bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating the Accuracy of Polarimetric Radar–Based Retrievals of Drop-Size Distribution Parameters and Rain Rate: An Application of Error Variance Separation Using Radar-Derived Spatial Correlations
Authors: Thurai M. , Bringi V. N. , Carey L. D. , Gatlin P. , Schultz E. , Petersen W. A. 
Published: January 2012

Abstract
The accuracy of retrieving the two drop size distribution (DSD) parameters, median volume diameter (D0), and normalized intercept parameter (NW), as well as rain rate (R), from polarimetric C-band radar data obtained during a cool-season, long-duration precipitation event in Huntsville, Alabama, is examined. The radar was operated in a special “near-dwelling” mode over two video disdrometers (2DVD) located 15 km away. The polarimetric radar–based retrieval algorithms for the DSD parameters and rain rate were obtained from simulations using the 2DVD measurements of the DSD. A unique feature of this paper is the radar-based estimation of the spatial correlation functions of the two DSD parameters and rain rate that are used to estimate the “point-to-area” variance. A detailed error variance separation is performed, including the aforementioned point-to-area variance, along with variance components due to the retrieval algorithm error, radar measurement error, and disdrometer sampling error. The spatial decorrelation distance was found to be smallest for the R (4.5 km) and largest for D0 (8.24 km). For log10(NW), it was 7.22 km. The proportion of the variance of the difference between radar-based estimates and 2DVD measurements that could be explained by the aforementioned errors was 100%, 57%, and 73% for D0, log10(NW), and R, respectively. The overall accuracy of the radar-based retrievals for the particular precipitation event quantified in terms of the fractional standard deviation were estimated to be 6.8%, 6%, and 21% for D0, log10(NW), and R, respectively. The normalized bias was &lt;1%. These correspond to time resolution of ~3 min and spatial resolution of ~1.5 km.
A Shortcut to Mean-Based Time Tradeoff Tariffs for the EQ-5D?
Authors: Rand-Hendriksen Kim , Augestad Liv Ariane , Dahl Fredrik A. , Kristiansen Ivar Sønbø , Stavem Knut 
Published: January 2012

Background EQ-5D valuation studies are usually performed using the time tradeoff (TTO) method, which is costly and time consuming. We focused on 2 properties that particularly characterize TTO: the initial choice task categorizing health states as better than death (BTD), worse than death (WTD), or equal to death (ETD), and unwillingness to trade (UTT) lifetime to improve health. The aim of this study was to estimate the value of the information to be gained from continuing the conventional TTO tasks beyond the initial question and the extent to which mean-based EQ-5D tariff values could be predicted through a simplified method of categorizing health states into BTD, WTD, ETD, and UTT. Methods We used data from the UK EQ-5D valuation study ( n = 2997). We designed an abbreviated system with only 4 values (collapsed TTO [cTTO]) based on the 4 response categories and assigned values as follows: WTD = −.5, ETD = 0, BTD = .5, and UTT = 1. Based on the mean cTTO scores for the valued health states, we created a regression-based cTTO tariff, which was compared with the conventional (full) TTO tariff (fTTO) by regressing 1) the fTTO means on cTTO means and 2) the fTTO tariff on the cTTO tariff. Results WTD values were unrelated to health state severity. Correlation between the means of fTTO and means of cTTO was >.999, and tariff values from fTTO correlated with tariff values from cTTO at r > .999. Conclusions Once respondents have classified health states as UTT, BTD, ETD, or WTD, the TTO procedure adds little further information to the tariff values. The WTD task fails to discriminate between good and bad health states. TTO valuation could likely be simplified using cTTO.
Perceptions of Shared Decision Making and Decision Aids Among Rural Primary Care Clinicians
Authors: King Valerie J. , Davis Melinda M. , Gorman Paul N. , Rugge J. Bruin , Fagnan L. J. 
Published: January 2012

Background Shared decision making (SDM) and decision aids (DAs) increase patients’ involvement in health care decisions and enhance satisfaction with their choices. Studies of SDM and DAs have primarily occurred in academic centers and large health systems, but most primary care is delivered in smaller practices, and over 20% of Americans live in rural areas, where poverty, disease prevalence, and limited access to care may increase the need for SDM and DAs. Objective To explore perceptions and practices of rural primary care clinicians regarding SDM and DAs. Design Cross-sectional survey. Setting and Participants Primary care clinicians affiliated with the Oregon Rural Practice-based Research Network. Results Surveys were returned by 181 of 231 eligible participants (78%); 174 could be analyzed. Two-thirds of participants were physicians, 84% practiced family medicine, and 55% were male. Sixty-five percent of respondents were unfamiliar with the term shared decision making, but following definition, 97% reported that they found the approach useful for conditions with multiple treatment options. Over 90% of clinicians perceived helping patients make decisions regarding chronic pain and health behavior change as moderate/hard in difficulty. Although 69% of respondents preferred that patients play an equal role in making decisions, they estimate that this happens only 35% of the time. Time was reported as the largest barrier to engaging in SDM (63%). Respondents were receptive to using DAs to facilitate SDM in print- (95%) or web-based formats (72%), and topic preference varied by clinician specialty and decision difficulty. Conclusions Rural clinicians recognized the value of SDM and were receptive to using DAs in multiple formats. Integration of DAs to facilitate SDM in routine patient care may require addressing practice operation and reimbursement.
Charting a Health Literacy Journey - overview and outcomes from a Stakeholder Workshop
Authors: Menzies Loic 
Published: January 2012

Through a combination of Personal, social, health and economic education (PSHE), Science, Healthy Schools and a range of other initiatives, we are increasingly preparing our children to understand key topics in health education. However, to what extent are we equipping them with a picture of a healthy, happy future and giving them the tools to access this? In June, The Royal Society for Public Health (RSPH) hosted a workshop entitled “Charting a Health Literacy Journey” to examine this. The workshop brought together a broad group of over 20 stakeholders from the health and education sectors. The aims of the day were to address the following six questions: What is health literacy? What does health literacy look like in action? What are the benefits of health literacy? How is health literacy reflected on the ground at present? How does health literacy fit with the current policy context? What are the options going forward? This report summarises the key findings of the workshop.
Engraftment of human HSCs in nonirradiated newborn NOD-scid IL2rγnull mice is enhanced by transgenic expression of membrane-bound human SCF
Authors: Brehm Michael A. , Racki Waldemar J. , Leif Jean , Burzenski Lisa , Hosur Vishnu , Wetmore Amber , Gott Bruce , Herlihy Mary , Ignotz Ronald , Dunn Raymond , Shultz Leonard D. , Greiner Dale L. 
Published: January 2012

Abstract
Immunodeficient mice engrafted with human HSCs support multidisciplinary translational experimentation, including the study of human hematopoiesis. Heightened levels of human HSC engraftment are observed in immunodeficient mice expressing mutations in the IL2-receptor common γ chain (IL2rg) gene, including NOD-scid IL2rγnull (NSG) mice. Engraftment of human HSC requires preconditioning of immunodeficient recipients, usually with irradiation. Such preconditioning increases the expression of stem cell factor (SCF), which is critical for HSC engraftment, proliferation, and survival. We hypothesized that transgenic expression of human membrane-bound stem cell factor Tg(hu-mSCF)] would increase levels of human HSC engraftment in nonirradiated NSG mice and eliminate complications associated with irradiation. Surprisingly, detectable levels of human CD45+ cell chimerism were observed after transplantation of cord blood–derived human HSCs into nonirradiated adult as well as newborn NSG mice. However, transgenic expression of human mSCF enabled heightened levels of human hematopoietic cell chimerism in the absence of irradiation. Moreover, nonirradiated NSG-Tg(hu-mSCF) mice engrafted as newborns with human HSCs rejected human skin grafts from a histoincompatible donor, indicating the development of a functional human immune system. These data provide a new immunodeficient mouse model that does not require irradiation preconditioning for human HSC engraftment and immune system development.
Overlapping and divergent signaling pathways of N-cadherin and VE-cadherin in endothelial cells
Authors: Giampietro Costanza , Taddei Andrea , Corada Monica , Sarra-Ferraris Gian Maria , Alcalay Myriam , Cavallaro Ugo , Orsenigo Fabrizio , Lampugnani Maria Grazia , Dejana Elisabetta 
Published: January 2012

AbstractEndothelial cells (ECs) express 2 members of the cadherin family, VE and N-cadherin. Although VE-cadherin induces EC homotypic adhesion, N-cadherin function in ECs remains largely unknown. EC-specific inactivation of either VE or N-cadherin leads to early fetal lethality suggesting that these cadherins play a nonredundant role in vascular development. We report here that VE-cadherin negatively controls junctional localization and expression of N-cadherin by limiting p120-catenin availability and reducing β-catenin transcriptional activity. Using EC lines expressing either VE or N-cadherin we found that both cadherins inhibit cell proliferation and apoptosis. Both trigger the phosphatidylinositol-3-OH-kinase (PI3K)–AKT-Forkhead-box protein-O1 (FoxO1) pathway and reduce β-catenin transcriptional activity. The extent of signaling correlates with the total level of cadherins regardless of the type of cadherin expressed. In contrast, basal and fibroblast growth factor (FGF)–induced cell motility is promoted by N-cadherin and strongly inhibited by VE-cadherin. This opposite effect is partly because of the ability of VE-cadherin to associate with FGF receptor and the density-enhanced phosphatase-1 (Dep-1) which, in turn, inhibits receptor signaling. We conclude that VE and N-cadherin have both additive and divergent effects on ECs. Differences in signaling are due, in part, to cadherin association with growth factor receptors and modulation of their downstream signaling.
Histone/protein deacetylases and T-cell immune responses
Authors: Akimova Tatiana , Beier Ulf H. , Liu Yujie , Wang Liqing , Hancock Wayne W. 
Published: January 2012

Abstract
Clinical and experimental studies show that inhibition of histone/protein deacetylases (HDAC) can have important anti-neoplastic effects through cytotoxic and proapoptotic mechanisms. There are also increasing data from nononcologic settings that HDAC inhibitors (HDACi) can exhibit useful anti-inflammatory effects in vitro and in vivo, unrelated to cytotoxicity or apoptosis. These effects can be cell-, tissue-, or context-dependent and can involve modulation of specific inflammatory signaling pathways as well as epigenetic mechanisms. We review recent advances in the understanding of how HDACi alter immune and inflammatory processes, with a particular focus on the effects of HDACi on T-cell biology, including the activation and functions of conventional T cells and the unique T-cell subset, composed of Foxp3+ T-regulatory cells. Although studies are still needed to tease out details of the various biologic roles of individual HDAC isoforms and their corresponding selective inhibitors, the anti-inflammatory effects of HDACi are already promising and may lead to new therapeutic avenues in transplantation and autoimmune diseases.
Distinct TLR adjuvants differentially stimulate systemic and local innate immune responses in nonhuman primates
Authors: Kwissa Marcin , Nakaya Helder I. , Oluoch Herold , Pulendran Bali 
Published: January 2012

Abstract
TLR ligands (TLR-Ls) represent novel vaccine adjuvants, but their immunologic effects in humans remain poorly defined in vivo. In the present study, we analyzed the innate responses stimulated by different TLR-Ls in rhesus macaques. MPL (TLR4-L), R-848 (TLR7/8-L), or cytosine-phosphate-guanine oligodeoxynucleotide (TLR9-L) induced a rapid and robust expansion of blood neutrophils, with a concomitant reduction in PBMCs. Furthermore, all TLR-Ls induced rapid (3-8 hours) expansion of CD14+ monocytes, but only TLR7/8-L and TLR9-L mobilized the CD14+CD16+ and CD14dimCD16++ monocytes, and only TLR7/8-L and TLR9-L induced activation of myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs), production of IP-10 and type-I IFN, and expression of type-I IFN–related and chemokine genes in the blood. In the draining lymph nodes (LNs), consistent with the effects in blood, all TLR-Ls induced expansion of CD14+ monocytes, but only TLR7/8-L and TLR9-L expanded the activated CD14+CD16+ cells. TLR4-L and TLR9-L differentially induced the expansion of mDCs and pDCs (1-3 days), but did not activate DCs. In contrast, TLR7/8-L did not induce DC expansion, but did activate mDCs. Finally, both TLR9-L and TLR7/8-L induced the expression of genes related to chemokines and type-I IFNs in LNs. Thus different TLR-Ls mediate distinct signatures of early innate responses both locally and systemically.
Differential switching to IgG and IgA in active smoking COPD patients and healthy controls
Authors: Brandsma Corry-Anke , Kerstjens Huib A.M. , van Geffen Wouter H. , Geerlings Marie , Postma Dirkje S. , Hylkema Machteld N. , Timens Wim 
Published: January 2012

Several studies have demonstrated the presence of B-cell follicles and autoantibodies in chronic obstructive pulmonary disease (COPD). It is unclear against which antigens this B-cell response is directed and whether it contributes to development or worsening of disease.We assessed different B-cell subsets in blood and lung tissue from COPD patients and controls, and compared differences in B-cell responsiveness to stimulation with lung-specific antigens.Active smoking induced an adaptive immune response with relatively high levels of (class-switched) memory B-cells in blood and immunoglobulin (Ig)G memory B-cells in the lung. COPD smokers showed more switching to IgG, whereas healthy smokers switched more to IgA. COPD patients had higher levels of memory B-cells in the lung and stimulation with lung-specific antigens induced higher numbers of anti-decorin antibody-producing cells in COPD patients compared with healthy controls.Differential switching to IgG and IgA indicates that the adaptive immune response to smoke differs between COPD patients and healthy controls. A higher level of memory B-cells in the lungs of COPD patients may reflect an antigen-specific immune response, which could be directed against decorin, as suggested by the induction of anti-decorin antibody-producing cells in response to antigen-specific stimulation in COPD patients.
Predicting survival in newly diagnosed idiopathic pulmonary fibrosis: a 3-year prospective study
Authors: Mura Marco , Porretta Maria A. , Bargagli Elena , Sergiacomi Gianluigi , Zompatori Maurizio , Sverzellati Nicola , Taglieri Amedeo , Mezzasalma Fabrizio , Rottoli Paola , Saltini Cesare , Rogliani Paola 
Published: January 2012

The natural history of idiopathic pulmonary fibrosis (IPF) is not well defined and its clinical course is variable. We sought to investigate the survival and incidence of acute exacerbations (AEs) and their significant predictors in newly diagnosed patients.70 patients newly diagnosed with IPF were prospectively followed for at least 3 yrs. Baseline evaluation included Medical Research Council dyspnoea score (MRCDS), 6-min walk test, pulmonary function tests, all of which were repeated at 6 months, and high-resolution computed tomography. A retrospective cohort of 68 patients was used for confirmation.Mean survival from the time of diagnosis was 30 months, with a 3-yr mortality of 46%. A Risk stratificatiOn ScorE (ROSE) based on MRCDS >3, 6-min walking distance ≤72% predicted and composite physiologic index >41 predicted 3-yr mortality with high specificity. 6-month progression of ROSE predicted rapid progression. 3-yr incidence of AE was 18.6%, mostly occurring in the first 18 months; risk factors for AE were concomitant emphysema and low diffusing coefficient of the lung for carbon monoxide. Results were confirmed in an independent cohort of patients.In newly diagnosed IPF, advanced disease at presentation, rapid progression and AEs are the determinants of 3-yr survival. The purpose of the multifactorial ROSE is to risk-stratify patients in order to predict survival and detect rapid disease progression.
Clinical validation of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis
Authors: Tortoli Enrico , Russo Cristina , Piersimoni Claudio , Mazzola Ester , Dal Monte Paola , Pascarella Michela , Borroni Emanuele , Mondo Alessandra , Piana Federica , Scarparo Claudio , Coltella Luana , Lombardi Giulia , Cirillo Daniela M. 
Published: January 2012

Extrapulmonary tuberculosis (EPTB) accounts for more than 20% of tuberculosis (TB) cases. Xpert MTB/RIF (Xpert) (Cepheid, Sunnyvale, CA, USA) is a fully automated amplification system, for which excellent results in the diagnosis of pulmonary TB in highly endemic countries have been recently reported. We aimed to assess the performance of the Xpert system in diagnosing EPTB in a low incidence setting.We investigated with Xpert a large number of consecutive extrapulmonary clinical specimens (1,476, corresponding to 1,068 patients) including both paediatric (494) and adult samples.We found, in comparison with a reference standard consisting of combination of culture and clinical diagnosis of TB, an overall sensitivity and specificity of 81.3% and 99.8% for Xpert, while the sensitivity of microscopy was 48%. For biopsies, urines, pus and cerebrospinal fluids the sensitivity exceeded 85%, while it was slightly under 80% for gastric aspirates. It was, in contrast, lower than 50% for cavitary fluids. High sensitivity and specificity (86.9% and 99.7%, respectively) were also obtained for paediatric specimens.Although the role of culture remains central in the microbiological diagnosis of EPTB, the sensitivity of Xpert in rapidly diagnosing the disease makes it a much better choice compared to smear microscopy. The ability to rule out the disease still remains suboptimal.
Noninvasive positive pressure ventilation in COPD
Authors: Windisch W. 
Published: January 2012

Educational aimsTo take up the ongoing debate on whether long-term noninvasive positive pressure ventilation (NPPV) should be applied in chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure.To elucidate the impact of NPPV techniques on NPPV success in COPD.To describe the technique and scientific evidence for the new concept of high-intensity NPPV.To provide practical considerations on how to commence high-intensity NPPV.To outline important unknowns regarding long-term NPPV in COPD patients.SummaryHome mechanical ventilation, as provided by long-term NPPV, is a widely accepted treatment option for many patient groups with chronic hypercapnic respiratory failure, including also those with COPD, even though the rationale for long-term NPPV in COPD patients is still disputed. This is based on clinical observations that conventional NPPV using assisted ventilation and low mean inspiratory pressures of <18 cmH2O reportedly failed to effectively improve respiratory function, most importantly gas exchange, while outcomes are also not convincingly improved by the addition of long-term NPPV to long-term oxygen treatment.Recently, however, a promising technique of NPPV has been described, which aims at maximally improving gas exchange by the use of controlled ventilation and considerably higher inspiratory pressures, typically ranging 20–40 cmH2O. This is known as high-intensity NPPV. This approach clearly contrasts with the conventional, low-intensity approach.High-intensity NPPV has been shown to improve physiological parameters such as breathing pattern, gas exchange and lung function. In addition, it also provides clinical benefits, with improvements in dyspnoea, walking distance and specific aspects of health-related quality of life. The superiority of high- over low-intensity NPPV has been clearly established by randomised crossover trials.Increasing evidence now exists to support the contention that long-term high-intensity NPPV offers a new therapeutic option in the treatment of hypercapnic COPD. However, the questions of whether high-intensity NPPV is also capable of improving survival and how to best select candidates to undergo long-term high-intensity NPPV remain pressing. This article also provides detailed practical descriptions of how to initiate high-intensity NPPV.
MIPHENO: data normalization for high throughput metabolite analysis
Authors: Bell Shannon M , Burgoon Lyle D , Last Robert L 
Published: January 2012

Abstract

Background
High throughput methodologies such as microarrays, mass spectrometry and plate-based small molecule screens are increasingly used to facilitate discoveries from gene function to drug candidate identification. These large-scale experiments are typically carried out over the course of months and years, often without the controls needed to compare directly across the dataset. Few methods are available to facilitate comparisons of high throughput metabolic data generated in batches where explicit in-group controls for normalization are lacking.

Results
Here we describe MIPHENO (Mutant Identification by Probabilistic High throughput-Enabled Normalization), an approach for post-hoc normalization of quantitative first-pass screening data in the absence of explicit in-group controls. This approach includes a quality control step and facilitates cross-experiment comparisons that decrease the false non-discovery rates, while maintaining the high accuracy needed to limit false positives in first-pass screening. Results from simulation show an improvement in both accuracy and false non-discovery rate over a range of population parameters (p < 2.2 × 10-16) and a modest but significant (p < 2.2 × 10-16) improvement in area under the receiver operator characteristic curve of 0.955 for MIPHENO vs 0.923 for a group-based statistic (z-score). Analysis of the high throughput phenotypic data from the Arabidopsis Chloroplast 2010 Project (http://www.plastid.msu.edu/) showed ~ 4-fold increase in the ability to detect previously described or expected phenotypes over the group based statistic.

Conclusions
Results demonstrate MIPHENO offers substantial benefit in improving the ability to detect putative mutant phenotypes from post-hoc analysis of large data sets. Additionally, it facilitates data interpretation and permits cross-dataset comparison where group-based controls are missing. MIPHENO is applicable to a wide range of high throughput screenings and the code is freely available as Additional file 1 as well as through an R package in CRAN.