bluuebunny/crossref_metadata_2025 huggingface dataset:
Autism spectrum disorder reporting in lower socioeconomic neighborhoods
Authors: Dickerson Aisha S , Rahbar Mohammad H , Pearson Deborah A , Kirby Russell S , Bakian Amanda V , Bilder Deborah A , Harrington Rebecca A , Pettygrove Sydney , Zahorodny Walter M , Moyé Lemuel A , Durkin Maureen , Slay Wingate Martha
Published: September 2016

Utilizing surveillance data from five sites participating in the Autism and Developmental Disabilities Monitoring Network, we investigated contributions of surveillance subject and census tract population sociodemographic characteristics on variation in autism spectrum disorder ascertainment and prevalence estimates from 2000 to 2008 using ordinal hierarchical models for 2489 tracts. Multivariable analyses showed a significant increase in ascertainment of autism spectrum disorder cases through both school and health sources, the optimal ascertainment scenario, for cases with college-educated mothers (adjusted odds ratio = 1.06, 95% confidence interval = 1.02–1.09). Results from our examination of sociodemographic factors of tract populations from which cases were drawn also showed that after controlling for other covariates, statistical significance remained for associations between optimal ascertainment and percentage of Hispanic residents (adjusted odds ratio = 0.93, 95% confidence interval = 0.88–0.99) and percentage of residents with at least a bachelor’s degree (adjusted odds ratio = 1.06, 95% confidence interval = 1.01–1.11). We identified sociodemographic factors associated with autism spectrum disorder prevalence estimates including race, ethnicity, education, and income. Determining which specific factors influence disparities is complicated; however, it appears that even in the presence of education, racial and ethnic disparities are still apparent. These results suggest disparities in access to autism spectrum disorder assessments and special education for autism spectrum disorder among ethnic groups may impact subsequent surveillance.
Experimental investigation of damage identification in beam structures based on the strain statistical moment
Authors: Wang Dansheng , Chen Zhen , Xiang Wei , Zhu Hongping
Published: September 2016

A new two-step damage detection technique based on the fourth strain statistical moment was recently proposed by the authors, and its sensitivity to local structural damage has been numerically demonstrated for beam-type structures. In this article, the proposed method is extended to an experimental beam to assess its feasibility and practicality. A simply supported steel beam was manufactured and subjected to Gaussian white-noise excitation before and after damage. The strain responses of each measurement point were recorded based on which fourth strain statistical moments were calculated. The proposed two-step technique was implemented to locate the damaged elements of the experimental beam, for which the damage sizes were identified based on the least-square updating algorithm. The experimental results show that the proposed fourth strain statistical moment index and the two-step damage detection technique are effective and feasible for beam-type structures.
On waging the ideological war: Against the hegemony of form
Authors: Narotzky Susana
Published: September 2016

This article seeks to rehabilitate the concept of ideology as a necessary tool of struggle against present-day capitalism. Post-structuralist epistemologies, by celebrating pluralism and the emergent character of knowledge and politics, have rendered the intellectual production of a unitary theory an obsolete remnant of a Modernist past. I contend that these well-meaning anti-authoritarian epistemologies unwillingly express the hegemony of a form that the Austrian school proposed for market competition in the first half of the 20th century. Based on ethnographic material of Spain, I acknowledge the need to develop a new conceptual framework that captures the singular experienced realities of the present but links them in a coherent unitary theoretical structure. The productive power of the ‘hegemony of form’ requires the construction of an ideology that may not only destroy it but also provide the basis of a counter-hegemony for producing a better future.
The jeweler’s loupe: Validation
Authors: Reyna Stephen
Published: September 2016

Validating and theorizing are understood as parts of a common intellectual practice – theory creation – to know why reality is, or is changing, the way it is. This essay’s goal is to encourage debate about the role of validation in anthropological practice, with the aim of increasing that role. Argument is presented in Socratic fashion by posing, and responding to, questions. The first question inquires: What is validation? The second asks: Is getting the facts important in validation? The third queries: How do you get the facts? The fourth probes: What about objectivity in a biased world? The fifth demands: Why are intersubjectivity and representativeness important? Finally, the sixth section asks: If you do validate, can you get to the truth of something? It is concluded that skilled validation creates approximate truth, which is as close to knowing what is that people get.
Toward a glocal theory for Iranian social sciences
Authors: Fakouhi Nasser
Published: September 2016

In this essay, I describe a perspective of what we may call a ‘Southern Theory’ in Iran. Historical and contemporary conditions in Iran have mediated against the development of such a theory, yet could, if reflexively approached, produce a glocal theory. In exploring the issue via Iran, I note the necessity of emphasizing the diversity of thought encompassed by the Southern Theory, and of considering the different time/spaces of the South. The essay has a critical approach regarding current social and scientific relations in and out of Iran in the social sciences in general, and particularly in anthropology. In this way, I try to rethink the question of English as a scientific lingua franca, considering the short and long consequences of such an approach.
Introducing a spatial perspective to analyze market dynamics
Authors: Castilhos Rodrigo B. , Dolbec Pierre-Yann , Veresiu Ela
Published: September 2016

Grounded in work on geography and markets, this article offers a conceptual framework to study the dynamics of markets through a spatial lens. The characteristics of four key spatial dimensions (place, territory, scale, and network) are explained and leveraged to provide distinct analytical vantage points and to conceptualize how various types of spaces matter differently in market dynamics. Findings from a qualitative meta-analysis identify 12 unique mechanisms tied to the four proposed spatial dimensions, which offer alternative theoretical avenues for unpacking market phenomena. These four spatial dimensions are then combined with 12 space-based mechanisms to offer novel research avenues for marketing scholars interested in market system dynamics.
Consumers’ collective action in market system dynamics
Authors: Kjeldgaard Dannie , Askegaard Søren , Rasmussen Jannick Ørnstedt , Østergaard Per
Published: September 2016

This article examines how consumers may work strategically to alter market dynamics through formally organized activities. We address this issue in the context of the Danish beer market and its evolution over the last two decades, with a specific empirical focus on the role of a formally organized consumer association. We draw on key tenets of recent advances in sociological field theory, which views social order as comprising multiple and related strategic action fields. From this perspective, we describe the Danish beer market and its transformation, with an emphasis on how Danish beer enthusiasts played a significant role in altering the logics of competition in the market, but also played a significant institutionalized role within the field itself. We theorize this activity as consumers’ collective action.
Nonfatal Gun Use in Intimate Partner Violence: A Systematic Review of the Literature
Authors: Sorenson Susan B. , Schut Rebecca A.
Published: September 2016

Guns figure prominently in the homicide of women by an intimate partner. Less is known, however, about their nonfatal use against an intimate partner. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched eight electronic databases and identified 10 original research articles that reported the prevalence of the nonfatal use of firearms against an intimate partner. Results indicate that (1) there is relatively little research on the subject of intimate partners’ nonfatal gun use against women. (2) The number of U.S. women alive today who have had an intimate partner use a gun against them is substantial: About 4.5 million have had an intimate partner threaten them with a gun and nearly 1 million have been shot or shot at by an intimate partner. Whether nonfatal gun use is limited to the extreme form of abuse (battering) or whether it occurs in the context of situational violence remains to be seen. Regardless, when it comes to the likely psychological impact, it may be a distinction without a difference; because guns can be lethal quickly and with relatively little effort, displaying or threatening with a gun can create a context known as coercive control, which facilitates chronic and escalating abuse. Implications for policy, practice, and research are discussed, all of which include expanding an implicit focus on homicide to include an intimate partner’s nonfatal use of a gun.
Parental Mediation in the Improvement of Narrative Skills of High-Functioning Individuals With Autism Spectrum Disorder
Authors: McCabe Allyssa , Hillier Ashleigh , Da Silva Cristiane Martins , Queenan Alexa , Tauras Mary
Published: September 2016

Individuals with autism spectrum disorder (ASD) produce impoverished personal narratives. We developed an intervention to improve parental talk with their son/daughter with ASD which would thereby improve the child’s narration. In this pilot study, we randomly assigned parents to an intervention group who received information about the importance of personal narratives and techniques for improving narration, or a wait-list control group. We compared changes in narration of those with ASD whose parents were in the intervention group versus the wait-list control group. Two recordings of parent–child conversations were scored for elaboration and topic-maintenance versus off-topic remarks. Elaboration skills showed significant improvement among intervention parents, which was related to child elaboration in the same conversation and several months later. Parents in the intervention group, but not control group, reported significant improvement in their son/daughter’s narration. Narrative skills intervention with parents is a promising corrective to the narration difficulties of those with ASD.
Clinical and Imaging Outcomes up to 1 Year Following Balloon Angioplasty for Isolated Penile Artery Stenoses in Patients With Erectile Dysfunction
Authors: Wang Tzung-Dau , Lee Wen-Jeng , Yang Shao-Chi , Lin Po-Chih , Tai Huai-Ching , Liu Shih-Ping , Huang Chien-Hua , Chen Wen-Jone , Chen Ming-Fong , Hsieh Ju-Ton
Published: September 2016

Purpose: To assess the angiographic and clinical outcomes in patients with erectile dysfunction and isolated penile artery stenoses treated by balloon angioplasty. Methods: In this prospective study, 22 patients (mean age 61.0±7.6 years, range 50–79) with erectile dysfunction and 34 isolated penile artery stenoses (mean 74.9%±9.1%) were enrolled and underwent balloon angioplasty. The mean International Index for Erectile Function–5 (IIEF-5) score at baseline was 10.3±4.5. The mean lesion length was 11.1±9.0 mm (mean reference vessel diameter 1.7±0.4 mm). The primary endpoint was in-segment restenosis ≥50% by pelvic computed tomography angiography (CTA) at 8 months. The 1-year sustained clinical success (IIEF-5 score ≥22 or a ≥4-point change in the IIEF-5 score and no later decline by ≥4) was the secondary outcome measure. Results: Procedural success was achieved in 31 (91%) of 34 stenotic lesions; there was 1 flow-limiting dissection and 2 arteries with >30% residual stenosis. At 8 months, 14 of 34 lesions in 13 of 22 patients had CTA-documented binary restenosis. At 1 year, sustained clinical success was achieved in 11 of 22 patients. Of the 9 patients not developing binary restenosis, 8 achieved sustained clinical success. Conclusion: Our findings establish the safety and efficacy of penile artery angioplasty for patients with erectile dysfunction and isolated penile artery stenoses. They also highlight the unmet need for a more enduring treatment strategy for penile artery stenotic disease.
Consensus-based sparse signal reconstruction algorithm for wireless sensor networks
Authors: Peng Bao , Zhao Zhi , Han Guangjie , Shen Jian
Published: September 2016

This article presents a distributed Bayesian reconstruction algorithm for wireless sensor networks to reconstruct the sparse signals based on variational sparse Bayesian learning and consensus filter. The proposed approach is able to address wireless sensor network applications for a fusion-center-free scenario. In the proposed approach, each node calculates the local information quantities using local measurement matrix and measurements. A consensus filter is then used to diffuse the local information quantities to other nodes and approximate the global information at each node. Then, the signals are reconstructed by variational approximation with resultant global information. Simulation results demonstrate that the proposed distributed approach converges to their centralized counterpart and has good recovery performance.
Direct-acting antivirals for the treatment of chronic hepatitis C in patients with chronic kidney disease
Authors: Kohli Anita , Alshati Ali , Georgie Fawaz , Manch Richard , Gish Robert G.
Published: September 2016

All-oral, direct-acting antivirals (DAAs) have significantly improved the efficacy and safety of chronic hepatitis C (CHC) treatment but their effectiveness and safety among patients with chronic kidney disease (CKD) remains poorly understood. Our aim was to assess the efficacy and safety of DAAs for treatment of CKD patients. The National Library of Medicine through PubMed was searched for studies evaluating the efficacy of DAAs for the treatment of patients with CKD stages 4 or 5, as defined by the Kidney Disease Outcomes Quality Initiative guidelines [i.e. glomerular filtration rate (GFR) 15–29 ml/min per 1.73 m2 and GFR <15 ml/min per 1.73 m2, respectively, or hemodialysis or peritoneal dialysis]. Randomized clinical trials (RCTs) and relevant cohort studies were included if they were published in English and included sustained viral response after 12 weeks (SVR12) as a primary or secondary endpoint. After applying inclusion and exclusion criteria, eight studies (one RCT and seven cohort studies) following 350 patients were selected. For patients with CKD stage 4 or 5, ± hemodialysis, the overwhelming majority of DAA regimens were well-tolerated and resulted in SVR12 rates of 90–100%. Most studies were small, with the exception of one RCT evaluating elbasvir and grazoprevir. Overall, treatment of CHC in patients with CKD is highly effective with SVR12 rates similar to those seen in patients without CKD and with acceptable adverse event profiles. In patients with hepatitis C virus (HCV) genotype (GT) 1a, 1b or 4 and Stage 4 or 5 CKD, the best evidence available is for the use of elbasvir and grazoprevir. This combination as well as the combination of paritaprevir/ritonavir/ombitasvir/dasabuvir for HCV GT-1b are recommended. More studies are needed to assess efficacy and adverse effects of DAAs and their impact on CKD patients and to fully elucidate the effect of curing CHC on the natural history and sequelae of renal disease in CHC patients with CKD.
Experimental studies of the effect of rapid afterburn on shock development of near-field explosions
Authors: Tyas Andrew , Reay Jonathan J , Fay Stephen D , Clarke Samuel D , Rigby Samuel E , Warren James A , Pope Daniel J
Published: September 2016

Many conventional high explosives do not contain sufficient internal oxygen to fully combust the gaseous products which result from detonation of the explosive material. Because of this, under-oxygenated explosives continue to burn after detonation. This process, called afterburn, is known to influence the late-time pressure and energy released by the explosive, which has particular significance for confined explosives. Recent experimental work at the University of Sheffield, along with a small number of previous studies, has shown that some afterburn occurs at timescales commensurate with the development of the shock wave. This article presents the results from a series of tests measuring the reflected pressure acting on a rigid target following the detonation of small explosive charges. High-speed video is used to capture the emerging structure of the detonation products and air shock, while the spatial and temporal distributions of the reflected pressure are recorded using an array of 17 Hopkinson pressure bars set flush with an effectively rigid target. Tests are conducted in inert atmospheres and oxygen-rich atmospheres in order to assess the contribution of rapid afterburn on the development of the shock front and interaction with a rigid target situated close to the explosive charge. The results show that early-stage afterburn has a significant influence on the reflected shock parameters in the near-field.
Risk-based blast-load modelling: Techniques, models and benefits
Authors: Netherton Michael D , Stewart Mark G
Published: September 2016

There are many deterministic blast-load methods currently in use, such as (1) those for the ready calculation of explosive pressure, impulse and duration; (2) the derivation of explosive safety distances; or (3) the determination of safety hazards (and other consequences) following an explosive’s detonation. In this article, we argue that deterministic blast-loading methods do not fully account for society’s usual acceptance (or rejection) of the risks associated with damage, safety and/or injury as a result of an explosive blast-load. This article details the state of the art of probabilistic blast-load modelling that supports a quantitative calculation of risk, with respect to damage, safety and injury. The probabilistic models draw data from the literature and from our own field trials. The article details the benefits that flow from this form of blast-load characterisation and concludes with a discussion on how probabilistic methods be used to derive cost–benefit advice with respect to any proposed risk mitigation solution.
Media Ecology and the Politics of Dissent: Representations of the Hong Kong Protests in The Guardian and China Daily
Authors: Veneti Anastasia , Karadimitriou Achilleas , Poulakidakos Stamatis
Published: September 2016

The phenomenon of protests, currently on the rise in worldwide democracies, is made known to citizens mainly through representations in the media. This article, responding to the need for a broader view of protest media coverage in an international context, examines the ways the 2014 Hong Kong (HK) protests were covered by the online versions of two highly influential and appealing newspapers, belonging to contrasting media systems: The Guardian and China Daily. By revising a typology of previously used frames and inventing new ones, this study conducts a quantitative content analysis of news articles with the view to (a) highlight similarities and differences in the media coverage of protests within the above-mentioned media systems, (b) find out whether the media coverage of such events with political ramifications is affected by the geopolitical interests of the countries. Based on our analysis, this study suggests the need for revising the protest paradigm as important factors—the protests’ momentum, the media systems, the new information communication technologies, and certain geopolitical interests—are involved in the dynamics surrounding media coverage of protests and as such they greatly influence the framing process. Moreover, our findings demonstrated that the media coverage of the 2014 HK protests by the two newspapers was reflective of both the media systems in which they function and the distinctive national standpoints.
15 Years of Protest and Media Technologies Scholarship: A Sociotechnical Timeline
Authors: Neumayer Christina , Rossi Luca
Published: September 2016

This article investigates the relationship between the invention of new media technologies and scholarship concerning protest and political engagement. Building on an innovative approach that moves beyond a systematic literature review, this article contributes to our understanding of scholarship concerning digital communication technologies and how they may have been adopted and shaped protest movements and political engagement. Based on visualizations, we draw a sociotechnical timeline of protest and media technology scholarship within three dimensions: technological development, methods and techniques, and the social phenomena under investigation. The article concludes by identifying major trends in protest and media technologies scholarship over the past 15 years. The sociotechnical timeline enhances our understanding of academic discourse at the intersection of protest and media technologies by highlighting shortcomings and potential for future research.
A narrative future for Europe–China economic relations after the financial crisis
Authors: Zhang Zhan
Published: September 2016

This article provides a detailed comparative analysis of how leading European media outlets—three elite newspapers from the United Kingdom, France, and Germany—reported economic news as it related to China from 2008, the beginning of the global financial crisis, until 2014. It illustrates the changing nature of European media perceptions of China and a growing interdependence between Europe and China after the financial crisis. Media messages directed toward domestic audiences and global stakeholders shaped public perceptions and influenced political, economic, and diplomatic narratives. In addition to a general increase in attention to news focused on China’s economy after the financial crisis, the three European newspapers also shared essentially the same news frames when they reported economic news about China. Some differences were noted, however, as the British and German newspapers focused on their domestic interests with China’s economy while the French newspaper preferred to discuss issues from the perspective of the European Union. All three newspapers were attentive to the pace of China’s rise and to the problems and obstacles of doing business in China as well as to China’s importance for Europe’s future economic development. The news narratives were dominated by a tension between hope and uncertainty.
China’s “peaceful rise/peaceful development”: A case study of media frames of the rise of China
Authors: Okuda Hiroko
Published: September 2016

This study examines English language legacy print media coverage of the rise of China. A critical analysis reveals that China is often cast as a threat to global peace and stability in news stories that focus on the pace of China’s economic development and military expansion. At the same time, much of this coverage also frames the United States as a superpower in decline. Many news articles describe the situation through the historical metaphor of “Thucydides trap”, a narrative frame that may serve to intensify tensions and increase the risk of conflict. While Beijing has sought to improve the country’s image abroad and to win greater support for its positions, this study found that the news narratives in English language publications might spark anxiety about China and its global ambitions.
Global warming: Chinese narratives of the future
Authors: Riley Patricia , Wang Rong , Wang Yuehan , Feng Lingyan
Published: September 2016

Anthropogenic Climate Change (climate change or global warming that is caused by human activity) is considered to be one of the key global concerns moving forward this century. The ongoing flow of communication around an issue can be seen as a co-production of strategic messaging that encompasses the voice of multiple stakeholders who have differing narratives that evolve over time. Individuals, governments, businesses, international agencies, and other organizations see themselves as key stakeholders in these evolving stories, and all are trying to develop their own visions and hopes for the future. This article suggests that many of these voices are engaged in a version of “ecological modernization,” a narrative that attempts to develop a win-win discourse of economic growth in conjunction with environmental sustainability under the premise of “doing well by doing good.” Data are from social media platforms in the Chinese language that are analyzed through topic and narrative analysis.
Significant Improvements Are Needed in HIV Care Continuum to Meet 90-90-90 Targets in Georgia
Authors: Chkhartishvili Nikoloz , Chokoshvili Otar , Dvali Natia , Abutidze Akaki , Sharvadze Lali , Tsertsvadze Tengiz
Published: September 2016

The objective of this report was to assess Georgia’s progress toward Joint United Nations Programme on HIV/AIDS 90-90-90 targets over the period between 2011 and 2015. The number of HIV-positive persons was estimated using Spectrum software. Number of persons diagnosed, on antiretroviral therapy (ART) and virally suppressed were quantified using data from the national AIDS health information system. By the end of 2015, out of the estimated 7100 persons living with HIV, 62% were diagnosed, 38% were on ART, and 32% were virally suppressed. There were improvements in each stage of cascade from 2011 to 2015: the proportion of diagnosed persons increased from 46% to 61%, ART coverage among diagnosed persons increased from 46% to 62%, and the proportion of virally suppressed patients among those on ART increased from 74% to 85%. Despite the progress, additional efforts are needed to reach the 90-90-90 targets. Reducing the number of people living with undiagnosed HIV will be critical for achieving goals.
Mobile or Not? Assessing the Instructional Value of Mobile Learning
Authors: Nickerson Catherine , Rapanta Chrysi , Goby Valerie Priscilla
Published: September 2016

Our aim was to explore the influence of mobile learning on students’ acquisition of conceptual knowledge of business communication, as well as on the development of their communication skills. We compared the performance of three groups of students according to the pedagogical approach that we used with them: a mobile learning group, a conventional group, and a control group. Our findings suggest that a mobile learning intervention leads to an improvement in student performance in a formal assessment and that it will also have a positive impact on learning outcomes.
Identifying and Understanding the Health Information Experiences and Preferences of Individuals With TBI, SCI, and Burn Injuries
Authors: Coffey Nathan T , Weinstein Ali A , Cai Cindy , Cassese Jimmy , Jones Rebecca , Shaewitz Dahlia , Garfinkel Steven
Published: September 2016

Introduction:

Traumatic brain injury, spinal cord injury, and burn injury can cause lifelong disability and changes in quality of life. In order to meet the challenges of postinjury life, various types of health information are needed. We sought to identify preferred sources of health information and services for persons with these injuries and discover how accessibility could be improved.

Methods:

Thirty-three persons with injury participated in semistructured interviews. Responses to interview questions were coded using NVivo.

Results:

Participants’ difficulties accessing health information varied by injury type and individually. The majority of respondents found information via the Internet and advocated its use when asked to describe their ideal health information system. Nearly all participants supported the development of a comprehensive care website. When searching for health information, participants sought doctor and support group networks, long-term health outcomes, and treatments specific to their injury.

Conclusion:

To optimize the quality of health information resources, Internet-based health-care platforms should add or highlight access points to connect patients to medical professionals and support networks while aggregating specialized, injury-specific research and treatment information.
Alteration of compacted GMZ bentonite by infiltration of alkaline solution
Authors: Bao Chen , Jiaxing Guo , Huixin Zhang
Published: September 2016

Concepts for geological disposal of high-level radioactive waste usually include bentonite buffer materials. Numerous studies have been performed with most usingWyoming bentonite. Gaomiaozi (GMZ) bentonite has been selected as a potential buffer/backfill material for the deep geological repository of high-level radioactive waste in China. In this context, the highly alkaline environment induced by cementitious materials in the repository is likely to alter montmorillonite, the main clay mineral in GMZ bentonite. This alteration may result in deterioration of the physical and/or chemical properties of the buffer material. To acquire quantitative data which would allow us to assess the dissolution of montmorillonite and changes in the diffusivity of hydroxide ions as well as their effects on the swelling pressure and permeability of the compacted GMZ bentonite, an experimental study was conducted under highly alkaline (NaOH solutions with various pH values were used), simulated groundwater conditions. The GMZ bentonite also contains cristobalite which may also have been dissolved. The microstructure of the compacted bentonite samples after the experiments was determined by mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM). Energy dispersive spectroscopy (EDX) was carried out to identify mineralogical changes. At pH >13, the permeability of specimens increased significantly; the swelling potential decreased with increasing pH. Furthermore, the pore volume and pore size of GMZ bentonite changed when exposed to alkaline solution, resulting in an increase in porosity and permeability. The main alteration mechanisms of compacted GMZ bentonite undergoing infiltration by highly alkaline solution are likely to be dissolution and modifications in terms of the microstructure and mineralogy.
Using direct oral anticoagulants (DOACs) in cancer and other high-risk populations
Authors: van Es Nick , Büller Harry R.
Published: September 2016

The major practical advantage of the direct oral anticoagulants (DOACs), comprising the thrombin inhibitor dabigatran and the factor Xa inhibitors apixaban, edoxaban, and rivaroxaban, over vitamin K antagonists is their fixed dosing without the need for laboratory monitoring. With the recent, rapid introduction of the DOACs for the treatment of acute venous thromboembolism (VTE), clinicians are now faced with various questions regarding the efficacy and safety of these compounds overall and in specific high-risk populations. The collective evidence from 6 large clinical trials involving 27,000 patients has demonstrated that DOACs are as effective as vitamin K antagonists (VKA) in preventing recurrent VTE while being associated with a significantly lower risk of major bleeding. These findings are consistent in subgroups of patients with pulmonary embolism, the elderly, and those patients with a high body weight or moderate renal insufficiency, making these agents suitable for a broad spectrum of patients with VTE. DOACs are also an attractive treatment option in patients with VTE and concomitant cancer, thrombotic antiphospholipid syndrome, or heparin-induced thrombocytopenia, but the currently available clinical data is insufficient to make evidence-based recommendations on the use of DOACs in these settings. Several studies evaluating the efficacy and safety of DOACs in these high-risk populations are underway.
Incidentally found pulmonary embolism: what's the clinician to do?
Authors: O'Connell Casey
Published: September 2016

Incidental pulmonary embolism (IPE) is a management challenge for the unsuspecting clinician. Patients with IPE frequently have signs or symptoms that are unrecognized as PE related, and their clots occur predominantly in the proximal pulmonary vasculature. There is uniformity in recommending anticoagulation for patients with IPE proximal to the subsegmental pulmonary vasculature, but prospective data are not currently available to guide the duration of therapy in this population. Several studies suggest that outcomes, including recurrence, mortality, and bleeding, are similar for patients with IPE and suspected PE, especially among those who also have cancer. Patients with isolated incidental subsegmental pulmonary embolism (ISSPE) are particularly challenging because some studies suggest that they can be managed without anticoagulation. Therefore, an algorithm is proposed to guide the evaluation and treatment of patients with ISSPE.
Is there a best TKI for chronic phase CML?
Authors: Larson Richard A.
Published: September 2016

The development of BCR/ABL1 tyrosine kinase inhibitors (TKIs) over the past 20 years has dramatically improved the outcomes for patients with every stage of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML). Clinicians now have access to 5 oral, generally well-tolerated, and highly effective TKIs. How should these agents be used for an individual patient to ensure the best possible duration and quality-of-life, to avoid treatment-related complications, and potentially to achieve a cure at an affordable cost? Because CML patients may need to continue TKI therapy indefinitely, the long-term safety of each treatment option must be considered. Evidence-based care requires an understanding of the optimal use of these drugs, their specific early and late toxicities, the prognostic significance of achieving treatment milestones, and the critical importance of molecular monitoring. Efficacy is important, but treatment choice does not depend only on efficacy. Choosing among various treatment options is informed by understanding the distinct benefits and risks of each agent, along with careful consideration of patient-specific factors, such as risk status, age, and comorbidities.
Patterns of resistance to B cell–receptor pathway antagonists in chronic lymphocytic leukemia and strategies for management
Authors: Woyach Jennifer A.
Published: September 2016

Small-molecule kinase inhibitors, especially the two Food and Drug Administration–approved agents idelalisib and ibrutinib, have changed the treatment landscape for patients with relapsed or refractory chronic lymphocytic leukemia (CLL). However, with these positive changes comes the new challenge of managing patients who relapse after these agents. The number of patients who have relapsed after taking idelalisib and ibrutinib is low, but as the drugs gain wider use and patients are treated for longer, this number is likely to grow. Because these patients can be challenging to manage effectively, coordinated efforts now to determine how and why patients relapse along with optimal treatment strategies are required to better serve our patients in the future. As well, identification of mechanisms of resistance is crucial to develop rational strategies for management. Current work has identified mechanisms of resistance to ibrutinib, and resistance to idelalisib is also under active investigation. In this review, we will discuss these mechanisms of resistance, as well as current and potential strategies for the management of kinase inhibitor-resistant CLL.
Prognostic markers and standard management of chronic lymphocytic leukemia
Authors: Stilgenbauer Stephan
Published: September 2016

Chronic lymphocytic leukemia (CLL) is usually diagnosed in early stage, asymptomatic patients, and, although a wealth of prognostic parameters have been identified, the standard approach is a “watch and wait” strategy irrespective of risk factors. Therapy is only indicated if “active disease” criteria (International Workshop on Chronic Lymphocytic Leukemia guidelines) are met, and the routine upfront treatment is a combination of CD20 antibody (rituximab, ofatumumab or obinutuzumab) and chemotherapy (fludarabine /cyclophosphamide, bendamustine, chlorambucil), with the choice mainly determined by physical fitness of the patient. The major subgroup in which this approach does not result into satisfactory efficacy is in CLL with 17p deletion (17p−) or TP53 mutation (TP53mut). Likewise, patients with a short initial response duration (i.e., <24-26 months) have a dismal outcome with chemoimmunotherapy salvage. Therefore, these patients have been referred to as “ultra high risk,” and, in these subgroups, novel agents such as signaling kinase inhibitors (also termed B-cell receptor signaling inhibitors; e.g., ibrutinib targeting Bruton tryosine kinase, idelalisib targeting phosphoinositide 3-kinase) and BCL2 antagonists (venetoclax, formerly ABT-199/GDC-0199) have shown dramatic efficacy. Ibrutinib and idelalisib are currently approved for the treatment of relapsed or refractory CLL or frontline treatment of 17p−/TP53mut CLL regardless of fitness. Therefore, these agents are challenging the concept of adjusting treatment to fitness and TP53 status, because they offer remarkable efficacy combined with exceptional tolerability. Nevertheless, it appears that 17p−/TP53mut retains an adverse prognostic impact, making additional improvement a primary research goal aimed at the development of the best combinations and/or sequences of these new agents, as well as prognostic and predictive markers guiding their use.
The five key things you need to know to manage adult patients with sickle cell disease
Authors: Lanzkron Sophie , Haywood Carlton
Published: September 2016

The lack of a strong evidence base to guide the management of adults with sickle cell disease (SCD) makes it difficult for patients to receive high quality care outside of specialty centers. As there is a dearth of providers with sickle cell expertise, the purpose of this article is to identify some of the key things every provider who manages the care of adults with SCD should know. Managing adults with SCD requires excellent clinical skills, as it can affect every organ and cause life-threatening complications but it also requires a willingness to manage patients who often have psychosocial issues that are complex and impact care and care delivery in very significant ways. We have chosen topics for which there is a limited evidence base but which have significant clinical consequences if left unrecognized or poorly managed. The topics that will be addressed include chronic pain, neurocognitive dysfunction, renal disease, venous thromboembolism, and avoiding the inappropriate use of red cell transfusions.
Implementing a blood utilization program to optimize transfusion practice
Authors: Savage William
Published: September 2016

Blood utilization review programs educate clinicians on guidelines for appropriate transfusion, review local transfusion practice, and provide feedback on transfusion trends. To gather data on transfusion practice, modern blood utilization programs leverage electronic medical records and computerized physician order entry with automated decision support. Data may be collected and feedback may be given in real-time for individual transfusions or retrospectively with aggregated data. Important elements for a successful program include a multidisciplinary group that can champion the effort, adequate documentation and data capture for transfusions, and regular discussions about trends with ordering clinicians. Blood utilization programs are popular because they can lower transfusion risk, improve quality outcomes, and lower costs.
When and why should patients with hematologic malignancies see a palliative care specialist?
Authors: LeBlanc Thomas W. , El-Jawahri Areej
Published: September 2016

Palliative care is a multidisciplinary approach to symptom management, psychosocial support, and assistance in treatment decision-making for patients with serious illness and their families. It emphasizes well-being at any point along the disease trajectory, regardless of prognosis. The term “palliative care” is often incorrectly used as a synonym for end-of-life care, or “hospice care”. However, palliative care does not require a terminal diagnosis or proximity to death, a misconception that we will address in this article. Multiple randomized clinical trials demonstrate the many benefits of early integration of palliative care for patients with cancer, including reductions in symptom burden, improvements in quality-of-life, mood, and overall survival, as well as improved caregiver outcomes. Thus, early concurrent palliative care integrated with cancer-directed care has emerged as a standard-of-care practice for patients with cancer. However, patients with hematologic malignancies rarely utilize palliative care services, despite their many unmet palliative care needs, and are much less likely to use palliative care compared to patients with solid tumors. In this article, we will define “palliative care” and address some common misconceptions regarding its role as part of high-quality care for patients with cancer. We will then review the evidence supporting the integration of palliative care into comprehensive cancer care, discuss perceived barriers to palliative care in hematologic malignancies, and suggest opportunities and triggers for earlier and more frequent palliative care referral in this population.
The antiphospholipid syndrome: still an enigma
Authors: Chaturvedi Shruti , McCrae Keith R.
Published: September 2016

Antiphospholipid syndrome (APS) is defined by clinical manifestations that include thrombosis and/or fetal loss or pregnancy morbidity in patients with antiphospholipid antibodies (aPL). Antiphospholipid antibodies are among the most common causes of acquired thrombophilia, but unlike most of the genetic thrombophilias are associated with both venous and arterial thrombosis. Despite an abundance of clinical and basic research on aPL, a unified mechanism that explains their prothrombotic activity has not been defined; this may reflect the heterogeneity of aPL and/or the fact that they may influence multiple pro- and/or antithrombotic pathways. Antiphospholipid antibodies are directed primarily toward phospholipid binding proteins rather than phospholipid per se, with the most common antigenic target being β2-glycoprotein 1 (β2GPI) although antibodies against other targets such as prothrombin are well described. Laboratory diagnosis of aPL depends upon the detection of a lupus anticoagulant (LA), which prolongs phospholipid-dependent anticoagulation tests, and/or anticardiolipin and anti-β2-glycoprotein 1 antibodies. Indefinite anticoagulation remains the mainstay of therapy for thrombotic APS, although new strategies that may improve outcomes are emerging. Preliminary reports suggest caution in the use of direct oral anticoagulants in patients with APS-associated thrombosis. Based on somewhat limited evidence, aspirin and low molecular weight heparin are recommended for obstetrical APS. There remains a pressing need for better understanding of the pathogenesis of APS in humans, for identification of clinical and laboratory parameters that define patients at greatest risk for APS-related events, and for targeted treatment of this common yet enigmatic disorder.
What's new in the diagnosis and pathophysiology of thrombotic thrombocytopenic purpura
Authors: Sadler J. Evan
Published: September 2016

Severe ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency causes thrombotic thrombocytopenic purpura (TTP), which is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and the absence of oliguric or anuric renal failure. However, some patients with this constellation of findings do not have ADAMTS13 deficiency, and some patients with ADAMTS13 deficiency have renal failure or relatively normal blood counts. Consequently, many investigators and clinicians have incorporated severe ADAMTS13 deficiency into the case definition of TTP. This change has facilitated the timely initiation of treatment for patients with atypical clinical features who otherwise would not be recognized as having TTP. Conversely, excluding severe ADAMTS13 deficiency focuses attention on the diagnosis and treatment of other causes of thrombotic microangiopathy that require different treatment. The rapid return of ADAMTS13 data is important to make the best use of this information.
Treatment of thrombotic thrombocytopenic purpura beyond therapeutic plasma exchange
Authors: Coppo Paul , Froissart Antoine
Published: September 2016

Daily therapeutic plasma exchange (TPE) transformed the historically fatal prognosis of acquired, anti-ADAMTS13 antibody-mediated thrombotic thrombocytopenic purpura (TTP), leading to the current overall survival rates of 80%-85%. However, relapses occur in ∼40% of patients and refractory disease with fatal outcomes still occurs. In this context, the introduction of rituximab has probably been the second major breakthrough in TTP management. Rituximab is now routinely recommended during the acute phase, typically in patients with a suboptimal response to treatment, or even as frontline therapy, with high response rates. In more severe patients, salvage strategies may include twice-daily TPE, pulses of cyclophosphamide, vincristine, as well as splenectomy in more desperate cases. In this life-threatening disease, relapse prevention represents a major goal. Persistent severe acquired ADAMTS13 deficiency in patients who are otherwise in remission is associated with a high risk of relapse and preemptive treatment with rituximab may be considered in this context. In the coming years, the TTP therapeutic landscape should be enriched by original strategies stemming from clinical experience and new agents that are currently being evaluated in large, ideally international, clinical trials. Promising agents under evaluation include N-acetylcysteine, bortezomib, recombinant ADAMTS13, and inhibitors of the glycoprotein-Ib/IX-von Willebrand factor axis.
Evidence for Janus kinase (JAK) inhibitors for the prevention of major morbid events in patients with myeloproliferative neoplasms (MPNs)
Authors: Pemmaraju Naveen , Mesa Ruben
Published: September 2016

A 69-year-old man presents with a Dynamic International Prognostic Scoring System (DIPSS) intermediate-risk 2 post polycythemia vera myelofibrosis with significant splenomegaly, 30 pound weight loss, constitutional symptoms, and 2% peripheral blood blasts. He has no other significant past medical history and no other major comorbid conditions. You are asked by the hematology fellow you are supervising whether or not treating this patient with a Janus kinase (JAK) inhibitor will decrease major morbid events.
B-cell receptor pathway modulators in NHL
Authors: Blum Kristie A.
Published: September 2016

With the recent success of the Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, and the phosphoinositide-3-kinase (PI3K) inhibitor, idelalisib, in the treatment of patients with relapsed or refractory non-Hodgkin's lymphoma (NHL), a number of new agents targeting the B-cell receptor (BCR) pathway are in clinical development. In addition, multiple trials combining these agents with conventional cytotoxic chemotherapy, immunomodulatory agents, monoclonal antibodies, or other kinase inhibitors are underway. This review will summarize the current data with the use of single agent and combination therapy with BCR inhibitors in NHL. In addition, commonly encountered as well as serious toxicities and hypothesized resistance mechanisms will be discussed. Lastly, this review will examine the future of these agents and opportunities to maneuver them into the front-line setting in selected NHL subtypes.