bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactive oxygen species-selective regulation of aortic inflammatory gene expression in Type 2 diabetes
Authors: Martín Alejandra San , Du Pingfeng , Dikalova Anna , Lassègue Bernard , Aleman María , Góngora María Carolina , Brown Kathryn , Joseph Giji , Harrison David G. , Taylor W. Robert , Jo Hanjoong , Griendling Kathy K.
Published: January 2007

Vascular diseases are a major complication of diabetes mellitus (DM), although their etiology is poorly understood. NADPH oxidase-derived reactive oxygen species (ROS) production and inflammation are potential mediators of DM-associated vascular diseases. Using db/db mice as a Type 2 diabetes model, we examined the relationship between NADPH oxidase-derived ROS and vascular inflammation. When compared with control m+/+ mice, aortas from 4- and 12-wk-old db/db mice had higher NADPH oxidase activity and increased superoxide levels, leading to NADPH oxidase-dependent impaired vasodilation at 12 wk. Diabetes progression from 4 to 12 wk led to increased Nox1, Nox4, and p22 phox subunit mRNAs and induced the expression of a group of matrix remodeling-related cytokines: connective tissue growth factor (CTGF), bone morphogenetic protein 4 (BMP-4), and osteopontin (OPN). After 8 wk of treatment with the superoxide scavenger Tempol, 12-wk-old db/db mice had lower superoxide production, reduced plasma glucose and lipids, and lower BMP-4 and OPN protein expression when compared with nontreated mice. No changes were observed with Tempol in CTGF or m+/+ mice. The ability of Tempol to reverse ROS production as well as OPN and BMP-4, but not CTGF, induction suggests that DM-induced vascular inflammation involves both ROS-sensitive and -insensitive pathways.
Estrogen modulates TNF-α-induced inflammatory responses in rat aortic smooth muscle cells through estrogen receptor-β activation
Authors: Xing Dongqi , Feng Wenguang , Miller Andrew P. , Weathington Nathaniel M. , Chen Yiu-Fai , Novak Lea , Blalock J. Edwin , Oparil Suzanne
Published: January 2007

We have previously shown that 17β-estradiol (E2) attenuates responses to endoluminal injury of the rat carotid artery, at least in part, by decreasing inflammatory mediator expression and neutrophil infiltration into the injured vessel, with a major effect on the neutrophil-specific chemokine cytokine-induced neutrophil chemoattractant (CINC)-2β. Current studies tested the hypothesis that activated rat aortic smooth muscle cells (RASMCs) express these same inflammatory mediators and induce neutrophil migration in vitro and that E2 inhibits these processes by an estrogen receptor (ER)-dependent mechanism. Quiescent RASMCs treated with E2, the ERα-selective agonist propyl pyrazole triol (PPT), the ERβ-selective agonist diarylpropiolnitrile (DPN), or vehicle for 24 h were stimulated with tumor necrosis factor (TNF)-α and processed for real-time RT-PCR, ELISA, or chemotaxis assays 6 h later. TNF-α stimulated and E2 attenuated mRNA expression of inflammatory mediators, including P-selectin, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, monocyte chemoattractant protein (MCP)-1, and CINC-2β. DPN dose dependently attenuated TNF-α-induced mRNA expression of CINC-2β, whereas PPT had no effect. The anti-inflammatory effects of DPN and E2 were blocked by the nonselective ER-inhibitor ICI-182,780. ELISA confirmed the TNF-α-induced increase and E2-induced inhibition of CINC-2β protein secretion. TNF-α treatment of RASMCs produced a twofold increase in neutrophil chemotactic activity of conditioned media; E2 and DPN treatment markedly inhibited this effect. E2 inhibits activated RASMC proinflammatory mediator expression and neutrophil chemotactic activity through an ERβ-dependent mechanism.
Effect of elastin degradation on carotid wall mechanics as assessed by a constituent-based biomechanical model
Authors: Fonck E. , Prod'hom G. , Roy S. , Augsburger L. , Rüfenacht D. A. , Stergiopulos N.
Published: January 2007

Arteries display a nonlinear anisotropic behavior dictated by the elastic properties and structural arrangement of its main constituents, elastin, collagen, and vascular smooth muscle. Elastin provides for structural integrity and for the compliance of the vessel at low pressure, whereas collagen gives the tensile resistance required at high pressures. Based on the model of Zulliger et al. (Zulliger MA, Rachev A, Stergiopulos N. Am J Physiol Heart Circ Physiol 287: H1335–H1343, 2004), which considers the contributions of elastin, collagen, and vascular smooth muscle cells (VSM) in an explicit form, we assessed the effects of enzymatic degradation of elastin on biomechanical properties of rabbit carotids. Pressure-diameter curves were obtained for controls and after elastin degradation, from which elastic and structural properties were derived. Data were fitted into the model of Zulliger et al. to assess elastic constants of elastin and collagen as well as the characteristics of the collagen engagement profile. The arterial segments were also prepared for histology to visualize and quantify elastin and collagen. Elastase treatment leads to a diameter enlargement, suggesting the existence of significant compressive prestresses within the wall. The elastic modulus was more ductile in treated arteries at low circumferential stretches and significantly greater at elevated circumferential stretches. Abrupt collagen fiber recruitment in elastase-treated arteries leads to a much stiffer vessel at high extensions. This change in collagen engagement properties results from structural alterations provoked by the degradation of elastin, suggesting a clear interaction between elastin and collagen, often neglected in previous constituent-based models of the arterial wall.
Cellular mechanisms of burn-related changes in contractility and its prevention by mesenteric lymph ligation
Authors: Kawai Kentaro , Kawai Tomoko , Sambol Justin T. , Xu Da-Zhong , Yuan Zhiqiang , Caputo Francis J. , Badami Chirag D. , Deitch Edwin A. , Yatani Atsuko
Published: January 2007

Major burn injury results in impairment of left ventricular (LV) contractile function. There is strong evidence to support the involvement of gut-derived factor(s) transported in mesenteric lymph in the development of burn-related contractile dysfunction; i.e., mesenteric lymph duct ligation (LDL) prevents burn-related contractile depression. However, the cellular mechanisms for altered myocardial contractility of postburn hearts are largely unknown, and the cellular basis for the salutary effects of LDL on cardiac function have not been investigated. We examined contractility, Ca2+ transients, and L-type Ca2+ currents ( ICa) in LV myocytes isolated from four groups of rats: 1) sham burn, 2) sham burn with LDL (sham + LDL), 3) burn (≈40% of total body surface area burn), and 4) burn with LDL (burn + LDL). Myocytes isolated from hearts at 24 h postburn had a depressed contractility (≈20%) at baseline and blunted responsiveness to elevation of bath Ca2+. Myocyte contractility was comparable in sham + LDL and sham burn hearts. LDL completely prevented burn-related changes in myocyte contractility. Mechanistically, the decrease in contractility in myocytes from postburn hearts occurred with a decrease in the amplitude of Ca2+ transients (≈20%) without changes in resting Ca2+ or Ca2+ content of the sarcoplasmic reticulum. On the other hand, ICa density was decreased (≈30%) in myocytes from postburn hearts, with unaltered voltage-dependent properties. Thus burn-related myocardial contractile dysfunction is linked with depressed myocyte contractility associated with a decrease in ICa density. These findings also provide strong evidence that mesenteric lymph is involved in the onset of burn-related cardiomyocyte dysfunction.
Hydrogen sulfide mediates vasoactivity in an O2-dependent manner
Authors: Koenitzer Jeffrey R. , Isbell T. Scott , Patel Hetal D. , Benavides Gloria A. , Dickinson Dale A. , Patel Rakesh P. , Darley-Usmar Victor M. , Lancaster Jack R. , Doeller Jeannette E. , Kraus David W.
Published: January 2007

Hydrogen sulfide (H2S) has recently been shown to have a signaling role in vascular cells. Similar to nitric oxide (NO), H2S is enzymatically produced by amino acid metabolism and can cause posttranslational modification of proteins, particularly at thiol residues. Molecular targets for H2S include ATP-sensitive K+channels, and H2S may interact with NO and heme proteins such as cyclooxygenase. It is well known that the reactions of NO in the vasculature are O2dependent, but this has not been addressed in most studies designed to elucidate the role of H2S in vascular function. This is important, since H2S reactions can be dramatically altered by the high concentrations of O2used in cell culture and organ bath experiments. To test the hypothesis that the effects of H2S on the vasculature are O2dependent, we have measured real-time levels of H2S and O2in respirometry and vessel tension experiments, as well as the associated vascular responses. A novel polarographic H2S sensor developed in our laboratory was used to measure H2S levels. Here we report that, in rat aorta, H2S concentrations that mediate rapid contraction at high O2levels cause rapid relaxation at lower physiological O2levels. At high O2, the vasoconstrictive effect of H2S suggests that it may not be H2S per se but, rather, a putative vasoactive oxidation product that mediates constriction. These data are interpreted in terms of the potential for H2S to modulate vascular tone in vivo.
Specific recruitment of CD4+CD25++regulatory T cells into the allograft in heart transplant recipients
Authors: Schmidt-Lucke Caroline , Aicher Alexandra , Romagnani Paola , Gareis Björn , Romagnani Sergio , Zeiher Andreas M. , Dimmeler Stefanie
Published: January 2007

Regulatory T cells (Treg) migrate into allografts and induce tolerance of the graft. Immunosuppressive Tregare found among CD4+CD25++T cells and specifically express the forkhead/winged transcription factor FOXP3. We hypothesized that activated T cells and Tregmight modulate the ongoing inflammation of the cardiac allograft (CA) and that the chronic inflammatory environment might influence the balance between these distinct cell types. We therefore quantified levels of activated T cells and CD4+CD25++Tregin the cardiac and systemic circulation in heart transplant recipients. To determine the influence of the allograft passage on these cells, transcardiac gradients were evaluated in CA recipients ( n = 22) compared with controls ( n = 18). Systemic levels of circulating Tregwere significantly lower in CA recipients (8.9 ± 1.3 μl) compared with controls (15.8 ± 1.6 μl; P = 0.002). Similarly, the proportion of Tregrelated to the total leukocyte number was significantly lower in CA recipients ( P < 0.01). In contrast, systemic levels of circulating activated CD4+T cells and of circulating plasmacytoid dendritic cells were similar in both groups. In transplant patients, numbers of Tregsignificantly decreased during transcardiac passage (3.0 ± 0.3 to 2.4 ± 0.3% of CD4+T cells, P < 0.01), and FOXP3+T cells invaded into the allograft. In contrast, numbers of activated CD4+T cells increased during passage through the allograft, even in the presence of effective immunosuppression. In conclusion, numbers of circulating immunosuppressive Tregare reduced in transplant recipients. Recruitment of Treginto the cardiac allograft during transcoronary passage may induce graft tolerance during subclinical inflammation potentially influencing allograft vasculopathy.
Mitochondrial reactive oxygen species-mediated signaling in endothelial cells
Authors: Zhang David X. , Gutterman David D.
Published: January 2007

Once thought of as toxic by-products of cellular metabolism, reactive oxygen species (ROS) have been implicated in a large variety of cell-signaling processes. Several enzymatic systems contribute to ROS production in vascular endothelial cells, including NA(D)PH oxidase, xanthine oxidase, uncoupled endothelial nitric oxide synthase, and the mitochondrial electron transport chain. The respiratory chain is the major source of ROS in most mammalian cells, but the role of mitochondria-derived ROS in vascular cell signaling has received little attention. A new paradigm has evolved in recent years postulating that, in addition to producing ATP, mitochondria also play a key role in cell signaling and regulate a variety of cellular functions. This review focuses on the emerging role of mitochondrial ROS as signaling molecules in vascular endothelial cells. Specifically, we discuss some recent findings that indicate that mitochondrial ROS regulate vascular endothelial function, focusing on major sites of ROS production in endothelial mitochondria, factors modulating mitochondrial ROS production, the physiological and clinical implications of endothelial mitochondrial ROS, and methodological considerations in the study of mitochondrial contribution to vascular ROS generation.
Sex-specific and exercise-acquired cardioprotection is abolished by sarcolemmal KATP channel blockade in the rat heart
Authors: Chicco Adam J. , Johnson Micah S. , Armstrong Casey J. , Lynch Joshua M. , Gardner Ryan T. , Fasen Geoff S. , Gillenwater Cody P. , Moore Russell L.
Published: January 2007

The present study was conducted to determine whether the infarct sparing effect of short-term exercise is dependent on the operation of the myocardial sarcolemmal ATP-sensitive K+ (KATP) channel. Adult male and female Sprague-Dawley rats were exercised on a motorized treadmill for 5 days. Twenty-four hours following the training or sedentary period, hearts were isolated and exposed to 1 h of regional ischemia followed by 2 h of reperfusion on a modified Langendorf apparatus in the presence or absence of the sarcolemmal KATP channel antagonist HMR-1098 (30 μM). Following the ischemia-reperfusion protocol, infarct size was determined as a percentage of the total ischemic zone at risk (ZAR). Short-term exercise reduced infarct size by 24% in males (32 ± 2% of ZAR; P < 0.01) and by 18% in females (26 ± 2% of ZAR; P < 0.05). Sarcolemmal KATP channel blockade abolished the training-induced cardioprotection in both males and females, increasing infarct size to 43 ± 3% and 52 ± 4% of ZAR, respectively. In the absence of HMR-1098, infarct size was significantly lower in sedentary females than in males (33 ± 4% vs. 42 ± 2% of ZAR, respectively; P < 0.01). However, the presence of HMR-1098 abolished this sex difference, increasing infarct size by 58% in the sedentary females ( P < 0.01) but having no effect on infarct size in sedentary males. This study demonstrates that the sex-specific and exercise-acquired resistance to myocardial ischemia-reperfusion injury is dependent on sarcolemmal KATP activity during ischemia.
Rapid onset of gene expression in lung, supportive of formation of alveolar septa, induced by refeeding mice after calorie restriction
Authors: Massaro Donald , Alexander Emma , Reiland Kristin , Hoffman Eric P. , Massaro Gloria DeCarlo , Clerch Linda Biadasz
Published: January 2007

Alveolar regenerative gene expression is unidentified partly because its onset, after a regenerative stimulus, is unknown. Toward addressing this void, we used a mouse model in which calorie restriction produces alveolar loss, and ad libitum access to food after calorie restriction induces alveolar regeneration. We selected four processes (cell replication, angiogenesis, extracellular matrix remodeling, and guided cell motion) that would be required to convert a flat segment of alveolar wall into a septum that increases gas-exchange surface area. Global gene expression supportive of processes required to form a septum was present within 3 h of allowing calorie-restricted mice food ad libitum. One hour after providing calorie-restricted mice food ad libitum, RNA-level expression supportive of cell replication was present with little evidence of expression supportive of angiogenesis, extracellular matrix remodeling, or guided cell motion. Cell replication was more directly assayed by measuring DNA synthesis in lung. This measurement was made 3 h after allowing calorie-restricted mice food ad libitum because translation may be delayed. Ad libitum food intake, following calorie restriction, elevated DNA synthesis. Thus RNA expression 1 h after allowing calorie-restricted mice food ad libitum supported increased cell replication; measurements at 3 h revealed increased DNA synthesis and RNA expression, supportive of the three other processes required to form a septum. These findings identify the first hour after providing calorie-restricted mice ad libitum access to food as the onset of gene expression in this model that supports processes needed for alveolar regeneration.
The human airway trypsin-like protease modulates the urokinase receptor (uPAR, CD87) structure and functions
Authors: Beaufort Nathalie , Leduc Dominique , Eguchi Hiroshi , Mengele Karin , Hellmann Daniela , Masegi Tsukio , Kamimura Takashi , Yasuoka Susumu , Fend Falko , Chignard Michel , Pidard Dominique
Published: January 2007

The human airway trypsin-like protease (HAT) is a respiratory epithelium-associated, type II transmembrane serine protease, which is also detected as an extracellular enzyme in lung fluids during airway inflammatory disorders. We have evaluated its capacity to affect the urokinase-type plasminogen activator receptor (uPAR), a membrane glycolipid-anchored, three-domain (D1D2D3) glycoprotein that plays a crucial role in innate immunity and inflammation by supporting cell migration and matrix degradation, with structure and biological properties that can be regulated via limited endoproteolysis. With the use of immunoblotting, flow immunocytometry, and ELISA analyses applied to a recombinant uPAR protein and to uPAR-expressing monocytic and human bronchial epithelial cells, it was shown that exposure of uPAR to soluble HAT in the range of 10–500 nM resulted in the proteolytic processing of the full-length (D1D2D3) into the truncated (D2D3) species, with cleavage occurring in the D1 to D2 linker sequence after arginine residues at position 83 and 89. Using immunohistochemistry, we found that both HAT and uPAR were expressed in the human bronchial epithelium. Moreover, transient cotransfection in epithelial cells showed that membrane coexpression of the two partners produced a constitutive and extensive shedding of the D1 domain, occurring for membrane-associated HAT concentrations in the nanomolar range. Because the truncated receptor was found to be unable to bind two of the major uPAR ligands, the adhesive matrix protein vitronectin and the serine protease urokinase, it thus appears that proteolytic regulation of uPAR by HAT is likely to modulate cell adherence and motility, as well as tissue remodeling during the inflammatory response in the airways.
NHE-RF1 protein rescues ΔF508-CFTR function
Authors: Bossard Florian , Robay Amal , Toumaniantz Gilles , Dahimene Shehrazade , Becq Frédéric , Merot Jean , Gauthier Chantal
Published: January 2007

In cystic fibrosis (CF), the ΔF508-CFTR anterograde trafficking from the endoplasmic reticulum to the plasma membrane is inefficient. New strategies for increasing the delivery of ΔF508-CFTR to the apical membranes are thus pathophysiologically relevant targets to study for CF treatment. Recent studies have demonstrated that PDZ-containing proteins play an essential role in determining polarized plasma membrane expression of ionic transporters. In the present study we have hypothesized that the PDZ-containing protein NHE-RF1, which binds to the carboxy terminus of CFTR, rescues ΔF508-CFTR expression in the apical membrane of epithelial cells. The plasmids encoding ΔF508-CFTR and NHE-RF1 were intranuclearly injected in A549 or Madin-Darby canine kidney (MDCK) cells, and ΔF508-CFTR channel activity was functionally assayed using SPQ fluorescent probe. Cells injected with ΔF508-CFTR alone presented a low chloride channel activity, whereas its coexpression with NHE-RF1 significantly increased both the basal and forskolin-activated chloride conductances. This last effect was lost with ΔF508-CFTR deleted of its 13 last amino acids or by injection of a specific NHE-RF1 antisense oligonucleotide, but not by NHE-RF1 sense oligonucleotide. Immunocytochemical analysis performed in MDCK cells transiently transfected with ΔF508-CFTR further revealed that NHE-RF1 specifically determined the apical plasma membrane expression of ΔF508-CFTR but not that of a trafficking defective mutant potassium channel (KCNQ1). These data demonstrate that the modulation of the expression level of CFTR protein partners, like NHE-RF1, can rescue ΔF508-CFTR activity.
Distribution of Clara cell secretory protein expression in the tracheobronchial airways of rhesus monkeys
Authors: Coppens John T. , Van Winkle Laura S. , Pinkerton Kent , Plopper Charles G.
Published: January 2007

Clara cell secretory protein (CCSP) is a protective lung protein that is believed to have antioxidant, immunomodulatory, and anticarcinogenic properties; to be present in all adult mammals; and to be well conserved in rodents, humans, and nonhuman primates. The rationale for this study is to define the distribution and abundance of CCSP in the airway epithelium and lavage fluid of the adult rhesus monkey and to provide information for evaluating CCSP as a marker of Clara cells and as a biomarker of lung health. Lung tissue and lavage fluid from 3-yr-old rhesus monkeys were examined using histopathology and immunohistochemistry. Proximal bronchi, midlevel bronchi, and terminal/respiratory bronchioles were compared for immunohistochemical localization of CCSP in three-dimensional whole mounts as well as in paraffin and Araldite sections. Immunoreactive CCSP was found in nonciliated cells throughout the airway epithelium. Proximal and midlevel airways had the highest labeling. CCSP decreased in distal airways, and respiratory bronchioles had little to no CCSP. CCSP in the most distal airways was in tall cuboidal cells adjacent to the pulmonary artery. Although a large number of cells were present in the terminal bronchioles that would be classified as Clara cells based on morphology (nonciliated cells with apical protrusions), only a small number stained positively for immunoreactive CCSP. Semiquantitative analysis of Western blots indicated that changes in lavage CCSP are consistent with, and may be predictive of, overall CCSP levels in the airway epithelium in this primate species that is phylogenetically similar to humans.
p42/p44 MAP kinase activation is localized to caveolae-free membrane domains in airway smooth muscle
Authors: Gosens Reinoud , Dueck Gordon , Gerthoffer William T. , Unruh Helmut , Zaagsma Johan , Meurs Herman , Halayko Andrew J.
Published: January 2007

Caveolae are abundant plasma membrane invaginations in airway smooth muscle that may function as preorganized signalosomes by sequestering and regulating proteins that control cell proliferation, including receptor tyrosine kinases (RTKs) and their signaling effectors. We previously demonstrated, however, that p42/p44 MAP kinase, a critical effector for cell proliferation, does not colocalize with RTKs in caveolae of quiescent airway myocytes. Therefore, we investigated the subcellular sites of growth factor-induced MAP kinase activation. In quiescent myocytes, though epidermal growth factor receptor (EGFR) was almost exclusively found in caveolae, p42/p44 MAP kinase, Grb2, and Raf-1 were absent from these membrane domains. EGF induced concomitant phosphorylation of caveolin-1 and p42/p44 MAP kinase; however, EGF did not promote the localization of p42/p44 MAP kinase, Grb2, or Raf-1 to caveolae. Interestingly, stimulation of muscarinic M2 and M3 receptors that were enriched in caveolae-deficient membranes also induced p42/p44 MAP kinase phosphorylation, but this occurred in the absence of caveolin-1 phosphorylation. This suggests that the localization of receptors to caveolae and interaction with caveolin-1 is not directly required for p42/p44 MAP kinase phosphorylation. Furthermore, we found that EGF exposure induced rapid translocation of EGFR from caveolae to caveolae-free membranes. EGFR trafficking coincided temporally with EGFR and p42/p44 MAP kinase phosphorylation. Collectively, this indicates that although caveolae sequester some receptors associated with p42/p44 MAP kinase activation, the site of its activation is associated with caveolae-free membrane domains. This reveals that directed trafficking of plasma membrane EGFR is an essential element of signal transduction leading to p42/p44 MAP kinase activation.
The Methodological Contribution of Günther Zuntz to the Text of Hebrews
Authors: Güting Eberhard
Published: January 2007

This essay seeks to bring into focus the methodological presuppositions and the specific approach of the textual critic and classical scholar Günther Zuntz. In his study, The Text of the Epistles (1953), Zuntz redefined the task of philological analysis. He insisted that recensio, examinatio, and emendatio need to be applied to the enormously accumulating evidence. Accepting Griesbach's notion of three large regional sources of New Testament texts, Zuntz criticized Griesbach's assumption that recensional activities, exerted a formative influence upon early regional texts. He was willing to demonstrate that each source of transmission is capable of testifying independently.
Approaches to Scripture in the Fourth Gospel and the Qumran Pesharim
Authors: Witmer Stephen
Published: January 2007

Many scholars have noticed similarities between the Fourth Gospel and the Qumran pesharim in their approaches to Scripture. However, comparisons between the two corpora are usually made in passing, often do not offer careful definition of what constitutes the pesher genre, and tend to isolate certain features for comparison. This essay begins from the conviction that it is important to carefully define the pesher genre before comparing it with the Fourth Gospel. After developing a definition based primarily on form and content, a broad-based comparison with the Fourth Gospel is carried out, giving attention to some previously overlooked similarities. In particular, it is demonstrated that John 6:31-58 is perhaps more pesher-like than any other passage in the Fourth Gospel. However, it is concluded that, while there are impressive similarities between the Fourth Gospel's exegesis and that of the pesharim, the differences are sufficient that it is not justifiable to speak of the former as pesher exegesis.
The Date of the Fannius Letter: Jos. Ant. 14.233
Authors: Zollschan Linda
Published: January 2007

The letter of safe-conduct to Jewish envoys in Jos. Ant. 14.233 is widely held, following Niese, to have been written by the consul of 161 B.C.E., C. Fannius Strabo although the letter is placed by Josephus among Roman documents that date to 49 B.C.E. The circumstances of the civil war go some way to explaining the extraordinary nature of this document: the element of danger present on Cos in 49 B.C.E., danger that was not present in the second c. B.C.E., the legend PR on the Asian cistophori of C. Fannius and the meaning of the phrase στρατηγòς νπατoς. The letter is addressed to the archons of Cos, a form of address found in the rst but not the second c. B.C.E. Research from the last three decades provide fresh considerations that argue for an identi cation of the author of the letter with C. Fannius, the governor of Asia in 49/8 B.C.E., a date which accords with the chronological position given by Josephus.
Philo of Alexandria and the Conquest of Canaan
Authors: Berthelot Katell
Published: January 2007

According to the Torah, the Hebrews were commanded either to expel or to exterminate the Canaanites who were living in Canaan at the time of the conquest. Philo seems to feel rather ill-at-ease about the literal meaning of these biblical passages. Besides allegory, he uses four hermeneutical strategies: 1) to pass over the problematic texts in silence; 2) to play with the meaning of certain Greek words; 3) to justify the destruction of the Canaanites from a moral point of view; 4) to rewrite the biblical account.
Familial Dimensions of Group Identity (II): "Mothers" and "Fathers" in Associations and Synagogues of the Greek World
Authors: Harland Philip
Published: January 2007

Fictive parental language (e.g. "mother of the synagogue," "father of the association") has drawn limited attention within two scholarly circles, namely, those who study diaspora synagogues, on the one hand, and ancient historians, on the other. is article brings these two scholarly interests together and argues, based on inscriptional evidence, that parental metaphors were more widespread and significant in cities and associations of the Greek East than o en acknowledged. Such terminology was an important way of expressing honour, hierarchy, and/or belonging within the association or community, and it could also pertain to functional leadership roles (rather than mere honorifics) in certain cases. e Jewish practice of calling figures "mother" or "father" of the synagogue can be better understood within this cultural framework and in relation to associations specifically.
The Origin of the Tradition
Authors: Cook Johann
Published: January 2007

The rabbinic tradition of the good and evil yesarim inherent in man is wide-spread in rabbinic and other sources. There seems to be a development from pre-Christian origins to fully-fledged later, Talmudic and Amoraic perspectives. This article traces this development from its later forms back to its possible origin via relevant Jewish texts from Hellenistic writings (Ben Sira and the LXX of Proverbs) and Qumran. It concludes that this tradition was already in use in Palestine during the 2nd century B.C.E.
Cost-Utility Analysis When Not Everyone Wants the Treatment: Modeling Split-Choice Bias
Authors: Lilford Richard , Girling Alan , Braunholtz David , Gillett Wayne , Gordon Jason , Brown Celia A. , Stevens Andrew
Published: January 2007

Not all clinically eligible patients will necessarily accept a new treatment. Cost-utility analysis recognizes this by multiplying the mean incremental expected utility (EU) by the participation rate to obtain the utility gain per head. However, the mean EU gain over all patients in a defined clinical category is traditionally used as a proxy for the mean EU gain over the subpopulation of acceptors. Even for clinically identical patients, this may lead to a biased assessment of total benefit because a patient motivated to accept the new treatment is likely to value its effects more favorably than a patient who declines. An analysis that ignores this tendency will be biased toward an underestimate of true benefits of a health technology (HT). The extent of this bias is described within a qualityadjusted life year-based utility model for a population of clinically indistinguishable patients who differ with respect to the values that they place on the possible health outcomes of an HT. The size of the bias is sensitive to the proportion of patients who accept the treatment, under both deterministic and probabilistic models of individual decision making. In all cases in which decision making is correlated with personal utility gain, the bias rises steeply as the proportion of acceptors declines.
Quality-of-Life Assessment When There Is a Loss of Income
Authors: Myers John , McCabe Steven , Gohmann Stephan
Published: January 2007

Purpose. The current study aims to provide the first empirical evidence demonstrating whether people automatically consider morbidity costs when assessing the quality of life for a health state.

Methods. One hundred eighty-one undergraduate students were randomly assigned to 1 of 2 groups: 1) those participants who were not informed of morbidity costs and 2) those participants who were informed of morbidity costs. Students were asked to read a description of a health state and to assign an assessment of quality of life for the health state described by the use of the paper standard gamble.

Results. The overall mean quality of life for the informed group was significantly lower than that of the uninformed group (P < 0.0001, F = 24.2, df = 1, 179). Similarly, there is a significant difference between illness severity levels in mean quality of life (P < 0.0001, F = 29.5, df = 2, 178). No statistically significant interaction between level of illness severity and prior knowledge was observed (P = 0.5904, F = 0.53, df = 2, 178). Therefore, the authors fit a model removing the interaction term.

Conclusion. This study demonstrates that those subjects informed of morbidity costs score quality of life lower than do subjects unin-formed of morbidity costs. To accurately represent the effectiveness of an intervention, the authors argue that morbidity costs should be included in the description of health states.
Further Insight into the Perception of Quantitative Information: Judgments of Gist in Treatment Decisions
Authors: Feldman-Stewart Deb , Brundage Michael D. , Zotov Vladimir
Published: January 2007

Purpose. To compare relative accuracy and relative response times (RTs) as well as impact of foreground and background colors in a treatment decision context of judging larger/smaller when the following elements are added to the graphics studied previously: 1) a number (the displayed percentage), 2) a referent scale, and 3) a number and a referent scale.

Method. An experiment compared pie charts, vertical bars, horizontal bars, digits, systematic ovals, and random ovals. On each trial, participants saw 2 percentages (in 1 format) and were asked to choose the larger chance of survival or the smaller chance of side effects. Outcomes were errors and RT. Formats were either black and white or blue and yellow; background color was either white or blue. Participants were 216 volunteers from the community older than 50 years.

Results. Formats with a number produced the same relative errors and relative RT as the formats with a number and scale. Formats with only a scale, however, shifted relative performance: Errors increased with more difficult formats (pie charts and random ovals by 3%-4% v. ∼ 1% with other formats), but RT decreased with easier formats (vertical bars, horizontal bars, and systematic ovals decreased 100-200 ms v. an increase of 0-300 ms with other formats). Vertical bars with scales were the fastest and most accurately processed. Neither foreground nor background color had any impact on either outcome.

Conclusions. For supporting older people’s judgments of relative extent, risk information is best presented using vertical bars with a scale; the format systematic ovals with a scale are among the next most easily processed.
Measuring Health Preferences for Health Utilities Index Mark 3 Health States: A Study of Feasibility and Preference Differences among Ethnic Groups in Singapore
Authors: Luo Nan , Wang Qinan , Feeny David , Chen Geraldine , Li Shu-Chuen , Thumboo Julian
Published: January 2007

Background. Little is known about the health preferences of Southeast Asians. The authors therefore investigated the feasibility of measuring health preferences of Chinese, Malays, and Indians in Singapore and compared their preference scores.

Methods. A stratified random sample of the Singaporean general population was interviewed to measure preferences for a set of health states defined by the Health Utilities Index Mark 3 (HUI3) using both the rating scale (RS) and the standard gamble (SG) methods. Feasibility of preference measurement was assessed using ratings of measurement tasks, task completion rates, and ranking of preference scores. Differences in preference scores across Chinese, Malays, and Indians were examined using analysis of variance models.

Results. Among 245 interviewed respondents (Chinese: 110, Malays: 73, Indians: 62), 97.1% and 95.1% successfully completed all the RS and SG measurement tasks, respectively; 70.1% and 75.3% judged the RS and SG tasks as “easy” or “very easy,” respectively. Interviewers rated 69.4% and 75.0% of these respondents as having “full comprehension” for the RS and SG tasks, respectively; “full concentration” was observed in 84.1% and 84.0% of these respondents for the RS and SG tasks, respectively. There were no significant differences in mean preference scores across Chinese, Malays, and Indians, with and without adjustment for effects of confounding variables.

Conclusions. RS and SG are feasible methods for measuring health preferences for Asians in Singapore; it appears that Chinese, Malays, and Indians in Singapore have similar preferences for HUI3 health states.
Why Are Clinicians Reluctant to Treat Smear-Negative Tuberculosis? An Inquiry about Treatment Thresholds in Rwanda
Authors: Basinga Paulin , Moreira Juan , Bisoffi Zeno , Bisig Bettina , Van den Ende Jef
Published: January 2007

Purpose. The diagnosis of tuberculosis remains controversial between clinicians and public health officers. Public health officials fear to treat too many patients; clinicians fear that truly diseased will be denied treatment. We wondered whether an analysis of the treatment threshold could help making the often intuitive decision to treat smear-negative cases more evidence based.

Methods. Eighteen clinicians and 10 public health specialists were asked for an intuitive estimate of their treatment threshold for tuberculosis and of key determinant factors for this threshold: the magnitude and subjective weight of mortality and morbidity due to both the disease and the treatment and risk and cost of the latter. With these factors, the authors calculated treatment thresholds and compared them to the intuitive thresholds of the interviewees. A prescriptive threshold was calculated based on literature data, omitting cost and subjective factors.

Results. The median overall intuitive treatment threshold was 52.5%, the calculated 11.9%, and the prescriptive 2.7%. For 2 factors, public health officers provided significantly lower values than clinicians: cost of treatment (median = $20 v. $300; U = 2.5; P = 0.0002); cost of life (median = $500 v. $5000; U = 17.5; P = 0.009).

Conclusion. These results suggest that clinicians and public health officers estimate wrongly the threshold even when using their own subjective estimate of influencing factors. Omitting treatment cost and subjective weight of provoked harm can result in a very low threshold. Sound training in threshold principles and providing tools to correctly assess data might help in making better decisions in tuberculosis in developing countries.
A Little Planning Goes a Long Way: Multilevel Allocation of HIV Prevention Resources
Authors: Zaric Gregory S. , Brandeau Margaret L.
Published: January 2007

Background. HIV prevention funds are often allocated by decision makers at multiple levels. High-level decision makers may allocate funds to regions, and regional decision makers then allocate those funds to specific programs. Often, funds are allocated proportionally (e.g., in proportion to HIV incidence) rather than efficiently (i.e., to maximize HIV infections averted). The authors investigate the impact of efficient and proportional allocation methods at 2 different decision levels.

Methods. The authors developed an optimization model of resource allocation at 2 levels—an aggregate upper level and multiple local levels—and considered efficient allocation and allocation proportional to HIV incidence. Using data from 40 U.S. states, they compared 4 strategies for allocating HIV prevention funds.

Results. The greatest health benefit (HIV infections averted) occurred when efficient allocations were made at both levels. When funds were allocated proportionally at the higher level and efficiently at the lower level, the health benefit was about 5% less than when efficient allocations were made at both levels. When funds were allocated efficiently at the higher level and proportionally at the lower level, the health benefit was 15% less than when efficient allocations were made at both levels. The least health benefit (23% less than when efficient allocations were made at both levels) occurred with proportional allocation at both levels.

Conclusions. Efficient allocation only at the higher level cannot overcome poor allocations at lower levels. Moreover, efficient allocation at the lower level is likely to yield greater gains than efficient allocation at the higher level. Thus, upper-level decision makers, such as donor organizations, should develop incentives to promote efficient allocation by lower-level decision makers.
Bedside Rationing by Health Practitioners: A Case Study in a Ugandan Hospital
Authors: Kapiriri Lydia , Martin Douglas K.
Published: January 2007

Purpose. The purpose of this study was to describe bedside rationing by health practitioners in a teaching hospital in Uganda.

Methods. This was a case study involving in-depth interviews. A modified thematic approach was used in data analysis. Types of decisions, the decision-making process, key players, and hospital-, medical-, and patient-related considerations in the process were identified. Klein’s 6 forms of rationing were used to identify the forms of rationing used. The setting was a tertiary hospital in Uganda. Theoretical sampling was used to identify 40 doctors and 16 nurses from the Departments of Medicine, Surgery, Paediatrics, and Obstetric and Gynaecology.

Results. Four types of bedside rationing decisions were identified: 1) which patients are seen first, 2) which treatment the patients receive, 3) which patients are admitted, and 4) which patients are taken to the operating theatre first. Hospital-related considerations regarding bedside rationing included the hospital budget and number of beds; medical-related considerations included the patient’s diagnosis and effectiveness of treatment; and patient-related considerations included poverty, social status, and age. All forms of rationing (denial, dilution, deflection, deterrence, delay, and termination) were practiced.

Conclusion. Although bedside rationing decisions in the study hospital seem somewhat similar to that in developed countries, the rationing of 1st-line drugs by health practitioners in Uganda is complex, difficult, and different from what has been described in industrialized countries. The complexity and severity of the consequences of the bedside decisions necessitate the development of resource-sensitive clinical guidelines and transparent decision-making processes to foster patients’ understanding of the reasons and the procedures and to ensure fair decision-making processes.
Assessing the Accuracy of Hospital Clinical Performance Measures
Authors: Normand Sharon-Lise T. , Wolf Robert E. , Ayanian John Z. , McNeil Barbara J.
Published: January 2007

Objective. To control costs and improve quality, payers are designing new hospital reimbursement policies that link payment to quality. The authors determine the extent to which quality measures discriminate hospitals into tiers in 2 geographic areas.

Data Sources. Administrative and medical record data for patients discharged with acute myocardial infarction (AMI) in 368 California and 81 Massachusetts hospitals.

Methods. Through simulation, the minimum numbers of patients per hospital needed to identify highquality hospitals with sensitivity ranging from 75% to 95% under a variety of clinical scenarios are determined.

Results. Massachusetts hospitals had twice the number of eligible patients per hospital than California hospitals. Regardless of state, few hospitals had sufficient sample size needed to achieve >85% sensitivity for high-variation quality measures.

Clinical Implications. Reliability of quality-based reimbursement systems relies on the distribution of the hospital sample sizes within geographic areas and the size of practice differences. Selection of conformance thresholds and sensitivity levels depends on the user of the information. To assess the usefulness of performance measures to tier hospitals, information regarding between-hospital variation in quality for specific clinical measures needs to be collected and reported.
Magnesium: Commodity or exotic?
Authors: King J. F.
Published: January 2007

The structural use of magnesium through the 20th century is briefly reviewed, highlighting fluctuating levels of development and use influenced by military applications in two World Wars. Development of more efficient processes, improved corrosion resistant alloys and availability of lower cost metal now offer potential for major expansion in magnesium consumption in the 21st century. A review of current worldwide use indicates major growth in structural transport applications. Apart from the obvious advantage of light weight, other important attributes making magnesium an attractive contender for transport applications are considered. Requirements for magnesium to compete effectively as a commodity material are reviewed. Key areas for development are commercial transport, aerospace and high performance uses. The most important is commercial transport. Significant developments in alloy technology and applications for die casting are described and more speculative growth in use of wrought components discussed. A similar review and analysis of developments for aerospace and high performance applications is given. Alloys developed and properties achieved differ significantly from those considered for higher volume commercial applications and include highly sophisticated alloying and manufacturing technology. Although the main theme is magnesium's potential as a commodity material, more exotic applications of magnesium alloys are reviewed. These include electrochemical alloys, space and missile applications, composite materials, non-equilibrium alloys and medical uses. Finally, the future priorities for development of technology and applications are examined by reference to a recent UK ‘road mapping’ exercise, which was in general accord with similar exercises in Japan, Germany and the USA.
Tribological behaviour of steel backed Al–Sn strip prepared via spray atomisation–deposition–rolling route
Authors: Tripathy M. R. , Kumar B. V. Manoj , Basu B. , Dube R. K. , Koria S. C.
Published: January 2007

In recent times, considerable effort has been put into develop process routes for making steel backed aluminium alloy strips for automotive bearing applications. Al–Sn alloys are considered to be potential candidates owing to their acceptable load bearing capacity with improved fatigue and wear resistance. In the present investigation, Al– xSn ( x=0, 10 and 20 wt-%) alloys were spray deposited on a steel substrate, and the resulting laminated strips were subjected to various degrees of warm rolling. The tribological performance of the steel backed Al–Sn strip was evaluated against bearing steel under fretting contacts. The fretting wear behaviour of the steel backed and warm rolled Al–10 wt-%Sn strips exhibits a decrease in wear rate with increasing amount of rolling. Scanning electron microscopy–energy dispersion spectroscopy (SEM–EDS) analyses reveal that the tribo-oxidation and adhesive wear are dominant material removal mechanisms on Al–Sn worn surfaces, while tribo-oxidation predominantly contributes to wear of pure Al.