bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation and Characterization of Bis-GMA/TEGDMA/Clay Nanocomposites at Low Filler Content Regimes
Authors: Mahmoodian Mehrnoosh , Pourabbas Behzad , Amirhosein Baghaee Arya
Published: December 2009

Photo-curable polymer/clay nanocomposites have been prepared using Bis-GMA/TEGDMA (50/50 wt%) and modified as well as unmodified clays at different loading levels <10 wt%. The dispersion state of the clay layers has been studied using wide-angle X-ray diffraction and transmission electron microscopy as the key factor affecting the properties of the final cured nanocomposites. Photopolymerization induced volume shrinkage and double bond conversion percent was determined using density measurement techniques and Fourier transform infrared spectroscopy in order to verify the opacity of the clay filler on polymerization characteristics. Mechanical properties (flexural strength, flexural modulus, and diametral tensile strength) of the photo-cured nanocomposites were also evaluated according to standard test methods provided for materials with dental application. The results showed that the exfoliation or intercalation of the layers play to be the key factor on polymerization features and the mechanical properties of the final nanocomposites. The dispersion state is determined, first, to be dependent to the compatibilization level of the clay and secondly to its content in the composition. Experiments carried out by thermogravimetric analysis revealed also the thermal property dependence to relative abundance of exfoliated/intercalated layers.
Permeability of Various Hybrid Composites Subjected to Extreme Thermal Cycling and Low-velocity Impacts
Authors: McVay Amelia C. , Johnson W.S.
Published: December 2009

This experimental exploratory study investigates the effects of embedding a ‘barrier’ layer within a graphite/epoxy composite during manufacture on reducing the permeability after thermal cycling and low velocity impact events. The baseline composite material was an eight ply graphite/epoxy system. Barrier layer candidates include aluminized Mylar®, aluminum foil, and two β-Ti 15-3 films. Cryogenic thermal cycling was performed on the hybrid composites and control composites to determine if the interleaved composites exhibited reduced permeability after thermal cycling as compared to the controls. Drop-weight impact tests were performed on the hybrids and controls to determine the effect of interleaving on the critical impact energy of the graphite/epoxy composites. The results of this research suggest that the addition of an embedded barrier layer can increase a graphite/epoxy composite’s resistance to low-velocity impacts, which cause permeation. This research indicates that hybrid composites are promising materials for applications where extreme temperatures and moderate impact loads are experienced.
Effect of Pre-debonding on Crack Bridging Behavior of Fiber-reinforced Cementitious Composite
Authors: Shin Kyung-Joon , Lee Kwang-Myong , Chang Sung-Pil
Published: December 2009

Among the large variety of methods that have been applied to overcome the problems encountered in cementitious materials fiber reinforcement is gaining large attraction owing to the high tensile resistance exhibited by the fibers. For effective analysis of the post-cracking behavior of the fiber-reinforced materials, numerous researchers have studied analytical methods to predict the behavior of such composite materials based on the behavior of a single fiber. However, these methods failed to consider the change of the fiber interface occurring during the cracking process. Accordingly, this study proposes a fiber-bridging model that can consider the pre-debonding effect created in the cracking process. Analytical examples are presented to explore the effect of pre-debonding on the pull-out behavior of a single fiber and the bridging relation of the crack plane. Moreover, the behavioral difference is analyzed with respect to the type of fiber. The results reveal the dependence of the pre-debonding effect on the pull-out state, the stress of the fiber and, particularly, the influence of the eventual overstepping of the tensile strength during the increase stage of the stress.
Characterization Methodology of Thermoset Resins for the Processing of Composite Materials — Case Study: CYCOM 890RTM Epoxy Resin
Authors: Khoun Loleï , Centea Timotei , Hubert Pascal
Published: December 2009

The resin characterization is a key element in the manufacturing of composite materials. Resin processing properties and their associated constitutive models are essential in order to define and optimize the processing parameters and predict the final properties of a composite structure. In this article, a comprehensive methodology is presented to characterize the main processing properties of a thermoset resin system. As a case study, the thermal, chemorheological, and thermomechanical properties of the CYCOM 890RTM epoxy resin were investigated. A cure kinetics model taking into account the diffusion was found to accurately predict resin cure kinetics behavior within the processing condition range. The developed resin rheological model accurately predicted the onset of resin gelation and the evolution of resin viscosity with temperature and degree-of-cure. The glass transition temperature and instantaneous elastic modulus were determined using also a rheometer in a solid torsion mode. Finally, volumetric changes, resin chemical shrinkage and coefficient of thermal expansion were investigated taking into account the chemical and thermal effects. In general, the detailed procedure and techniques presented in this work can be applied to the intensive characterization of a wide range of thermoset resin systems.
Quality Assured Science: Managerialism in Forensic Biology
Authors: Leslie Myles
Published: December 2009

This article takes as its point of departure the idea that the adoption of managerial principles to ensure the quality of DNA evidence is an accident of history which has changed the ways forensic biology is conducted and forensic biologists think. I begin by defining managerialism and tracking its entry into the contentious world of forensic biology, asking how it is that a focus on efficiency and precise process control is affecting these labs. My analysis unfolds in two parts. I first look at the external inspection routines that assure quality in forensic labs and the degree to which these routines represent ‘‘self” rather than ‘‘peer” assessment. I next look at the internal lab quality assurance (QA) routines that facilitate managerial control of technical and scientific workers, noting that QA is a trope flexible enough to govern both the numerically auditable and quasirobotic activities of technicians along with the less tangible more consensus-based human interactions of scientists. Illustrating that ‘‘science” is being pushed aside by management imperatives, I examine the consequences of this new emphasis for both the lab workers and the criminal justice system.
Intimacy status, attachment, separation-individuation patterns, and identity status in female university students
Authors: Årseth Annie K. , Kroger Jane , Martinussen Monica , Bakken Guro
Published: December 2009

This research examined attachment style, separation-individuation patterns, and identity status in relation to intimacy capacity among emerging adulthood women. Some 100 Norwegian university students, aged 18—29 years (M = 22.4; SD = 2.5) completed the Intimacy Status Interview, the Relationship Questionnaire, the Separation-Individuation Test of Adolescence, and the Extended Objective Measure of Ego Identity Status-II. Results showed that intimate women had a higher secure attachment score than pseudointimate women and a lower fearful attachment score compared to pseudointimate and merger women. Pseudointimates and mergers showed greater separation-individuation difficulties compared to intimate women; pseudointimates had significantly higher rejection expectancy, dependency denial, and separation anxiety scores, while mergers had significantly higher separation anxiety scores than intimates. Few relationships emerged between identity development and intimacy capacity.
The contradictions of identity-work for parents of visibly adopted children
Authors: Harrigan Meredith Marko
Published: December 2009

As the number of families formed through visible adoption continues to increase, so too does the need to understand how members communicatively experience their families. Grounded in the interpretive paradigm and framed by relational dialectics theory, the researcher conducted 31 interviews with 40 parents to investigate what, if any, contradictions parents experience as they engage in identity-work. The researcher describes six contradictions active in parents’ identity-work: (i) similarity and difference, (ii) invisibility and visibility, (iii) integration and distance, (iv) fortune and loss, (v) openness and closedness and (vi) community and privacy. Implications of these findings are discussed to provide insight to researchers and individuals who interact with members of families formed through visible adoption.
Parent—adolescent relationship qualities, internal working models, and attachment styles as predictors of adolescents’ interactions with friends
Authors: Shomaker Lauren B. , Furman Wyndol
Published: December 2009

This study examined how parent—adolescent relationship qualities and adolescents’ representations of relationships with parents were related to interactions in 200 adolescent—close friend dyads. Adolescents and friends were observed discussing problems during a series of structured tasks. Negative interactions with mothers were significantly related to adolescents’ greater conflict with friends, poorer focus on tasks, and poorer communication skills. Security of working models (as assessed by interview) was significantly associated with qualities of friendship interactions, whereas security of attachment styles (as assessed by questionnaire) was not. More dismissing (versus secure) working models were associated with poorer focus on problem discussions and weaker communication skills with friends, even after accounting for gender differences and current parent—adolescent relationship qualities.
Safe time limits of aortic cross-clamping and cardiopulmonary bypass in adult cardiac surgery
Authors: Nissinen Juha , Biancari Fausto , Wistbacka Jan-Ola , Peltola Timo , Loponen Pertti , Tarkiainen Pekka , Virkkilä Markku , Tarkka Matti
Published: December 2009

Objectives: We evaluated the impact of aortic cross-clamping time (XCT) and cardiopulmonary bypass time (CPBT) on the immediate and late outcome after adult cardiac surgery and attempted to identify their safe time limits.

Methods: This study includes 3280 patients who underwent adult cardiac surgery of various complexities. Myocardial protection was achieved with tepid continuous antegrade/retrograde blood cardioplegia.

Results: Receiver operating characteristics (ROC) curve analysis showed that XCT (area under the curve, AUC: 0.66), CPBT (AUC: 0.73) and CPBT with unclamped aorta (AUC: 0.77) were significantly associated with 30-day postoperative mortality. XCT of increasing 30-minute intervals (Odds Ratio (OR) 1.21, 95%C.I. 1.01-1.52) and CPBT of increasing 30-minute intervals (OR 1.47, 95%C.I. 1.27-1.71) were independent predictors of 30-day mortality. The best cutoff value for XCT was 150 min (30-day death: 1.8% vs. 12.2%, adjusted OR 3.07, 95%C.I. 1.48-6.39, accuracy 91.5%) and for CPBT 240 min (30-day death: 1.9% vs. 31.5%, adjusted OR 8.78, 95%C.I. 4.64-16.61, accuracy 96.0%). These parameters were significantly associated also with postoperative morbidity, particularly with postoperative stroke.

Conclusions: XCT and CPBT are predictors of immediate postoperative morbidity and mortality. In our experience, cardiac procedures with CPBT<240 min and XCT<150 min were associated with a rather low risk of immediate postoperative adverse events independently of the complexity of surgery patient’s operative risk.
Transitions between care settings at the end of life in The Netherlands: results from a nationwide study
Authors: Abarshi Ebun , Echteld Michael , Van den Block Lieve , Donker Gé , Deliens Luc , Onwuteaka-Philipsen Bregje
Published: December 2009

Multiple transitions between care settings in the last phase of life could jeopardize continuity of care and overall end-of-life patient care. Using a mortality follow-back study, we examined the nature and prevalence of transitions between Dutch care settings in the last 3 months of life, and identified potential characteristics associated with them. During the 2-year study period, 690 registered patients died ‘totally expectedly and non-suddenly’. These made 709 transitions in the last 3 months, which involved a hospital two times out of three, and covered 43 distinct care trajectories. The most frequent trajectory was home-to-hospital (48%). Forty-six percent experienced one or more transitions in their last month of life. Male gender, multi-morbidities, and absence of GP awareness of a patient’s wish for place of death were associated with having a transition in the last 30 days of life; age of ≤85 years, having an infection and the absence of a palliative-centred treatment goal were associated with terminal hospitalization for ≥7 days. Although the majority of the ‘totally expected and non-sudden’ deaths occurred at home, transitions to hospitals were relatively frequent. To minimize abrupt or frequent transitions just before death, timely recognition of the palliative phase of dying is important.
Inviting the absent members: examining how caregivers’ participation affects hospice team communication
Authors: Wittenberg-Lyles Elaine , Oliver Debra Parker , Demiris George , Burt Stephanie , Regehr Kelly
Published: December 2009

This paper is a secondary observation of a larger pilot study. The Assessing Caregivers for Team Intervention via Video Encounters intervention project enabled caregiver participation in hospice interdisciplinary team meetings. This paper used the team observation scale to assess the impact of caregiver involvement on team structure, process, and outcome. Comparisons were made between traditional team meetings and the team meetings that involved caregivers by using videotapes of both. Analysis found that team meetings with participating caregivers had better team outcomes, with more patient-centered goals, increased discussion of biopsychosocial problems, and the development of interdisciplinary care plans occurring more often than in the traditional hospice team meetings. Findings from this study show benefits for inclusion of caregivers in hospice team meetings.
Manifestation Determinations Under the New Individuals With Disabilities Education Act
Authors: Zirkel Perry A.
Published: December 2009

This article provides an update of a previous analysis of the case law concerning manifestation determinations culminating in the revised pertinent provisions of the Individuals with Disabilities Education Act (IDEA) 2004. Specifically, the update consists of a synthesis of the legislative history, Office of Special Education Programs interpretations, and published hearing and review officer and court decisions that provide legal guidance as to the application of the manifestation provisions of IDEA 2004 and its 2006 regulations. The results reveal that thus far (a) the hearing and review officer and court decisions applying the new, causality criteria have continued at a higher but still modest rate (i.e., frequency per year) as the case law under the prior criteria; (b) the conduct in question remained focused primarily on drugs and, in various forms, violence; (c) specific learning disability and other health impairment (attention-deficit/hyperactivity disorder) continued to predominate as the disabilities at issue, but the Diagnostic and Statistical Manual of Mental Disorders diagnosis of oppositional defiant disorder became more frequent than in the prior case law; (d) the only new notable decisional factor was burden of proof; (e) the outcomes of the new case law has, with an unexpected but limited reduction, continued to predominate in favor of determinations that the child’s disciplined conduct was not a manifestation of the child’s disability; and (f) procedural issues have played a limited role in terms of reversing such district manifestation determinations.
Central Venous Saturation: A Prognostic Tool in Cardiac Surgery patients
Authors: Nogueira Pedro M. , Mendonça- Filho Hugo T. , Campos Luiz Antonio , Gomes Renato V. , Felipe Alexandre R. , Fernandes Marco A. , Villela-Nogueira Cristiane A. , Rocco José R.
Published: December 2009

Background: Central venous oxygen saturation (ScvO2) is a valuable prognostic marker in sepsis. However, its value in cardiac surgery has not been assessed yet. This study aimed at evaluating ScvO2 as a tool for predicting short-term organ dysfunction (OD) after cardiac surgery. Methods: A prospective cohort including cardiac surgery patients submitted to a goal-oriented therapy to maintain ScvO2 above 70% was studied. Postoperative blood samples collected at 30 minutes (T1), 6 hours (T2), and 24 hours (T3) for ScvO2 measurement were selected to further analysis. Two groups were formed according to the absence (G0) or presence (G1) of OD defined as a Sequential Organ Failure Assessment (SOFA) score ≥5 on the third postoperative day. A logistic regression analysis was performed to identify the variables independently associated with OD on the third postoperative day. Results: From the 246 patients included, 54 (22%) developed OD and were defined as G1. The mortality rates in G0 and G1 were 1.6% and 31.5%, respectively (P < .001). In the comparative analysis between G0 and G1, the ScvO2 values were remarkably lower in G1 at T1 (66.2 ± 9.2 vs 62.3 ± 11.6; P = .009), T2 (69.6 ± 5.9 vs 63.5 ± 9.4; P ≤ .001), and T3 (69.6 ± 5.6 vs 64.6 ± 6.4; P ≤ .001). The variables independently associated with OD in the final logistic regression model were Cleveland score (95% CI: 1.13-1.44; OR: 1.27; P < .001), lactate at T3 (95% CI:1.21-3.15; OR 1.95; P = .006), BE at T3 (95% CI:0.69-0.93; OR 0.80; P = .005); ScvO2 at T2 (95% CI:0.86-0.96; OR 0.91; P = .002), and ScvO2 at T3 (95% CI:0.83-0.95; OR 0.89; P = .002). Conclusion: Postoperative ScvO2 can be a valuable tool to predict OD after major cardiac surgeries. Its kinetics should be carefully followed in that setting.
Studies on the Relative Degradation and Interfacial Properties Between Jute/Polypropylene and Jute/Natural Rubber Composites
Authors: Khan Ruhul A. , Haque M.E. , Huq Tanzina , Khan Mubarak A. , Zaman Haydar U. , Fatema Konica J. , Al-Mamun MD , Khan Avik , Ahmad Mohamad Asri
Published: December 2009

Jute fabrics (hessian cloth) reinforced polypropylene (PP) matrix composites (30% fiber by weight) were fabricated by compression molding. Tensile strength (TS), tensile modulus (TM), and percentage elongation at break (Eb) of the composites were found to be 32 MPa, 740 MPa, and 16%, respectively. Then jute fabrics reinforced solid natural rubber (NR)-based composites (30% fiber by weight) were also fabricated and it was found that TS, TM, and Eb of the jute/NR composites were 14 MPa, 120 MPa, and 94%, respectively. The mechanical properties of jute/PP and jute/NR composites were compared. Six weeks of degradation of the composites were performed in aqueous medium and it was found that jute/NR composites lost much of its original strength and modulus compared to that of the jute/PP composites. Interfacial shear strength (IFSS) of the jute/PP and jute/NR systems was investigated by using the single fiber fragmentation tests. The IFSS of jute/PP and jute/NR systems appeared to be 2.16 and 0.89 MPa, respectively. Fracture side of the composites was also studied by scanning electron microscope and suggested better fiber matrix adhesion between jute fiber and PP.
Can we characterise ‘openness’ in the Holocene palaeoenvironmental record? Modern analogue studies of insect faunas and pollen spectra from Dunham Massey deer park and Epping Forest, England
Authors: Smith David , Whitehouse Nicki , Bunting M. Jane , Chapman Henry
Published: December 2009

This paper examines the degree to which tree-associated Coleoptera (beetles) and pollen could be used to predict the degree of ‘openness’ in woodland. The results from two modern insect and pollen analogue studies from ponds at Dunham Massey, Cheshire and Epping Forest, Greater London are presented. We explore the reliability of modern pollen rain and sub-fossil beetle assemblages to represent varying degrees of canopy cover for up to 1000 m from a sampling site. Modern woodland canopy structure around the study sites has been assessed using GIS-based mapping at increasing radial distances as an independent check on the modern insect and pollen data sets. These preliminary results suggest that it is possible to use tree-associated Coleoptera to assess the degree of local vegetation openness. In addition, it appears that insect remains may indicate the relative intensity of land use by grazing animals. Our results also suggest most insects are collected from within a 100—200 m radius of the sampling site. The pollen results suggest that local vegetation and density of woodland in the immediate area of the sampling site can have a strong role in determining the pollen signal.
Health-related quality of life, smoking and carotid atherosclerosis in white British women with systemic lupus erythematosus
Authors: Barta Z. , Harrison MJ , Wangrangsimakul T. , Shelmerdine J. , Teh L-S. , Pattrick M. , Edlin H. , Dale N. , Ahmad Y. , Bruce IN
Published: December 2009

We tested the hypothesis that carotid atherosclerosis in systemic lupus erythematosus (SLE) is associated with poor health-related quality of life (HRQOL), which is independent of any association with traditional risk factors (TRFs), lifestyle and socioeconomic factors. Women with SLE completed the RAND Medical Outcome Study 36-Item Short-Form Health Survey version 1 (MOS SF-36). B-mode Doppler examination of the carotid arteries determined the presence of atherosclerotic plaque. The association between carotid plaque and HRQOL domains was analysed using logistic regression models with sequential adjustments for age, TRFs, education level and employment status. We studied 181 women, 47 (26%) of whom had carotid plaque. Carotid plaque was significantly associated with lower levels of physical functioning (p = 0.047), vitality (p = 0.04), role emotional (p = 0.04) and mental health subscales (p = 0.01) and lower mental component summary score (MCS) (p = 0.03). These associations were no longer significant after adjustment for age and TRFs, especially smoking. Smokers had lower physical functioning, vitality and mental health and more bodily pain. The association between carotid plaque and HRQOL was not independent of TRFs and smoking was a key mediator of the associations found. Poor HRQOL in smokers will need addressing as part of any smoking cessation strategies in SLE patients.
Couples Counseling Directive Technique: A (Mis)communication Model to Promote Insight, Catharsis, Disclosure, and Problem Resolution
Authors: Mahaffey Barbara A.
Published: December 2009

A psychoeducational model for improving couple communication is proposed. An important goal in couples counseling is to assist couples in resolving communication conflicts. The proposed communication model helps to establish a therapeutic environment that encourages insight, therapeutic alliance formation, catharsis, self-disclosure, symptom relief, and positive outcome.
Questionnaires and Lived Experience: Strategies of Coping With the Quantitative Frame
Authors: Galasiński Dariusz , Kozłowska Olga
Published: December 2009

The article focuses on informants’ interaction with questionnaires as a method of collecting data and analyzes how the informants struggle with the reality imposed on them by the instruments’ items. Focusing on a social psychological questionnaire used to explore experience, the authors challenge the link between the data that are collected and what is concluded from them, and particularly the notion that such conclusions offer insight into informants’ experiences. The data the article is based on come from a session in which informants were asked to complete a questionnaire designed to examine feelings and behaviors after a job loss and to “think aloud” while doing it. The authors describe three strategies of dealing with the questionnaire frame: rejecting it, constructing experience in a way that matches the instrument, and, finally, reformulating the questionnaire’s questions. The article concludes by arguing that the process of filling in a questionnaire results in the experiences that the instrument is designed to examine being made irrelevant and their complexity far too great for a-contextual quantification.
Lifting the Lid on Sexuality and Ageing
Authors: Fenge Lee-Ann , Fannin Ann , Armstrong Andrew , Hicks Christina , Taylor Val
Published: December 2009

This article offers ‘insider perspectives’ on participatory action research (PAR) by exploring the reflective narratives of older volunteer researchers who were involved in a recent participatory action research project into the needs, experiences and aspirations of older lesbian women and gay men (OLGs) living in Dorset, England. It explores in their own words the experiences of being a volunteer researcher on a project that explored the marginalized identities of older lesbians and gay men. The Gay and Grey project was funded for three years by the Big Lottery Fund, and was a joint initiative between Help and Care, a voluntary agency working with older people in Dorset, and Bournemouth University. In this article the volunteers offer narrative reflections on their involvement in this project, and what it meant to them. The tensions in participatory action research will be explored in terms of the different expectations of stake-holders in the research. Consideration will be given to what can be learnt from the narratives of volunteer researchers, and the issues of inclusivity within marginalized voices.
The Deep Plunge
Authors: Sakamoto Izumi , Ku Jane , Wei Yi
Published: December 2009

A grounded theory study examined the socio-cultural adaptation experiences of ‘earlier’ Mainland Chinese skilled immigrants; ‘earlier’ refers to those residing in Canada longer than three years and therefore no longer considered ‘newcomers’ eligible for federal government-sponsored settlement programs. Analysis of 29 in-depth interviews and four focus groups involving 29 participants yielded an over-arching theme of luocha (deep plunge). Luocha describes the enormous gap skilled immigrants experienced between their current life in Canada and their pre-immigration life in China, and contextualizes the many challenges associated with their sociocultural adaptation (settlement) experiences. At the same time, these immigrants also discussed various coping strategies that they employed to deal with this deep plunge. Recommendations for social service provision and social policy are discussed.
Mesopic spectral sensitivity curves by a colour-matching method
Authors: Polymeropoulos G. , Topalis FV
Published: December 2009

A new model for mesopic spectral sensitivity curves is realised, using the colorimetric method. Trichromatic colour matches to five monochromatic stimuli are made within the mesopic range of vision at various levels of power using monochromatic primaries. The proposed model is a linear combination of the V10(λ) and V'(λ) standard spectral sensitivity curves and is characterised by a coefficient depending on radiance. The values of this coefficient are first estimated from the colorimetric results using the least squares method. Then, they are fine tuned by an optimisation procedure. This model gives comparable results to other models based on visual performance.
Advancing our understanding of osteocyte cell biology
Authors: Dayong Guo  , Bonewald Lynda F.
Published: December 2009

Osteocytes were the forgotten bone cell until the bone community could become convinced that these cells do serve an important role in bone function and maintenance. In this review we trace the history of osteocyte characterization and present some of the major observations that are leading to the conclusion that these cells are not passive placeholders residing in the bone matrix, but are indeed, major orchestrators of bone remodeling.
Glucocorticoid-induced osteoporosis: treatment update and review
Authors: Fraser Lisa-Ann , Adachi Jonathan D.
Published: December 2009

Glucocorticoid-induced osteoporosis (GIO) is a serious consequence of glucocorticoid therapy leading to fractures in 30—50% of patients. A wide range of protective medications have been studied in this condition including calcium, vitamin D, vitamin D analogs, oral and intravenous bisphosphonates, sex hormones, anabolic agents and calcitonin. The mechanism of action, and evidence for these therapies, are reviewed — focusing on important trials and new evidence. Recently published guidelines are also reviewed and compared. Bisphosphonates are currently the recommended first-line therapy for the prevention and treatment of GIO. They have been shown to increase bone mineral density (BMD) at the spine and hip and to decrease the incidence of vertebral fractures (especially in postmenopausal women). Testosterone therapy and female hormone replacement therapy (HRT) have been found to increase lumbar spine BMD in hypogonadal patients on glucocorticoid therapy, but effects on hip BMD have not been consistent and there is no fracture data in the GIO population. Similarly, calcitonin increases lumbar spine BMD but has no proven fracture efficacy. The effect of selective estrogen receptor modulators, the oral contraceptive pill and strontium on GIO is relatively unknown. Parathyroid hormone (PTH 1-34) and zoledronic acid have emerged as exciting new options for the treatment of GIO. Both therapies have been found to result in gains in BMD at the spine and hip that are either noninferior or superior to those seen with oral bisphosphonate therapy. PTH 1-34 has also been found to decrease the incidence of new vertebral fractures and may be an option in high-risk patients established on long-term glucocorticoid therapy.
Optimizing treatment of von Willebrand disease by using phenotypic and molecular data
Authors: Rodeghiero Francesco , Castaman Giancarlo , Tosetto Alberto
Published: December 2009

The wide clinical spectrum of von Willebrand disease (VWD), its complex pathophysiology and its classification into distinct quantitative (type 1 or type 3) and qualitative (type 2) types with further subtle distinctions have prevented most clinicians from establishing a straightforward approach to diagnosing and treating this inherited bleeding disorder. The results of studies involving large cohorts of patients with a wide range of bleeding manifestations and variable von Willebrand factor (VWF) reduction have recently become available. These data have allowed the proposal of minimal criteria for a clinically useful diagnosis and for differentiating patients with mild VWD from subjects with borderline or only slightly reduced VWF levels who will not benefit from a specific diagnosis. These criteria are based on measurement of VWF ristocetin cofactor (VWF:RCo), VWF antigen (VWF:Ag), factor VIII and a standardized bleeding score (BS). Demonstration of the inheritance of the disorder could help to classify patients for whom insufficient hemostatic challenges may produce a falsely reassuring BS (like in children). Using this approach, mild VWD appears to be mostly composed of type 1 cases. Complemented by the results of desmopressin trial infusion, these parameters form the basis for a clinically oriented classification of all forms of VWD and may be useful for selecting the best treatment according to the severity of the disease. Although few molecular data have revealed practical utility, there is no doubt that the clarification of the molecular pathophysiology of VWD has allowed the unification of this complex disorder into a simple conceptual framework. This framework underlies the proposed utilization of simple phenotypic markers for optimizing treatments in individual patients.
Drug-induced thrombocytopenia: pathogenesis, evaluation, and management
Authors: George James N. , Aster Richard H.
Published: December 2009

Although drugs are a common cause of acute immune-mediated thrombocytopenia in adults, the drug etiology is often initially unrecognized. Most cases of drug-induced thrombocytopenia (DITP) are caused by drug-dependent antibodies that are specific for the drug structure and bind tightly to platelets by their Fab regions but only in the presence of the drug. A comprehensive database of 1301 published reports describing 317 drugs, available at www.ouhsc.edu/platelets, provides information on the level of evidence for a causal relation to thrombocytopenia. Typically, DITP occurs 1 to 2 weeks after beginning a new drug or suddenly after a single dose when a drug has previously been taken intermittently. However, severe thrombocytopenia can occur immediately after the first administration of antithrombotic agents that block fibrinogen binding to platelet GP IIb-IIIa, such as abciximab, tirofiban, and eptifibatide. Recovery from DITP usually begins within 1 to 2 days of stopping the drug and is typically complete within a week. Drug-dependent antibodies can persist for many years; therefore, it is important that the drug etiology be confirmed and the drug be avoided thereafter.
Mechanisms of anti-D action in the prevention of hemolytic disease of the fetus and newborn
Authors: Brinc Davor , Lazarus Alan H.
Published: December 2009

Anti-D is routinely and effectively used to prevent hemolytic disease of the fetus and newborn (HDFN) caused by the antibody response to the D antigen on fetal RBCs. Anti-D is a polyclonal IgG product purified from the plasma of D-alloimmunized individuals. The mechanism of anti-D has not been fully elucidated. Antigenic epitopes are not fully masked by anti-D and are available for immune system recognition. However, a correlation has frequently been observed between anti-D-mediated RBC clearance and prevention of the antibody response, suggesting that anti-D may be able to destroy RBCs without triggering the adaptive immune response. Anti-D-opsonized RBCs may also elicit inhibitory FcγRIIB signaling in B cells and prevent B cell activation. The ability of antigen-specific IgG to inhibit antibody responses has also been observed in a variety of animal models immunized with a vast array of different antigens, such as sheep RBCs (SRBC). This effect has been referred to as antibody-mediated immune suppression (AMIS). In animal models, IgG inhibits the antibody response, but the T-cell response and memory may still be intact. IgG does not mask all epitopes, and IgG-mediated RBC clearance or FcγRIIB-mediated B-cell inhibition do not appear to mediate the AMIS effect. Instead, IgG appears to selectively disrupt B cell priming, although the exact mechanism remains obscure. While the applicability of animal models of AMIS to understanding the true mechanism of anti-D remains uncertain, the models have nevertheless provided us with insights into the possible IgG effects on the immune response.
Newborn screening for non-sickling hemoglobinopathies
Authors: Hoppe Carolyn C.
Published: December 2009

The hemoglobinopathies encompass a heterogeneous group of disorders associated with mutations in both the alpha-globin and beta-globin genes. Non-sickling disorders are found primarily in individuals of Mediterranean, Asian and Southeast Asian ancestry. With rapid growth in the Asian and Hispanic segments of the US population, the geographic distribution of hemoglobinopathies is expected to become significantly different from what it is today. The epidemiologic changes in the prevalence of non-sickling hemoglobin disorders have important implications for future public health programs, including newborn screening.

The purpose of newborn screening for hemoglobinopathies is to identify clinically significant disorders and provide early education and specialized care prior to the onset of clinical symptoms. Although newborn screening for sickle cell disease is mandated in all states, screening for non-sickling hemoglobinopathies is directed in only one state and limited to reporting of a presumptive diagnosis in most other states. Early delivery of comprehensive care, as well as new and potentially curative therapies, has significantly improved the prognosis for affected patients. This review will consider the increasing prevalence of once uncommon hemoglobinopathies in the US, highlighting the rationale for expanding newborn screening beyond sickle cell disorders.
Hereditary hemochromatosis: insights from the Hemochromatosis and Iron Overload Screening (HEIRS) Study
Authors: McLaren Gordon D. , Gordeuk Victor R.
Published: December 2009

Hemochromatosis comprises a group of inherited disorders resulting from mutations of genes involved in regulating iron metabolism. The multicenter, multi-ethnic Hemochromatosis and Iron Overload Screening (HEIRS) Study screened ~100,000 participants in the US and Canada, testing for HFE mutations, serum ferritin and transferrin saturation. As in other studies, HFE C282Y homozygosity was common in Caucasians but rare in other ethnic groups, and there was a marked heterogeneity of disease expression in C282Y homozygotes. Nevertheless, this genotype was often associated with elevations of serum ferritin and transferrin saturation and with iron stores of more than four grams in men but not in women. If liver biopsy was performed, in some cases because of evidence of hepatic dysfunction, fibrosis or cirrhosis was often found. Combined elevations of serum ferritin and transferrin saturation were observed in non-C282Y homozygotes of all ethnic groups, most prominently Asians, but not often with iron stores of more than four grams. Future studies to discover modifier genes that affect phenotypic expression in C282Y hemochromatosis should help identify patients who are at greatest risk of developing iron overload and who may benefit from continued monitoring of iron status to detect progressive iron loading.
Molecular mechanisms of normal iron homeostasis
Authors: Zhang An-Sheng , Enns Caroline A.
Published: December 2009

Humans possess elegant control mechanisms to maintain iron homeostasis by coordinately regulating iron absorption, iron recycling, and mobilization of stored iron. Dietary iron absorption is regulated locally by hypoxia inducible factor (HIF) signaling and iron-regulatory proteins (IRPs) in enterocytes and systematically by hepatic hepcidin, the central iron regulatory hormone. Hepcidin not only controls the rate of iron absorption but also determines iron mobilization from stores through negatively modulating the function of ferroportin, the only identified cellular iron exporter to date. The regulation of hepatic hepcidin is accomplished by the coordinated activity of multiple proteins through different signaling pathways. Recent studies have greatly expanded the knowledge in the understanding of hepcidin expression and regulation by the bone morphogenetic protein (BMP) signaling, the erythroid factors, and inflammation. In this review, we mainly focus on the roles of recently identified proteins in the regulation of iron homeostasis.
Non-invasive assessment of tissue iron overload
Authors: Fischer Roland , Harmatz Paul R.
Published: December 2009

In recent years, there has been increasing interest in non-invasive iron measurement, especially of the liver and heart, in patients with iron overload. Serum ferritin still remains an essential monitoring parameter in intervals between liver iron measurements; however, confounding factors such as inflammation, chelation treatment changes and the specific disease have to be taken into account. Liver iron measurements can now routinely be performed in clinical applications either by quantitative magnetic resonance imaging (MRI) using the transverse magnetic relaxation rate R2 or R2* (1/T2*) or by biomagnetic liver susceptometry. For iron measurements in the heart, the single-breathhold multi-echo MRI-R2* method has become a standard modality and is now applied in clinical settings beyond research studies. In other tissues like the pancreas, pituitary, and brain, different MRI methods are employed, but their clinical benefit has yet to be proven.
ASH evidence-based guidelines: should asymptomatic patients with antiphospholipid antibodies receive primary prophylaxis to prevent thrombosis?
Authors: Metjian Ara , Lim Wendy
Published: December 2009

A 35-year-old female presents with a prolonged activated partial thromboplastin time (aPTT) on routine testing, which is found to be due to a lupus anticoagulant. She has no medical issues, no personal or family history of thrombosis, no history of pregnancy loss, and no symptoms suggestive of an underlying rheumatologic disorder. She is a non-smoker and does not take oral contraceptives. You are asked to provide recommendations regarding the need for primary thromboprophylaxis. As you begin your literature search, you formulate the following clinical question: “In asymptomatic patients with antiphospholipid antibodies, does primary prophylaxis prevent thrombotic complications?”
Pathogenesis of thrombosis
Authors: Furie Bruce
Published: December 2009

The hemostatic process is a host defense mechanism to preserve the integrity of the closed high pressure circulatory system. This process must remain inactive but poised to minimize extravasation of blood from the vasculature following tissue injury. Given the complexity of the hemostatic mechanism, paradigms developed from biochemical and cell biological approaches have been revisited by studying thrombus formation in a live animal by intravital microscopy. Many of these paradigms have proven accurate, but others need to be reconsidered given the results of whole animal experiments.
ASH evidence-based guidelines: statins in the prevention of venous thromboembolism
Authors: Evans Natalie S. , Green David
Published: December 2009

A 42-year-old woman under your care for the management of obesity calls you because she has a sister who had a pulmonary embolism. The patient recently read that statin medications are associated with a lower risk of venous thromboembolism (VTE) and wonders whether she should take a statin drug to prevent the development of pulmonary emboli.
Pregnancy-associated thrombosis
Authors: James Andra H.
Published: December 2009

The main reason for the increased risk of thromboembolism in pregnancy is hypercoagulability, which has likely evolved to protect women from the bleeding challenges of miscarriage and childbirth. Women are at a 4- to 5-fold increased risk of thromboembolism during pregnancy and the postpartum period compared with when they are not pregnant. Eighty percent of the thromboembolic events in pregnancy are venous, with an incidence of 0.49 to 1.72 per 1000 pregnancies. Risk factors include a history of thrombosis, inherited and acquired thrombophilia, maternal age greater than 35, certain medical conditions, and various complications of pregnancy and childbirth. Despite the increased risk of venous thromboembolism (VTE) during pregnancy and the postpartum period, most women do not require anticoagulation. Candidates include women with current VTE, a history of VTE, thrombophilia and a history of poor pregnancy outcome, or risk factors for postpartum VTE. The intensity of the anticoagulation will depend on the indication and the monitoring will depend on the intensity. At the time of delivery, anticoagulation should be manipulated to reduce the risk of bleeding complications while minimizing the risk of thrombosis. There are no large trials of anticoagulants in pregnancy, and recommendations are based on case series, extrapolations from nonpregnant patients and the opinion of experts. Nonetheless, anticoagulants are believed to improve the outcome of pregnancy for women who have, or have had, VTE.
Prevention of venous thromboembolism: consensus, controversies, and challenges
Authors: Selby Rita , Geerts William
Published: December 2009

The last 50 years have witnessed a multitude of publications evaluating the efficacy, safety and cost effectiveness of many different thromboprophylaxis interventions. There is widespread consensus that thromboprophylaxis safely reduces morbidity and mortality. More than 25 evidence-based guidelines, published since 1986, also recommend routine thromboprophylaxis in the majority of hospitalized patients. As a result, thromboprophylaxis is recognized as a key safety priority for hospitals. Some of the remaining areas of controversy that will be discussed in this paper include the role of individual risk assessments to determine thrombosis risk and prophylaxis, replacement of low-dose heparin by low-molecular-weight heparin (LMWH), the optimal duration of prophylaxis, the role of combined thromboprophylaxis modalities, the safety of anticoagulant prophylaxis with regional analgesia, the use of LMWHs in chronic renal insufficiency, and the emerging role of new oral anticoagulants as thromboprophylactic agents. Despite the overwhelming evidence supporting thromboprophylaxis, rates of thromboprophylaxis use remain far from optimal. Successful implementation strategies to bridge this knowledge:care gap are the most important current challenges in this area. These strategies must be multifaceted, utilizing local, systems-based approaches as well as legislation and incentives that reinforce best practices.
ASH evidence-based guidelines: what is the role of inferior vena cava filters in the perioperative prevention of venous thromboembolism in bariatric surgery patients?
Authors: Rajasekhar Anita , Crowther Mark A.
Published: December 2009

A 38-year-old morbidly obese male (BMI > 50 kg/m2) presents for an elective gastric bypass surgery. He has no personal or family history of venous thromboembolism or hypercoaguability. You are asked by his primary team whether he should receive a retrievable inferior vena cava filter preoperatively for venous thromboembolism prophylaxis.
Integrative therapies for children with hematological malignancies
Authors: Kelly Kara M.
Published: December 2009

Evidence for integrative therapies (IT) in children with hematological malignancies is slowly evolving. The ideal model of integrative pediatric oncology would offer IT modalities that are deemed safe and effective in conjunction with effective conventional medical treatments. Because of potential interactions, herbs and other dietary supplements should be used with caution, especially during active therapy. Health and wellness should be the emphasis, with IT therapies supporting health promotion and key disease prevention strategies for childhood cancer survivors. All uses, responses, and effects of IT therapies should be carefully documented. A desire to use IT therapies may be an effort to become an active participant in the healing process. Health care providers should encourage, not discourage, this partnership.
Supplements for immune enhancement in hematologic malignancies
Authors: Sze Daniel Man-Yuen , Chan Godfrey Chi-Fung
Published: December 2009

This brief review aims to discuss the various cellular immunological aspects and related mechanisms of the use of specific components from traditional herbal medicines. We begin with lessons learned from thalidomide as an effective single drug with multiple mechanisms of action to treat multiple myeloma. Examples of “supplements” or integrative therapy will be drawn from arsenic trioxide, medicinal mushrooms including Coriolus vesicular and Ganoderma lucidum, followed by the discussion of beta-glucans affecting various immunological important cellular subsets. Different classes of compounds may enhance distinct immune cell populations that might contribute to a multi-targeted holistic effects on anti-cancer treatment. Finally, we conclude by highlighting an herbal formulation PHY906 as a potential adjunct to chemotherapy that might become one of the first US Food and Drug Administration (FDA) approved oral herbal medicines for anti-cancer adjunct treatment.