bluuebunny/crossref_metadata_2025 huggingface dataset:
Institutional Arsenals for Democracy? The Postcoup Effects of Conscript Militaries
Authors: Vasquez Joseph Paul , Powell Jonathan
Published: October 2019

Recent years have seen increased study of military coups. While this generally emphasizes coups as a dependent variable, there is a growing debate as to how coups influence a country’s long-term political trajectory. This literature includes a handful of studies that claim coups against authoritarian regimes can act for the public good and provide a boost to the state’s democratization prospects. Causal mechanisms have included factors such as aid conditionality, economic interdependence, and foreign pressure more generally. We argue that this growing body of work can benefit from increased attention given to those who carry out coups: the armed forces. Specifically, we argue that coups reflecting a larger societal interest, be it the removal of a dictator or the desire for democracy after a dictator’s ouster, are more likely undertaken by conscript armies. A cross-national exploration of over 170 coups suggests that conscript militaries are in fact significantly more likely to oversee democratic transitions following military coups. Beyond contributing to a broader literature on civil–military relations, the article points to important policy implications for developing nations.
Phone Speech Recognition Improvement in Noisy Environment: Use of a Bluetooth Accessory
Authors: Martínez Basterra Zuriñe , Fernández de Pinedo Mercedes , Rey Jorge Alberto , Palicio Idoia , Soriano-Reixach Maria Montserrat , Urreta Iratxe , Altuna Mariezcurena Xabier
Published: October 2019

Objective:

To evaluate speech understanding in noise and patient satisfaction using the new Cochlear Wireless Phone Clip device.

Material and Methods:

Twenty-nine experienced cochlear implant (CI) users (>6 months usage) were situated in a soundproof room where a 65 dB SPL Spanish cocktail noise was generated continuously from 4 loudspeakers. Lists of disyllabic words were presented through the clinic landline telephone to the patients. Patients were tested first holding the phone and then with the Cochlear Phone Clip© paired to the CP910 using various mixing ratios (2:1, 4:1, and Phone Clip© only).

Results:

Statistically significant ( P < .001) improvement of speech recognition performance was found in cell phone usage by wireless transmission and also when using this new device. Kepler questionnaire results showed that before using Phone Clip in everyday life, 55.2% of patients described themselves highly or greatly affected by their deafness for telephone use and 80% moderately to greatly affected. Kim questionnaire results showed statistically significant differences ( P < .001) in the subjective satisfaction of the Bluetooth-implemented CI compared to the conventional mode for sound quality, noise interference, and sound accuracy.

Conclusions:

The wireless Phone Clip© device helps implanted people to improve subjective and objective speech recognition performance through the phone in noisy environments.
Cochlear Implant Surgery: How to Fix Receiver/Stimulator Avoiding Extrusion
Authors: Gatto Annalisa , Tofanelli Margherita , Piccinato Alice , Antonio Jamile Karina , Zucchini Simone , Achilli Vittorio Pietro , Tirelli Giancarlo
Published: October 2019

Cochlear implant (CI) surgery is generally safe and associated with a limited number of complications, among which the extrusion of the receiver/stimulator (R/S) or the electrode misplacement and migration might require a CI re-implantation. The aim of this pilot study is to describe a new technique to firmly fix the R/S using the Mitek suture anchors system (Depuy Mitek Surgical Products, Inc. Raynham, Massachusetts). We tested two different models and in our experience, the web of suture created with this device can improve the stability of the bond of the R/S to the underlying curved bone surface. So, this system resulted in a less laborious manner keeping low the complication rate.
A systematic review of the application and psychometric properties of the graded Wolf Motor Function Test
Authors: Turtle Beverley , Porter-Armstrong Alison , Stinson May
Published: October 2019

Introduction

Adapted from the Wolf Motor Function Test, the graded Wolf Motor Function Test is an upper limb activity assessment for use following stroke and brain injury. The aim of this systematic review was to identify and appraise evidence where the test has been used or has undergone psychometric evaluation.

Method

A systematic review of five databases was conducted to identify studies reporting the graded Wolf Motor Function Test using a keyword search. Intervention and clinical measurement studies were eligible for inclusion. Data quality was assessed using the adapted Critical Appraisal Skills Programme questions and the Consensus-based Standards for the Selection of Health Measurement Instruments Risk of Bias checklist.

Results

Twelve studies, of mostly low quality, were included. Studies included one randomised controlled trial, 10 pre- and post-studies and one clinical measurement study. All studies involved participants following stroke. Reliability was the only measurement property assessed in two studies, which were of a ‘doubtful’ and ‘poor’ quality.

Conclusion

Low quality studies impede the ability of clinicians and researchers to best determine the applicability of the graded Wolf Motor Function Test to patient groups and research contexts. Further exploration of the psychometric properties of the graded Wolf Motor Function Test is recommended across stroke populations using rigorous design methods.
On resistance in human geography
Authors: Hughes Sarah M.
Published: October 2019

This paper outlines scholarship on resistance within geography. Its contention is that conceptualisations of resistance are characterised by a predetermination of form that particular actions or actors must assume to constitute resistance. Asking what we risk ignoring if we only focus on predetermined, recognisable resistant forms, the paper revisits some of the fundamental assumptions (of intention, linearity and opposition) that underpin accounts of resistance. It calls for geographers to engage with resistance in emergence. The paper concludes by detailing what this might look like in practice, including intersections with work on potentiality, incoherent subjects, agentic materiality and speculative futures.
Self-Questioning Strategy for Struggling Readers: A Synthesis
Authors: Daniel Johny , Williams Kelly J.
Published: October 2019

This review examined the effects of self-questioning (SQ) strategy instruction on reading comprehension outcomes for students with learning disabilities and struggling readers in Grades K-12. Our literature search, encompassing the past 53 years (1965–2018) of research, found 10 studies that fit our inclusion criteria. Reviewed studies included eight group design and two single-case design studies. Overall, the effects of SQ strategy instruction on students’ reading comprehension outcomes were mixed. No clear trends of the effects of SQ strategy intervention were associated with participants’ grade level and type of instruction (explicit or nonexplicit instruction). Effects of the total number of hours of SQ strategy instruction on students’ reading outcomes varied slightly with medium to large effects for students receiving two or more total hours of strategy instruction.
Credible Effects: The Impact of Disclosure of Material Connections Within Online Product Reviews
Authors: Steward Michelle D. , Burns Alvin C. , Morgan Felicia N. , Roehm Michelle L.
Published: October 2019

Online product reviews are an influential source of information for consumers. With pressures to have readily available reviews, businesses must determine the best strategy for obtaining them. In 2009, for the first time in 29 years, the Federal Trade Commission (FTC) updated endorsement guidelines to address concerns over possible deception within online reviews. Since that time, the FTC has issued four additional statements underlining its concerns and providing additional examples of how to comply. In 2017, the first action of enforcement was made against individuals failing to adhere to these guidelines. In light of the FTC’s guidelines and pressures to have reviews, businesses must ask which type of affiliated reviewers, if any, are the most influential. As to reviewer credibility, the literature offers contradictory predictions. Through three experiments with a total of 1,077 consumers, the authors examine effects of reviewer affiliation. The findings affirm the spirit of the FTC’s updated guidelines. However, affiliation comes at a cost. Depending on the competitive context, the cost may be worth the benefits.
Drosophila Cryptochrome: Variations in Blue
Authors: Foley Lauren E. , Emery Patrick
Published: October 2019

CRYPTOCHROMES (CRYs) are structurally related to ultraviolet (UV)/blue-sensitive DNA repair enzymes called photolyases but lack the ability to repair pyrimidine dimers generated by UV exposure. First identified in plants, CRYs have proven to be involved in light detection and various light-dependent processes in a broad range of organisms. In Drosophila, CRY’s best understood role is the cell-autonomous synchronization of circadian clocks. However, CRY also contributes to the amplitude of circadian oscillations in a light-independent manner, controls arousal and UV avoidance, influences visual photoreception, and plays a key role in magnetic field detection. Here, we review our current understanding of the mechanisms underlying CRY’s various circadian and noncircadian functions in fruit flies.
Addressing Health and Well-Being Through State Policy: Understanding Barriers and Opportunities for Policy-Making to Prevent Adverse Childhood Experiences (ACEs) in South Carolina
Authors: Srivastav Aditi , Spencer Mindi , Thrasher James F. , Strompolis Melissa , Crouch Elizabeth , Davis Rachel E.
Published: October 2019

Purpose:

As adverse childhood experiences (ACEs) become increasingly recognized as a root cause of unhealthy behaviors, researchers, practitioners, and legislators seek to understand policy strategies to prevent and mitigate its effects. Given the high prevalence of ACEs, policies that address ACEs can meaningfully prevent disease in adulthood and improve population health. We sought to understand barriers and opportunities for policies to prevent and mitigate ACEs by exploring state legislator perspectives.

Setting and Participants:

Twenty-four current state legislators in South Carolina.

Design:

In 2018, we conducted semistructured interviews with 24 state legislators. Participants were recruited using maximum variation sampling. The researchers individually analyzed each interview transcript using focused coding qualitative techniques. A high inter-rater agreement was demonstrated (κ = .76 to .87), and discrepancies were resolved through discussion.

Method:

The data collection and analysis were guided by Multiple Streams Theory, which identifies 3 key components (attention to the problem, decisions about policy options, and the impact of political landscape) that can lead windows of opportunity for passing policies.

Results:

Legislators identified several factors that can influence the passage of legislation on ACEs: awareness of ACEs; gaps in understanding about what can be done about ACEs; the use of data and stories that contextualize the problem of ACEs; capitalizing on the bipartisanship of children’s issues; and linking to current ACEs-related issues on the policy agenda, such as school safety and violence prevention and the opioid epidemic.

Conclusion:

Public health researchers and practitioners should focus on the factors identified to advocate for policies that prevent ACEs and/or address their health consequences.
Entrepreneurial narratives and concept teaching and learning
Authors: Wang Longlong
Published: October 2019

Entrepreneurship education (EE) is facing a tension between practical valence and academic institutionalization. As a consequence, we know very little about how story-based pedagogy is implemented in the classroom, though various entrepreneurial narratives have been institutionalized into EE programs. This article examines how one Chinese teacher thematically constructs six nascent entrepreneurs to illustrate the concept of entrepreneurship in a classroom setting. The findings suggest that the entrepreneurial narratives used by the teacher are different in structure from those reported by entrepreneurship studies, because entrepreneurial stories narrated by teachers are non-participant life stories. This article argues that narrative is an important tool for teachers to personalize their conceptualization of entrepreneurship. Such conceptualization, embedded in both the structure and the content of narratives, facilitates entrepreneurial teaching and learning in a holistic, instantiated, and impactful way. The article also demonstrates that teachers can create additional learning opportunities, by resorting to specific narrative features and thematic construction. It concludes with critical reflections on entrepreneurial narrative, story-based pedagogy, and EE research and calls for more classroom-based research in the field.
On ‘modified human agents’: John Lilly and the paranoid style in American neuroscience
Authors: Williams Charlie
Published: October 2019

The personal papers of the neurophysiologist John C. Lilly at Stanford University hold a classified paper he wrote in the late 1950s on the behavioural modification and control of ‘human agents’. The paper provides an unnerving prognosis of the future application of Lilly’s research, then being carried out at the National Institute of Mental Health. Lilly claimed that the use of sensory isolation, electrostimulation of the brain, and the recording and mapping of brain activity could be used to gain ‘push-button’ control over motivation and behaviour. This research, wrote Lilly, could eventually lead to ‘master-slave controls directly of one brain over another’. The paper is an explicit example of Lilly’s preparedness to align his research towards Cold War military aims. It is not, however, the research for which Lilly is best known. During the 1960s and 1970s, Lilly developed cult status as a far-out guru of consciousness exploration, promoting the use of psychedelics and sensory isolation tanks. Lilly argued that, rather than being used as tools of brainwashing, these techniques could be employed by the individual to regain control of their own mind and retain a sense of agency over their thoughts and actions. This article examines the scientific, intellectual, and cultural relationship between the sciences of brainwashing and psychedelic mind alteration. Through an analysis of Lilly’s autobiographical writings, I also show how paranoid ideas about brainwashing and mind control provide an important lens for understanding the trajectory of Lilly’s research.
Model to predict motion sickness within autonomous vehicles
Authors: Salter Spencer , Diels Cyriel , Herriotts Paul , Kanarachos Stratis , Thake Doug
Published: October 2019

Background:

Motion sickness is common within most forms of transport; it affects most of the population who experience varied symptoms at some stage in their lives. Thus far, there has been no specific method to quantify the predicted levels of motion sickness for a given vehicle design, task and route.

Objective:

To develop a motion sickness virtual prediction tool that includes the following inputs: human motion, vision, vehicle motion, occupant task and vehicle design.

Method:

A time domain analysis using a multi-body systems approach has been developed to provide the raw data for post-processing of vehicle motion, occupant motion and vision, based on a virtual route designed to provoke motion sickness, while the digital occupant undertakes a specific non-driving related task.

Results:

Predicted motion sickness levels are shared for a simple positional sweep of a vehicle cabin due to a prescribed motion and task. Two additional examples are shared within this study; first, it was found that the model can predict the difference found between sitting forwards and backwards in an autonomous vehicle. Second, analysis of a respected and independent study into auxiliary display height shows that the model can predict both relative and absolute levels between the two display heights congruent to the original physical experiment.

Conclusion:

It has been shown that the tool has been successful in predicting motion sickness in autonomous vehicles and is therefore of great use in guiding new future mobility solutions in the ability to tune vehicle dynamics and control alongside vision and design attributes.
Clustered allocation as a way of understanding historical controls: Components of variation and regulatory considerations
Authors: Collignon Olivier , Schritz Anna , Senn Stephen J , Spezia Riccardo
Published: October 2019

There has been increasing interest in recent years in the possibility of increasing the efficiency of clinical trials by using historical controls. There has been a general recognition that in replacing concurrent by historical controls, the potential for bias is serious and requires some down-weighting to the apparent amount of historical information available. However, such approaches have generally assumed that what is required is some modification to the standard inferential model offered by the parallel group trial. In our opinion, the correct starting point that requires modification is a trial in which treatments are allocated to clusters. This immediately shows that the amount of information available is governed not just by the number of historical patients but also by the number of centres and of historical studies. Furthermore, once one accepts that external patients may be used as controls, this raises the issue as to which patients should be used. Thus, abandoning concurrent control has implications for many aspects of design and analysis of trials, including (a) identification, pre-specification and agreement on a suitable historical dataset; (b) an agreed, enforceable and checkable plan for recruiting the experimental arm; (c) a finalised analysis plan prior to beginning the trial and (d) use of a hierarchical model with sufficient complexity. We discuss these issues and suggest approaches to design and analysis making extensive reference to the partially randomised Therapeutic Arthritis Research and Gastrointestinal Event Trial study. We also compare some Bayesian and frequentist approaches and provide some important regulatory considerations. We conclude that effective use of historical data will require considerable circumspection and discipline.
Inference about binocular sensitivity and specificity of screening tests for paired organs
Authors: Tsou Tsung-Shan , Hsiao Wei-Cheng
Published: October 2019

Recently Perera et al. introduced two new binocular accuracy measures to evaluate diagnostic tests for paired organs. They adopted the Gaussian copula model to account for correlation between fellow eyes. As the measures are functions of several joint probabilities and due to the nature of the joint models, variations of the estimates for the two new measures were assessed via bootstrapping. We provide a different approach to inference about the two interesting and innovative measures. In our opinion, when patients are independent, the binomial models suffice for inference about the parameters of interest. Inference becomes simple and straightforward. We perform numerical studies and analyse the data set as of Perera et al. for illustration. Also, we investigate thru simulations the issue of robustness of the Gaussian copula and the binomial models under model misspecification.
Breast Milk Feeding Practices and Barriers and Supports Experienced by Mother–Infant Dyads With Cleft Lip and/or Palate
Authors: Madhoun Lauren L. , Crerand Canice E. , Keim Sarah , Baylis Adriane L.
Published: October 2019

Objective:

To examine trends in breast milk provision and to characterize the breast milk feeding practices experienced by mother–infant dyads with cleft lip and/or palate (CL/P) in a large US sample.

Design:

Cross-sectional study.

Methods:

An online survey was distributed through cleft-related social media sites in the United States and in a single cleft lip and palate clinic. Statistical analyses included Kruskal-Wallis H tests and post hoc Mann-Whitney tests to examine group differences based on cleft type and prenatal versus postnatal cleft diagnosis. Linear regression was used to estimate associations between obtained variables.

Participants:

One hundred fifty biological mothers of infants (8-14 months of age) with CL/P (15% cleft lip, 29% cleft palate, 56% cleft lip and palate).

Results:

Forty-six percent of mothers of infants with CL/P provided breast milk to their infant for at least 6 months. Five percent of infants ever fed at breast, and 43% received pumped breast milk via bottle. The most commonly reported supports included lactation consultants, nurses, feeding therapists, and online support groups. Feeding therapy was received by 48% of infants.

Conclusions:

A lower percentage of mothers of infants with CL/P reported providing breast milk compared to national estimates of the general population of infants without clefting. Results suggested there are multiple barriers, as well as numerous medical and psychosocial supports that facilitated breast milk feeding success. Implications for care are discussed.
Faith-Based Education and SDG4: The Catholic Case
Authors: Patriarca Giovanni , Valentini Diana M.
Published: October 2019

Faith-based education has played a major role worldwide. In its schools, vocational centers, and universities, Catholic education tends to form an integral human person though the holistic synthesis of faith, culture, and life. Such an interrelated commitment highlights a global responsibility for the common good and a sustainable future, sharing the SDG4’s targets and promoting a culture of encounter.
Using a Reflective Diary Method to Investigate the Experiences of Paid Home Care Workers Caring for People With Dementia
Authors: Travers Cheryl , Schneider Justine , Perry-Young Lucy , Wilkinson Samantha , Scales Kezia , Pollock Kristian
Published: October 2019

This article reports on the use of an innovative reflective diary method with paid home care workers caring for people with dementia. It examines the key features of the diary design, recruitment and training of participants, diarists’ approaches and responses to diary-keeping, and evaluates the use of diaries in this context. Following training, 11 volunteers (all female) employed by a U.K.-based home care organization kept diaries of their experiences of caring for those with dementia. Using specially designed diaries, they wrote about their visits to clients for a period of approximately 4 months and were remunerated for up to 16 extra hours at their usual hourly rate of pay. Overall, home care workers engaged well with the process, keeping regular, lengthy, timely, and reflective diary entries. Diary-keeping provided a means for these workers to express their emotions about their work, while enhancing their self-insight and care practices. We demonstrate the feasibility of diaries for research with this occupational group and conclude that the written reflexivity employed in diaries can document, enrich, and improve the work of these caregivers.
School-based physical education: Physical activity and implementation barriers in Vietnamese elementary schools
Authors: To Quyen G , Wharton Lee , Gallegos Danielle , Stylianou Michalis , Do Dung V , To Kien G , Tran Hanh TM , Trost Stewart G
Published: October 2019

Information about the Vietnamese physical education (PE) programme is limited due to a lack of relevant studies. Using the Health Optimising Physical Education as a conceptual framework, this study examined students’ physical activity (PA) levels in the fifth-grade PE programme in Vietnam and barriers to programme implementation. Eight schools (28 PE classes) were randomly selected for assessing students’ PA levels, lesson context, and PA promotion during PE lessons using the System for Observing Fitness Instruction Time. In-depth interviews were also conducted with school administrators, PE instructors, and classroom teachers using semi-structured guides to examine barriers influencing the implementation of the current PE programme. Results showed students spent 33% of PE time in moderate–vigorous physical activity (MVPA), which is less than the international recommendation of 50%. The amount of MVPA varied by school type, instructor gender and qualification. Programme implementation was negatively affected by the current structure that limits autonomy, a proclivity for a “one size fits all” approach to teaching PE, and limited motivation for PE instructors to improve their teaching. The low perceived value of PE, lack of support and professional development for existing PE instructors, and an over-emphasis on sports training due to available financial incentives were also identified as important barriers that affected programme implementation. Addressing these barriers could help improve the quality of the Vietnamese PE programme.
Book review: Ellison, S. H. 2018: Domesticating Democracy: The Politics of Conflict Resolution in Bolivia
Authors: Iyer Soundarya
Published: October 2019

Ellison, S. H. 2018: Domesticating Democracy: The Politics of Conflict Resolution in Bolivia. Durham and London: Duke University Press. 296 pp. US$99.95 (Cloth), US$26.95 (Paperback). ISBN: 978-0-8223-7093-2 (Cloth), 978-0-8223-7108-3 (Paperback).
Book review: Bhabha, J. 2018: Can We Solve the Migration Crisis?
Authors: Pragya KC
Published: October 2019

Bhabha, J. 2018: Can We Solve the Migration Crisis? Cambridge: Polity Press. 140 pp. £35.00 (Cloth), £9.99 (Paperback). ISBN: 978 1 509 51939 2 (Cloth), 978 1 509 51940 8 (Paperback).
Is Spontaneity Overrated? The Value of Cortical Stimulation–Induced Seizures
Authors: Velez-Ruiz Naymee
Published: October 2019

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Effect of Alteplase Administration on International Normalized Ratio in Patients With Acute Ischemic Stroke
Authors: Erdman Michael J. , Davidson K. Erin , Haller J. Tyler , Shah Samarth , Gross Whitney , Andrews Jessica , Patel Alicia , Jones G. Morgan
Published: October 2019

Background/Objective:

Alteplase may elevate international normalized ratio (INR) results, although the exact rate of elevation occurrence is not firmly established in the literature. The purpose of this study is to determine the occurrence rate of INR elevation following alteplase administration. We also aimed to determine what factors are independently associated with the development of elevated INR following alteplase administration for ischemic stroke.

Methods:

We conducted a multicenter, retrospective, cohort study of patients who received alteplase for acute ischemic stroke. Patients were screened for baseline INR measurement and a repeat value within 24 hours of alteplase administration. The primary outcome was the percent of patients who experienced ≥0.4-point increase in INR. Secondary outcomes included the rate of adverse bleeding events and identification of factors independently associated with elevated INR following alteplase administration.

Results and Conclusions:

Two hundred and sixty-one patients were included, with 44 (16.9%) patients having an INR increase of 0.4 or more. Patients with an INR increase ≥0.4 experienced a nonstatistically significant increase in bleeding episodes (8.8% vs 18.2%; P = .10). We identified African American race (odds ratio, 3.48, 95% confidence interval, 1.5-7.6; P = .002) as an independent predictor of INR increase ≥0.04. An INR elevation is common following receipt of alteplase for ischemic stroke. Those of African American race were at increased risk of INR elevation; however, more studies are needed to determine whether these patients are at a higher bleeding risk as a result of INR elevation.
When Voting Becomes Protest: Mapping Determinants of Collective Action Onto Voting Behavior
Authors: Otjes Simon , Stroebe Katherine , Postmes Tom
Published: October 2019

Do people signal protest by bringing out a protest vote when they feel they have been collectively disadvantaged? Political scientists have been interested in “protest voting” yet theoretical understanding is limited. Social psychologists have studied other forms of collective protest extensively. The present study integrates insights from the political science approach to protest voting and the social psychological approach to protest behavior to study how a context of perceived collective disadvantage influences voting for protest parties. We conducted a field study with a quasi-experimental design. This allowed us to study effects of a plausibly exogenous variable—the presence versus absence of societal disadvantage (the experience of man-made earthquakes)—on both determinants of and on subsequent protest voting. Results reveal that the presence of earthquakes affects levels of protest voting via (national) trust, regional identification, and perceptions of efficacy.
Roadblocks and Opportunities to the Implementation of Novel Therapies for Acute Kidney Injury: A Narrative Review
Authors: Misra Paraish S. , Silva e Silva Vanessa , Collister David
Published: October 2019

Background:

Acute kidney injury (AKI) is a complex and heterogeneous clinical syndrome with limited effective treatment options. Therefore, a coherent research structure considering AKI pathophysiology, treatment, translation, and implementation is critical to advancing patient care in this area.

Purpose of review:

In this narrative review, we discuss novel therapies for AKI from their journey from bench to bedside to population and focus on roadblocks and opportunities to their successful implementation.

Sources of information:

Peer-reviewed articles, opinion pieces from research leaders and research funding agencies, and clinical and research expertise.

Methods:

This narrative review details the challenges of translation of preclinical studies in AKI and highlights trending research areas and innovative designs in the field. Key developments in preclinical research, clinical trials, and knowledge translation are discussed. Furthermore, this article discusses the current need to involve patients in clinical research and the barriers and opportunities for effective knowledge translation.

Key findings:

Preclinical studies have largely been unsuccessful in generating novel therapies for AKI, due both to the complexity and heterogeneity of the disease, as well as the limitations of commonly available preclinical models of AKI. The emergence of kidney organoid technology may be an opportunity to reverse this trend. However, the roadblocks encountered at the bench have not precluded researchers from running well-designed and impactful clinical trials, and the field of renal replacement therapy in AKI is highlighted as an area that has been particularly active. Meanwhile, knowledge translation initiatives are bolstered by the presence of large administrative databases to permit ongoing monitoring of clinical practices and outcomes, with research output from such evaluations having the potential to directly impact patient care and inform the generation of meaningful clinical practice guidelines.

Limitations:

There are limited objective data examining the process of knowledge creation and translation in AKI, and as such the opinions and research areas of the authors are significantly drawn upon in the discussion.

Implications:

The use of an organized knowledge-to-action framework involving multiple stakeholders, especially patient partners, is critical to translating basic research findings to improvements in patient care in AKI, an area where effective treatment options are lacking.
Managing Indolent Lymphomas in Relapse
Authors: Cabanillas Fernando , Horning Sandra , Kaminski Mark , Champlin Richard
Published: October 2019

The front-line management of stage IV indolent non-Hodgkin's lymphoma has ranged from the watch-and-wait approach to intensive experimental regimens such as high-dose chemotherapy and bone marrow transplant. With this broad spectrum of regimens to choose from the decision has become a challenging exercise for both patients and oncologists. With the recent introduction of new agents such as rituximab, fludarabine, and combinations based on these, the management of relapsed cases can be similarly confusing. More aggressive approaches such as high-dose chemotherapy with autologous bone marrow transplant and more recently allogeneic bone marrow transplant have also been used. Recently the technique of “mini-allo transplants” has been introduced. It utilizes a less myelosuppressive conditioning chemotherapy regimen based on fludarabine which is immunosuppressive enough to allow engraftment of the donor marrow. Since it is less myelotoxic it is better tolerated, and this has allowed us to significantly extend the age cut-off for allogeneic transplants. All these advances provide us with a more extensive armamentarium, but at the same time they confront physicians with new challenges in choosing from a large and continuously growing therapeutic menu.

In this review of the alternative therapies a panel of three expert hemato-oncologists each discuss their approach to the management of a 49-year-old patient with a relapsed indolent follicular lymphoma. Dr. Horning discusses the traditional alternatives available for this patient such as standard chemotherapy combinations or the watch-and-wait approach in Section I. In Section II, Dr. Kaminski reviews the different therapeutic monoclonal antibody options such as rituximab, Bexxar (Iodine-labeled anti-CD20) and Ytrium-labeled anti-CD20 antibody. Allogeneic transplants are increasingly more popular for the treatment of indolent lymphomas because they can provide an immune-mediated graft-versus-lymphoma effect. In Section III, Dr. Richard Champlin reviews various transplant options including autologous, allogeneic and mini-allogeneic transplants.
Hodgkin's Lymphoma
Authors: Linch David C. , Gosden Roger G. , Tulandi Togas , Tan Seang-Lin , Hancock Stephen L.
Published: October 2019

This review focuses on the different treatment options available for the treatment of Hodgkin's disease, with an emphasis on the importance of the long-term sequelae of these therapies.

In Section I, Dr. Linch reviews the current status of Hodgkin's disease treatment. Survival rates have improved over the last three decades due both to better initial therapies and associated supportive care and to the success of salvage therapy. Unlike most other malignancies, a similar survival endpoint can be achieved by different means, e.g., intensive initial therapy resulting in a low relapse rate or less intensive initial therapy and more reliance on salvage therapy. Overall survival has thus become a difficult end-point for clinical trials of primary therapy, and the value of disease-free survival as an end-point can also be questioned. Quality-of-life issues are to the fore of clinical decision and include the psychological trauma of relapse and fertility status. Patient choice is increasingly important. The high level of success in treating Hodgkin's disease also means that attention must be focused on the very long term results and in this context the occurrence of second malignancies is a major issue.

In Section II, Dr. Gosden with Dr. Tulandi and Dr. Tan review the risks of infertility following radio-therapy and chemotherapy and address the actions that can be taken to overcome this problem, particularly for females and prepubertal boys and girls. Particular attention is paid to the recent developments in ovarian cryopreservation and harvesting immature germ cells.

In Section III, Dr. Hancock gives a comprehensive update of the incidence of secondary acute leukemia, non-Hodgkin's lymphoma and solid tumors in a large population of patients treated for Hodgkin's disease. The roles of radiotherapy, chemotherapy and combined modality treatment as risk factors contributing to the development of these secondary malignancies are reviewed. The importance of efforts to prevent late-occurring solid tumors such as lung cancer through smoking cessation programs and early detection by screening for cancers of the breast, thyroid and skin are emphasized.
Bone Marrow Transplantation for Non-Malignant Disease
Authors: Sullivan Keith M. , Parkman Robertson , Walters Mark C.
Published: October 2019

This article reviews the experience in hematopoietic stem cell transplantation (HSCT) for non-malignant disease. HSCT has long been applied as treatment of life-threatening congenital immunodeficiency and metabolic diseases. In Section I, Dr. Parkman reviews that experience for severe combined immunodeficiency, Wiscott-Aldrich syndrome, hyper IGM syndrome, Chédiak-Higashi disease and hereditary lymphohistiocytosis. The value of HSCT in genetic metabolic diseases such as osteopetrosis, osteogenesis imperfecta and the storage diseases are reviewed. In Section II, Dr. Walters reviews the experience over the last decade with allogeneic stem cell transplantation in patients with thalassemia major and sickle cell disease. In Section III, Dr. Sullivan reviews the more recent investigations using stem cell transplantation in patients with advanced autoimmune diseases such as systemic sclerosis, systemic lupus erythematosus, multiple sclerosis and juvenile rheumatoid arthritis. The pathogenesis and outcome with conventional care of these patients, the selection criteria and current results for HSCT, and the future directions in clinical research and patient care using this modality are addressed.
Current Approaches to the Management of Hemochromatosis
Authors: Brissot Pierre , de Bels Frédéric
Published: October 2019

The term hemochromatosis encompasses at least four types of genetic iron overload conditions, most of them recently distinguished from one another as a result of the identification of a series of genes related to iron metabolism. At least three of these entities (HFE hemochromatosis, juvenile hemochromatosis and transferrin receptor 2 hemochromatosis) involve systemic hepcidin deficiency as a key pathogenetic factor. Major advances in the management of hemochromatosis influence the diagnostic approach to the disease, with the development of an overall non invasive strategy, mainly based on clinical, biological (iron parameters and genetic testing), and imaging (especially magnetic resonance imaging) data. Therapeutic management remains, on the curative side, dominated by phlebotomy (venesection), practical aspects of which have been recently revisited by the Guidelines Department of the French “Haute Autorité de Santé.” However, innovative treatment approaches, based on the improved pathophysiological understanding of these diseases and the progress in iron chelation therapy, are emerging. Preventive therapy, focused on family screening, remains a key part of the management of hemochromatosis.
Pathobiology and Molecular Profiling of Peripheral T-Cell Lymphomas
Authors: de Leval Laurence , Gaulard Philippe
Published: October 2019

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare diseases, usually manifesting clinical aggressiveness. Although important novel insights into the pathobiology of nodal PTCL have been gained recently from molecular profiling studies and clinico-pathological analyses, the pathogenetic molecular lesions remain to be deciphered for most entities. Angioimmunoblastic T-cell lymphoma (AITL) comprises CD4+ CXCL13+ neoplastic cells displaying overlapping immunophenotypical and molecular features with normal follicular helper T cells. This derivation might account for the presence of a prominent non-neoplastic component in AITL tissues and the clinical manifestations of the disease reflective of an immunological dysfunction. ALK+ anaplastic large cell lymphoma (ALCL), defined by ALK gene translocation with various gene partners, is composed of CD30+ ALK+ cells with a cytotoxic phenotype and usually carries a good prognosis. ALK– ALCL, now considered as a distinct disease entity, is morphologically and immunophenotypically similar to ALK+ ALCL, except for ALK expression, but has distinctive molecular features. PTCL, not otherwise specified (PTCL, NOS), the largest PTCL category, which is derived from activated CD4+ (or CD8+) T cells, is markedly heterogeneous, including at the molecular level. Gene expression profiling approaches have identified novel biomarkers of potential therapeutic interest, and suggest the existence of molecularly distinct PTCL, NOS subgroups.
Making a diagnosis of VWD
Authors: Branchford Brian R. , Di Paola Jorge
Published: October 2019

A clear understanding of the molecular basis of VWD can guide the choice and interpretation of appropriate diagnostic tests. This review briefly describes the lifecycle and molecular interactions of VWF and how they lead to the current clinical classification. It also includes a brief discussion of the differential diagnosis and general workup of mucocutaneous bleeding, a review of the various VWD subtypes, and pertinent laboratory assays for each, including genetic tests. Finally, common testing pitfalls and diagnostic dilemmas are covered, including the challenge created by the overlap of borderline low VWF levels and mild bleeding.
Childhood immune thrombocytopenia: role of rituximab, recombinant thrombopoietin, and other new therapeutics
Authors: Journeycake Janna M.
Published: October 2019

Childhood immune thrombocytopenia (ITP) is often considered a benign hematologic disorder. However, 30% of affected children will have a prolonged course and 5%-10% will develop chronic severe refractory disease. Until recently, the only proven therapeutic option for chronic severe ITP was splenectomy, but newer alternatives are now being studied. However, because immunosuppressive agents such as rituximab are not approved for use in ITP and the thrombopoietin receptor agonists are not yet approved in children, the decision to use alternatives to splenectomy needs to be considered carefully. This review describes the factors that should affect decisions to treat ITP at diagnosis and compares the options for the occasional child in whom ITP does not resolve within the first year.
Dos and don'ts in diagnosing antiphospholipid syndrome
Authors: Rand Jacob H. , Wolgast Lucia R.
Published: October 2019

Antiphospholipid syndrome (APS) is an acquired autoimmune thrombotic tendency that is identified by the presence of abnormal antiphospholipid laboratory tests in patients who have a history of vascular thrombosis and/or pregnancy complications including recurrent spontaneous miscarriages and a group of other complications due to placental insufficiency. Diagnostic testing for APS is often problematic because of many misconceptions regarding these empirically derived assays. This chapter is intended to provide hematology-oncology consultants with practical information about the uses and limitations of assays used to diagnose APS.
Coagulation assays and anticoagulant monitoring
Authors: Funk Dorothy M. (Adcock)
Published: October 2019

Anticoagulant therapy, including conventional agents and a variety of new oral, fast-acting drugs, is prescribed for millions of patients annually. Each anticoagulant varies in its effect on routine and specialty coagulation assays and each drug may require distinct laboratory assay(s) to measure drug concentration or activity. This review provides an overview of the assorted assays that can measure anticoagulant drug concentration or activity and includes key assay interferences. The effect of these conventional and new anticoagulant agents on specialty coagulation assays used to evaluate for bleeding or clotting disorders, and whether this impact is physiological or factitious, is included. Also provided is a short review of superwarfarin poisoning and features distinguishing this from warfarin overdose. Knowledge of clinically significant pearls and pitfalls pertinent to coagulation assays in relation to anticoagulant therapy are important to optimize patient care.
Thrombocytopenia, bleeding, and use of platelet transfusions in sick neonates
Authors: Stanworth Simon J.
Published: October 2019

Survival rates for infants born prematurely have improved significantly, in part due to better supportive care such as RBC transfusion. The role of platelet transfusions in neonates is more controversial. Neonatal thrombocytopenia is common in premature infants. The primary causal factors are intrauterine growth restriction/maternal hypertension, in which the infant presents with thrombocytopenia soon after birth, and sepsis/necrotizing enterocolitis, which are the common morbidities associated with thrombocytopenia in neonates > 72 hours of age. There is no evidence of a relationship between platelet count and occurrence of major hemorrhage, and cardiorespiratory problems are considered the main etiological factors in the development of intraventricular and periventricular hemorrhage in the neonatal period. Platelet transfusions are used commonly as prophylaxis in premature neonates with thrombocytopenia. However, there is widespread variation in the pretransfusion thresholds for platelet count and evidence of marked disparities in platelet transfusion practice between hospitals and countries. Platelet transfusions are biological agents and as such are associated with risks. Unlike other patient groups, specifically patients with hematological malignancies, there have been no recent clinical trials undertaken comparing different thresholds for platelet transfusion in premature neonates. Therefore, there is no evidence base with which to inform safe and effective practice for prophylactic platelet transfusions. There is a need for randomized controlled trials to define the optimal use of platelet transfusions in premature neonates, who at present are transfused heavily with platelets.
Is there a role for warfarin anymore?
Authors: Jacobson Alan
Published: October 2019

Reduction of atrial fibrillation–associated stroke risk has become the leading indication for warfarin use. Optimal management of warfarin can only be achieved with a relatively complex infrastructure. Alternative anticoagulant agents have been developed, and 3 have demonstrated effectiveness, safety, and adherence that are comparable or superior to warfarin in the clinical trial setting. None of the novel agents requires routine laboratory testing to demonstrate effective anticoagulation. Whereas these new agents present potential advantages, such as fixed dosing and dramatically reduced intracranial hemorrhaging, they are also subject to caveats that ought to be considered in the context of an “ideal” anticoagulant. If used casually, they have the potential to worsen rather than improve health care outcomes. There is little question that the management burden of the novel agents will be less than with warfarin. However, with a hemorrhagic risk that was similar to warfarin in these trials, there will likely remain a significant need for both baseline education and some level of focused interval follow-up to assess for bleeding risk and adherence considerations. These novel agents offer a definite advance in the available management options for thromboembolic disease, but until we understand the requirements for safe and effective use in the routine clinical setting, we will not be able to establish the extent to which they should replace warfarin.