bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinematic performance of a parabolic gear tooth with two parabolic coefficients
Authors: Yang Hsueh-Cheng , Pai P Frank
Published: September 2016

This paper presents design imaginary skew rack cutters having teeth of two parabolic coefficients to generate spur and helical gears. First, a mathematical model of the imaginary rack cutter having teeth of two parabolic coefficients is derived using geometric relations and coordinate transformation. After the relationship between the coordinate system of the imaginary rack cutter and that of the helical gear pair is set up, a family of imaginary rack cutter surfaces is obtained using the homogeneous coordinate transformation matrix to transfer the coordinate system of the rack cutters to that of the helical gear. Based on the gear theory, the equations of meshing between the rack cutter and the helical gear are determined. Substituting the equations of meshing into the family of imaginary rack cutter surfaces, a pinion and a gear are generated and their geometries are plotted using an in-house software package. Based on the assembly errors, tooth contact analysis is performed to determine the influences of kinematic assembly errors and the parabolic coefficients. Results show that maximum parabolic coefficient value of the imaginary skew rack cutter exists in order to avoid undercutting and it can be determined.
Household energy requirements in two medium-sized Thai cities with different population densities
Authors: Kunvitaya Arkarlat , Dhakal Shobhakar
Published: September 2016

Studies on the implications of population density on energy consumption in small and medium-sized cities in low- and middle-income countries are limited. This paper estimates and analyses energy consumption, using a diverse set of methods, to compare two medium-sized cities in Thailand with similar urban forms and socioeconomic characteristics but different population densities – namely, the less dense city Chaiyaphum and denser city Roi Et. The results reveal that the annual household electricity consumption per capita of these two cities is similar, showing no implications of density. However, private transport energy consumption per capita in Chaiyaphum is 22 per cent higher, supporting the hypothesis that a less dense city will have higher transport energy consumption. The key factor identified is the greater distance travelled by households located in the peri-urban areas in the less dense city. This has important policy implications for urban planning and urban development practices in Thailand.
The Parent Experience of Assessment Scale (PEAS): Development and Relation to Parent Satisfaction
Authors: Austin Cynthia A. , Finn Stephen F. , Keith Timothy Z. , Tharinger Deborah J. , Fernando April D.
Published: September 2016

This study outlines the development of the Parent Experience of Assessment Scale (PEAS), which is based on principles of Therapeutic Assessment. The study includes pilot testing of a 64-item questionnaire across 134 participants, with psychometric analyses utilizing confirmatory factor analysis. The revised version consists of 24 items across five subscales with appropriate internal consistency reliability (alphas from .76 to .88). The PEAS demonstrates statistically significant relations with general parent satisfaction, with two subscales indicating significant direct effects via structural equation modeling. The PEAS has the potential utility to provide more nuanced clinical and investigative feedback regarding the parent process during child psychological assessment.
A new tangent stiffness-based formulation to study the free vibration behavior of a transversely loaded Timoshenko beam with geometric nonlinearity
Authors: Das Debabrata
Published: September 2016

A new formulation is introduced to study the free vibration behavior of a statically loaded beam with geometric nonlinearity. The tangent stiffness of the statically loaded beam is used to investigate the free vibration behavior of the beam about its loaded configuration. The problem is formulated for a linearly tapered beam, and a uniform beam is obtained as a special case. Energy principles based on the variational approach are used to derive the governing equations for the static and dynamic problems. The Ritz method of approximate displacement field is followed to solve the governing equations. The Ritz coefficients are used to derive the tangent stiffness of the loaded beam. Components of the tangent stiffness matrix are derived for a Timoshenko beam with von Kármán-type nonlinearity. Illustrative results are presented for four different classical boundary conditions having in-plane restraint. Results for the first two modes of transverse vibration are presented in the nondimensional deflection-frequency plane. Validation of the work is carried out using finite element software ANSYS. The formulation is new of its kind and can be used for any displacement-based problem following the Ritz method.
Wind effects on rough-walled and smooth-walled large cooling towers
Authors: Cheng XX , Zhao L , Ge YJ , Dong R , Demartino C
Published: September 2016

Adding vertical ribs is recognized as a useful practice for reducing wind effects on cooling towers. However, ribs are rarely used on cooling towers in China since Chinese Codes are insufficient to support the design of rough-walled cooling towers, and an “understanding” hampers the use of ribs, which thinks that increased surface roughness has limited effects on the maximum internal forces that control the structural design. To this end, wind tunnel model tests in both uniform flow field with negligible free-stream turbulence and atmospheric boundary layer (ABL) turbulent flow field are carried out in this article to meticulously study and quantify the surface roughness effects on both static and dynamic wind loads for the purpose of improving Chinese Codes first. Subsequently, a further step is taken to obtain wind effects on a full-scale large cooling tower at a high Re, which are employed to validate the results obtained in the wind tunnel. Finally, the veracity of the model test results is discussed by investigating the Reynolds number (Re) effects on them. It has been proved that the model test results for atmospheric boundary layer flow field are all obtained in the range of Re-independence and the conclusions drawn from model tests and full-scale measurements basically agree, so most model test results presented in this article can be directly applied to the full-scale condition without corrections.
Towards a strong program in the sociology of war, the military and civil society
Authors: West Brad , Matthewman Steve
Published: September 2016

In this article we make the case for a strong program of sociological research into war, the military and their symmetry with civil society, pointing to the ways in which sociology has failed to appreciate their relationship as a central feature of modernity. We particularly emphasize the need for a multi-dimensional comprehension of militarization and the relationships between representation, belief and action in conflict and post-conflict environments. We conclude that a strong sociology of the war and the military requires a greater appreciation of the influence of organized state violence on the shaping of contemporary social relations, breaking with weak traditions that only comprehend the significance of military institutions and warfare through analysing capital and other material and political forces.
The ‘native’s point of view’ in the anthropology of migration
Authors: De Genova Nicholas
Published: September 2016

Under contemporary conditions of “globalization, ” any anthropology of migration must confront the seeming paradox that our “globalized” era is profoundly marked by a proliferation of new (historically-specific) formations of the cultural politics of nativism (or what may be otherwise depicted in terms of “autocthony,” or “xenophobia”). Notably, during this same period, we have likewise witnessed the ascendancy of a reanimated anthropological dogma of cultural essentialism, in the guise of (pseudo-) “ontological” notions of irreducible and essentially incommensurable “difference.” This article examines the implications for an anthropology of migration that contemplates seriously the implications of the affinities between the sort of disciplinary nativism that derives from the pluralist commitments of cultural essentialism with the anti-immigrant politics of nativism that has become a defining and increasingly pervasive feature of our global political present.
The units of scientific anthropological origin narratives
Authors: Marks Jonathan
Published: September 2016

Biological anthropology often treats its species as if they were natural, zoological units. While biologists sometimes acknowledge the contested aspects of species, I argue that the taxa in our own ancestry are different from those in zoology more generally, by virtue of their roles as characters or elements in our scientific origin myth.
Positioning theory: An introduction
Authors: Schiller Nina Glick
Published: September 2016

What is theory? Who does theory? And what can theory do? Is theory important as humans strive to explain, understand, and speak to the nature of their lives? For the re-launch of Anthropological Theory, Julia Eckert, Stephen Reyna, and Nina Glick Schiller, the new editors, challenged members of the Editorial Board to offer their understanding of the nature of anthropological theory. In response, 12 contributors discussed the central theoretical questions and debates that are confronting anthropology, which they collectively understand as a project that explores what it means to be human and whether the human project can survive. Contributors highlight the importance of positioning theory in relationship to the historic project of decolonizing anthropology, current debates about ‘southern theory’ and the ontological turn, and the need to place theory in relationship to structures of power. In ‘Positioning Theory: An Introduction’, I note the way each contributor approaches the question of who is theory for and whose voice it represents, examining theory as both tool and vision in struggles to understand the world and in transformative struggles for social justice.
Cultural Adaptation of Dialectical Behavior Therapy for a Chinese International Student With Eating Disorder and Depression
Authors: Cheng Pei-Han , Merrick Elizabeth
Published: September 2016

Limited information exists on the application of evidence-based treatments for eating disorders among diverse populations. An increasing number of international and immigrant clients provides a pressing need for culturally responsive treatments. This case study highlights an eating disorder treatment that incorporates dialectical behavior therapy and cultural adaptation guidelines. This study explicates a culturally adapted dialectical behavior therapy (DBT) treatment of a 24-year-old female Chinese international student suffering from an eating disorder, depression, and cultural adjustment issues. In particular, this case addresses Chinese cultural values, including conformity, interdependence, and filial piety, and how these values intersect with the client’s presenting issues and treatment. Cultural modifications made to the case conceptualization and dialectical behavior therapy are discussed. The client reported a significant decrease in distress, an increase in the quality of social relationships, and an increase in satisfaction with social roles. These results provide support for the effectiveness and importance of integrating cultural adaptation and evidence-based treatment. Clinical implications and recommendations for clinicians and students are provided.
Research Note
Authors: Piquero Alex R. , Jennings Wesley G.
Published: September 2016

Although the use of financial penalties is pervasive in the justice system, there has been limited (and mostly dated) empirical research that has investigated the effect of financial costs incurred by juvenile offenders and the extent to which such costs relate to the likelihood of recidivism and reintegration into society. This study uses data from a large cohort of adolescent offenders to examine how demographics and case characteristics relate to financial penalties imposed by the justice system and the degree to which such monetary penalties are related to recidivism in a 2-year follow-up. Results suggest that financial penalties increase the likelihood of recidivism. Study limitations and directions for future research are also discussed.
Distinguished Scholar Invited Essay
Authors: Ashforth Blake E.
Published: September 2016

Identity and identification remain very popular constructs for organizational scholars, regularly generating a bounty of provocative research. To help maintain the generativity of these root constructs, I suggest four “course corrections” for our explorations, namely, focusing more on (1) the core aspect of identification, that is, the definition of self in terms of a target; (2) other targets of identification aside from the organization; (3) the dark side of identification; and (4) perspectives of identity beyond social identity theory/self-categorization theory.
Getting It “Right”
Authors: Barrera Alinne Z. , Dunn Laura B. , Nichols Alexandra , Reardon Sonia , Muñoz Ricardo F.
Published: September 2016

Ethical principles in conducting technology-based research require effective and efficient methods of ensuring adequate informed consent. This study examined how well participants understood the informed consent form for an online postpartum depression trial. Pregnant women ( N = 1,179) who consented to the trial demonstrated an understanding of the purpose (86.1%) and procedures of the study (75.8%), and the minimal risks associated with answering sensitive questions online (79%). Almost all (99.6%) understood that psychological treatment was not offered. Participants with current depression incorrectly indicated that participation would replace current psychological treatment relative to participants with a lifetime or no depression history (19.6% vs. 13.5 % vs. 10.4%, respectively) and that there were no associated risks with participation (29.6% vs.17.6% vs. 16.7%, respectively). Findings provide initial evidence that most individuals who seek online psychological resources are informed consumers.
A shock tube facility to generate blast loading on structures
Authors: Aune Vegard , Fagerholt Egil , Langseth Magnus , Børvik Tore
Published: September 2016

This study evaluates the performance of a new shock tube facility used to produce blast loading in controlled laboratory environments. The facility was found to generate a planar shock wave over the tube cross section by measuring the pressure distribution on a massive steel plate located at the end of the tube. The properties of the shock wave proved to be a function of driver length and driver pressure, and the positive phase of the measured pressure–time histories was similar to those generated from actual far-field explosive detonations. However, the shock tube is also suited to investigate fluid–structure interaction effects and the behaviour of materials in blast events. This was demonstrated using a three-dimensional digital image correlation technique to measure the deformation field of thin steel plates. Synchronization of the three-dimensional digital image correlation and pressure measurements enabled a thorough investigation of the entire experiment and identification of fluid–structure interaction effects. Finally, one-dimensional numerical simulations were performed to investigate the wave patterns during the experiments.
An Analysis of Turkish Pre-Service Teachers’ Knowledge of Autism Spectrum Disorder
Authors: Rakap Salih , Balikci Serife , Parlak-Rakap Asiye , Kalkan Sinan
Published: September 2016

The purpose of the present study was to investigate knowledge of autism among teacher candidates who are likely to have the initial contact with children with autism within public school system in Turkey. Five hundred and four senior pre-service teachers who were enrolled in four different teacher education programs participated in the study. Data were collected using a survey package at the end of spring semester during the last year of college. Results indicated that pre-service teachers across programs had limited knowledge of autism and its characteristics. Findings of the present study call for the development of pre- and in-service training programs for teachers of children with autism. Further implications of findings for future research and practice are discussed.
Understanding Determinants of Racial and Ethnic Disparities in Viral Load Suppression
Authors: Feller Daniel J. , Agins Bruce D.
Published: September 2016

Racial and ethnic disparities in viral load suppression (VLS) have been well documented among people living with HIV (PLWH). The authors hypothesized that a contemporary analytic technique could reveal factors underlying these disparities and provide more explanatory power than broad stereotypes. Classification and regression tree analysis was used to detect factors associated with VLS among 11 419 adult PLWH receiving treatment from 186 New York State HIV clinics in 2013. A total of 8885 (77.8%) patients were virally suppressed. The algorithm identified 8 mutually exclusive subgroups characterized by age, housing stability, drug use, and insurance status but neither race nor ethnicity. Our findings suggest that racial and ethnic disparities in VLS exist but likely reflect underlying social and behavioral determinants of health.
Does Postsecondary Persistence in STEM Vary by Gender?
Authors: King Barbara
Published: September 2016

The underrepresentation of women in science, technology, engineering, and mathematics (STEM) is often explained by women’s greater likelihood to leave STEM at each key juncture from elementary school into the workforce. It is important to examine this more closely and look for points in the pipeline where gender equity exists. This study uses nationally representative data from a recent cohort of college students to investigate thoroughly gender differences in STEM persistence. Results indicate that no significant gender differences in persistence exist. This finding holds among those in computer science, engineering, mathematics, and physical science, and for those in life science. Additionally, the results are unchanged if the sample is limited to degree earners and are robust to the inclusion of individual and institutional variables. Although it is clear that women are less likely to choose certain STEM majors, those who do are no less likely to earn a STEM degree.
A Ghost from the Past
Authors: Chapman H.R.
Published: September 2016

This narrative illustrates how childhood trauma can influence the ability to cope with dental fear and treatment. It also demonstrates that a sympathetic dentist with the appropriate training can help these patients to overcome their dental fear and give them the skills to deal with other problems.
Influence of sample preparation on MX-80 bentonite microstructure
Authors: Matusewicz M. , Pulkkanen V.-M. , Olin M.
Published: September 2016

Compacted bentonite is to be used as a buffer material between waste canisters and the bedrock in the deep geological disposal of high-level nuclear waste in several countries. In spite of the fact that such large bentonite systems have long equilibration times, estimation of the material properties and performance in repository conditions is often based on short-term, laboratory-scale experiments. Sample-preparation procedures in these experiments may differ from the natural evolution of the bentonite in the repository, however, affecting the bentonite properties. The present study reports the influence on the structure of clay tactoids of four different preparation procedures of water-saturated, compacted MX-80 bentonite samples using four target dry bulk densities. Small-angle X-ray scattering was used to illustrate the differences between the samples. The different treatments of the bentonite samples may lead to different structural features. Clear differences between low-density samples prepared using different procedures were observed. The influence of the preparation methods was less, but still noticeable, for the high-density samples.
Anticoagulants in children and adolescents
Authors: Young Guy
Published: September 2016

Thrombotic complications are increasing at a steady and significant rate in children, resulting in the more widespread use of anticoagulation in this population. Anticoagulant drugs in children can be divided into the older multitargeted agents (heparin, low-molecular-weight heparin, and warfarin) and the newer targeted agents (argatroban, bivalirudin, and fondaparinux). This review will compare and contrast the multitargeted and targeted anticoagulants and suggest situations in which it may be appropriate to use argatroban, bivalirudin, and fondaparinux. The various agents differ in their pharmacokinetics, requirements for therapeutic drug monitoring, frequency of administration, efficacy, and adverse effects. The targeted anticoagulants have properties that may make them more attractive for use in specific clinical situations. Prospective clinical trial data are presented supporting the current and future use of these agents in children.
Hemolytic disease of the fetus and newborn: managing the mother, fetus, and newborn
Authors: Delaney Meghan , Matthews Dana C.
Published: September 2016

Hemolytic disease of the fetus and newborn (HDFN) affects 3/100 000 to 80/100 000 patients per year. It is due to maternal blood group antibodies that cause fetal red cell destruction and in some cases, marrow suppression. This process leads to fetal anemia, and in severe cases can progress to edema, ascites, heart failure, and death. Infants affected with HDFN can have hyperbilirubinemia in the acute phase and hyporegenerative anemia for weeks to months after birth. The diagnosis and management of pregnant women with HDFN is based on laboratory and radiographic monitoring. Fetuses with marked anemia may require intervention with intrauterine transfusion. HDFN due to RhD can be prevented by RhIg administration. Prevention for other causal blood group specificities is less studied.
Using genetic diagnostics in hemophilia and von Willebrand disease
Authors: Swystun Laura L. , James Paula
Published: September 2016

Most bleeding disorders encountered in clinical practice will be diagnosed, at least initially, by phenotypic assays. However, since the characterization of the genes that encode coagulation factors in the 1980s, significant progress has been made in translating this knowledge for diagnostic and therapeutic purposes. For hemophilia A and B, molecular genetic testing to determine carrier status, prenatal diagnosis, and likelihood of inhibitor development or anaphylaxis to infused coagulation factor concentrates is an established component of comprehensive clinical management. In contrast, although significant recent advances in our understanding of the molecular genetic basis of von Willebrand disease (VWD) have allowed for the development of rational approaches to genetic diagnostics, questions remain about this complex genetic disorder and how to incorporate emerging knowledge into diagnostic strategies. This article will review the state-of-the-art for molecular diagnostics for both hemophilia and VWD.
The unique aspects of presentation and diagnosis of hemophagocytic lymphohistiocytosis in adults
Authors: Nikiforow Sarah , Berliner Nancy
Published: September 2016

Hemophagocytic lymphohistiocytosis (HLH) was initially described as an inflammatory condition affecting young children but is increasingly diagnosed in adults. Presenting features such as fever, cytopenias, phagocytosis, elevated ferritin, and increased levels of soluble IL-2 receptor are common in both age groups, but the prevalence of several clinical and biochemical criteria differ between pediatric and adult patients. Specifically, an elevated ferritin level does not have the same specificity for HLH in adults, and many other inflammatory conditions need to be considered in the differential. In contrast to the high incidence of infectious triggers seen in pediatric HLH, HLH in adults is often precipitated by a hematologic malignancy. Malignancy-associated HLH has unique manifestations and a uniformly very poor prognosis. Given these differences, diagnostic scoring systems unique to adult HLH have been proposed, and additional prognostic clinical and immunologic parameters are being explored. Although a genetic predisposition is increasingly found to underlie cases of adult-onset HLH, the mutations are less likely to be bi-allelic and differ slightly from those seen in pediatric cases of familial HLH. The facilitating genetic and environmental factors governing presentation of HLH in adults remain elusive. Understanding the clinical aspects and pathophysiology specific to adults with HLH is necessary to tailor therapies derived in pediatric disease to this under-recognized population.
Diagnosis and treatment of sideroblastic anemias: from defective heme synthesis to abnormal RNA splicing
Authors: Cazzola Mario , Malcovati Luca
Published: September 2016

The sideroblastic anemias are a heterogeneous group of inherited and acquired disorders characterized by the presence of ring sideroblasts in the bone marrow. X-linked sideroblastic anemia (XLSA) is caused by germline mutations in ALAS2. Hemizygous males have a hypochromic microcytic anemia, which is generally mild to moderate and is caused by defective heme synthesis and ineffective erythropoiesis. XLSA is a typical iron-loading anemia; although most patients are responsive to pyridoxine, treatment of iron overload is also important in the management of these patients. Autosomal recessive sideroblastic anemia attributable to mutations in SLC25A38, a member of the mitochondrial carrier family, is a severe disease: patients present in infancy with microcytic anemia, which soon becomes transfusion dependent. Conservative therapy includes regular red cell transfusion and iron chelation, whereas allogenic stem cell transplantation represents the only curative treatment. Refractory anemia with ring sideroblasts (RARS) is a myelodysplastic syndrome characterized mainly by anemia attributable to ineffective erythropoiesis. The clinical course of RARS is generally indolent, but there is a tendency to worsening of anemia over time, so that most patients become transfusion dependent in the long run. More than 90% of these patients carry somatic mutations in SF3B1, a gene encoding a core component of the RNA splicing machinery. These mutations cause misrecognition of 3′ splice sites in downstream genes, resulting in truncated gene products and/or decreased expression attributable to nonsense-mediated RNA decay; this explains the multifactorial pathogenesis of RARS. Variants of RARS include refractory cytopenia with multilineage dysplasia and ring sideroblasts, and RARS associated with marked thrombocytosis; these variants involve additional genetic lesions. Inhibitors of molecules of the transforming growth factor-β superfamily have been shown recently to target ineffective erythropoiesis and ameliorate anemia both in animal models of myelodysplastic syndrome and in RARS patients.
Acquired bleeding disorders in the elderly
Authors: Kruse-Jarres Rebecca
Published: September 2016

The hemostatic balance changes with advancing age which may be due to factors such as platelet activation, increase of certain clotting factor proteins, slowing of the fibrinolytic system, and modification of the endothelium and blood flow. Generally, this predisposes the elderly to thrombosis rather than bleeding. It often necessitates antiplatelet or anticoagulation therapy, which can cause significant bleeding problems in an aging population. Additionally, changing renal function, modification in immune regulation, and a multitude of other disease processes, can give rise to acquired bleeding disorders. Bleeding can prove difficult to treat in a dynamic environment and in a population that may have underlying thrombotic risk factors.

This article discusses some specific challenges of acquired bleeding arising in the elderly. The use of anticoagulation and nonsteroidal anti-inflammatory medications is prevalent in the treatment of the elderly and predisposes them to increased bleeding risk as their physiology changes. When prescribing and monitoring these therapies, it is exceedingly important to weigh thrombotic versus bleeding risks. There are additional rare acquired bleeding disorders that predominantly affect the elderly. One of them is acquired hemophilia, which is an autoimmune disorder arising from antibodies against factor VIII. The treatment challenge rests in the use of hemostatic agents in a population that is already at increased risk for thrombotic complications. Another rare disorder of intensifying interest, acquired von Willebrand syndrome, has a multitude of etiologic mechanisms. Understanding the underlying pathophysiology is essential in making a treatment decision for this disorder.
Bleeding complications in immune thrombocytopenia
Authors: Arnold Donald M.
Published: September 2016

Bleeding manifestations in patients with immune thrombocytopenia (ITP) range from mild skin bruises to life-threatening intracranial hemorrhage (ICH). Severe bleeding is distinctly uncommon when the platelet count is >30 × 109/L and usually only occurs when the platelet count falls <10 × 109/L. Based on estimates from clinical studies, ITP registries and administrative databases, the frequency of ICH in patients with ITP is ∼0.5% in children and 1.5% in adults. Estimates of severe (non-ICH) bleeding are difficult to obtain because of the lack of standardized case definitions; the lack of a universally accepted, ITP-specific bleeding assessment tool; and the omission of reporting bleeding outcomes in many clinical studies. In practice, the presence of bleeding should dictate whether or not treatment is needed because many patients, especially children, can be safely managed with observation alone. Guiding principles for the management of ITP, based on the bleeding risk are: (1) Decide when treatment is needed and when it can safely be withheld; (2) for patients with chronic ITP, use the least toxic treatment at the lowest dose; (3) emergency treatment of severe thrombocytopenia-associated bleeding requires combination therapy; and (4) early aggressive therapy may result in durable platelet count responses.
Coagulopathy in liver disease: a balancing act
Authors: Kujovich Jody L.
Published: September 2016

Liver disease results in complex alterations of all 3 phases of hemostasis. It is now recognized that hemostasis is rebalanced in chronic liver disease. The fall in clotting factor levels is accompanied by a parallel fall in anticoagulant proteins. High von Willebrand factor levels counteract defects in primary hemostasis. Conventional coagulation tests do not fully reflect the derangement in hemostasis and do not accurately predict the risk of bleeding. Global coagulation assays (thrombin generation, thromboelastography) reflect the interaction between procoagulant factors, anticoagulant factors, platelets, and the fibrinolytic system and show promise for assessing bleeding risk and guiding therapy. These assays are not yet commercially approved or validated. Prevention of bleeding should not be aimed at correcting conventional coagulation tests. Thrombopoietin receptor agonists were shown to increase the platelet count in cirrhotic patients undergoing invasive procedures but may increase the risk of thrombosis. Rebalanced hemostasis in liver disease is precarious and may be tipped toward hemorrhage or thrombosis depending on coexisting circumstantial risk factors. Bacterial infection may impair hemostasis in cirrhosis by triggering the release of endogenous heparinoids. There are no evidence-based guidelines for hemostatic therapy of acute hemorrhage in liver disease. There is currently inadequate evidence to support the use of recombinant FVIIa, prothrombin complex concentrates, or tranexamic acid in acute variceal or other hemorrhage.
Molecular monitoring in CML and the prospects for treatment-free remissions
Authors: Deininger Michael W.
Published: September 2016

Monitoring treatment responses in chronic myeloid leukemia (CML) is based on complete blood counts (CBCs) to determine hematologic response, karyotyping of bone marrow metaphase cells to delineate cytogenetic response and quantitative reverse transcription polymerase chain reaction (qPCR) to quantify expression of BCR-ABL1 mRNA (molecular response; MR) in peripheral blood. Fluorescence in situ hybridization (FISH) to identify BCR-ABL1 in interphase nuclei and mutational analysis of the BCR-ABL1 kinase domain (KD) are used in certain clinical circumstances. As most patients treated with tyrosine kinase inhibitors (TKIs) achieve complete cytogenetic responses (CCyRs), qPCR with its increased sensitivity and dynamic range has become the main tool used to monitor CML patients. Landmark analyses of large TKI trials have established MR milestones that identify patients with high risk of failure, are the basis of consensus management guidelines, and have led to a strong push toward qPCR test standardization. Today many laboratories report BCR-ABL1 qPCR results on the international scale (IS), a system based on the conversion of laboratory-specific numerical values to conform to a universal scale. The fact that qPCR is technically demanding and liable to assay variations poses considerable challenges for its routine clinical use. This is important as the prevalence of patients on chronic TKI therapy increases and critical clinical decisions are made based on qPCR results, for example if discontinuation of TKI therapy should be considered. Here we will review the current state of molecular monitoring in CML, focusing on qPCR, the definition of TKI failure and the results of TKI discontinuation studies.
Maintenance therapy for multiple myeloma in the era of novel agents
Authors: Facon Thierry
Published: September 2016

Despite many recent advances in the treatment of multiple myeloma, the course of the disease is characterized by a repeating pattern of periods of remission and relapse as patients cycle through the available treatment options. Evidence is mounting that long-term maintenance therapy may help suppress residual disease after definitive therapy, prolonging remission and delaying relapse. For patients undergoing autologous stem cell transplantation (ASCT), lenalidomide maintenance therapy has been shown to improve progression-free survival (PFS); however, it is still unclear whether this translates into extended overall survival (OS). For patients ineligible for ASCT, continuous therapy with lenalidomide and low-dose dexamethasone was shown to improve PFS and OS (interim analysis) compared with a standard, fixed-duration regimen of melphalan, prednisone, and thalidomide in a large phase 3 trial. Other trials have also investigated thalidomide and bortezomib maintenance for ASCT patients, and both agents have been evaluated as continuous therapy for those who are ASCT ineligible. However, some important questions regarding the optimal regimen and duration of therapy must be answered by prospective clinical trials before maintenance therapy, and continuous therapy should be considered routine practice. This article reviews the available data on the use of maintenance or continuous therapy strategies and highlights ongoing trials that will help to further define the role of these strategies in the management of patients with newly diagnosed multiple myeloma.
Surveying the landscape of MDS/MPN research: overlap among the overlap syndromes?
Authors: Padron Eric
Published: September 2016

The myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) lie at the interphase of phenotypically opposing bone marrow malignancies. They are characterized by concomitant features of bone marrow failure and myeloproliferation and are generally associated with a poor prognosis. Although much is unknown with respect to the clinical course and molecular biology of MDS/MPNs, emerging research is beginning to uncover the key defining characteristics of this designation. In this review, we will discuss the features of MDS/MPN diseases that unify there clinical and molecular course and those that define distinct disease entities. We will discuss advances in genetics and MDS/MPN modeling, as well as translational discoveries that are anticipated to inform the diagnosis, prognostication, and treatment of MDS/MPNs in the near future.
Management of adult Ph-positive acute lymphoblastic leukemia
Authors: Chiaretti Sabina , Foà Robin
Published: September 2016

Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) has been regarded for decades as the ALL subgroup with the worse outcome. It represents the most frequent genetic subtype of adult ALL, and increases progressively with age. The introduction of tyrosine kinase inhibitors (TKIs) has enabled to obtain complete hematologic remissions (CHRs) in virtually all patients, including the elderly, to improve disease-free survival and overall survival, as well as to increase the percentage of patients who can undergo an allogeneic stem cell transplant (allo-SCT).

The current management of adult Ph+ ALL patients relies on the use of a TKI with or without chemotherapy followed by an allo-SCT, which still remains the only curative option. Minimal residual disease screening is permitting not only a better stratification of patients, but has also allowed to reconsider the role of autologous stem cell transplant for a set of patients who do not have a donor or are not eligible for an allo-SCT. At present, clinical challenges are represented by the emergence of resistant mutations, particularly the gatekeeper T315I, for which alternative approaches, comprising novel TKIs or therapies based on the combination of TKI with immunotherapeutic strategies, are being considered in order to overcome resistance.
Managing older patients with hemophilia
Authors: Angelini Dana , Sood Suman L.
Published: September 2016

With access to safe factor products, the life expectancy of persons with hemophilia (PWHs) has increased almost 10-fold over the past 7 decades. Unfortunately, hand in hand with this success comes the burden of aging. As PWHs age, they are subject to develop many of the same risk factors as the general population, including increasing rates of hypertension, obesity, and diabetes. Such comorbidities predispose them to chronic diseases, such as cardiovascular disease and chronic kidney disease, although how their coagulopathy affects the expression of these conditions remains unclear. The older hemophilia population faces additional challenges, such as chronic joint arthropathy, which provokes falls and fractures, and complications related to HIV and hepatitis C infections, which greatly affect the incidence of cancer and liver disease. In light of the paucity of evidence-based guidelines to direct therapy, a new challenge has arisen for hematologists to optimally manage these complex age-related issues. In general, elderly PWHs should be treated similarly to their peers without hemophilia, with the addition of factor replacement therapy as appropriate. Primary prevention of risk factors should be emphasized, and close coordination between specialties is essential. This review will focus on common complications affecting the older hemophilia population, including cardiovascular disease, malignancy, liver disease, renal insufficiency, and joint disease.
How can we improve on the already impressive results in pediatric ALL?
Authors: Thomas Angela
Published: September 2016

The past 70 years have seen childhood acute lymphoblastic leukemia move from a fatal disease with a survival of barely 4 months to a curable disease in >85% of patients. It has become clear that as treatment has intensified, more children are cured but at the expense of increased toxicity which for some can cause significant long-term morbidity and even mortality. The drive in more recent years has been to identify sensitive markers of disease and response to treatment to allow a reduction in therapy in those who do not require it and more intensive treatment in those who do. Clinical characteristics have been used to stratify patients into different risk groups and this, coupled with following response at a molecular level, has done much to tailor treatment to the patient. Considerable research has been focused on the molecular characteristics of the leukemia itself to elucidate the biologic mechanisms underlying both the disease and the comparative or absolute resistance of some types of leukemia. These molecular markers can also act as targets for novel therapies, which require newer trial methodologies to prove their utility. There has been less focus on the biology of the patient but it is clear that some patients are more susceptible to adverse events and toxicities than others. Through the use of pharmacogenomics, modification to therapy may be appropriate in certain patients based on their genetic profile. As novel therapies become available, suitable controlled trials in children are essential for their safe use in this population and will ensure that children are not denied timely access to advances in treatment.
Optimizing hydroxyurea therapy for sickle cell anemia
Authors: Ware Russell E.
Published: September 2016

Hydroxyurea has proven efficacy in numerous clinical trials as a disease-modifying treatment for patients with sickle cell anemia (SCA) but is currently under-used in clinical practice. To improve the effectiveness of hydroxyurea therapy, efforts should be directed toward broadening the clinical treatment indications, optimizing the daily dosage, and emphasizing the benefits of early and extended treatment. Here, various issues related to hydroxyurea treatment are discussed, focusing on both published evidence and clinical experience. Specific guidance is provided regarding important but potentially unfamiliar aspects of hydroxyurea treatment for SCA, such as escalating to maximum tolerated dose, treating in the setting of cerebrovascular disease, switching from chronic transfusions to hydroxyurea, and using serial phlebotomy to alleviate iron overload. Future research directions to optimize hydroxyurea therapy are also discussed, including personalized dosing based on pharmacokinetic modeling, prediction of fetal hemoglobin responses based on pharmacogenomics, and the risks and benefits of hydroxyurea for non-SCA genotypes and during pregnancy/lactation. Another critical initiative is the introduction of hydroxyurea safely and effectively into global regions that have a high disease burden of SCA but limited resources, such as sub-Saharan Africa, the Caribbean, and India. Final considerations emphasize the long-term goal of optimizing hydroxyurea therapy, which is to help treatment become accepted as standard of care for all patients with SCA.
Spanning the canyon between stem cell transplantation and palliative care
Authors: Roeland Eric , Ku Grace
Published: September 2016

Stem cell transplantation (SCT) and palliative care (PC) may initially appear to be distant extremes in the continuum of care of patients with hematologic malignancies, opposed by multiple obstacles preventing their integration. Rather, we will posit that both fields share many similarities and have much to learn from one another. PC has increasing relevance in cancer care given recent studies that link PC to improved quality-of-life, survival, and decreased cost of care. Understanding modern conceptualizations of PC and its role within SCT is key. Through the report of a single academic medical center experience with an integrated SCT and PC model over the last decade, we will discuss future opportunities for strengthening collaboration between SCT and PC. PC in SCT should be considered from the day of diagnosis and tied to need, not to prognosis.
Patient-reported outcomes in clinical practice
Authors: Dobrozsi Sarah , Panepinto Julie
Published: September 2016

Patient-reported outcome (PRO) measurement plays an increasingly important role in health care and understanding health outcomes. PROs are any report of a patient's health status that comes directly from the patient, and can measure patient symptoms, patient function, and quality-of-life. PROs have been used successfully to assess impairment in a clinical setting. Use of PROs to systematically quantify the patient experience provides valuable data to assist with clinical care; however, initiating use of PROs in clinical practice can be daunting. Here we provide suggestions for implementation of PROs and examples of opportunities to use PROs to tailor individual patient therapy to improve patient outcomes, patient–physician communication, and the quality of care for hematology/oncology patients.
Hodgkin lymphoma in children and adolescents: improving the therapeutic index
Authors: Kelly Kara M.
Published: September 2016

Hodgkin lymphoma (HL) is a highly curable form of childhood cancer, with estimated 5 year survival rates exceeding 98%. However, the establishment of a “standard of care” approach to its management is complicated by the recognition that long-term overall survival declines in part from delayed effects of therapy and that there continue to be subgroups of patients at risk for relapse for which prognostic criteria cannot adequately define. This challenge has resulted in the development of various strategies aimed at identifying the optimal balance between maintaining overall survival and avoidance of long-term morbidity of therapy, often representing strategies quite different from those used for adults with HL. More precise risk stratification and methods for assessing the chemosensitivity of HL through imaging studies and biomarkers are in evolution. Recent advances in the understanding of the biology of HL have led to the introduction of targeted therapies in both the frontline and relapsed settings. However, significant barriers exist in the development of new combination therapies, necessitating collaborative studies across pediatric HL research consortia and in conjunction with adult groups for the adolescent and young adult (AYA) population with HL.
Zebras and hen's teeth: recognition and management of rare T and NK lymphomas
Authors: Mehta–Shah Neha , Horwitz Steven
Published: September 2016

Although all the peripheral T-cell lymphomas are uncommon, there are some entities that are truly rare. Subtypes, such as enteropathy-associated T-cell lymphoma, hepatosplenic T-cell lymphoma, extranodal NK/T-cell lymphoma, and subcutaneous panniculitis-like T-cell lymphoma, have an approximate annual incidence in United States of <500 each. In these very rare subtypes, there is limited data to guide clinical decision-making. As such, our treatment decisions are often based on extrapolation, case series, personal experience, and biases. We summarize the existing data regarding initial management of these entities and compare how that management follows paradigms established for the more common T-cell lymphomas.