bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring evidence-policy linkages in health research plans: A case study from six countries
Authors: Syed Shamsuzzoha B , Hyder Adnan A , Bloom Gerald , Sundaram Sandhya , Bhuiya Abbas , Zhenzhong Zhang , Kanjilal Barun , Oladepo Oladimeji , Pariyo George , Peters David H ,   Future Health Systems: Innovation for Equity
Published: March 2008

Abstract
The complex evidence-policy interface in low and middle income country settings is receiving increasing attention. Future Health Systems (FHS): Innovations for Equity, is a research consortium conducting health systems explorations in six Asian and African countries: Bangladesh, India, China, Afghanistan, Uganda, and Nigeria. The cross-country research consortium provides a unique opportunity to explore the research-policy interface. Three key activities were undertaken during the initial phase of this five-year project. First, key considerations in strengthening evidence-policy linkages in health system research were developed by FHS researchers through workshops and electronic communications. Four key considerations in strengthening evidence-policy linkages are postulated: development context; research characteristics; decision-making processes; and stakeholder engagement. Second, these four considerations were applied to research proposals in each of the six countries to highlight features in the research plans that potentially strengthen the research-policy interface and opportunities for improvement. Finally, the utility of the approach for setting research priorities in health policy and systems research was reflected upon. These three activities yielded interesting findings. First, developmental consideration with four dimensions – poverty, vulnerabilities, capabilities, and health shocks – provides an entry point in examining research-policy interfaces in the six settings. Second, research plans focused upon on the ground realities in specific countries strengthens the interface. Third, focusing on research prioritized by decision-makers, within a politicized health arena, enhances chances of research influencing action. Lastly, early and continued engagement of multiple stakeholders, from local to national levels, is conducive to enhanced communication at the interface. The approach described has four main utilities: first, systematic analyses of research proposals using key considerations ensure such issues are incorporated into research proposals; second, the exact meaning, significance, and inter-relatedness of these considerations can be explored within the research itself; third, cross-country learning can be enhanced; and finally, translation of evidence into action may be facilitated. Health systems research proposals in low and middle income countries should include reflection on transferring research findings into policy. Such deliberations may be informed by employing the four key considerations suggested in this paper in analyzing research proposals.
Careful adjustment of Epo non-viral gene therapy for β-thalassemic anaemia treatment
Authors: Fabre Emmanuelle E , Bigey Pascal , Beuzard Yves , Scherman Daniel , Payen Emmanuel 
Published: March 2008

AbstractBackgroundIn situproduction of a secreted therapeutic protein is one of the major gene therapy applications. Nevertheless, the plasmatic secretion peak of transgenic protein may be deleterious in many gene therapy applications including Epo gene therapy. Epo gene transfer appears to be a promising alternative to recombinant Epo therapy for severe anaemia treatment despite polycythemia was reached in many previous studies. Therefore, an accurate level of transgene expression is required for Epo application safety. The aim of this study was to adapt posology and administration schedule of a chosen therapeutic gene to avoid this potentially toxic plasmatic peak and maintain treatment efficiency. The therapeutic potential of repeated muscular electrotransfer of light Epo-plasmid doses was evaluated for anaemia treatment in β-thalassemic mice.MethodsMuscular electrotransfer of 1 μg, 1.5 μg, 2 μg 4 μg or 6 μg of Epo-plasmid was performed in β-thalassemic mice. Electrotransfer was repeated first after 3.5 or 5 weeks first as a initiating dose and then according to hematocrit evolution.ResultsMuscular electrotransfer of the 1.5 μg Epo-plasmid dose repeated first after 5 weeks and then every 3 months was sufficient to restore a subnormal hematrocrit in β-thalassemic mice for more than 9 months.ConclusionThis strategy led to efficient, long-lasting and non-toxic treatment of β-thalassemic mouse anaemia avoiding the deleterious initial hematocrit peak and maintaining a normal hematocrit with small fluctuation amplitude. This repeat delivery protocol of light doses of therapeutic gene could be applied to a wide variety of candidate genes as it leads to therapeutic effect reiterations and increases safety by allowing careful therapeutic adjustments.
Adrenergic gene polymorphisms and cardiovascular risk in the NHLBI-sponsored Women's Ischemia Syndrome Evaluation
Authors: Pacanowski Michael A , Zineh Issam , Li Haihong , Johnson B Delia , Cooper-DeHoff Rhonda M , Bittner Vera , McNamara Dennis M , Sharaf Barry L , Merz C Noel Bairey , Pepine Carl J , Johnson Julie A 
Published: March 2008

Abstract

Background
Adrenergic gene polymorphisms are associated with cardiovascular and metabolic phenotypes. We investigated the influence of adrenergic gene polymorphisms on cardiovascular risk in women with suspected myocardial ischemia.

Methods
We genotyped 628 women referred for coronary angiography for eight polymorphisms in the α1A-, β1-, β2- and β3-adrenergic receptors (ADRA1A, ADRB1, ADRB2, ADRB3, respectively), and their signaling proteins, G-protein β 3 subunit (GNB3) and G-protein α subunit (GNAS). We compared the incidence of death, myocardial infarction, stroke, or heart failure between genotype groups in all women and women without obstructive coronary stenoses.

Results
After a median of 5.8 years of follow-up, 115 women had an event. Patients with the ADRB1 Gly389 polymorphism were at higher risk for the composite outcome due to higher rates of myocardial infarction (adjusted hazard ratio [HR] 3.63, 95% confidence interval [95%CI] 1.17–11.28; Gly/Gly vs. Arg/Arg HR 4.14, 95%CI 0.88–19.6). The risk associated with ADRB1 Gly389 was limited to those without obstructive CAD (n = 400, Pinteraction = 0.03), albeit marginally significant in this subset (HR 1.71, 95%CI 0.91–3.19). Additionally, women without obstructive CAD carrying the ADRB3 Arg64 variant were at higher risk for the composite endpoint (HR 2.10, 95%CI 1.05–4.24) due to subtle increases in risk for all of the individual endpoints. No genetic associations were present in women with obstructive CAD.

Conclusion
In this exploratory analysis, common coding polymorphisms in the β1- and β3-adrenergic receptors increased cardiovascular risk in women referred for diagnostic angiography, and could improve risk assessment, particularly for women without evidence of obstructive CAD.

Trial Registration
ClinicalTrials.gov NCT00000554.
Dietary potassium supplementation improves vascular structure and ameliorates the damage caused by cerebral ischemia in normotensive rats
Authors: Rigsby Christine' S , Pollock David M , Dorrance Anne M 
Published: March 2008

Abstract

Background
Dietary potassium supplementation in hypertensive rats is cardioprotective. This protection includes a blood pressure independent reduction in the amount of damage caused by cerebral ischemia. Therefore, we hypothesized that dietary potassium supplementation would improve the outcome of ischemic stroke by improving cerebral vessel structure in normotensive rats.

Methods
Wistar Kyoto (WKY) rats were fed a high (HK) or low potassium (LK) diet for six weeks from six weeks of age. At the end of treatment, cerebral ischemia was induced by middle cerebral artery (MCA) occlusion and the resultant infarct was quantified and expressed as a percentage of the hemisphere infarcted (%HI). MCA structure was assessed in an additional group of rats using a pressurized arteriograph.

Results
The cerebral infarct was significantly smaller in rats fed the HK diet, compared to rats fed the LK diet (21 ± 5.4 vs 33.5 ± 4.8 %HI HK vs LK p < 0.05). Vessel structure was improved in WKY rats fed the HK diet as indicated by an increase in the MCA lumen (298 ± 6.3 vs 276 ± 3.9 μm HK vs LK p < 0.05) and outer diameters (322 ± 7.6 vs 305 ± 4.8 μm HK vs LK p < 0.05). Wall thickness and area were unchanged, suggesting an outward euthrophic remodelling process. The HK diet had no effect on body weight or telemetry blood pressure.

Conclusion
These studies are the first to show a beneficial effect of dietary potassium in rats with normal blood pressure.
The first case report of dental floss pick-related injury presenting with massive hemoptysis: A case report
Authors: Huang Chun-Ta , Ho Chao-Chi , Tsai Yi-Ju , Yang Pan-Chyr 
Published: March 2008

Abstract

Introduction
A tracheobronchial foreign body is a rarely mentioned cause of massive hemoptysis. Although an aspirated toothpick is a well-known cause of traumatic injury to the respiratory tract, a similar device called a dental floss pick, which is much larger than a toothpick, has never been described as a tracheobronchial foreign body.

Case presentation
We report a case of massive hemoptysis in a 32-year-old man due to a dental floss pick in the left main bronchus. Flexible fiberoptic bronchoscopy was successful in removing the foreign body.

Conclusion
Tracheobronchial foreign body can be a medical emergency requiring immediate intervention and massive hemoptysis may be the presenting symptom. Flexible fiberoptic bronchoscopy is recommended as the first-line treatment modality for tracheobronchial foreign body removal. A dental floss pick may present as a tracheobronchial foreign body and can reside in the airway asymptomatically for many years.
Differentiation of angiogenic burden in human cancer xenografts using a perfusion-type optical contrast agent (SIDAG)
Authors: Wall Alexander , Persigehl Thorsten , Hauff Peter , Licha Kai , Schirner Michael , Müller Silke , von Wallbrunn Angelika , Matuszewski Lars , Heindel Walter , Bremer Christoph 
Published: March 2008

Abstract
Introduction
Use of fluorescence imaging in oncology is evolving rapidly, and nontargeted fluorochromes are currently being investigated for clinical application. Here, we investigated whether the degree of tumour angiogenesis can be assessed in vivo by planar and tomographic methods using the perfusion-type cyanine dye SIDAG (1,1'-bis- [4-sulfobutyl]indotricarbocyanine-5,5'-dicarboxylic acid diglucamide monosodium).

Method
Mice were xenografted with moderately (MCF7, DU4475) or highly vascularized (HT1080, MDA-MB435) tumours and scanned up to 24 hours after intravenous SIDAG injection using fluorescence reflectance imaging. Contrast-to-noise ratio was calculated for all tumours, and fluorochrome accumulation was quantified using fluorescence-mediated tomography. The vascular volume fraction of the xenografts, serving as a surrogate marker for angiogenesis, was measured using magnetic resonance imaging, and blood vessel profile (BVP) density and vascular endothelial growth factor expression were determined.

Results
SIDAG accumulation correlated well with angiogenic burden, with maximum contrast to noise ratio for MDA-MB435 (P < 0.0001), followed by HT1080, MCF7 and DU4475 tumours. Fluorescence-mediated tomography revealed 4.6-fold higher fluorochrome concentrations in MDA-MB435 than in DU4475 tumours (229 ± 90 nmol/l versus 49 ± 22 nmol/l; P < 0.05). The vascular volume fraction was 4.5-fold (3.58 ± 0.9% versus 0.8 ± 0.53%; P < 0.01), blood vessel profile density 5-fold (399 ± 36 BVPs/mm2 versus 78 ± 16 BVPs/mm2) and vascular endothelial growth factor expression 4-fold higher for MDA-MB435 than for DU4475 tumours.

Conclusion
Our data suggest that perfusion-type cyanine dyes allow assessment of angiogenesis in vivo using planar or tomographic imaging technology. They may thus facilitate characterization of solid tumours.
Functionally important segments in proteins dissected using Gene Ontology and geometric clustering of peptide fragments
Authors: Manikandan Karuppasamy , Pal Debnath , Ramakumar Suryanarayanarao , Brener Nathan E , Iyengar Sitharama S , Seetharaman Guna 
Published: March 2008

AbstractWe have developed a geometric clustering algorithm using backbone φ,ψ angles to group conformationally similar peptide fragments of any length. By labeling each fragment in the cluster with the level-specific Gene Ontology 'molecular function' term of its protein, we are able to compute statistics for molecular function-propensity and p-value of individual fragments in the cluster. Clustering-cum-statistical analysis for peptide fragments 8 residues in length and with only trans peptide bonds shows that molecular function propensities ≥20 and p-values ≤0.05 can dissect fragments within a protein linked to the molecular function.
Pivotal Advance: Th-1 cytokines inhibit, and Th-2 cytokines promote fibrocyte differentiation
Authors: Shao Diane D , Suresh Rahul , Vakil Varsha , Gomer Richard H , Pilling Darrell 
Published: March 2008

AbstractCD14+ peripheral blood monocytes can differentiate into fibroblast-like cells called fibrocytes, which are associated with and are at least partially responsible for wound healing and fibrosis in multiple organ systems. Signals regulating fibrocyte differentiation are poorly understood. In this study, we find that when added to human PBMCs cultured in serum-free medium, the profibrotic cytokines IL-4 and IL-13 promote fibrocyte differentiation without inducing fibrocyte or fibrocyte precursor proliferation. We also find that the potent, antifibrotic cytokines IFN-γ and IL-12 inhibit fibrocyte differentiation. In our culture system, IL-1β, IL-3, IL-6, IL-7, IL-16, GM-CSF, M-CSF, fetal liver tyrosine kinase 3, insulin growth factor 1, vascular endothelial growth factor, and TNF-α had no significant effect on fibrocyte differentiation. IL-4, IL-13, and IFN-γ act directly on monocytes to regulate fibrocyte differentiation, and IL-12 acts indirectly, possibly through CD16-positive NK cells. We previously identified the plasma protein serum amyloid P (SAP) as a potent inhibitor of fibrocyte differentiation. When added together, the fibrocyte-inhibitory activity of SAP dominates the profibrocyte activities of IL-4 and IL-13. The profibrocyte activities of IL-4 and IL-13 and the fibrocyte-inhibitory activities of IFN-γ and IL-12 counteract each other in a concentration-dependent manner. These results indicate that the complex mix of cytokines and plasma proteins present in inflammatory lesions, wounds, and fibrosis will influence fibrocyte differentiation.
Efficacy, Toxicity, and Quality of Life in Older Women With Early-Stage Breast Cancer Treated With Letrozole or Placebo After 5 Years of Tamoxifen: NCIC CTG Intergroup Trial MA.17
Authors: Muss Hyman B. , Tu Dongsheng , Ingle James N. , Martino Silvana , Robert Nicholas J. , Pater Joseph L. , Whelan Timothy J. , Palmer Michael J. , Piccart Martine J. , Shepherd Lois E. , Pritchard Kathleen I. , He Zhi , Goss Paul E. 
Published: March 2008

Purpose National Cancer Institute of Canada Clinical Trials Group trial MA.17 randomly assigned 5,187 postmenopausal, hormone-receptor–positive patients with early breast cancer who completed 5 years of tamoxifen to receive either letrozole or placebo. At 30 months median follow-up, letrozole significantly improved disease-free survival (DFS) in all patients and overall survival (OS) in node-positive patients. Breast cancer incidence increases with age and more than 1,300 women age 70 years or older were enrolled onto MA.17, making it ideal to explore the benefits, toxicities, and quality of life (QOL) impact of letrozole on older women. Patients and Methods In this study, 5,169 randomly assigned patients were divided into three age groups: younger than 60 years (n = 2,152), 60 to 69 years (n = 1,694), and ≥ 70 years (n = 1,323). Log-rank test was used to compare differences in DFS, distant-disease–free survival, and OS between age and treatment groups, and Cox models were used to estimate hazard ratios and associated 95% CIs. QOL was measured using the Medical Outcomes Short Form-36 and the Menopause-Specific Quality-of-Life questionnaire. Results At 4 years, DFS demonstrated statistically significant differences favoring letrozole only in patients age younger than 60 years (hazard ratio = 0.46; P = .0004); there was no interaction between age and treatment, indicating a similar effect of letrozole among all age groups. There was no difference in toxicity or QOL at 24 months among letrozole- and placebo-treated patients age ≥ 70 years. Conclusion Healthy patients age 70 years and older completing 5 years of tamoxifen should be considered for extended adjuvant therapy with letrozole.
Letrozole Compared With Tamoxifen for Elderly Patients With Endocrine-Responsive Early Breast Cancer: The BIG 1-98 Trial
Authors: Crivellari Diana , Sun Zhuoxin , Coates Alan S. , Price Karen N. , Thürlimann Beat , Mouridsen Henning , Mauriac Louis , Forbes John F. , Paridaens Robert J. , Castiglione-Gertsch Monica , Gelber Richard D. , Colleoni Marco , Láng István , Del Mastro Lucia , Gladieff Laurence , Rabaglio Manuela , Smith Ian E. , Chirgwin Jacquie H. , Goldhirsch Aron 
Published: March 2008

Purpose To explore potential differences in efficacy, treatment completion, and adverse events (AEs) in elderly women receiving adjuvant tamoxifen or letrozole for five years in the Breast International Group (BIG) 1-98 trial. Methods This report includes the 4,922 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial. The median follow-up was 40.4 months. Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was used to examine the patterns of differences in disease-free survival and incidences of AEs according to age. In addition, three categoric age groups were defined: “younger postmenopausal” patients were younger than 65 years (n = 3,127), “older” patients were 65 to 74 years old (n = 1,500), and “elderly” patients were 75 years of age or older (n = 295). Results Efficacy results for subpopulations defined by age were similar to the overall trial results: Letrozole significantly improved disease-free survival (DFS), the primary end point, compared with tamoxifen. Elderly patients were less likely to complete trial treatment, but at rates that were similar in the two treatment groups. The incidence of bone fractures, observed more often in the letrozole group, did not differ by age. In elderly patients, letrozole had a significantly higher incidence of any grade 3 to 5 protocol-specified non-fracture AE compared with tamoxifen (P = .002), but differences were not significant for thromboembolic or cardiac AEs. Conclusion Adjuvant treatment with letrozole had superior efficacy (DFS) compared with tamoxifen in all age groups. On the basis of a small number of patients older than 75 years (6%), age per se should not unduly affect the choice of adjuvant endocrine therapy.
Integrin-Mediated Expression of Bone Formation-Related Genes in Osteoblast-Like Cells in Response to Fluid Shear Stress: Roles of Extracellular Matrix, Shc, and Mitogen-Activated Protein Kinase
Authors: Lee Ding-Yu , Yeh Chiuan-Ren , Chang Shun-Fu , Lee Pei-Ling , Chien Shu , Cheng Cheng-Kung , Chiu Jeng-Jiann 
Published: March 2008

Abstract
Integrins play significant roles in mechanical responses of cells on extracellular matrix (ECM). We studied the roles of integrins and ECM proteins (fibronectin [FN], type I collagen [COL1], and laminin [LM]) in shear-mediated signaling and the expression of bone formation-related genes (early growth response-1 [Egr-1], c-fos, cyclooxygenase-2 [Cox-2], and osteopontin [OPN]) in human osteosarcoma MG63 cells. MG63 cells on FN, COL1, and LM were kept as controls or subjected to shear stress (12 dynes/cm2), and the association of αvβ3 and β1 integrins with Shc, phosphorylation of mitogen-activated protein kinases (MAPKs, i.e., extracellular signal-regulated kinase [ERK], c-jun-NH2-terminal kinase [JNK], and p38), and expressions of Egr-1, c-fos, Cox-2, and OPN were determined. In MG63 cells, shear stress induces sustained associations of αvβ3 and β1 with Shc when seeded on FN, but sustained associations of only β1 with Shc when seeded on COL1/LM. Shear inductions of MAPKs and bone formation-related genes were sustained (24 h) in cells on FN, but some of these responses were transient in cells on COL1/LM. The shear activations of ERK, JNK, and p38 were mediated by integrins and Shc, and these pathways differentially modulated the downstream bone formation-related gene expression. Our findings showed that β1 integrin plays predominant roles for shear-induced signaling and gene expression in osteoblast-like MG63 cells on FN, COL1, and LM and that αvβ3 also plays significant roles for such responses in cells on FN. The β1/Shc association leads to the activation of ERK, which is critical for shear induction of bone formation-related genes in osteoblast-like cells.
Die Aussetzung als strafrechtsdogmatischer Mikrokosmos
Authors: Heger Martin 
Published: March 2008

Abstract

I. Einleitung

Seit jeher ist der Straftatbestand der Aussetzung vor allem Gegenstand wissenschaftlicher Kontroversen. Seine praktische Bedeutung war bis zur Neufassung durch das 6. Strafrechtsreformgesetz (StrRG) gering: und obwohl die tatbestandliche Ausweitung von § 221 eigentlich das Gegenteil erwarten ließ, spricht das weitgehende Fehlen veröffentlichter Rechtsprechung zur Neufassung des § 221 für eine weiterhin geringe praktische Relevanz. Vielleicht lassen die bereits unmittelbar nach der Neufassung zutage getretenen dogmatischen Kontroversen die Strafjustiz bei der Anwendung von § 221 zögern. So wäre in einem kürzlich in Berlin entschiedenen Fall, als ein Vater seine dreijährige Tochter vier Stunden im Strandbad Weißensee in einem eingezäunten Spielbereich zurückgelassen hat, um währenddessen ein Fitnessstudio aufzusuchen, neben einer Verurteilung wegen Verletzung der Fürsorge- und Erziehungspflicht (§ 171) auch eine Strafbarkeit wegen Aussetzung denkbar gewesen, zumal § 171 durch § 221 verdrängt wird.
Intergenerational Earnings Mobility in Italy
Authors: Mocetti Sauro 
Published: March 2008

Abstract
This paper contributes to the growing number of studies on intergenerational mobility by providing a measure of earnings elasticity for Italy. The absence of an appropriate data set is overcome by adopting the two-sample two-stage least squares method. The analysis, based on the Survey of Household Income and Wealth, shows that intergenerational mobility is lower in Italy than it is in other developed countries. We also examine the reasons why the long-term labor market success of children is related to that of their fathers.