bluuebunny/crossref_metadata_2025 huggingface dataset:
Living on the threshold: The spatial experience of living alone with dementia
Authors: De Witt Lorna , Ploeg Jenny , Black Margaret
Published: April 2009

The purpose of this qualitative study was to understand the meaning of living alone for older people with dementia. Fourteen audio-taped open-ended interviews were conducted with eight such older women in Ontario, Canada. The data were analyzed using an adaptation of van Manen's method. Heidegger's philosophy informed interpretation of the findings through the theme living on the threshold. The study findings deepen understanding of `space' and `place' in the experience of living alone with dementia. Participants sought the middle-ground of dialectical tensions within the threshold space and shared insights about their spatial experience of: (a) being here, (b) being there, (c) being out, and (d) keeping out. These older women risked losing their threshold space when admitting to mistakes as their illness progressed. The authors conclude with examples of how this spatial interpretation may inform and improve communication with and care of older people in similar circumstances.
Supportive living environments: A first concept of a dwelling designed for older adults with dementia
Authors: Van Hoof Joost , Kort Helianthe S.M.
Published: April 2009

The vast majority of older adults want to remain living independently at home, with or without a sufficient amount of professional home care, even when overall health is starting to decline. The ageing of society and the increase in the number of very old elders goes together with an increase in the number of people with dementia. About two thirds of the diagnosed people in the Netherlands live at home. Dementia has severe implications to the quality of daily life, in particular to independent functioning. This sets extra demands to living environments. Older adults with dementia and their partners ask for living environments that support independence, compensate for declining vitality, and lower the burden of family care. For this purpose, a first concept of a design for a dementia dwelling is presented in this paper, which incorporates modifications in terms of architecture, interior design, the indoor environment, and technological solutions. These design features were derived from literature search and focus group sessions. Current design guidelines are frequently based on practical experience only, and therefore, more systematic field research should be carried out to find evidence for the various design modifications. Also, it needs to be studied how the design features of the dementia dwelling can be incorporated into the existing housing stock.
Toward a Multi-Level, Ecological Approach to the Primary Prevention of Sexual Assault
Authors: Casey Erin A. , Lindhorst Taryn P.
Published: April 2009

Although sexual assault prevention programs have been increasingly successful at improving knowledge about sexual violence and decreasing rape-supportive attitudes and beliefs among participants, reducing sexually assaultive conduct itself remains an elusive outcome. This review considers efforts to support change for individuals by creating prevention strategies that target peer network and community-level factors that support sexual violence. To this end, the article examines successful ecological prevention models from other prevention fields, identifies the components of multilevel prevention that appear critical to efficacy and discusses their application to existing and emerging sexual violence prevention strategies.
Intimate Partner Violence Among Asian Immigrant Communities
Authors: Lee Yeon-Shim , Hadeed Linda
Published: April 2009

Intimate partner violence (IPV) is a serious epidemic among Asian immigrant communities. Yet little is known about the scope, nature, and related contextual, cultural, and social factors of IPV among this population. In particular, the lack of research has been evident in examining health and mental health outcomes of IPV and service utilization, revealing notable gaps in health disparities which result in a failure to provide relevant services and law enforcement protection for battered Asian immigrant women. This article examines critically the growing body of literature on IPV among Asian immigrant populations in several areas: (a) the context of IPV: cultural, social, and individual/familial, (b) prevalence of IPV, (c) physical health and increased risk for sexually transmitted disease and HIV/AIDS, (d) mental health consequences and substance use, (e) social support and help-seeking behaviors, and (f) barriers to service utilization. Future directions for practice, policy, and research are discussed.
Exploring Dispositional Resistance to Change
Authors: Saksvik Ingvild Berg , Hetland Hilde
Published: April 2009

The aim of the study was to explore the relationship between Oreg’s recently developed scale on Resistance To Change (RTC) and its four sub factors and personality traits of the Five Factor Model (FFM). The sample consisted of 259 participants. Findings revealed that neuroticism correlated positively with the RTC Scale, while extraversion, openness to experience and agreeableness showed negative correlations with the RTC scale. Neuroticism correlated positively with three of the RTC sub factors, Routine seeking (RS), Emotional reaction (ER), and Short-term thinking (ST) respectively. Extraversion correlated negatively with the same three factors. Openness to experience correlation negatively with RS, while agreeableness correlated negatively with RS and ST. Conscientiousness correlated negatively with ST, but positively with RS. A regression analysis supported most of these findings. Use of the RTC scale could have special implications for managers in organizations making them more aware of diversity among employees.
Leader’s ICT Usage’s Influence on Follower’s Positive Work Attitudes Via Perceived Leader-Follower Relations
Authors: Börekçi Dilek Yılmaz
Published: April 2009

In this study, leader’s information and communication technology (ICT) usage in conducting business and in communication is indicated as having influence on follower’s positive work attitudes through the mediation of perceived leader-follower relations. Mediated regression analyses were conducted based on the followers’ perceptions data. The study revealed that ICT usage by leader affects follower’s perceptions related to his or her relation with his or her leader, which in turn influence follower’s positive work attitudes such as loyalty, trust, satisfaction, and perceived distributive justice.
Between Life and Death
Authors: Cherukuri Suvarna , Britton Dana M. , Subramaniam Mangala
Published: April 2009

This study presents an analysis of the population and crimes of women in a state prison for women in Hyderabad, India. Women in India are disproportionately incarcerated for violent crimes, in particular, offenses related to dowry. Using qualitative data gathered from interviews with 49 women, the authors examine the context of their lives and their paths to prison. Ultimately, the authors make a case for an intersectional analysis, one that seeks to understand the lives of women in a matrix of inequalities shaped by caste, class, and gender.
Gender, Sexuality, Power and Drug Acquisition Strategies Among Adolescent Girls Who Use Meth
Authors: Lopez Vera , Jurik Nancy , Gilliard-Matthews Stacia
Published: April 2009

This study drew on social construction of gender and reflexive methodological approaches to examine how adolescent girls procured meth within the context of relationships with boys and men. A total of 18 incarcerated adolescent girls, aged 14 to 17 years, were interviewed about their meth-using experiences. The findings indicate that girls used five relationship strategies and one nonrelationship strategy to procure meth on the streets. Close examination revealed that girls' meth procurement strategies, with few exceptions, occurred in ways resonant with culturally dominant views of femininity (referred to hereafter as emphasized femininities). However, most girls presented themselves in interviews as breaking out of culturally prescribed constraints and crafting their own version of femininity. However, their agency was contextualized or limited by the social power relations that surrounded them.
Real Men Use Nonlethals
Authors: Wozniak Jesse , Uggen Christopher
Published: April 2009

In recent years, a range of new nonlethal weapons have been introduced for use by police officers, military personnel, and other consumers. This article examines how manufacturers are employing ideals of masculinity as both physical dominance and technical expertise in marketing these weapons to police officials. Based on a case study of a major weapons manufacturer's educational and sales conference, the authors explore how marketing appeals are adapted to suit a hypermasculine police subculture. Connell's theory of masculinities is employed to understand how such a tightly defined subculture absorbs challenges to its core values of hegemonic hypermasculinity and reimagines itself to keep those core values intact.
On Quantitizing
Authors: Sandelowski Margarete , Voils Corrine I. , Knafl George
Published: April 2009

Quantitizing, commonly understood to refer to the numerical translation, transformation, or conversion of qualitative data, has become a staple of mixed methods research. Typically glossed are the foundational assumptions, judgments, and compromises involved in converting disparate data sets into each other and whether such conversions advance inquiry. Among these assumptions are that qualitative and quantitative data constitute two kinds of data, that quantitizing constitutes a unidirectional process essentially different from qualitizing, and that counting is an unambiguous process. Among the judgments are deciding what and how to count. Among the compromises are balancing numerical precision with narrative complexity. The standpoints of ``conditional complementarity,'' ``critical remediation,'' and ``analytic alternation'' clarify the added value of converting qualitative data into quantitative form.
Physical Activity Transitions and Chronic Disease
Authors: Heath Gregory W.
Published: April 2009

The 20th century in the United States has experienced a dramatic increase in life expectancy among adult men and women, an increase unprecedented in the history of this country. As a result, the pattern of disease and conditions most responsible for death in the United States shifted during the past century from infectious diseases and unintentional injuries to the current array of the leading causes of mortality dominated by the chronic diseases. During this same period, daily lifestyle dramatically shifted from a life full of active living to one of inactivity. The argument has been made that in the case of human beings, there has been little or no change in our genotype within the past 50 years. However, there have been major changes documented in the living environment among economically developed societies during this same time period. Through the collection of epidemiologic, clinical, and experimental findings, evidence suggests that physical inactivity is associated with the onset of chronic diseases of our day. Trends in physical inactivity, evident through the monitoring of transport, recreation, sport, and purposeful activity, have demonstrated that the current lifestyle of the 21st century has contributed substantially to the chronic disease burden in the United States and elsewhere. By addressing the domains that influence physical activity behaviors including the environment (both physical and social/cultural), health systems access, and behavioral correlates of physical activity and inactivity, the current chronic disease crisis potentially can be addressed.
Review: Prostate capsule sparing radical cystectomy: oncologic safety and clinical outcome
Authors: Klotz Laurence
Published: April 2009

Objectives: Prostate capsule sparing radical cystectomy (PSRC) is a modification of the traditional surgical approach to radical cystectomy and neobladder, which offers the prospect of improved preservation of erectile function and continence.

Methods: This is a review of the literature regarding the oncologic and quality of life outcomes of this approach for transitional cell carcinoma of the bladder, and a comparison of these results to conventional cystoprostatectomy and neobladder.

Results: There are a limited number of studies addressing prostate capsule or prostate sparing cystectomy. All are retrospective, non-comparative and not uniform in terms of patient selection and technique. Long-term follow-up is lacking. The incidence of synchronous and or metachronous prostate cancer and TCC of the prostatic urethra is lower than that found in conventional cystoprostatectomy. This is likely due to pre-operative patient selection, restricting the procedure to those with no evidence of prostatic involvement by either disease. The local recurrence rate is 5%, comparable to standard cystoprostatectomy. Recurrence free and overall survival rates are comparable.
Review: TRP family proteins in the lower urinary tract: translating basic science into new clinical prospective
Authors: Lazzeri Massimo , Costantini Elisabetta , Porena Massimo
Published: April 2009

The lower urinary tract (LUT) is densely innervated by capsaicin-sensitive primary afferent neurons, a sub set of sensory nerves, in a number of species including humans. These fibers exhibit both a sensory (afferent) function, including the regulation of the micturition reflex and the perception of pain, and an `efferent' function, involved in the detrusor smooth muscle contractility and plasma protein extravasation. The discovery of specific binding sites for capsaicin, the pungent ingredient of red chilli, initiated a rush that ended up with the cloning of the `vanilloid receptor', which belongs to the TRP (transient receptor potential) family. Here we reviewed the knowledge about the presumable functions of TRP family proteins in the LUT as regulators of bladder reflex activity, pain perception and cell differentiation. This review will focus on experimental evidence and promising clinical applications of targeting these proteins for the treatment of detrusor overactivity and bladder pain syndrome. As TRP receptor ligands may promote cellular death, and inhibit the growth of normal and neoplastic cells, the translation of basic science evidence into new clinical prospective for bladder and prostate cancer will be shown.
Review: Use of nomograms for predictions of outcome in patients with advanced bladder cancer
Authors: Shariat Shahrokh F. , Karakiewicz Pierre I. , Godoy Guilherme , Lerner Seth P.
Published: April 2009

Introduction: Accurate estimates of risk are essential for physicians if they are to recommend a specific management to patients with bladder cancer. In this review, we discuss the criteria for the evaluation of nomograms and review current available nomograms for advanced bladder cancer.

Methods: A retrospective review of the Pubmed database between 2002 and 2008 was performed using the keywords `nomogram' and `bladder'. We limited the articles to advanced bladder cancer. We recorded input variables, prediction form, number of patients used to develop the prediction tools, the outcome being predicted, prediction tool-specific features, predictive accuracy, and whether validation was performed.

Results: We discuss the characteristics needed to evaluate nomograms such as predictive accuracy, calibration, generalizability, level of complexity, effect of competing risks, conditional probabilities, and head-to-head comparison with other prediction methods. The predictive accuracies of the pre-cystectomy tools (n = 2) range from ~65—75% and that of the post-cystectomy tools (n = 5) range from ~75—80%. While some of these nomograms are well-calibrated and outperform AJCC staging, none has been externally validated. To date, four studies demonstrated a statistically significant improvement in predictive accuracy of nomograms by including biomarkers.

Conclusions: Nomograms provide accurate individualized estimates of outcomes. They currently represent the most accurate and discriminatory decision-making aids tools for predicting outcomes in patients with bladder cancer. Use of current nomograms could improve current selection of patients for standard therapy and investigational trial design by ensuring homogeneous groups. The addition of biological markers to the currently available nomograms using clinical and pathologic data holds the promise of improving prediction and refining management of patients with bladder cancer.
Review: Second-look nephroscopy after percutaneous nephrolithotomy
Authors: Knudsen Bodo E.
Published: April 2009

Percutaneous nephrolithotomy (PCNL) is the standard of care for the management of large renal stone burdens. Residual stones after PCNL may be cleared with a second-look nephroscopy. Determining whether a patient should undergo a second-look procedure is based on both the intraoperative findings and the post-operative imaging. Aggressive intraoperative flexible nephroscopy, may reduce the need for routine second-look nephroscopy. Post-operative computed tomograpahy (CT) imaging is the most sensitive method for detecting residual stone fragments. When a clinically significant residual stone burden exists a second-look procedure may be performed in an effort to render the patient stone-free. In most instances the procedure can be performed in an ambulatory facility under conscious intravenous sedation. Future prospective study determining the threshold of fragment size after PCNL that warrants second-look nephroscopy is needed.
Review: Methodological quality in medical evidence, quo vadis?
Authors: Diaz-Insua Mireya
Published: April 2009

Efforts in research quality have led to a diffusion of publication guidelines for high-quality reporting of medical evidence with the aim to instill transparency to its evaluation. The maturity of this process has led to a second stage in which a surplus of scales measuring methodological quality is in place. However, there is no clear consensus as to which of these guidelines should be recommended for usage and how to integrate the methodological quality information into the evidence synthesis process. One major challenge that these scales poses is the fact that slight modifications performed to them in order to adapt to a specific research and/ or management question requires revalidation of the scale's properties, a clearly impractical endeavor. This article proposes a potential alternative to this challenge through the formulation of a framework in which quality elements are divided into tiers. This layering aims at separating quality constructs that should be uniformly present across all studies and thus could be validated from constructs that are question-specific and less likely to undergo a formal validation process. An example of this framework applied to the urological literature is presented.
Study on static strain aging of 6082 aluminium alloy
Authors: Dadbakhsh S. , Karimi Taheri A.
Published: April 2009

In this study both the quench aging and static strain aging kinetics of a 6082 Al alloy were investigated at a temperature range of 130–200°C using the Vickers hardness and tensile test. The activation energy and dislocation density were determined at different stages of the aging phenomenon. The former was used to analyse the kinetics of aging and the latter to interpret the competition of strengthening and recovery mechanisms during aging. It is shown that different activation energies are achieved depending on the aging time and temperature relating to formation of appropriate precipitates at different stages of aging. Moreover, it is revealed that prestrain reduces the activation energy. A linear equation is proposed between the dislocation density and the plastic strain after static strain aging. The competition of recovery with strengthening mechanisms during strain aging is discussed with regard to dislocation density after aging.
Grain boundary segregation in Ni-base (718 plus) superalloy
Authors: Ding R.
Published: April 2009

Segregation of phosphorus and molybdenum to grain boundaries in a commercial grade Ni-base (718 plus) superalloy subjected to different heat treatments has been examined using a field emission gun scanning transmission electron microscope with energy dispersive X-ray microanalysis. The results indicate that P and Mo concentrations at grain boundaries increase in linear manner with the square root of aging time.
Investigation of secondary phase effect on 2205 DSS fracture toughness
Authors: Calliari I. , Straffelini G. , Ramous E.
Published: April 2009

The fracture toughness properties of duplex stainless steels (DSS) are strongly reduced by intermetallic phases, precipitating at 600–1000°C. In this investigation, the embrittlement effect induced by a low content of these phases has been studied in a 2205 DSS, by means of instrumented Charpy V impact testing. Different contents of intermetallic phases have been produced by isothermal treatments at 800–950°C. The microstructure has been analysed by scanning electron microscope/backscattered electron images. The impact test results, the examination of the fracture surfaces and of the cross-sections close to the notch root allows us to elucidate the role of secondary phases contents in reducing impact fracture toughness. When the quantity of secondary phases is <0·5%, these precipitates are rare and insignificant, reducing the absorbed energy by facilitating a ductile fracture. When the content is >1%, the fracture is completely brittle. The plastic deformation at the notch root and in the resisting section provokes a secondary phase breakage with a high density microcrack formation, inducing an easy nucleation and propagation of the final fracture crack. When the content of secondary phases is between 0·5 and 1%, fracture is mixed. Both the sigma σ and chi χ phases have been found to be responsible for the embrittling of the 2205 DSS, and fracture toughness mainly depends on their density and dimension.
Wear performance and mechanical properties of 80 wt-%Al2O3/20 wt-%YSZ cutting inserts at different sintering rates and soaking times
Authors: Hao J. K. C. , Azhar A. Z. A. , Ratnam M. M. , Ahmad Z. A.
Published: April 2009

A series of ceramic tools with different sintering conditions based on zirconia toughened alumina (ZTA) was produced. Experiments on ZTA cutting tools with different sintering rates and soaking times were carried out. Cutting inserts with80 wt-% alumina (Al2O3)/20 wt-% yttria stabilised zirconia (YSZ), in which Al2O3 and YSZ powders are mixed, was compacted and sintered at 1600°C using solid state sintering. Mechanical and physical properties such as wear resistance, hardness HV30, fracture toughness and microstructure were analysed. Mild steel (AISI 1018) was used as the workpiece for wear resistance study. It was observed that a slower sintering rate induces better mechanical properties on the cutting tool. With increasing the sintering rate from 2 to 8°C min−1, the wear area increased from 0·0443 to 0·118 mm2. The hardness of the samples decreased from 1563·5 to 1313·8 HV, while the fracture toughness also decreased from 4·709 to 3·95 MPa m1/2. For the effect of increasing sintering soaking time from 120 to 300 min, the wear area decreased from greatest (0·1939 mm2) to lowest (0·0797 mm2). Similarly, microstructural coarsening within ZTA was found to produce a fracture toughness increase from 3·95 to 6·374 MPa m1/2. The influence of phase polymorphic transformation on the improvement of the mechanical properties is discussed.
Improving tensile and compressive strengths of magnesium by blending it with aluminium
Authors: Thakur S. K. , Paramsothy M. , Gupta M.
Published: April 2009

In the present study, Mg based composite containing Al particles was fabricated by blending the Al particles in the Mg powder, followed by hot compaction, two directional microwave sintering and hot extrusion. Microstructural characterisation of the as extruded composite samples revealed a fairly uniform distribution of aluminium with some minor clustering and minimal porosity in the composite. X-ray diffraction results indicate the presence of Al2Mg3 intermetallics at the interface between Mg and Al. Mechanical properties characterisation revealed that the addition of Al particles resulted in an increase in macrohardness, interfacial microhardness, 0·2% yield strength and ultimate tensile strength (both in compression and tension). However, the ductility of the composite was found to be decreased by the addition of Al particles in the Mg matrix. The fractured samples after tensile testing showed a brittle mode of fracture with cleavage steps; however, the fractured sample after compression test showed the presence of single crack with multiple shear band formations.
Experimental study on effect of temperature on mechanical properties of graphite fibre reinforced Al matrix composites
Authors: Zhang Y. H. , Wu G. H.
Published: April 2009

A continuous graphite fibre reinforced aluminium matrix composite (Grf/Al) with 60 vol.-% Grf content was produced by squeeze casting technology. The composite was dense and macroscopically homogeneous, and only a small amount of aluminium carbide was found in the Gr/Al interface. Tensile and bending strengths of Grf/Al composites have been measured in the temperature range between −40 and 100°C. With increasing tested temperatures, the tensile and bending strengths of Grf/Al composites were enhanced from 891 to 1095 MPa and from 967 to 1234 MPa respectively. The temperature dependence mechanisms of composite strength were analysed in terms of changing of residual stress and mechanical properties of matrix respectively.
Interfacial reaction layer in resistance spot welded joint between aluminium alloy and austenitic stainless steel
Authors: Qiu R. F. , Iwamoto C. , Satonaka S.
Published: April 2009

The interfacial reaction layers of resistance spot welded joint made from aluminium alloy and austenitic stainless steel consisted of a mixed layer of Fe2Al5 and FeAl3 and an approximately 35 nm thick layer of FeAl2 beside steel. The reaction blocks in aluminium near the welding interface were observed, which were estimated as a hexagonal AlFeCr having a=2·451 nm and c=0·758 nm based on analysis of high resolution transmission electron microscope (HRTEM) image and selected area electron diffraction patterns (SADP).
Comparative study of dynamic impact properties and microstructures of weldable and unweldable aluminium–scandium (Al–Sc) alloys
Authors: Lee W.-S. , Chen T.-H.
Published: April 2009

The dynamic deformation behaviours of two Al–Sc alloys, one weldable and one unweldable, are investigated at strain rates ranging from 1·2 × 103 to 5·9 × 103 s–1 and temperatures of –100, 25 and 300°C respectively, using a compressive split Hopkinson pressure bar. The fracture features and microstructures of the impacted specimens are examined using scanning electron microscopy and transmission electron microscopy respectively. The stress–strain relationships indicate that for both alloys, the flow stress, work hardening rate and strain rate sensitivity increase with increasing strain rate, but decrease with increasing temperature. Moreover, the flow stress, work hardening rate and strain rate sensitivity are higher in the unweldable Al–Sc alloy than in the weldable alloy. In both alloys, the activation volume is dominated by a thermally activated mechanism and increases as the temperature increases or the strain rate decreases. Additionally, the fracture strain reduces with increasing strain rate and decreasing temperature. In describing the plastic deformation behaviour of the two Al–Sc alloys using the Zerilli–Armstrong fcc constitutive model, the error between the predicted flow stress and the measured stress is found to be <5%. The scanning electron microscopy observations reveal that the surfaces of the fractured specimens are characterised by transgranular dimpled features, which are indicative of a ductile fracture mode. The dimple like structures on the fracture surfaces of the unweldable Al–Sc alloy are shallower than those on the fracture surfaces of the weldable Al–Sc alloy, which indicates that the weldable Al–Sc alloy has a better ductility than the unweldable Al–Sc alloy. The transmission electron microscopy images show that the microstructures of the two alloys contain different types of precipitates. Specifically, the unweldable Al–Sc alloy contains both Al3Sc and Al2Cu particles, whereas the weldable Al–Sc alloy contains Al3Sc precipitates only. These particles prevent dislocation motion, and therefore prompt a significant strengthening effect. The transmission electron microscopy observations also reveal that in both alloys, the dislocation density increases with increasing strain rate, but decreases with increasing temperature. Furthermore, it is found that the dislocation density of the unweldable Al–Sc alloy is higher than that of the weldable Al–Sc alloy. In other words, the dislocation cells in the unweldable Al–Sc alloy are smaller than those in the weldable Al–Sc alloy. Thus, it is inferred that the unweldable Al–Sc alloy has a higher flow stress than the weldable Al–Sc alloy.
Brazing of carbon fibre reinforced SiC composite and Ti alloy using Cu–Ti–C filler materials
Authors: Xiong J. H. , Huang J. H. , Wang Z. P. , Ban Y. H. , Zhang H. , Zhao X. K.
Published: April 2009

Carbon fibre reinforced SiC (Cf/SiC) was successfully joined to Ti alloys with Cu–Ti–C mixed powder by brazing. Microstructures of the brazed joints were investigated by SEM, EDS and XRD. The mechanical properties of the brazed joints were measured by a mechanical testing machine. The results showed that the performed joints have dense bonding layers reinforced by residual graphite and in situ synthesised TiC from the reaction of C and Ti in the bonding layers. The composite brazing layers relaxed the thermal stress of the joints effectively. These characteristics were beneficial to the joints, of which the shear strength was remarkably higher than the optimal shear strengths of the joints brazed with pure Cu–Ti.
Antimyeloperoxidase antibodies rapidly induce α4-integrin–dependent glomerular neutrophil adhesion
Authors: Kuligowski Michael P. , Kwan Rain Y. Q. , Lo Cecilia , Wong Cyndi , James Will G. , Bourges Dorothee , Ooi Joshua D. , Abeynaike Latasha D. , Hall Pam , Kitching A. Richard , Hickey Michael J.
Published: April 2009

Patients with antineutrophil cytoplasmic antibodies (ANCAs) frequently develop severe vasculitis and glomerulonephritis. Although ANCAs, particularly antimyeloperoxidase (anti-MPO), have been shown to promote leukocyte adhesion in postcapillary venules, their ability to promote adhesion in the glomerular vasculature is less clear. We used intravital microscopy to examine glomerular leukocyte adhesion induced by anti-MPO. In mice pretreated with LPS, 50 μg anti-MPO induced LFA-1–dependent adhesion in glomeruli. In concert with this finding, in mice pretreated with LPS, more than 80% of circulating neutrophils bound anti-MPO within 5 minutes of intravenous administration. However, even in the absence of LPS, more than 40% of circulating neutrophils bound anti-MPO in vivo, a response not seen in MPO−/− mice. In addition, a higher dose of anti-MPO (200 μg) induced robust glomerular leukocyte adhesion in the absence of LPS. The latter response was β2-integrin independent, instead requiring the α4-integrin, which was up-regulated on neutrophils in response to anti-MPO. These data indicate that anti-MPO antibodies bind to circulating neutrophils, and can induce glomerular leukocyte adhesion via multiple pathways. Lower doses induce adhesion only after an infection-related stimulus, whereas higher doses are capable of inducing responses in the absence of an additional inflammatory stimulus, via alternative adhesion mechanisms.
A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing monocytes, blood “resident” monocytes, and embryonic macrophages suggests common functions and developmental relationships
Authors: Pucci Ferdinando , Venneri Mary Anna , Biziato Daniela , Nonis Alessandro , Moi Davide , Sica Antonio , Di Serio Clelia , Naldini Luigi , De Palma Michele
Published: April 2009

We previously showed that Tie2-expressing monocytes (TEMs) have nonredundant proangiogenic activity in tumors. Here, we compared the gene expression profile of tumor-infiltrating TEMs with that of tumor-associated macrophages (TAMs), spleen-derived Gr1+Cd11b+ neutrophils/myeloid-derived suppressor cells, circulating “inflammatory” and “resident” monocytes, and tumor-derived endothelial cells (ECs) by quantitative polymerase chain reaction–based gene arrays. TEMs sharply differed from ECs and Gr1+Cd11b+ cells but were highly related to TAMs. Nevertheless, several genes were differentially expressed between TEMs and TAMs, highlighting a TEM signature consistent with enhanced proangiogenic/tissue-remodeling activity and lower proinflammatory activity. We validated these findings in models of oncogenesis and transgenic mice expressing a microRNA-regulated Tie2-GFP reporter. Remarkably, resident monocytes and TEMs on one hand, and inflammatory monocytes and TAMs on the other hand, expressed coordinated gene expression profiles, suggesting that the 2 blood monocyte subsets are committed to distinct extravascular fates in the tumor microenvironment. We further showed that a prominent proportion of embryonic/fetal macrophages, which participate in tissue morphogenesis, expressed distinguishing TEM genes. It is tempting to speculate that Tie2+ embryonic/fetal macrophages, resident blood monocytes, and tumor-infiltrating TEMs represent distinct developmental stages of a TEM lineage committed to execute physiologic proangiogenic and tissue-remodeling programs, which can be coopted by tumors.
The level of monocyte turnover predicts disease progression in the macaque model of AIDS
Authors: Hasegawa Atsuhiko , Liu Huining , Ling Binhua , Borda Juan T. , Alvarez Xavier , Sugimoto Chie , Vinet-Oliphant Heather , Kim Woong-Ki , Williams Kenneth C. , Ribeiro Ruy M. , Lackner Andrew A. , Veazey Ronald S. , Kuroda Marcelo J.
Published: April 2009

It is widely accepted that destruction of CD4+ T cells and viral load are the primary markers for immunodeficiency in HIV-1–infected humans and in simian immunodeficiency virus (SIV)–infected macaques. However, monocyte/macrophages are also important targets of HIV/SIV infection and a critical link between innate and adaptive immunity. We therefore examined whether changes in cells of the monocyte/macrophage lineage could be linked to the pathogenesis of AIDS in the rhesus macaque model. Here, we show that massive turnover of peripheral monocytes associated with death of tissue macrophages correlates with AIDS progression in macaques. More importantly, the level of monocyte turnover was not linked to the CD4+ T-cell count and was a better predictive marker for AIDS progression than was viral load or lymphocyte activation. Our results show the importance of monocyte/macrophages in the pathogenesis of AIDS and suggest the dynamic changes of the monocyte/macrophages as a new marker for AIDS progression.
Transcriptomic and metabolic responses of Staphylococcus aureus exposed to supra-physiological temperatures
Authors: Fleury Bénédicte , Kelley William L , Lew Daniel , Götz Friedrich , Proctor Richard A , Vaudaux Pierre
Published: April 2009

Background

Previous evaluation by different molecular and physiological assays of Staphylococcus aureus (S. aureus) responses to heat shock exposure yielded a still fragmentary view of the mechanisms determining bacterial survival or death at supra-physiological temperatures. This study analyzed diverse facets of S. aureus heat-shock adjustment by recording global transcriptomic and metabolic responses of bacterial cultures shifted for 10 min from 37°C to a sub-lethal (43°C) or eventually lethal (48°C) temperature. A relevant metabolic model of the combined action of specific stress response mechanisms with more general, energy-regulating metabolic pathways in heat-shocked S. aureus is presented.

Results

While S. aureus cultures shifted to 43°C or left at 37°C showed marginal differences in growth and survival rates, bacterial cultures exposed to 48°C showed a rapid growth arrest followed by a subsequent decline in viable counts. The most substantial heat shock-induced changes at both 43°C and 48°C occurred in transcript levels of HrcA- and CtsR-regulated genes, encoding classical chaperones DnaK and GroESL, and some Hsp100/Clp ATPases components, respectively. Other metabolic pathways up-regulated by S. aureus exposure at 48°C included genes encoding several enzymes coping with oxidative stress, and DNA damage, or/and impaired osmotic balance. Some major components of the pentose phosphate cycle and gluconeogenesis were also up-regulated, which reflected depletion of free glucose by bacterial cultures grown in Mueller-Hinton broth prior to heat shock. In contrast, most purine- and pyrimidine-synthesis pathway components and amino acyl-tRNA synthetases were down-regulated at 48°C, as well as arginine deiminase and major fermentative pathway components, such as alcohol, lactate and formate dehydrogenases. Despite the heat-induced, increased requirements for ATP-dependent macromolecular repair mechanisms combined with declining energy sources, intracellular ATP levels remained remarkably constant during heat shock.

Conclusion

The sequential loss of replication and viability at 48°C cannot be explained by significant reductions in intracellular ATP levels, but may reflect ATP rerouting for macromolecular repair mechanisms and cell survival. Our metabolic model also suggests that heat-stressed S. aureus should down-regulate the production of potential, DNA-damaging reactive oxygen species that might result from electron transport-generated ATP, involving excessive levels of free heavy metals, in particular iron.
Expression of iron-related genes in human brain and brain tumors
Authors: Hänninen Milla M , Haapasalo Joonas , Haapasalo Hannu , Fleming Robert E , Britton Robert S , Bacon Bruce R , Parkkila Seppo
Published: April 2009

Background

Defective iron homeostasis may be involved in the development of some diseases within the central nervous system. Although the expression of genes involved in normal iron balance has been intensively studied in other tissues, little is known about their expression in the brain. We investigated the mRNA levels of hepcidin (HAMP), HFE, neogenin (NEO1), transferrin receptor 1 (TFRC), transferrin receptor 2 (TFR2), and hemojuvelin (HFE2) in normal human brain, brain tumors, and astrocytoma cell lines. The specimens included 5 normal brain tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2 oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines.

Results

Except for hemojuvelin, all genes studied had detectable levels of mRNA. In most tumor types, the pattern of gene expression was diverse. Notable findings include high expression of transferrin receptor 1 in the hippocampus and medulla oblongata compared to other brain regions, low expression of HFE in normal brain with elevated HFE expression in meningiomas, and absence of hepcidin mRNA in astrocytoma cell lines despite expression in normal brain and tumor specimens.

Conclusion

These results indicate that several iron-related genes are expressed in normal brain, and that their expression may be dysregulated in brain tumors.
How parents choose to use CAM: a systematic review of theoretical models
Authors: Lorenc Ava , Ilan-Clarke Yael , Robinson Nicola , Blair Mitch
Published: April 2009

Background

Complementary and Alternative Medicine (CAM) is widely used throughout the UK and the Western world. CAM is commonly used for children and the decision-making process to use CAM is affected by numerous factors. Most research on CAM use lacks a theoretical framework and is largely based on bivariate statistics. The aim of this review was to identify a conceptual model which could be used to explain the decision-making process in parental choice of CAM.

Methods

A systematic search of the literature was carried out. A two-stage selection process with predetermined inclusion/exclusion criteria identified studies using a theoretical framework depicting the interaction of psychological factors involved in the CAM decision process. Papers were critically appraised and findings summarised.

Results

Twenty two studies using a theoretical model to predict CAM use were included in the final review; only one examined child use. Seven different models were identified. The most commonly used and successful model was Andersen's Sociobehavioural Model (SBM). Two papers proposed modifications to the SBM for CAM use. Six qualitative studies developed their own model.

Conclusion

The SBM modified for CAM use, which incorporates both psychological and pragmatic determinants, was identified as the best conceptual model of CAM use. This model provides a valuable framework for future research, and could be used to explain child CAM use. An understanding of the decision making process is crucial in promoting shared decision making between healthcare practitioners and parents and could inform service delivery, guidance and policy.
The effect of varying analytical methods on estimates of anti-malarial clinical efficacy
Authors: Verret Wendy J , Dorsey Grant , Nosten Francois , Price Ric N
Published: April 2009

Background

Analytical approaches for the interpretation of anti-malarial clinical trials vary considerably. The aim of this study was to quantify the magnitude of the differences between efficacy estimates derived from these approaches and identify the factors underlying these differences.

Methods

Data from studies conducted in Africa and Thailand were compiled and the risk estimates of treatment failure, adjusted and unadjusted by genotyping, were derived by three methods (intention to treat (ITT), modified intention to treat (mITT) and per protocol (PP)) and then compared.

Results

29 clinical trials (15 from Africa and 14 from Thailand) with a total of 65 treatment arms (38 from Africa and 27 from Thailand) were included in the analysis. Of the 15,409 patients enrolled, 2,637 (17.1%) had incomplete follow up for the unadjusted analysis and 4,489 (33.4%) for the adjusted analysis. Estimates of treatment failure were consistently higher when derived from the ITT or PP analyses compared to the mITT approach. In the unadjusted analyses the median difference between the ITT and mITT estimates was greater in Thai studies (11.4% [range 2.1–31.8]) compared to African Studies (1.8% [range 0–11.7]). In the adjusted analyses the median difference between PP and mITT estimates was 1.7%, but ranged from 0 to 30.9%. The discrepancy between estimates was correlated significantly with the proportion of patients with incomplete follow-up; p < 0.0001. The proportion of studies with a major difference (> 5%) between adjusted PP and mITT was 28% (16/57), with the risk difference greater in African (37% 14/38) compared to Thai studies (11% 2/19). In the African studies, a major difference in the adjusted estimates was significantly more likely in studies in high transmission sites (62% 8/13) compared to studies in moderate transmission sites (24% 6/25); p = 0.035.

Conclusion

Estimates of anti-malarial clinical efficacy vary significantly depending on the analytical methodology from which they are derived. In order to monitor temporal and spatial trends in anti-malarial efficacy, standardized analytical tools need to be applied in a transparent and systematic manner.
Ritonavir blocks AKT signaling, activates apoptosis and inhibits migration and invasion in ovarian cancer cells
Authors: Kumar Sanjeev , Bryant Christopher S , Chamala Sreedhar , Qazi Aamer , Seward Shelly , Pal Jagannath , Steffes Christopher P , Weaver Donald W , Morris Robert , Malone John M , Shammas Masood A , Prasad Madhu , Batchu Ramesh B
Published: April 2009

Background

Ovarian cancer is the leading cause of mortality from gynecological malignancies, often undetectable in early stages. The difficulty of detecting the disease in its early stages and the propensity of ovarian cancer cells to develop resistance to known chemotherapeutic treatments dramatically decreases the 5-year survival rate. Chemotherapy with paclitaxel after surgery increases median survival only by 2 to 3 years in stage IV disease highlights the need for more effective drugs. The human immunodeficiency virus (HIV) infection is characterized by increased risk of several solid tumors due to its inherent nature of weakening of immune system. Recent observations point to a lower incidence of some cancers in patients treated with protease inhibitor (PI) cocktail treatment known as HAART (Highly Active Anti-Retroviral Therapy).

Results

Here we show that ritonavir, a HIV protease inhibitor effectively induced cell cycle arrest and apoptosis in ovarian cell lines MDH-2774 and SKOV-3 in a dose dependent manner. Over a 3 day period with 20 μM ritonavir resulted in the cell death of over 60% for MDAH-2774 compared with 55% in case of SKOV-3 cell line. Ritonavir caused G1 cell cycle arrest of the ovarian cancer cells, mediated by down modulating levels of RB phosphorylation and depleting the G1 cyclins, cyclin-dependent kinase and increasing their inhibitors as determined by gene profile analysis. Interestingly, the treatment of ritonavir decreased the amount of phosphorylated AKT in a dose-dependent manner. Furthermore, inhibition of AKT by specific siRNA synergistically increased the efficacy of the ritonavir-induced apoptosis. These results indicate that the addition of the AKT inhibitor may increase the therapeutic efficacy of ritonavir.

Conclusion

Our results demonstrate a potential use of ritonavir for ovarian cancer with additive effects in conjunction with conventional chemotherapeutic regimens. Since ritonavir is clinically approved for human use for HIV, drug repositioning for ovarian cancer could accelerate the process of traditional drug development. This would reduce risks, limit the costs and decrease the time needed to bring the drug from bench to bedside.