chemokines, and related TLR gene products as established from cDNA array, immunoassay, and cytokine antibody array analyses. Interestingly, the unique patterns of affected genes, cytokines, and chemokines measured identify these receptors as critical players in the clinically established immunomodulation observed for hMSCs. Lastly, hMSC migration was promoted by TLR ligand exposure as demonstrated by transwell migration assays. Conversely, disruption of TLRs by neutralizing TLR antibodies compromised hMSC migration. This study defines a novel TLR-driven stress and immune modulating response for hMSCs that is critical to consider in the design of stem cell-based therapies.


Journal ArticleDOI
TL;DR: This work provides comprehensive data and improved methods for studying the role of commensal microbiota in macaque models of GI diseases and provides a model for the large-scale screening of the human gut microbiome.
Abstract: The vertebrate gut harbors a vast community of bacterial mutualists, the composition of which is modulated by the host immune system. Many gastrointestinal (GI) diseases are expected to be associated with disruptions of host-bacterial interactions, but relatively few comprehensive studies have been reported. We have used the rhesus macaque model to investigate forces shaping GI bacterial communities. We used DNA bar coding and pyrosequencing to characterize 141,000 sequences of 16S rRNA genes obtained from 100 uncultured GI bacterial samples, allowing quantitative analysis of community composition in health and disease. Microbial communities of macaques were distinct from those of mice and humans in both abundance and types of taxa present. The macaque communities differed among samples from intestinal mucosa, colonic contents, and stool, paralleling studies of humans. Communities also differed among animals, over time within individual animals, and between males and females. To investigate changes associated with disease, samples of colonic contents taken at necropsy were compared between healthy animals and animals with colitis and undergoing antibiotic therapy. Communities from diseased and healthy animals also differed significantly in composition. This work provides comprehensive data and improved methods for studying the role of commensal microbiota in macaque models of GI diseases and provides a model for the large-scale screening of the human gut microbiome.


Journal ArticleDOI
TL;DR: In this article, a series of radiocarbon-dated sediment cores from the Mississippi Delta were used to analyse late Holocene deposits and assess compaction rates, and they found that millennial-scale compaction rate primarily associated with peat can reach 5mm per year, values that exceed recent model predictions.
Abstract: Coastal subsidence causes sea-level rise, shoreline erosion and wetland loss, which poses a threat to coastal populations. This is especially evident in the Mississippi Delta in the southern United States, which was devastated by Hurricane Katrina in 2005. The loss of protective wetlands is considered a critical factor in the extensive flood damage. The causes of subsidence in coastal Louisiana, attributed to factors as diverse as shallow compaction and deep crustal processes, remain controversial. Current estimates of subsidence rates vary by several orders of magnitude. Here, we use a series of radiocarbon-dated sediment cores from the Mississippi Delta to analyse late Holocene deposits and assess compaction rates. We find that millennial-scale compaction rates primarily associated with peat can reach 5mm per year, values that exceed recent model predictions. Locally and on timescales of decades to centuries, rates are likely to be 10 mm or more per year. We conclude that compaction of Holocene strata contributes significantly to the exceptionally high rates of relative sea-level rise and coastal wetland loss in the Mississippi Delta, and is likely to cause subsidence in other organic-rich and often densely populated coastal plains.

Journal ArticleDOI
TL;DR: Consumption of green leafy vegetables and fruit was associated with a lower hazard of diabetes, whereas consumption of fruit juices may be associated with an increased hazard among women.
Abstract: OBJECTIVE—The purpose of this study was to examine the association between fruit, vegetable, and fruit juice intake and development of type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 71,346 female nurses aged 38–63 years who were free of cardiovascular disease, cancer, and diabetes in 1984 were followed for 18 years, and dietary information was collected using a semiquantitative food frequency questionnaire every 4 years. Diagnosis of diabetes was self-reported. RESULTS—During follow-up, 4,529 cases of diabetes were documented, and the cumulative incidence of diabetes was 7.4%. An increase of three servings/day in total fruit and vegetable consumption was not associated with development of diabetes (multivariate-adjusted hazard ratio 0.99 [95% CI 0.94–1.05]), whereas the same increase in whole fruit consumption was associated with a lower hazard of diabetes (0.82 [0.72–0.94]). An increase of 1 serving/day in green leafy vegetable consumption was associated with a modestly lower hazard of diabetes (0.91 [0.84–0.98]), whereas the same change in fruit juice intake was associated with an increased hazard of diabetes (1.18 [1.10–1.26]). CONCLUSIONS—Consumption of green leafy vegetables and fruit was associated with a lower hazard of diabetes, whereas consumption of fruit juices may be associated with an increased hazard among women.

Journal ArticleDOI
TL;DR: The observed beneficial effects of hMSCs were largely explained by their modulation of inflammatory and immune responses, apparently by alternative activation of microglia and/or macrophages.
Abstract: Human mesenchymal stromal cells (hMSCs) were injected into the hippocampus of adult mice 1 day after transient global ischemia. The hMSCs both improved neurologic function and markedly decreased neuronal cell death of the hippocampus. Microarray assays indicated that ischemia up-regulated 586 mouse genes. The hMSCs persisted for 10% of the ischemia-induced genes, most of which were involved in inflammatory and immune responses. The hMSCs also up-regulated three mouse genes, including the neuroprotective gene Ym1 that is expressed by activated microglia/macrophages. In addition, the transcriptomes of the hMSC changed with up-regulation of 170 human genes and down-regulation of 54 human genes. Protein assays of the hippocampus demonstrated increased expression in microglia/macrophages of Ym1, the cell survival factor insulin-like growth factor 1, galectin-3, cytokines reflective of a type 2 T cell immune bias, and the major histocompatibility complex II. The observed beneficial effects of hMSCs were largely explained by their modulation of inflammatory and immune responses, apparently by alternative activation of microglia and/or macrophages.

Journal ArticleDOI
TL;DR: More boys displayed bully, victim, and bully-victim behaviors than girls, and more girls reported finding active solutions such as blocking the harasser when faced with cyberbullying.
Abstract: Cyberbullying, harassment through the use of information and communication technology such as cell phones and the Internet, is an emerging phenomenon all around the world. Extensive research on aggression and bullying is guiding educators' understanding of cyberbullying. Yet the gap between the advancement in technology and the dearth of study on cyberbullying suggests that more research is needed to understand the scope of this form of bullying. In order to fill the gap in literature, 269 secondary school Turkish students were surveyed on their engagement in and coping strategies for cyberbullying. The results show that 35.7% of the students displayed bully behaviors, and 23.8% of the students displayed bully-victim behaviors. Only 5.9% of the students were victims. More boys displayed bully, victim, and bully-victim behaviors than girls. When faced with cyberbullying, 25% of the students reported telling their peers and parents about the cyberbullying incident, and 30.6% of the students reporte...

01 Dec 2008
TL;DR: In this article, the authors suggest that unreasonable experimental effectiveness arises from natural scale independence, and they advocate a shift in emphasis in experimental stratigraphy and geomorphology away from classical dynamical scaling and towards a quantitative understanding of the origins and limits of scale independence.
Abstract: The growth of quantitative analysis and prediction in Earth-surface science has been accompanied by growth in experimental stratigraphy and geomorphology. Experimenters have grown increasingly bold in targeting landscape elements from channel reaches up to the entire erosional networks and depositional basins, often using very small facilities. The experiments produce spatial structure and kinematics that, although imperfect, compare well with natural systems despite differences of spatial scale, time scale, material properties, and number of active processes. Experiments have been particularly useful in studying a wide range of forms of self-organized (autogenic) complexity that occur in morphodynamic systems. Autogenic dynamics creates much of the spatial structure we see in the landscape and in preserved strata, and is strongly associated with sediment storage and release. The observed consistency between experimental and field systems despite large differences in governing dimensionless numbers is what we mean by “unreasonable effectiveness”. We suggest that unreasonable experimental effectiveness arises from natural scale independence. We generalize existing ideas to relate internal similarity, in which a small part of a system is similar to the larger system, to external similarity, in which a small copy of a system is similar to the larger system. We propose that internal similarity implies external similarity, though not the converse. The external similarity of landscape experiments to natural landscapes suggests that natural scale independence may be even more characteristic of morphodynamics than it is of better studied cases such as turbulence. We urge a shift in emphasis in experimental stratigraphy and geomorphology away from classical dynamical scaling and towards a quantitative understanding of the origins and limits of scale independence. Other research areas with strong growth potential in experimental surface dynamics include physical–biotic interactions, cohesive effects, stochastic processes, the interplay of structural and geomorphic self-organization, extraction of quantitative process information from landscape and stratigraphic records, and closer interaction between experimentation and theory.

Journal ArticleDOI
TL;DR: Assessment of the activities of the subtype B plasmas against chimeric HIV-2 viruses bearing various fragments of the membrane proximal external region of HIV-1 gp41 revealed mixed patterns, implying that MPER neutralization was not dominated by any single specificity akin to known MPER-specific monoclonal Abs.
Abstract: Identifying the viral epitopes targeted by broad neutralizing antibodies (NAbs) that sometimes develop in human immunodeficiency virus type 1 (HIV-1)-infected subjects should assist in the design of vaccines to elicit similar responses. Here, we investigated the activities of a panel of 24 broadly neutralizing plasmas from subtype B- and C-infected donors using a series of complementary mapping methods, focusing mostly on JR-FL as a prototype subtype B primary isolate. Adsorption with gp120 immobilized on beads revealed that an often large but variable fraction of plasma neutralization was directed to gp120 and that in some cases, neutralization was largely mediated by CD4 binding site (CD4bs) Abs. The results of a native polyacrylamide gel electrophoresis assay using JR-FL trimers further suggested that half of the subtype B and a smaller fraction of subtype C plasmas contained a significant proportion of NAbs directed to the CD4bs. Anti-gp41 neutralizing activity was detected in several plasmas of both subtypes, but in all but one case, constituted only a minor fraction of the overall neutralization activity. Assessment of the activities of the subtype B plasmas against chimeric HIV-2 viruses bearing various fragments of the membrane proximal external region (MPER) of HIV-1 gp41 revealed mixed patterns, implying that MPER neutralization was not dominated by any single specificity akin to known MPER-specific monoclonal Abs. V3 and 2G12-like NAbs appeared to make little or no contribution to JR-FL neutralization titers. Overall, we observed significant titers of anti-CD4bs NAbs in several plasmas, but approximately two-thirds of the neutralizing activity remained undefined, suggesting the existence of NAbs with specificities unlike any characterized to date.

Journal ArticleDOI
TL;DR: A review of the published literature over the last 30 years found that PCCs offer a rapid and specific method for replacing vitamin K‐dependent clotting factors and restoring normal hemostasis in the context of over‐coagulation.
Abstract: Over-anticoagulation is a common problem with warfarin therapy and can lead to major or life-threatening bleeding. The goal of urgent warfarin reversal is to elevate or replace vitamin K-dependent clotting factors. In the United States, fresh frozen plasma (FFP) is considered the standard of care for warfarin reversal. Prothrombin complex concentrates (PCCs) offer an alternative to FFP for rapidly replacing deficient clotting factors and correcting the international normalized ratio (INR). However, few prospective clinical trials have been conducted to evaluate the effectiveness of these concentrates relative to other treatment modalities. A review of the published literature over the last 30 years found that PCCs offer a rapid and specific method for replacing vitamin K-dependent clotting factors and restoring normal hemostasis in the context of over-coagulation. In those studies in which PCCs were compared with FFP, PCCs were found more effective in shortening the time to INR correction and were associated with a low risk of thrombotic adverse events. Evidence-based treatment guidelines are needed to optimize the use of PCCs for warfarin reversal.

Journal ArticleDOI
TL;DR: In this exploratory study in patients with clinically progressive IPF, etanercept was well tolerated and, although there were no differences in the predefined endpoints, a decreased rate of disease progression was observed on several measures.
Abstract: Rationale: An efficacious medical therapy for idiopathic pulmonary fibrosis (IPF) remains elusive.Objectives: To explore the efficacy and safety of etanercept in the treatment of IPF.Methods: This was a randomized, prospective, double-blind, placebo-controlled, multicenter exploratory trial in subjects with clinically progressive IPF. Primary endpoints included changes in the percentage of predicted FVC and lung diffusing capacity for carbon monoxide corrected for hemoglobin (DlCOHb) and change in the alveolar to arterial oxygen pressure difference P(a–a)O2 at rest from baseline over 48 weeks.Measurements and Main Results: Eighty-eight subjects received subcutaneous etanercept (25 mg) or placebo twice weekly as their sole treatment for IPF. No differences in baseline demographics and disease status were detected between treatment groups; the mean time from first diagnosis was 13.6 months and mean FVC was 63.9% of predicted. At 48 weeks, no significant differences in efficacy endpoints were observed betwee...

Journal ArticleDOI
TL;DR: The resources that individual directors bring to corporate boards are largely a function of their human and social capital as discussed by the authors, and although research has explored the value of having former federal governm...
Abstract: The resources that individual directors bring to corporate boards are largely a function of their human and social capital. Although research has explored the value of having former federal governm...

Journal ArticleDOI
TL;DR: Functional analysis of genes that were differentially expressed in rASCs and hBMSCs revealed that pathways involved in cell cycle, cell cycle checkpoints, protein-ubiquitination, and apoptosis were altered.
Abstract: Mesenchymal stem cells (MSC) derived from bone marrow stem cells (BMSC) and adipose tissue stem cells (ASC) of humans and rhesus macaques were evaluated for their cell cycle properties during protracted culture in vitro. Human ASCs (hASC) and rhesus BMSCs (rBMSC) underwent significantly more total population doublings than human BMSCs (hBMSC) and rhesus ASCs (rASC). The cell cycle profile of all MSCs was altered as cultures aged. hMSCs underwent an increase in the frequency of cells in the S phase at P20 and P30. However, rhesus MSCs from both sources developed a distinct polyploid population of cells at P20, which progressed to aneuploidy by P30. Karyotype analysis of MSCs revealed the development of tetraploid or aneuploid karyotypes in the rhesus cells at P20 or P30. Analysis of the transcriptome of the MSCs from early and late passages revealed significant alterations in the patterns of gene expression (8.8% of the genes were differentially expressed in hBMSCs versus hASCs, and 5.5% in rBMSCs versus rASCs). Gene expression changes were much less evident within the same cell type as aging occurred (0.7% in hMSCs and 0.9% in rMSC). Gene ontology analysis showed that functions involved in protein catabolism and regulation of pol II transcription were overrepresented in rASCs, whereas the regulation of I kappa B/nuclear factor-kappaB cascade were overrepresented in hBMSCs. Functional analysis of genes that were differentially expressed in rASCs and hBMSCs revealed that pathways involved in cell cycle, cell cycle checkpoints, protein-ubiquitination, and apoptosis were altered.

Journal ArticleDOI
TL;DR: There is evidence in this review, that membrane actions of estrogens, which activate these rapid signaling cascades, can also potentiate nuclear transcription in both the central nervous system and in non-neuronal cell lines.

Journal ArticleDOI
TL;DR: This work examines, with a particular emphasis on human retrotransposon activity, several newly discovered aspects of mammalian retrotransposition biology, and considers their potential impact on host biology as well as their ultimate implications for the nature of the TE-host relationship.
Abstract: Transposable elements (TEs) have shared an exceptionally long coexistence with their host organisms and have come to occupy a significant fraction of eukaryotic genomes. The bulk of the expansion occurring within mammalian genomes has arisen from the activity of type I retrotransposons, which amplify in a "copy-and-paste" fashion through an RNA intermediate. For better or worse, the sequences of these retrotransposons are now wedded to the genomes of their mammalian hosts. Although there are several reported instances of the positive contribution of mobile elements to their host genomes, these discoveries have occurred alongside growing evidence of the role of TEs in human disease and genetic instability. Here we examine, with a particular emphasis on human retrotransposon activity, several newly discovered aspects of mammalian retrotransposon biology. We consider their potential impact on host biology as well as their ultimate implications for the nature of the TE-host relationship.

Journal ArticleDOI
TL;DR: An FFP to PRBC ratio close to 1:1 confers a survival advantage in patients requiring massive transfusion, and univariate and multivariate analysis were used to assess the relationship between outcome and predictors.
Abstract: analysis. The primary research question was the impact of initial FFP:PRBC ratio on mortality. Other variables for analysis included patient age, gender, mechanism, and Injury Severity Scale score. Both univariate and multivariate analysis were used to assess the relationship between outcome and predictors. Results: A total of 2,746 patients underwent surgical intervention of which 1,985 (72.2%) received no transfusion. Of those that received transfusion, 626 (22.8%) received 10 units of PRBC. Out of the 626 patients that received 10 units PRBC received FFP. In univariate analysis, a significant difference in mortality was found in patients who received >10 units of PRBC (26% vs. 87.5%) when FFP:PRBC ratio was 1:1 versus 1:4 (p 0.0001). Multivariate analysis in the group of patients that received >10 units of PRBC showed a FFP:PRBC ratio of 1:4 was consistent with increased risk of mortality (relative risk, 18.88; 95% CI, 6.32–56.36; p 0.001), when compared with a ratio of 1:1. Patients who received <10 units of PRBC had a trend toward increased mortality (21.2% vs.11.8%) when the FFP:PRBC ratio was 1:4 versus 1:1 (p: 0.06).