bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation and Properties of Wheat Straw Fiber-polypropylene Composites. Part II. Investigation of Surface Treatments on the Thermo-mechanical and Rheological Properties of the Composites
Authors: Mingzhu Pan  , Zhang S.Y. , Dingguo Zhou
Published: December 2009

Composites made of polypropylene (PP) and wheat straw fiber treated by alkalization, acetylation, and maleic anhydride polypropylene (MAPP) were prepared, and the dynamic mechanical, thermal, and rheological properties of the treated composites have been investigated. The PP composites reinforced with the treated wheat straw fiber exhibited higher brittleness. The melt flow studies were carried out at the temperature of 170, 180, and 190°C and shear rate of 0.01—0.1 s—1. The PP composites reinforced with the alkalized wheat straw fiber showed the high melt viscosity due to the strong chemical interaction among polymer and wheat straw fiber. The introduction of MAPP to the system increased the flow behavior of the polymer dispersed the wheat straw fiber uniformly, and decreased the melt viscosity. The PP composites introduced by 2 wt% MAPP showed the lowest storage flexural modulus (E′) over the entire temperature range from 25—150°C, due to better compatibility between the wheat straw fiber and matrix. The PP composites made of with 20 wt% alkalized and MAPP treated wheat straw fiber showed the highest E′. The differential scanning calorimeter (DSC) study revealed that introducing the wheat straw fiber to PP matrix increased the melting temperature and crystallization temperature. The PP composites reinforced with the alkalized and MAPP treated fiber had the highest rate of crystallization as a consequent of the co-effect of alkalization and esterfication.
Development of Aluminum-based Hybrid Composites with Graphite Nanofibers/Alumina Short Fibers: Processing and Characterization
Authors: Babu J.S.S. , Prabhakaran Nair K. , Unnikrishnan G. , Kang C.G.
Published: December 2009

In this study, aluminum-based hybrid composites were developed and characterized. Initially, a hybrid preform was fabricated using graphite nanofibers (GNFs) and alumina short fibers (Al2O3sf) with the total volume fraction of fiber at 10, 15, and 20%. The hybrid preforms were then infiltrated with aluminum alloy (A356), and the microstructure and mechanical properties of the hybrid composites were evaluated. The Taguchi approach to experimental design was used to identify those process parameters that had the largest effects on hardness and porosity of the preform. The amount of binder was found to have the largest effect on hardness; volume fraction of fiber affected porosity most significantly. Scanning electron microscopy observations indicated that alumina short fibers were well dispersed within the aluminum matrix. Although GNFs formed clusters in certain regions, their distribution within the short-fiber network was relatively good. The hardness of these composites was found to be higher than that of Al/Al2O3sf mono-composites; however, their tensile strength and compressive strength were reduced considerably. This is attributed to the presence of agglomerated GNFs, which may weaken load sharing between the Al matrix and Al2O3sf.
Optimal Excitation Frequency of Lamb Waves for Delamination Detection in CFRP Laminates
Authors: Hu N. , Liu Y. , Li Y. , Peng X. , Yan B.
Published: December 2009

To improve the reliability of delamination detection techniques based on Lamb waves for carbon fibre reinforced plastics (CFRP) composite laminates, the influence of excitation frequency of Lamb waves on the intensity of reflected waves from a delamination in cross-ply CFRP delaminated beams was investigated. The A0 Lamb wave mode was chosen although the conclusion in this work is also applicable to S0 mode. A Chebyshev pseudospectral Mindlin plate element proposed by authors was employed to simulate the A 0 mode propagation and the interaction of the A0 mode with the delamination. Numerical results show that the sensitivity of A0 mode to the delamination at different frequencies is remarkably different. Each delamination with different lengths or different locations along the through-thickness direction of the laminates generally has at least one or more optimal excitation frequencies which can generate the strongest reflected wave signals from the delamination. The reason for this phenomenon was also investigated by analyzing the natural vibration of the local upper- and lower-delaminated regions. The optimal excitation frequencies were identified to be close to the resonant frequencies of the local delaminated regions with pure flexural vibration modes similar to the deformation pattern of A0 mode.
A Generalized Aggregation-Disintegration Model for the Frequency of Severe Terrorist Attacks
Authors: Clauset Aaron , Wiegel Frederik W.
Published: December 2009

The authors present and analyze a model of the frequency of severe terrorist attacks, which generalizes the recently proposed model of Johnson et al. This model, which is based on the notion of self-organized criticality and which describes how terrorist cells might aggregate and disintegrate over time, predicts that the distribution of attack severities should follow a power-law form with an exponent of α = 5/2. This prediction is in good agreement with current empirical estimates for terrorist attacks worldwide, which give α = 2.4 ± 0.2 and which the authors show is independent of certain details of the model. The authors close by discussing the utility of this model for understanding terrorism and the behavior of terrorist organizations and mention several productive ways it could be extended mathematically or tested empirically.
Protest, Deterrence, and Escalation: The Strategic Calculus of Government Repression
Authors: Pierskalla Jan Henryk
Published: December 2009

The theoretical literature on government repression has mostly taken a choice theoretic perspective, wherein either the protest group optimally chooses a protest tactic in response to government behavior or the government optimally chooses a repression strategy. This approach is insufficient for capturing the strategic nature of protest and repression. The theoretical shortcomings of this approach are reflected in contradictory empirical findings on the effects of repression on dissent. The article develops an extensive strategic game between the government and an opposition group that allows one to identify the conditions for successful deterrence or protest. Introducing incomplete information and a third-party threat additionally produces equilibria with repression and escalating violence. The model produces novel testable hypotheses that shed new light on the effect of repression on dissent, the likelihood of violence, and the possibility of a coup. Implications for the domestic democratic peace and “murder in the middle” hypothesis are drawn.
Information entropy based interaction model and optimization method for swarm intelligence
Authors: Yunlong Zhu  , Xiaoxian He  , Kunyuan Hu  , Ben Niu
Published: December 2009

Inspired by social insects, swarm intelligence has been hotly investigated in recent years as an innovative artificial intelligence technique for solving problems. In this paper, we mainly focus on the information interaction of individuals in swarm intelligence. By using information entropy H(X) and mutual information I(X;Y) of information theory to evaluate the information quality and interaction efficiency, respectively, the interaction model is proposed. Within this model, individuals’ information is evaluated with uniform standards, so that more excellent individuals can be selected to influence other individuals by interaction. We validated this model with the route-exchange algorithm, which is proposed for combinatorial optimization. Seven benchmarks of the Traveling Salesman Problem are tested in the experiments. The results are compared with other heuristic algorithms.
Knowing How to Sleepwalk: Placing Expert Evidence in the Midst of an English Jury Trial
Authors: Scheffer Thomas
Published: December 2009

In this case study I argue that experts, to gain relevance in a jury trial, need to fit into a manifold division of knowing. They do so by borrowing and sharing diverse knowledges. These exchanges place the modest expert testimony right into an authoritative and powerful decision-making apparatus. This argument derives from an ethnographic study of a ‘‘sleepwalking defense.’’ The division of knowing embraces the certified facts, the instructed case, the competing expertise, and the common sense. As a conclusion, I identify the experts’ twofold relevance. Experts perform the case as undecided and decidable. They provide exclusive knowledge and affirm a set of other knowledges. By ‘‘knowing’’ and ‘‘not knowing,’’ the experts perform individual modesty and systemic immodesty by the same token.
Attachment and conflict communication in adult romantic relationships
Authors: Domingue Rachel , Mollen Debra
Published: December 2009

This study explored the connections between adult attachment styles (i.e., secure, preoccupied, fearful-avoidant, dismissing) and communication patterns during conflict (i.e., mutual constructive, demand-withdraw, mutual avoidance, and withholding). Specifically, this study examined how the combination of both partners’ attachment styles, or couple type (i.e., secure-secure, secure-insecure, insecure-insecure), related to self-reported conflict communication patterns. Couples had been together for at least two years (i.e., in a dating, cohabitating, engaged, or marital relationship). Participants included 43 different-sex couples and 10 same-sex couples, who lived primarily in a large metropolitan area in the southwestern US. Secure-secure couples reported the most mutually constructive communication, while the insecure-insecure couples group reported the most demand-withdraw and mutual avoidance and withholding communication. Implications for counseling with couples and families are discussed.
Investigating a four-pathway model of adult attachment orientation and health
Authors: Sadava Stanley W. , Busseri Michael A. , Molnar Danielle S. , Perrier Colin P. K. , DeCourville Nancy
Published: December 2009

We tested a model, derived from attachment theory, linking adult attachment orientation to health through four hypothesized intervening paths: affect, stress, social support, and health-risk behavior. Questionnaires were administered to 623 university students and 219 addiction treatment clients. In both samples, attachment avoidance and attachment anxiety dimensions were indirectly, rather than directly, related to lower subjective ratings of health. In both samples, data were consistent with the affect and stress pathways linking attachment to health. Results for the social support and health-risk behavior pathways were less robust. Results were consistent for male and female respondents. Findings are discussed in terms of attachment theory and the affect regulation processes linking attachment and health. Implications are considered, along with directions for future research.
Early Intervention Programs for Children With Behavior Problems and At Risk for Developing Antisocial Behaviors: Evidence- and Research-Based Practices
Authors: Maag John W. , Katsiyannis Antonis
Published: December 2009

The number of children who would be eligible for, and benefit from, early intervention programs has dramatically increased during the past several years. However, those programs would have to meet the U.S. Department of Education’s criteria for being evidence based. Some programs that have proven successful would not be eligible but rather be considered data based by educational researchers. The purpose of this article is to review the major early intervention programs for children at risk for developing conduct problems and to determine which ones could be considered evidence based, research based, or neither. Issues related to determining whether a program is evidence based versus data based are presented, along with those addressing program efficacy and access for eligible children.
Correction Factors for the Analytical Transverse Stiffness of Unidirectional Fiber Composites
Authors: Lim Teik-Cheng
Published: December 2009

An analytical expression for the transverse elastic stiffness of unidirectional fiber composites is developed in this paper. Based on a basic solution adopting 1D analysis of square fiber cross-section, analytical results from (i) simplified 3D analysis using square fiber cross-section, and (ii) 1D analysis using circular fiber cross-section lead to Poisson’s ratio and geometrical correction, respectively. The Poisson’s ratio correction factor is shown to be a factor to the Young’s Modulus of matrix material while the geometrical correction factor is shown to be a factor to the fiber volume fraction. A geometrical correction function, which describes the fiber-matrix boundary with respect to the representative volume element, is identified. This function transforms results based on square fiber to those of circular fiber cross-section. Comparison of the Poisson’s ratio and geometrically corrected transverse moduli to experimental results reveal good agreement.
Preparation and Characterization of Conducting Poly(ethylene terephthalate)/ Polypyrrole Composite Fibers
Authors: Aydin Z. , Karakişla M. , Saçak M.
Published: December 2009

The conducting poly(ethylene terephthalate) (PET)/polypyrrole (PPy) composite fibers were prepared by chemical polymerization of pyrrole in the presence of PET fibers using various oxidants. The most suitable medium from the points of the lowest electrical surface resistivity and the highest PPy content of composite fibers was observed to be aqueous hydrochloride acid solution with K2S2O8, and the pyrrole concentrations of 0.08 M and 0.04 M, respectively. Characterization of conducting composite fibers was performed by surface resistivity, density, and diameter measurements, FTIR, TGA, optical microscope, and SEM techniques.
Firewood collection strategies at Dutch wetland sites in the process of Neolithisation
Authors: Out Welmoed A.
Published: December 2009

This article investigates the firewood collection strategies at late Mesolithic and early and middle Neolithic Dutch wetland sites dating to 5500—3400 cal BC. It provides an overview of published and unpublished data of unworked, uncarbonised wood and wood charcoal from 15 sites in 3 regions. It is assumed that the unworked wood primarily represents the natural vegetation. The comparison of the wood and charcoal shows that the main factor influencing firewood collection is availability, as indicated by the use of a broad range of taxa and the predominant use of the most common taxa (primarily Alnus glutinosa ). There are additional indications of selective use and avoidance of taxa for fuel that vary between the regions. The preliminary comparison of data from sites without and with domesticates does not show any differences in fuel use that can be related to the Neolithisation process, suggesting that human impact did not change to any extent during the investigated period.
U-series dates of Great Barrier Reef corals suggest at least +0.7 m sea level ~7000 years ago
Authors: Yu Ke-fu , Zhao Jian-xin
Published: December 2009

Strong evidence from field observation and high-precision TIMS U-series dating of exposed in situ massive corals and exposed microatolls on Magnetic Island, Great Barrier Reef, indicates that the relative sea level was at least 0.7 m higher than present ~7000 calendar years (cal yr) ago, and culminated to at least ~1.6 m higher than present ~5800 cal yr ago. The present sea level was probably first reached around 7300—7100 cal yr ago. Together with the youngest age (2236 ± 27 cal yr) of an exposed microatoll colony, the data suggest past sea-level highstands occurred between 7200 and 2200 cal yr ago, lasting for 5000 years. This study represents the first attempt to date sea-level indicators from the Great Barrier Reef by the high-precision U-series method. The results are broadly consistent with a sea-level reconstruction based on a compilation and re-examination of 115 calibrated 14C dates from eastern Australia by Lewis et al. (2008).
Bone marrow infection caused by Mycobacterium avium complex in a patient with systemic lupus erythematosus
Authors: Yazisiz V. , Erbasan F. , Inan D. , Ongut G. , Akkaya BK , Alp A. , Terzioglu E.
Published: December 2009

Systemic lupus erythematosus (SLE) is a disease with wide range of signs and symptoms. SLE patients have increased infective diathesis, and infections are a very important cause of death in these patients. Infections can sometimes mimic the signs and symptoms of SLE. Thus, it is important to recognize that infection can induce a lupus flare-up or can be difficult to distinguish from a lupus flare-up. We describe a 36-year-old female patient with SLE, who presented with skin lesions and pancytopenia, and clinical manifestations similar to a flare-up of SLE. Bone marrow examination revealed infection with Mycobacterium avium complex (MAC). The patient had no history or clinical evidence of pulmonary involvement. This patient is the first case of invasive bone marrow MAC infection in SLE. With this unique case, we would like to emphasize that SLE patients can also be infected by non-tuberculous mycobacteria, and that bone marrow examination for tuberculosis as well as for non-tuberculosis mycobacteria should be considered in SLE patients with refractory pancytopenia.
Lytic bone lesions in lupus-associated myelofibrosis
Authors: Sacré K. , Aguilar C. , Deligny C. , Choudat L. , Koch P. , Arfi S. , Papo T.
Published: December 2009

Myelofibrosis is associated with numerous causes other than hematologic malignant neoplasms, including autoimmune diseases. We describe a 44-year-old woman who suffered bone lytic lesions with extramedullary haematopoiesis in the setting of myelofibrosis associated with systemic lupus erythematosus.
The Emerging Politics of DHS Fusion Centers
Authors: Monahan Torin , Palmer Neal A.
Published: December 2009

This article explores public concerns about the US Department of Homeland Security’s data ‘fusion centers’. These centers, which are proliferating across all US states, coordinate data-sharing among state and local police, intelligence agencies, and private companies. The primary goal of fusion centers is to engage in intelligence-sharing for counter-terrorism purposes. However, they have been used for a variety of other purposes, such as basic policing, spying on social movement organizations, or restricting legal public activities such as taking photographs. Drawing upon a comprehensive analysis of media publications from 2002 to 2008, we identify and discuss three primary categories of concern with fusion centers: (1) their ineffectiveness, particularly given the financial expense, the statistical unlikelihood of terrorist attacks, and the pressing need for other law enforcement support; (2) the potential for mission creep, where the functions of fusion centers expand beyond their originally intended purposes to encompass things like all-hazards preparedness; and (3) the violation of civil liberties, especially through racial profiling or First Amendment violations.
Beyond the ‘Salvation’ Paradigm: Responsibility To Protect (Others) vs the Power of Protecting Oneself
Authors: Mégret Frédéric
Published: December 2009

The emergence of the idea of a ‘responsibility to protect’ has dominated debates about what should be done to stop atrocities. I argue that, despite notable progress, R2P remains embedded in a vision of ‘international’ rescue as primarily coming from outside, and as such ends up neglecting the very real and often much more decisive role that ‘people’ — individuals, civil society, resistance movements — have had in protecting themselves. I argue for a rehabilitation of the role of resistance to atrocities, a better understanding of how the international intervention paradigm may affect it, and a new understanding of the proper role of the international community — one of helping people to help themselves in the face of massive violence.
Third-Generation Civil—Military Relations
Authors: Rosén Frederik
Published: December 2009

Counterinsurgency strategies employed by the US military in Afghanistan have led to the US military embarking on civil governance reform. This has created new forms of civil—military relations with Afghan and international counterparts. These relations appear less dramatic than ‘conventional’ civil—military relations, in that they do not create the same visible alignment on the ground between military and non-military identities. In addition, the increased merging of civil and military work areas creates a new complexity that stems from semantic confusion. This complexity is mostly about norms and principles, in that the core puzzle is the more general question of what kinds of tasks the military should and should not do, rather than about violent consequences to civilians and questions of neutrality. This article proposes the term ‘third-generation civil—military relations’ to capture and examine the conceptual challenges that stem from the merging of military and civil work areas in Afghanistan’s reconstruction.
Internal Energy Based Analysis on Mechanism of Spindle Speed Variation for Regenerative Chatter Control
Authors: Zhang H. , Ni J.
Published: December 2009

Among machining chatter control methods, spindle speed variation (SSV) method is certified as a feasible and effective way: machining chatter can be suppressed by continuously and periodically fluctuating the spindle speed of the machine tool. Although with its substantial value, the SSV method has not yet gained enough acceptance in the industrial machining applications. One of the reasons is the inadequacy of theoretical and practical study on the mechanism of the SSV method for machining chatter suppression. In this paper the mechanism of the SSV method for chatter suppression is revealed by means of internal energy analysis. The theoretical analysis is based on a nonlinear delay differential equation (NLDDE) as the model of regenerative machining chatter. This approach can provide more practical and feasible analytical results than small perturbative approaches. The analytical results demonstrate the machining stability increment of SSV cutting in the mathematical and physical sense, and provide practical suggestions for selection of SSV cutting parameters. Numerical simulations and experimental SSV cutting testing outcomes have coincidence with the analytical results.
“Trouble Comes in Threes”
Authors: Athens Lonnie
Published: December 2009

Pop becomes entangled in an ever growing web of problems. His wife, Herikula, nags him to accompany her and their two daughters to the island of Samos for a long visit with her parents, although he cannot find anyone one to manage his café in his absence. Later at the cafe, a robber threatens Pop’s life with a gun, which Herikula takes as omen from God that he should take his family to Samos before something else bad happens to him. After finally finding someone to manage his café Pop discovers while in Samos that the manager is embezzling the café’s funds. Pop must cut his visit short to Samos to resolve yet another problem that he looks at from his characteristically philosophical perspective.
Challenging Gender Role Stereotypes and Creating Pathways for Goal Achievement
Authors: Boddy Jennifer
Published: December 2009

This article critically examines the success of the Map Your Future women’s mentoring programme (MYF) in challenging gender role norms with a group of women from four socio-economically disadvantaged communities of a large Australian provincial city. MYF was underpinned by a ‘feminist-strengths’ perspective and used a social intervention research framework to guide programme development, implementation and evaluation. Participants, who were predominantly of Anglo-Celtic ethnicity, came from communities where there was a persistent cultural expectation that women work within the home. Unemployment was significantly higher, one-parent families more common, the median weekly household income lower and completion of secondary education well below the state average in all communities (Australian Bureau of Statistics [ABS], 2006). The findings suggest that group mentoring with women, from cultures where care-giving is valued over education and career opportunities, can assist women to broaden their educational and career interests and enable them to explore their hopes and goals for the future unconstrained by gender role norms.
Low von Willebrand factor: sometimes a risk factor and sometimes a disease
Authors: Sadler J. Evan
Published: December 2009

A sufficiently low level of von Willebrand factor (VWF) predisposes to bleeding that can be quite serious, and low VWF is a diagnostic feature of von Willebrand disease (VWD) type 1, which is characterized by partial quantitative deficiency of VWF. Recent groundbreaking studies of patients with VWD type 1 have delineated several pathophysiologic mechanisms that determine the plasma concentration of VWF, but the relationship between VWF level and the likelihood of bleeding remains less well understood. In part, this problem reflects the broad range of VWF levels in the population, so that the distinction between “normal” and “low” is arbitrary. The risk of bleeding certainly increases as the VWF level decreases, but the relationship is not very strong until the VWF level is very low. Furthermore, mild bleeding symptoms are common in apparently healthy populations and have many causes other than defects in VWF, which can make it impossible to attribute bleeding to any single factor, such as low VWF. These difficulties might be resolved by an epidemiologic approach to VWF and other risk factors for bleeding, analogous to how physicians manage multiple risk factors for cardiovascular disease or venous thromboembolism.
Hemophagocytic lymphohistiocytosis (HLH) and related disorders
Authors: Filipovich Alexandra H.
Published: December 2009

Hemophagocytic lymphohistiocytosis (HLH), which has many genetic causes, is characterized by multi-system inflammation. HLH is a reactive process resulting from prolonged and excessive activation of antigen presenting cells (macrophages, histiocytes) and CD8+ T cells. Hemophagocytosis, which is mediated through the CD163 heme-scavenging receptor, is a hallmark of activated macrophages/histiocytes and is the characteristic finding for which the disorder was named. The majority of genetic causes identified to date affect the cytotoxic function of NK and T cells, crippling immunologic mechanisms that mediate natural immune contraction. The predominant clinical findings of HLH are fevers (often hectic and persistent), cytopenias, hepatitis and splenomegaly. Due to the life-threatening implications of the diagnosis of genetically determined HLH, antiinflammatory therapy, often consisting of steroids, etoposide or antithymocyte globulin (ATG), should be instituted promptly, followed by curative hematopoietic cell transplantation. Secondary HLH, associated with autoimmune disorders or viral infections in teens and adults, also carries a significant mortality rate and should be managed in consultation with specialists familiar with the diagnosis and treatment of such disorders.
New insights into the biology of Wiskott-Aldrich syndrome (WAS)
Authors: Thrasher Adrian J.
Published: December 2009

The Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency disease with a characteristic clinical phenotype that includes thrombocytopenia with small platelets, eczema, recurrent infections due to immunodeficiency, and an increased incidence of autoimmune manifestations and malignancies. The identification of the molecular defect in the WAS gene has broadened the clinical spectrum of disease to include chronic or intermittent X-linked thrombocytopenia (XLT), a relatively mild form of WAS, and X-linked neutropenia (XLN) due to an arrest of myelopoiesis. The pathophysiological mechanisms relate to defective actin polymerization in hematopoietic cells as a result of deficient or dysregulated activity of the WAS protein (WASp). The severity of disease is variable and somewhat predictable from genotype. Treatment strategies therefore range from conservative through to early definitive intervention by using allogeneic hematopoietic stem cell transplantation and potentially somatic gene therapy. All aspects of the condition from clinical presentation to molecular pathology and basic cellular mechanisms have been reviewed recently.
Primary immunodeficiencies (PIDs) presenting with cytopenias
Authors: Notarangelo Luigi D.
Published: December 2009

Autoimmune manifestations are increasingly being recognized as a component of several forms of primary immunodeficiencies (PID). Defects in purging of self-reactive T and B cells, impaired Fas-mediated apoptosis, abnormalities in development and/or function of regulatory T cells, and persistence of immune activation as a result of inability to clear infections have been shown to account for this association. Among autoimmune manifestations in patients with PID, cytopenias are particularly common. Up to 80% of patients with autoimmune lymphoproliferative syndrome (ALPS) have autoantibodies, and autoimmune hemolytic anemia and immune thrombocytopenia have been reported in 23% and 51% of ALPS patients, and may even mark the onset of the disease. ALPS-associated cytopenias are often refractory to conventional treatment and represent a therapeutic challenge. Autoimmune manifestations occur in 22% to 48% of patients with common variable immunodeficiencies (CVIDs), and are more frequent among CVID patients with splenomegaly and granulomatous disease. Finally, autoimmune cytopenias have been reported also in patients with combined immunodeficiency. In particular, autoimmune hemolytic anemia is very common among infants with nucleoside phosphorylase deficiency. While immune suppression may be beneficial in these cases, full resolution of the autoimmune manifestations ultimately depends on immune reconstitution, which is typically provided by hematopoietic cell transplantation.
Thrombocytosis
Authors: Skoda Radek C.
Published: December 2009

Major progress in understanding the pathogenesis in patients with thrombocytosis has been made by identifying mutations in the key regulators of thrombopoietin: the thrombopoietin receptor MPL and JAK2. Together, these mutations can be found in 50% to 60% of patients with essential thrombocythemia or primary myelofibrosis and in 10% to 20% of hereditary thrombocytosis. A decrease in expression of the Mpl protein can cause thrombocytosis even in the absence of mutations in the coding sequence, due to a shift in the balance between stimulation of signaling in megakaryopoiesis and removal of thrombopoietin by receptor mediated internalization in platelets. When present in a heterozygous state the JAK2-V617F mutation preferentially stimulates megakaryopoiesis and in most cases manifests as essential thrombocythemia (ET), whereas homozygous JAK2-V617F reduces megakaryopoiesis in favor of increased erythropoiesis, resulting in polycythemia vera and/or myelofibrosis. In 30% to 40% of patients with ET or primary myelofibrosis (PMF) and in 80% to 90% of pedigrees with hereditary thrombocytosis the disease-causing gene remains unknown. Ongoing genetic and genomic screens have identified genes that, when mutated, can cause thrombocytosis in mouse models. A more complete picture of the pathways that regulate megakaryopoisis and platelet production will be important for finding new ways of controlling platelet production in patients with thrombocytosis.
Molecular biology of the Rh system: clinical considerations for transfusion in sickle cell disease
Authors: Chou Stella T. , Westhoff Connie M.
Published: December 2009

The last decade has witnessed an abundance of information detailing the genetic diversity of the RH locus which has exceeded all estimates predicted by serology. Well over 120 RHD and over 60 different RHCE alleles have been documented, and new alleles are still being discovered. For clinical transfusion medicine, RH genetic testing can now be used to determine RHD zygosity, resolve D antigen status, and detect altered RHD and RHCE genes in individuals at risk for producing antibodies to high-incidence Rh antigens, particularly patients with sickle cell disease (SCD).
Heparin-induced thrombocytopenia: when a low platelet count is a mandate for anticoagulation
Authors: Ortel Thomas L.
Published: December 2009

Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder caused by the development of antibodies to platelet factor 4 (PF4) and heparin. The thrombocytopenia is typically moderate, with a median platelet count nadir of ~50 to 60 × 109 platelets/L. Severe thrombocytopenia has been described in patients with HIT, and in these patients antibody levels are high and severe clinical outcomes have been reported (eg, disseminated intravascular coagulation with microvascular thrombosis). The timing of the thrombocytopenia in relation to the initiation of heparin therapy is critically important, with the platelet count beginning to drop within 5 to 10 days of starting heparin. A more rapid drop in the platelet count can occur in patients who have been recently exposed to heparin (within the preceding 3 months), due to preformed anti-heparin/PF4 antibodies. A delayed form of HIT has also been described that develops within days or weeks after the heparin has been discontinued. In contrast to other drug-induced thrombocytopenias, HIT is characterized by an increased risk for thromboembolic complications, primarily venous thromboembolism. Heparin and all heparin-containing products should be discontinued and an alternative, non-heparin anticoagulant initiated. Alternative agents that have been used effectively in patients with HIT include lepirudin, argatroban, bivalirudin, and danaparoid, although the last agent is not available in North America. Fondaparinux has been used in a small number of patients with HIT and generally appears to be safe. Warfarin therapy should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated, and vitamin K should be administered to patients receiving warfarin at the time of diagnosis of HIT.
Antiphospholipid antibody syndrome
Authors: Lim Wendy
Published: December 2009

The antiphospholipid antibody syndrome (APS) is defined by the persistent presence of antiphospholipid antibodies in patients with recurrent venous or arterial thromboembolism or pregnancy morbidity. Anti-thrombotic therapy is the mainstay of treatment given the high risk of recurrent thromboembolism that characterizes this condition. Despite the prothrombotic nature of APS, thrombocytopenia is present in a proportion of patients. which can complicate management and limit the use of antithrombotic therapy. The mechanism of APS-associated thrombocytopenia is multifactorial and its relation to thrombotic risk poorly characterized. However, the presence of thrombocytopenia does not appear to reduce thrombotic risk in patients with APS, who can develop thromboembolic complications necessitating antithrombotic treatment. In these cases, treatment of the thrombocytopenia may be necessary to facilitate administration of antithrombotic agents. Clinical trials have demonstrated that patients with antiphospholipid antibodies and venous thromboembolism should be treated with vitamin K antagonists (warfarin); that ischemic stroke may be treated with aspirin or warfarin; and that women with recurrent pregnancy loss should receive prophylactic-dose heparin and aspirin. However, application of these trial results to patients with APS-associated thrombocytopenia can be challenging since there are limited data on the optimal use of antithrombotic agents in this setting. Issues such as determining the platelet threshold at which antithrombotic agents can be safely used and managing patients with both bleeding and thromboembolic complications remain unresolved. Ultimately the risks and benefits of antithrombotic therapy, balanced against the severity of the thrombocytopenia and its potential bleeding risks, need to be assessed using an individualized patient approach.
Thrombocytopenia and thrombosis in disseminated intravascular coagulation (DIC)
Authors: Kitchens Craig S.
Published: December 2009

Disseminated intravascular coagulation (DIC) is the physiologic result of pathologic overstimulation of the coagulation system. Despite multiple triggers, a myriad of laboratory abnormalities, and a clinical presentation ranging from gross hemostatic failure to life-threatening thrombosis, or even both simultaneously, a simplified clinical approach augmented by a few readily available tests allows prompt identification of the process and elucidation of treatment opportunities. Platelet counts in DIC may be low, especially in acute sepsis-associated DIC, yet increased in malignancy-associated chronic DIC. Thrombotic risk is not a function of the platelet count, and thrombocytopenia does not protect the patient from thrombosis. The stratification of both thrombotic risk and hemorrhagic risk will be addressed.
Hb H disease: clinical course and disease modifiers
Authors: Fucharoen Suthat , Viprakasit Vip
Published: December 2009

Hemoglobin H (Hb H) disease is the most common form of thalassemia intermedia and has many features that require careful consideration in management. In the majority of cases, Hb H disease results from double heterozygosity for α0-thalassemia due to deletions that remove both linked α-globin genes on chromosome 16, and deletional α+-thalassemia from single α-globin gene deletions (--/−α). However, Hb H disease may occur from interactions between α0-thalassemia with non-deletional mutations (αTα or αT) or with abnormal hemoglobins such as Hb Constant Spring, Hb Paksé, Hb Quong Sze, and Hb Pak Num Po. In a steady state, patients with Hb H diseases have hemoglobin levels around 9 to 10 g/dL; however, during hemolytic crisis, which frequently develops in or after acute infections with high fever, the hemoglobin level may drop significantly and patients can develop shock or renal shutdown. Even though splenectomy leads to significant elevation of hemoglobin levels, it is not recommended because the majority of patients do well with said steady-state hemoglobin levels. Patients with non-deletional Hb H disease are usually more anemic with significant splenomegaly, and some may require regular blood transfusions and be even as severe as “Hb H hydrops fetalis.” However, there is no clear genotype-phenotype correlation associated with this severe clinical syndrome since patients with identical genotypes do not necessary show the same severity. This suggests that other genetic and environmental factors play a role in modifying the degree of clinical severity in patients with non-deletional Hb H disease.
Antiplatelet agents
Authors: Varon David , Spectre Galia
Published: December 2009

The introduction of aspirin as an anti-thrombotic agent some 50 years ago has changed the therapeutic approach in cardiovascular medicine. Since platelets play a key role in the development of arterial thrombosis, antiplatelet drugs serve as a cornerstone in the prevention and the treatment of these conditions. After many years of a “monopoly” of aspirin, ADP receptor P2Y12 inhibitors were introduced with a significant improvement in clinical outcome. Nowadays dual antiplatelet therapy is the common practice for both acute events and secondary prevention in selected groups of patients. Another revolution was the development of potent inhibitors of the platelet integrin GPIIbIIIa, which significantly improved the outcome of percutaneous interventions (PCI), in cardiology. The improved efficacy of multiple-drug therapy is associated with an increased risk of bleeding, which raises the issue of the dosing of these drugs. Recently, numerous studies have reported a variable laboratory response to aspirin and clopidogrel, which correlates with clinical outcome. Several mechanisms have been proposed to cause this variable response, including genetic variability, disease burden and others. A major obstacle in this field is the lack of a standardized method for testing these responses, and thus some studies cannot be compared to others. Ongoing studies are currently investigating the potential translation of these observations into clinical practice. Such studies may lead to a change in the paradigm of antiplatelet therapy, where individual dose adjustment may improve efficacy and safety. Finally, a variety of new drugs are currently in different stages of development, including new P2Y12 receptor inhibitors, thromboxane receptor blockers, direct thrombin inhibitors and other signaling pathway inhibitors including oral GPIIbIIIa inhibitors. Thus, antiplatelet therapy is currently under intensive development toward multiple-drug therapy and personal-dose adjustment, which may improve clinical outcome.
Evaluation and management of stroke
Authors: Cucchiara Brett L.
Published: December 2009

In contrast to myocardial infarction, stroke is a heterogeneous disease with multiple different causes. Determination of stroke mechanism is critical to choosing optimal therapy to prevent recurrence. This article reviews the diagnostic approach to stroke and prognostic and treatment implications of specific stroke mechanisms. Data on the role of antiplatelet and anticoagulant therapy in secondary stroke prevention, as well as the role of these agents and thrombolytic therapy in acute stroke treatment are reviewed. Situations of particular relevance to the practicing hematologist—stroke in the young, patients with multiple recurrent strokes, patients with abnormal hypercoagulable laboratory testing, and treatment of intracerebral hemorrhage following thrombolytic therapy—are discussed.
Darwin and evolutionary tales in leukemia
Authors: Greaves Mel
Published: December 2009

All cancers evolve by a process of genetic diversification and “natural selection” akin to the process first described by Charles Darwin for species evolution. The evolutionary, natural history of childhood acute lymphoblastic leukemia (ALL) is almost entirely covert, clinically silent and well advanced by the point of diagnosis. It has, however, been possible to backtrack this process by molecular scrutiny of appropriate clinical samples: (i) leukemic clones in monozygotic twins that are either concordant or discordant for ALL; (ii) archived neonatal blood spots or Guthrie cards from individuals who later developed leukemia; and (iii) stored, viable cord blood cells. These studies indicate prenatal initiation of leukemia by chromosome translocation and gene fusion (or hyperdiploidy) and the post-natal acquisition of multiple, gene copy number alterations (CNAs), mostly deletions. The prenatal or first “hit” occurs very commonly, exceeding the clinical rate of ALL by some 100× and indicating a low rate of penetrance or evolutionary progression. The acquisition of the critical, secondary CNAs requires some Darwinian selective advantage to expand numbers of cells at risk, and the cytokine TGF beta is able to exercise this function. The clonal architecture of ALL has been investigated by single cell analysis with multicolor probes to mutant genes. The data reveal not a linear sequence of mutation acquisition with clonal succession but rather considerable complexity with a tree-like or branching structure of genetically distinct subclones very reminiscent of Darwin’s original 1837 evolutionary divergence diagram. This evolutionary pattern has important implications for stem cells in ALL, for the origins of relapse and for therapeutic targeting.
The bridge between patient and doctor: the shift from CAM to integrative medicine
Authors: Diehl Volker
Published: December 2009

Integrative medicine (IM) has become a major challenge for doctors and nurses, as well as psychologists and many other disciplines involved in the endeavor to help patients to better tolerate the burden of toxic therapies and give patients tools so they can actively participate in their “salutogenesis.” IM encompasses psycho-oncology, acupuncture, and physical and mental exercises to restore vital capacities lost due to toxic therapies; furthermore, it aims to replenish nutritional and metabolic deficits during and after cancer treatment. IM gains an ever increasing importance in the face of the rapidly growing number of cancer survivors demanding more than just evidence-based diagnostic and therapeutic strategies. IM has to prove its value and justification by filling the gap between unproven methods of alternative medicine, still used by many cancer patients, and academic conventional medicine, which often does not satisfy the emotional and spiritual needs of cancer patients.
Clinical approach to marrow failure
Authors: Shimamura Akiko
Published: December 2009

The treatment and medical management of aplastic anemia fundamentally differ between patients with inherited versus acquired marrow failure; however, the diagnosis of an inherited bone marrow failure syndrome is frequently obscure. Recent exciting advances in our understanding of the molecular pathophysiology of the inherited bone marrow failure syndromes have resulted in a profusion of new tests to aid in diagnosis. This in turn has raised questions regarding the appropriate choice of testing for the patient presenting with aplastic anemia. Important clues to the diagnosis of an inherited marrow failure syndrome may be gleaned from careful attention to the clinical history, physical exam, and laboratory workup.
Telomeres and marrow failure
Authors: Calado Rodrigo T.
Published: December 2009

Telomeres, repeat sequences at the ends of chromosomes, are protective chromosomal structures highly conserved from primitive organisms to humans. Telomeres inevitably shorten with every cell cycle, and telomere attrition has been hypothesized to be fundamental to normal senescence of cells, tissues, and organisms. Molecular mechanisms have evolved to maintain their length and protective function; telomerase (TERT) is a reverse transcriptase enzyme that uses an RNA molecule (TERC) as the template to elongate the 3′ ends of telomeres. Shelterin is a collection of DNA-binding proteins that cover and protect telomeres. The recent discovery of inherited mutations in genes that function to repair telomeres as etiologic in a range of human diseases, which have clinical manifestations in diverse tissues, including the hematopoietic tissue, suggests that defects in telomere repair and protection can cause organ failure. Dyskeratosis congenita is the prototype of telomere diseases; it is characterized by bone marrow failure, mucocutaneous abnormalities, pulmonary fibrosis, liver cirrhosis, and increased susceptibility to cancer, including acute myeloid leukemia. Aplastic anemia, acute myeloid leukemia, and idiopathic pulmonary fibrosis also are associated with inherited mutations in telomere repair or protection genes. Additionally, telomere defects associate with predisposition to hematologic malignancy and epithelial tumors. Telomere erosion is abnormally rapid in patients with mutations in telomerase genes but also after hematopoietic stem cell transplant, and telomeres are naturally shorter in older individuals—all conditions associated with higher rates of malignant diseases. In human tissue culture, short telomeres produce end-to-end chromosome fusion, nonreciprocal translocations, and aneuploidy.