bluuebunny/crossref_metadata_2025_split huggingface dataset:
Back‐ and fore‐grounding ontology: exploring the linkages between critical realism, pragmatism, and methodologies in health & rehabilitation sciences
Authors: DeForge Ryan , Shaw Jay 
Published: July 2011

DEFORGE R and SHAW J. Nursing Inquiry 2012; 19: 83–95 Back‐ and fore‐grounding ontology: exploring the linkages between critical realism, pragmatism, and methodologies in health & rehabilitation sciencesAs two doctoral candidates in a health and rehabilitation sciences program, we describe in this paper our respective paradigmatic locations along a quite nonlinear ontological‐epistemological‐axiological‐methodological chain. In a turn‐taking fashion, we unpack the tenets of critical realism and pragmatism, and then trace the linkages from these paradigmatic locations through to the methodological choices that address a community‐based research problem. Beyond serving as an answer to calls for academics in training to demonstrate philosophical‐theoretical‐methodological integrity and coherence in their scholarship, this paper represents critical realism and its fore‐grounding of a deeply stratified ontology in reflexive relation to pragmatism and its back‐grounding of ontology. We conclude by considering the merits and challenges of conducting research from within singular versus proliferate paradigmatic perspectives.
Variations in early gross motor milestones and in the age of walking in Japanese children
Authors: Kimura‐Ohba Shihoko , Sawada Akiko , Shiotani Yuka , Matsuzawa Shigeyuki , Awaya Tomonari , Ikeda Hiroko , Okada Masako , Tomiwa Kiyotaka 
Published: July 2011

AbstractBackground: Gross motor development is usually assessed in terms of age of achievement of motor milestones. Although there is generally an impression of faster development if the milestones are achieved at younger ages, no longitudinal studies have been done on the associations between the milestones, especially in Japan. As a part of the Japan Children's Study, the purpose of the present study was to determine whether the achievement of gross motor milestones in infancy is related with the age of walking.Methods: This was a prospective cohort study of 290 healthy and term infants born in a district of Osaka City, Japan. Three milestones (rolling over, sitting, and crawling) were observed in the laboratory for infants aged at 4 and 9 months by a pediatrician and a developmental psychologist, and the age of walking was confirmed in questionnaires filled in by the parents at 18 and 27 months.Results: Children who could roll over at 4 months, and sit and crawl at 9 months, walked earlier than children who could not roll over, sit and crawl, respectively. With regard to crawling, children who were creeping had a 1 month delay in walking, and those who could not move forward had a 2 month delay compared to typical crawlers. On multiple regression analysis these three milestones were positively associated with walking: rolling over (β= 0.567), sitting (β= 1.973) and crawling (β= 1.473).Conclusion: The age and the patterns of sitting, crawling and rolling over were all related to the age of independent walking among Japanese infants. Consideration of milestone definition and variations is essential in medical check‐up.
Evaluating the role of prophylaxis in the management of invasive fungal infections in patients with hematologic malignancy
Authors: Cornely Oliver A. , Aversa Franco , Cook Perry , Jones Brian , Michallet Mauricette , Shea Thomas , Vallejo Carlos 
Published: July 2011

AbstractInvasive fungal infection (IFI) is a persistent problem among critically ill and immunocompromised patients, especially hematopoietic stem cell transplant or solid organ transplant recipients, or patients on intensive chemotherapy for acute leukemia. Although numerous antifungal agents are available, IFI remains a serious problem because of obstacles to timely diagnosis and high morbidity and mortality rates associated with such infection. Improvements in treatment of underlying diseases have rapidly expanded the patient populations at risk for IFI with increased use of immunosuppressants, aggressive chemotherapy, broad‐spectrum antibiotics, and narrow‐spectrum antifungal prophylaxis. There are various treatment strategies that can be used to manage IFI: prophylaxis, empiric, preemptive, and directed. As the infection progresses, the prospect of successfully treating an infection diminishes; conversely, the earlier the intervention, the greater the possibility of unnecessary treatment. This article discusses the epidemiology of the most important fungal pathogens, identifies high‐risk patient groups and risk factors associated with IFI, and critically evaluates the advantages and disadvantages of available diagnostic tests and treatment strategies and the rationale for antifungal prophylaxis. For patients at high risk for IFI, antifungal prophylaxis is an attractive strategy, and numerous randomized, controlled clinical studies have documented the benefit of such prophylaxis as well as the most efficacious of currently available agents.
Antitumor Activity of Metal-Chelating Compound Dp44mT Is Mediated by Formation of a Redox-Active Copper Complex That Accumulates in Lysosomes
Authors: Lovejoy David B. , Jansson Patric J. , Brunk Ulf T. , Wong Jacky , Ponka Prem , Richardson Des R. 
Published: July 2011

Abstract
The metal-chelating compound Dp44mT is a di-2-pyridylketone thiosemicarbazone (DpT) which displays potent and selective antitumor activity. This compound is receiving translational attention, but its mechanism is poorly understood. Here, we report that Dp44mT targets lysosome integrity through copper binding. Studies using the lysosomotropic fluorochrome acridine orange established that the copper–Dp44mT complex (Cu[Dp44mT]) disrupted lysosomes. This targeting was confirmed with pepstatin A–BODIPY FL, which showed redistribution of cathepsin D to the cytosol with ensuing cleavage of the proapoptotic BH3 protein Bid. Redox activity of Cu[Dp44mT] caused cellular depletion of glutathione, and lysosomal damage was prevented by cotreatment with the glutathione precursor N-acetylcysteine. Copper binding was essential for the potent antitumor activity of Dp44mT, as coincubation with nontoxic copper chelators markedly attenuated its cytotoxicity. Taken together, our studies show how the lysosomal apoptotic pathway can be selectively activated in cancer cells by sequestration of redox-active copper. Our findings define a novel generalized strategy to selectively target lysosome function for chemotherapeutic intervention against cancer. Cancer Res; 71(17); 5871–80. ©2011 AACR.
Specific PET Imaging of xC− Transporter Activity Using a 18F-Labeled Glutamate Derivative Reveals a Dominant Pathway in Tumor Metabolism
Authors: Koglin Norman , Mueller Andre , Berndt Mathias , Schmitt-Willich Heribert , Toschi Luisella , Stephens Andrew W. , Gekeler Volker , Friebe Matthias , Dinkelborg Ludger M. 
Published: July 2011

Abstract
Purpose: 18F-labeled small molecules targeting adaptations of tumor metabolism possess the potential for early tumor detection with high sensitivity and specificity by positron emission tomography (PET) imaging. Compounds tracing deranged pathways other than glycolysis may have advantages in situations where 2-[18F]fluoro-2-deoxy-d-glucose (FDG) has limitations. The aim of this study was the generation of a metabolically stable 18F-labeled glutamate analogue for PET imaging of tumors.
Experimental Design: Derivatives of l-glutamate were investigated in cell competition assays to characterize the responsible transporter. An automated radiosynthesis was established for the most promising candidate. The resulting 18F-labeled PET tracer was characterized in a panel of in vitro and in vivo tumor models. Tumor specificity was investigated in the turpentine oil-induced inflammation model in rats.
Results: A fluoropropyl substituted glutamate derivative showed strong inhibition in cell uptake assays. The radiosynthesis was established for (4S)-4-(3-[18F]fluoropropyl)-l-glutamate (BAY 94-9392). Tracer uptake studies and analysis of knockdown cells showed specific transport of BAY 94-9392 via the cystine/glutamate exchanger designated as system xC−. No metabolites were observed in mouse blood and tumor cells. PET imaging with excellent tumor visualization and high tumor to background ratios was achieved in preclinical tumor models. In addition, BAY 94-9392 did not accumulate in inflammatory lesions in contrast to FDG.
Conclusions: BAY 94-9392 is a new tumor-specific PET tracer which could be useful to examine system xC− activity in vivo as a possible hallmark of tumor oxidative stress. Both preclinical and clinical studies are in progress for further characterization. Clin Cancer Res; 17(18); 6000–11. ©2011 AACR.
Intramural Activation During Early Human Ventricular Fibrillation
Authors: Nair Krishnakumar , Umapathy Karthikeyan , Farid Talha , Masse Stephane , Mueller Erin , Sivanandan Radhika V. , Poku Kwaku , Rao Vivek , Nair Vidhya , Butany Jagdish , Ideker Raymond E. , Nanthakumar Kumaraswamy 
Published: July 2011

Background—
We investigated patterns of intramural activation in early human ventricular fibrillation (VF) and hypothesized that intramural reentry colocalizes to sites with increased intramural fibrosis.

Methods and Results—

Thirteen human Langendorff hearts were used for this study. Twenty-five plunge needles (4 unipoles/needle) were used to map 100 intramural sites. For the global mapping component, 11 20-s episodes of early VF were studied in 6 hearts. Simultaneous activation of all 4 electrodes was the most common pattern observed in 48.7% of needles, followed by an endocardial-to-epicardial activation pattern (9.8% of needles) and epicardial-to-endocardial activation pattern (5.5% of needles); 19.3% of needles had nonuniform multidirectional patterns. In 2 orthogonal planes, 1 parallel and 1 perpendicular to the epicardium and endocardium, reentry was detected in 14.3% of beats at any 1 level, and 5.8% of these were transmural. Simultaneous mapping of the epicardium and endocardium in 5 hearts detected concurrently rotating rotors with similar chirality and cycle length, suggesting the presence of transmural scroll waves (n=6), which was confirmed by high-resolution fixed-space mapping in 2 of those hearts plus 1 additional heart. Transmural optical mapping in 1 additional heart confirmed simultaneous epicardial and endocardial activation. Histopathology revealed greater fibrosis at sites of reentry compared to areas without (53.3±11.9% versus 27.5±2.4%,
P
=0.02).

Conclusions—
Intramural activation patterns suggest that early human VF does not organize as multiple reentrant wavefronts but is best explained by transmural scroll wave activation. Intramural reentry localizes to regions of greater intramural fibrosis.
Relation of Peripheral Collagen Markers to Death and Hospitalization in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Krum Henry , Elsik Maros , Schneider Hans G. , Ptaszynska Agata , Black Marion , Carson Peter E. , Komajda Michel , Massie Barry M. , McKelvie Robert S. , McMurray John J. , Zile Michael R. , Anand Inder S. 
Published: July 2011

Background—
Heart failure with preserved ejection fraction (HFPEF) is a common and increasing public health problem. Myocardial fibrosis is a key pathological feature of HFPEF. Peripheral collagen markers may reflect this excess fibrosis; however, the relation of these markers to prognosis in patients with HFPEF has not as yet been determined.

Methods and Results—

This substudy of the Irbesartan in Heart Failure With Preserved Systolic Function (I-PRESERVE) trial measured plasma levels of procollagen type I amino-terminal peptide, procollagen type III amino-terminal peptide, and osteopontin in 334 patients with HFPEF. Measurements were performed at baseline and 6 months after randomization to placebo or irbesartan 300 mg/day. The relation of baseline collagen markers to the I-PRESERVE primary end point (all-cause death and hospitalization for prespecified cardiovascular causes) was evaluated by single and multivariable analysis. Similar evaluations were performed for all-cause death alone as well as heart failure events (death or hospitalization because of heart failure). Increased plasma levels of collagen markers at baseline were associated with increased frequency of the study primary end point for all collagen markers. For each 10-μg/L increase in procollagen type I amino-terminal peptide, the hazard ratio (HR) for the primary end point was 1.09 (95% CI, 1.052 to 1.13;
P
<0.0001); for each 10-μg/L increase in procollagen type III amino-terminal peptide procollagen type I amino-terminal peptide, the HR was 2.47 (95% CI, 0.97 to 6.33;
P
=0.059); and for each 10-nmol/L increase in osteopontin, the HR was 1.084 (95% CI, 1.026 to 1.15;
P
=0.004). No variable remained significant as an independent predictor when introduced into a multivariable model. Both treatment groups tended to reduce collagen markers, with the reduction significantly greater for placebo versus irbesartan for procollagen type III amino-terminal peptide only (
P
=0.0185).

Conclusions—
Increased peripheral collagen turnover markers were not independently associated with increased mortality and cardiovascular hospitalization in an HFPEF population on multivariable analysis but were associated on single-variable analysis. These findings provide some support to the hypothesis that pathological fibrosis in the heart, and possibly the peripheral vasculature, may be contributory to adverse clinical outcomes in patients with HFPEF.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00095238.
Supercells in Environments with Atypical Hodographs
Authors: Blanchard David O. 
Published: July 2011

Abstract
An unusual severe weather event with supercell thunderstorms developed across portions of northern Arizona in the midst of the warm-season North American monsoon—a regime characteristically dominated by a subtropical upper-level high over the southwestern United States. The approach of a midlatitude, cold-core, upper-level low brought an environment of enhanced shear and increased instability supportive of supercells. This atypical system is described and how a correct interpretation of the winds and hodograph would allow a forecaster to maintain situational awareness is discussed.
HLA mismatch direction in cord blood transplantation: impact on outcome and implications for cord blood unit selection
Authors: Stevens Cladd E. , Carrier Carmelita , Carpenter Carol , Sung Dorothy , Scaradavou Andromachi 
Published: July 2011

AbstractDonor-recipient human leukocyte antigen mismatch level affects the outcome of unrelated cord blood (CB) transplantation. To identify possible “permissive” mismatches, we examined the relationship between direction of human leukocyte antigen mismatch (“vector”) and transplantation outcomes in 1202 recipients of single CB units from the New York Blood Center National Cord Blood Program treated in United States Centers from 1993-2006. Altogether, 98 donor/patient pairs had only unidirectional mismatches: 58 in the graft-versus-host (GVH) direction only (GVH-O) and 40 in the host-versus-graft or rejection direction only (R-O). Engraftment was faster in patients with GVH-O mismatches compared with those with 1 bidirectional mismatch (hazard ratio [HR] = 1.6, P = .003). In addition, patients with hematologic malignancies given GVH-O grafts had lower transplantation-related mortality (HR = 0.5, P = .062), overall mortality (HR = 0.5, P = .019), and treatment failure (HR = 0.5, P = .016), resulting in outcomes similar to those of matched CB grafts. In contrast, R-O mismatches had slower engraftment, higher graft failure, and higher relapse rates (HR = 2.4, P = .010). Based on our findings, CB search algorithms should be modified to identify unidirectional mismatches. We recommend that transplant centers give priority to GVH-O-mismatched units over other mismatches and avoid selecting R-O mismatches, if possible.
Characterization of four conventional dendritic cell subsets in human skin-draining lymph nodes in relation to T-cell activation
Authors: van de Ven Rieneke , van den Hout Mari F. C. M. , Lindenberg Jelle J. , Sluijter Berbel J. R. , van Leeuwen Paul A. M. , Lougheed Sinéad M. , Meijer Sybren , van den Tol M. Petrousjka , Scheper Rik J. , de Gruijl Tanja D. 
Published: July 2011

Abstract
To increase (tumor) vaccine efficacy, there is an urgent need for phenotypic and functional characterization of human dendritic cell (DC) subsets residing in lymphoid tissues. In this study we identified and functionally tested 4 human conventional DC (cDC) subsets within skin-draining sentinel lymph nodes (SLNs) from early-stage melanoma patients. These SLNs were all tumor negative and were removed on average 44 days after excision of the primary melanoma. As such, they were considered representative of steady-state conditions. On comparison with skin-migrated cDC, 2 CD1a+ subsets were identified as most likely skin-derived CD11cint Langerhans cells (LC) with intracellular langerin and E-cadherin expression or as CD11chi dermal DCs with variable expression of langerin. Two other CD1a− LN-residing cDC subsets were characterized as CD14−BDCA3hiCD103− and CD14+BDCA3loCD103+, respectively. Whereas the CD1a+ skin-derived subsets displayed greater levels of phenotypic maturation, they were associated with lower levels of inflammatory cytokine release and were inferior in terms of allogeneic T-cell priming and IFNγ induction. Thus, despite their higher maturation state, skin-derived cDCs (and LCs in particular) proved inferior T-cell activators compared with the CD1a− cDC subsets residing in melanoma-draining LNs. These observations should be considered in the design of DC-targeting immunotherapies.
CD3 limits the efficacy of TCR gene therapy in vivo
Authors: Ahmadi Maryam , King Judith W. , Xue Shao-An , Voisine Cécile , Holler Angelika , Wright Graham P. , Waxman Jonathan , Morris Emma , Stauss Hans J. 
Published: July 2011

AbstractThe function of T-cell receptor (TCR) gene modified T cells is dependent on efficient surface expression of the introduced TCR α/β heterodimer. We tested whether endogenous CD3 chains are rate-limiting for TCR expression and antigen-specific T-cell function. We show that co-transfer of CD3 and TCR genes into primary murine T cells enhanced TCR expression and antigen-specific T-cell function in vitro. Peptide titration experiments showed that T cells expressing introduced CD3 and TCR genes recognized lower concentration of antigen than T cells expressing TCR only. In vivo imaging revealed that TCR+CD3 gene modified T cells infiltrated tumors faster and in larger numbers, which resulted in more rapid tumor elimination compared with T cells modified by TCR only. After tumor clearance, TCR+CD3 engineered T cells persisted in larger numbers than TCR-only T cells and mounted a more effective memory response when rechallenged with antigen. The data demonstrate that provision of additional CD3 molecules is an effective strategy to enhance the avidity, anti-tumor activity and functional memory formation of TCR gene modified T cells in vivo.
Fitness for radical treatment of lung cancer patients
Authors: Charloux A. 
Published: July 2011

Educational aimsTo discuss the strengths and weaknesses of lung function tests, exercise tests and split-function studies used to assess fitness before lung resectionTo outline the importance of the perioperative management of lung cancer patientsTo understand the lack of clear recommendations and the need for further studies to assess fitness before chemoradiotherapySummarySurgical pulmonary resection and chemoradiotherapy both induce significant mortality and morbidity in lung cancer patients. Many studies have intended to identify the patients at increased risk of treatment-induced complications. In this review, we will describe the various tests proposed to assess fitness before radical treatment of lung cancer. We will also consider the strategies aimed at using the less invasive and most powerful investigations, summarised as functional algorithms in scientific societies' guidelines. The main recent studies, published after the guidelines were available, will also be reviewed.
SIV antigen immunization induces transient antigen-specific T cell responses and selectively activates viral replication in draining lymph nodes in retroviral suppressed rhesus macaques
Authors: Hu Haitao , Gama Lucio , Aye Pyone P , Clements Janice E , Barry Peter A , Lackner Andrew A , Weissman Drew 
Published: July 2011

Abstract

Background
HIV infection causes a qualitative and quantitative loss of CD4+ T cell immunity. The institution of anti-retroviral therapy (ART) restores CD4+ T cell responses to many pathogens, but HIV-specific responses remain deficient. Similarly, therapeutic immunization with HIV antigens of chronically infected, ART treated subjects results in poor induction of HIV-specific CD4 responses. In this study, we used a macaque model of ART treatment during chronic infection to study the virologic consequences of SIV antigen stimulation in lymph nodes early after immunization. Rhesus CMV (RhCMV) seropositive, Mamu A*01 positive rhesus macaques were chronically infected with SIVmac251 and treated with ART. The immune and viral responses to SIV gag and RhCMV pp65 antigen immunization in draining lymph nodes and peripheral blood were analyzed. Animals were immunized on contralateral sides with SIV gag and RhCMV pp65 encoding plasmids, which allowed lymph nodes draining each antigen to be obtained at the same time from the same animal for direct comparison.

Results
We observed that both SIV and RhCMV immunizations stimulated transient antigen-specific T cell responses in draining lymph nodes. The RhCMV-specific responses were potent and sustained (50 days post-immunization) in the periphery, while the SIV-specific responses were transient and extinguished quickly. The SIV antigen stimulation selectively induced transient SIV replication in draining lymph nodes.

Conclusions
The data are consistent with a model whereby viral replication in response to SIV antigen stimulation limits the generation of SIV antigen-specific responses and suggests a potential mechanism for the early loss and poor HIV-specific CD4+ T cell response observed in HIV-infected individuals.