bluuebunny/crossref_metadata_2025 huggingface dataset:
‘By our metaphors you shall know us’: The ‘fix’ of geographical political economy
Authors: Bok Rachel
Published: October 2018

This paper traces the transformative travels of the metaphor of the ‘fix’ across the unbounded terrain of geographical political economy. It argues for taking the fix seriously as a root metaphor of the field, a signifier of its history and theory-cultures. Critically excavating the entwined genealogies of the metaphor and the field, it illuminates several historically successive and thematic moments of ‘fix thinking’, including: the spatial fix (1980s); institutional and spatio-temporal fixes of regulationist-theoretical approaches (1990s); and the scalar fix of state rescaling theory (2000s). It reviews these stages and their broader intellectual and political implications for critical geographical scholarship.
River stresses in anthropogenic times: Large-scale global patterns and extended environmental timelines
Authors: Macklin Mark G , Lewin John
Published: October 2018

Global perspectives on the complexities of environmental change impacts associated with past and present human activity are needed for the food and water security challenges of the twenty-first century. This is especially true for rivers, for which the onset and persistence of a range in human activities, altering their function and form, have been temporally and spatially variable. Ancient civilisations, states and empires extended geographically to cover sub-continental areas where their river modifying activities became linked to regional Earth system stresses arising from climate and land use change. We present a new interpretative framework for characterising and classifying human impact on river systems, emphasising that this has taken place over decadal to millennial time periods on a sub-continental scale. This 16-element classification and documentation of different human transformations, including land management, urbanisation, industry and engineering activities, is used to explore anthropogenic channel and floodplain disruptions that have followed each other in different sequences in different places. It is significant that these inadvertent and deliberate human interventions have also taken place in parallel with contrasting climatic fluctuations that have been sub-continental in scale and varied in time. We assess the influence of the dominant modes of regional climate variability (monsoons, El Niño Southern Oscillation, Indian Ocean Dipole, North Atlantic Oscillation, Pacific Decadal Oscillation and Siberian High) on the speed and pattern of river system adjustment to anthropogenic perturbations. Some river civilisations have proved resilient to change given their adaptive management, while others have been overwhelmed by climate-related changes in river morphodynamics. We conclude that integrated socioeconomic, climatic and hydromorphological histories provide usefully instructive antecedents for sensibly managing, as they evolve, the even more serious coupled environmental stresses likely in the future.
Autologous Chondrocyte Implantation and Tibial Tubercle Osteotomy for Patellofemoral Chondral Defects: Improved Pain Relief and Occupational Outcomes Among US Army Servicemembers
Authors: Zarkadis Nicholas J. , Belmont Philip J. , Zachilli Michael A. , Holland Courtney A. , Kinsler Allison R. , Todd Michael S. , Pallis Mark P. , Waterman Brian R.
Published: October 2018

Background:

The occupational and functional results of patellofemoral autologous chondrocyte implantation (ACI) are underreported. This investigation sought to establish clinical outcomes and rates for return to work in a predominantly high-demand military cohort undergoing this procedure.

Purpose:

To determine the return-to-work, pain relief, and perioperative complication rates in a high-demand athletic cohort undergoing patellofemoral ACI.

Study Design:

Case series; Level of evidence, 4.

Methods:

All military servicemembers from 2 military medical centers undergoing ACI for high-grade patellofemoral chondral defects between 2006 and 2014 were identified, and data were abstracted from their medical records and clinical databases. Demographic and surgical variables were obtained for patients with at least 2 years of postoperative follow-up, and perioperative complications, rates of return to work, and survivorship from revision were quantified.

Results:

Seventy-two patients (72%) had >2-year follow-up and had patellofemoral ACI for high-grade chondral defects, with 66 knees (91%) undergoing a concomitant offloading tibial tubercle osteotomy. Mean follow-up was 4.3 years (range, 2.0-9.9 years). The mean ± SD age was 34.4 ± 6.1 years; 86% were male; and 57% were involved in military occupational specialties of heavy or very heavy demand. Second-generation patellofemoral ACI with a type I/III collagen membrane was used for 85% of knees. Most defects were isolated to the patella (n = 40, 55%). The mean total defect surface area was 4.5 ± 2.9 cm2 (range, 2.7-13.5 cm2). Fifty-six servicemembers (78%) returned to their occupational specialties. Three patients (4.1%) were classified as having surgical failures, requiring subsequent knee arthroplasty (n = 2) or a revision chondral procedure (n = 1). Mean visual analog scores improved significantly from 6.5 ± 1.5 to 3.2 ± 2.1 ( P < .0001). Multivariate analysis identified use of a periosteal patch as the only significant independent predictor for surgical ( P = .013) and overall ( P = .033) failures. Age <30 years ( P = .019), female sex ( P = .019), and regular tobacco use ( P = .011) were independent predictors of overall failure.

Conclusion:

For patellofemoral chondral defects without a failed primary procedure, second-generation ACI successfully returned to work 78% of patients of moderate to very heavy occupational demand with significantly decreased patient-reported knee pain. Risk factors after ACI for patellofemoral articular lesions for overall failure were age <30 years, female sex, and tobacco use, while surgical and overall failures were associated with periosteal patch use.
Role of particle size in assessment of physico-chemical properties and trace elements of Indian fly ash
Authors: Kumar Satish , Singh Jashanpreet , Mohapatra S. K.
Published: October 2018

In this paper, the effect of particle size on the physico-chemical, mineralogical, and leaching behavior of Indian fly ash was studied. Experiments were carried out to study the leaching of different elements such as Mg, Cr, Zn, Pb, Mn, Fe, Cu, Co, Mo, and Ni from Indian fly ash. During the experiments, the liquid-to-solid (L/S) ratio of the fly ash was taken as 9/1, 8/2, 7/3, 3/2, 1/1, and 2/3. The effect of four different particle size ranges (below 53, 53–75, 75–106, and 106–150 μm) of fly ash was analyzed. The ASTMD-3987 method was used to analyze the presence of trace elements from fly ash. In the ASTM D-3987 method, distilled water was used for extraction of leachate. Fly ash slurry samples were agitated in a lubricating type temperature-controlled Remi orbital shaker for a time duration of 18 hours with speed of 100 revolutions per minute (rpm) at a temperature of 25ºC. Distilled water does not save cost as well as being easily available. The leaching test of trace elements from fly ash was investigated at different pH conditions in order to predict the environmental effect from the ash disposal on the groundwater quality. Results revealed that pH of slurry suspension increases with increase in particle size. The pH value of fly ash slurries was negligibly affected by the decrease in L/S ratio for all particle sizes. Fine particles of fly ash produce a more harmful effect as compared to the coarser range of fly ash particles.
Transborder identities, bias, and third-party conflict management
Authors: Yazici Emir
Published: October 2018

Which third parties are more likely to manage interstate conflicts? Once they do, what kind of conflict management methods do they use? I argue that ethnic, language, and/or religious ties between a potential third party and disputant states can affect both the likelihood and the type of conflict management. If there are strong identity ties (ethnic, language, and/or religious) between the majority group in a potential third-party state and the majority group in one of the disputant states, both the likelihood of conflict management in general and the likelihood of economic conflict management in particular should increase. Equally stronger identity ties between a potential third party and both disputants should also increase the likelihood of conflict management in which third parties use verbal and diplomatic conflict management methods since they do not harm any of the disputants. Empirical findings based on a dataset covering the militarized interstate disputes between 1946 and 2011 support my theoretical expectations. These findings contribute to the literature by exploring the role of transborder identities—in addition to material factors such as alliance, trade partnership, or joint regime type—in management of interstate conflicts by third parties.
Enabling cultural safety in Indigenous primary healthcare
Authors: Muise Gertie Mai
Published: October 2018

The Aboriginal Health Access Centre (AHAC) and Aboriginal Community Health Centre Model of Wholistic Health and Wellbeing is critical to addressing inequities and barriers that limit access to comprehensive primary healthcare for Indigenous people. Even with this model in place, there are multiple points of intersection with mainstream healthcare service providers across health sectors. Further, there is considerable cultural diversity among Indigenous healthcare staff and professional groups. These factors place Indigenous people at risk of culturally unsafe experiences causing harm. Given this, it is essential that leaders focus on cultural safety education to address both intercultural frictions within the Indigenous centres and systemic and structural racism widespread within the broader healthcare system. This article explores how one AHAC has undertaken to examine these complex challenges, while offering some direction on leadership within the sector.
Thermal degradation kinetics of PP/PLA nanocomposite blends
Authors: Mandal Dev K , Bhunia Haripada , Bajpai Pramod K
Published: October 2018

In this article, the effect of adding polylactide (PLA) and nanoclay on the thermal stability of polypropylene (PP) films was analyzed using thermogravimetric analysis. The thermal degradation kinetic parameters such as activation energy ( Ea), order of reaction ( n), and frequency factor (ln ( Z)) of the samples were studied over a temperature range of 30–550°C. Analyses were performed under nitrogen atmosphere with four different heating rates (i.e. 5, 10, 15, and 20°C min−1). The Ea was calculated by Kissinger, Kim–Park, and Flynn–Wall methods. The Ea value of PP was much higher than PLA, whereas the addition of PLA and nanoclay in PP decreased the Ea. The addition of compatibilizer increased the compatibility and Ea of blended films upto some extent. The lifetime of PP was found to be decreased with the addition of PLA and nanoclay. Studies indicated that the thermal degradation behavior and lifetime of the investigated samples depend on the fractions of constituents and heating rates.
Nonlinear stability of CNT-reinforced composite cylindrical panels with elastically restrained straight edges under combined thermomechanical loading conditions
Authors: Trang Le Thi Nhu , Van Tung Hoang
Published: October 2018

This article investigates the nonlinear stability of composite cylindrical panels (CPs) reinforced by carbon nanotubes (CNTs), resting on elastic foundations and subjected to combined thermomechanical loading conditions. CNTs are embedded into matrix phase through uniform distribution or functionally graded distribution. Material properties of constituents are assumed to be temperature dependent and effective elastic moduli of carbon nanotube–reinforced composite are estimated by the extended rule of mixture. Nonlinear governing equations of geometrically imperfect panels are based on first-order shear deformation theory accounting for elastic foundations and tangential constraint of straight edges. Analytical solutions are assumed to satisfy simply supported boundary conditions and closed-form expressions relating load and deflection are derived through Galerkin method. Numerical examples show the effects of preexisting nondestabilizing loads, distribution patterns, panel curvature, in-plane condition of unloaded edges, thermal environments, initial imperfection, and elastic foundations on the nonlinear stability of nanocomposite CPs under combined loading conditions.
Numerical and experimental analysis of single tie push tests on different shapes of concrete sleepers in ballasted tracks
Authors: Jing GQ , Aela P , Fu H , Yin H
Published: October 2018

The lateral displacement of sleepers is one of the key issues in railroads, which is caused by different factors such as the geometry of the ballast layer as well as the shape of the sleepers. Several methods have been proposed to improve the lateral resistance of sleepers on ballasted tracks. In this paper, a series of single tie push tests have been carried out to assess the performance of end-winged, middle-winged, and bumped sleepers on ballasted tracks with a variety of shoulder ballast widths and heights. Based on the experimental results, 500 mm and 150 mm were proposed as the optimum shoulder width and height, respectively. In addition, among the abovementioned sleepers, the EW_sleeper shows a significant increase in the total lateral resistance. Discrete element method (DEM) simulations were performed using PFC3D to determine the optimum size of the EW_sleeper wings. It was found that using a pair of wings measuring 14 cm in length and 13 cm in width can increase the lateral resistance compared to other alternatives.
Suboptimal trajectory programming for unmanned aerial vehicles with dynamic obstacle avoidance
Authors: Guo Hang , Fu Wen-xing , Fu Bin , Chen Kang , Yan Jie
Published: October 2018

With regard to the dynamic obstacles current unmanned aerial vehicles encountered in practical applications, an integral suboptimal trajectory programming method was proposed. It tackled with multiple constraints simultaneously while guiding the unmanned aerial vehicle to execute autonomous avoidance maneuver. The kinetics of both unmanned aerial vehicle and dynamic obstacles were established with appropriate hypotheses. Then it was assumed that the unmanned aerial vehicle was faced with terminal constraints and control constraints in the whole duration. Meanwhile, the performance index was established as minimum control efforts. The initial trajectory was generated according to optimized model predictive static programming. Next, the slack variables were introduced to transform the inequality constraints arising from dynamic obstacle avoidance into equality constraints. In addition, sliding mode control theory was utilized to determine these slack variables' dynamics by designing the approaching law of sliding mode. Then the avoidance trajectory for single or multiple dynamic obstacles was developed by this combined method. At last, a further trajectory optimization was conducted by differential dynamic programming. Consequently, the integral problem was solved step by step and numerical simulations demonstrated that the integral method possessed high computational efficiency.
A new age-period-cohort model for cancer surveillance research
Authors: Rosenberg Philip S
Published: October 2018

We develop a new age-period-cohort model for cancer surveillance research; the theory and methods are broadly applicable. In the new model, cohort deviations are weighted to account for the variable number of periods that each cohort is observed. Weighting ensures that the fitted rates can be naturally expressed as a function of age × a function of period × a function of cohort. Furthermore, the age, period, and cohort deviations are split into orthogonal quadratic components plus higher-order terms. These decompositions enable powerful combination significance tests of first- and second-order age, period, and cohort effects. The regression parameters of the orthogonal quadratic polynomials (global curvatures) quantify how fast on average the trends in the rates are changing. Importantly, the global curvature for cohort determines the least squares slope of the expected annual percentage changes by age group versus age (local drifts), thereby providing a powerful one-degree-of-freedom test of age-period interactions. We introduce new estimable functions, including age gradients that quantify the rate of change of the longitudinal and cross-sectional age curves at each attained age, and gradient shifts that quantify how the cross-sectional age trend varies by period. We illustrate the new model using nationally representative multiple myeloma incidence. Comprehensive proofs are given in technical appendices. We provide an R package.
Facilitators and Barriers of Participation in “Uptime” Activities in Girls and Women With Rett Syndrome: Perspectives From Parents and Professionals
Authors: Stahlhut Michelle , Esbensen Bente Appel , Larsen Jane Lunding , Bisgaard Anne-Marie , Downs Jenny , Nordmark Eva
Published: October 2018

Rett syndrome (RTT) is a rare neurodevelopmental disorder usually affecting females. It is associated with intellectual and multiple disabilities leading to a high level of dependency in all aspects of daily living including participation in physical activities. This study explored facilitators and barriers to “uptime” (non-sedentary) activities in Danish girls and women with RTT as perceived by parents and professionals using focus groups. Through thematic analysis, one central theme emerged: a constant balance to do the best thing for the girl or woman. Within the central theme, five subthemes of facilitators and barriers were identified relating to the individual and the physical, organizational, social, and attitudinal environments. Environmental barriers can be reduced through policy and management-level changes in health promotion and strong advocacy of physical activity by health professionals. Targeting both facilitators and barriers of “uptime” activities enables the planning and implementing of health-promoting interventions in individuals with RTT.
Development and Preliminary Evaluation of a Pain Management Manual for Hospice Providers to Support and Educate Family Caregivers
Authors: Chi Nai-Ching , Han Soojeong , Barani Emelia , Parker Oliver Debra , Washington Karla T. , Lewis Frances Marcus , Walker Amy , Demiris George
Published: October 2018

Background:

Family caregivers encounter many barriers to managing patients’ pain in the home hospice setting. However, there are limited clinically applicable resources for hospice providers to help family caregivers identify and address these barriers.

Aim:

To develop a pain management manual for hospice providers to support family caregivers and conduct a preliminary providers’ evaluation of the manual.

Design and Participants:

A pain management manual was developed and structured into 3 parts: (1) 5 common pain management case scenarios based on a secondary data analysis of a hospice clinical trial; (2) a list of suggested assessment questions and strategies for each case scenario was developed based on a caregiver framework; and (3) pain educational material was included from established clinical guidelines. The manual was vetted by 5 experts and then was evaluated by interviewing 25 hospice providers. Interview data were analyzed using thematic analysis.

Results:

The hospice providers found that the manual could potentially serve as a reference in their practice and be a source for their continuing education. They suggested enhancing the clarity of the case scenarios and adding additional strategies to the manual. Moreover, they suggested expanding the paper-based version and developing a web-based platform to deliver the content would maximize its utility.

Conclusions:

The manual has the potential to be integrated into routine hospice care to improve the quality of pain management.
The making of professional values in the age of accountability
Authors: Afdal Hilde Wågsås , Afdal Geir
Published: October 2018

Changing conditions in the realm of teacher professionalism have consequences for teachers’ professional values and ethics. To a large degree, the literature concludes that increases in accountability policies seem to result in more restricted space for teachers’ professional values and ethical autonomy. Less attention has been given to which kinds and forms of ethics and value logics teachers negotiate and prefer in situations involving accountability policies. In this paper, we analyze how the Union of Education Norway negotiated teacher values in the process of developing their professional ethics code and the final code text. Previous research has shown clashes and struggles between two value systems, or as a change from traditional professional to neoliberal values. However, based on the analyses in this article, a third relation is suggested—one where increased accountability creates a paradoxical situation for teachers’ professional values and ethics—in which the professional ethics of opposition may analytically empty teacher practice of ethical aspects and where professional ethics of engagement may lead to decreased conditions for ethical engagement.
Synthesis and characterization of fluoro-silicone polyacrylate latex emulsified with novel green surfactants
Authors: Chen Lijun , Shao Tantan , Gong Yilu
Published: October 2018

The novel fluoro-silicone polyacrylate latex was successfully synthesized in the presence of a novel green mixed emulsifier of β-cyclodextrin ( β-CD) and sodium lauroyl glutamate (SLG) by semi-continuous seeded emulsion polymerization, which was initiated with potassium persulphate. Methyl methacrylate (MMA) and butyl acrylate (BA) were used as the main monomers, while hexafluorobutyl methacrylate (HFMA) and vinyltriethoxysilane (VTES) were used as the functional monomers. The resultant latex and its film were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry and contact angle determinator, respectively. The optimum conditions of preparing the fluoro-silicone polyacrylate latex are as follows: the amount of compound emulsifiers are 7.0%; β-CD: SLG = 1:2; the amount of initiator is 0.7%; the appropriate proportion of main monomer of MMA: BA = 1:1; and the amounts of HFMA and VTES are 6.0% and 4.0%, respectively. In this case, the resultant latex has high conversion rate, low gel rate and good stability. Results showed that both thermal stability and hydrophobic property of the latex are improved with the incorporation of a small amount of HFMA and VTES.
Valuing Play in Survivor: A Constructionist Approach to Multiplayer Games
Authors: Carter Marcus
Published: October 2018

The U.S. televised game Survivor is fascinating for the study of multiplayer games because the winner of a season of Survivor is not dictated by the rules. Instead, a “jury” of eliminated players vote for which of the remaining two to three contestants deserve to win the US$1,000,000 prize, based entirely on their personal opinion. In this article, I present an analysis of Final Tribal Council, where this decision is made, revealing the key themes that influence this decision. I subsequently propose a social constructionist approach to understanding and researching multiplayer games as moral economies, where diverse types of play are given different values by players. I argue that this approach provides a useful theoretical framework for an integrated understanding of how both game and nongame elements work to influence player behavior and experience.
Opioid prescribing and dispensing: Experiences and perspectives from a survey of community pharmacists practising in the province of Quebec
Authors: Dubé Pierre-André , Vachon Julien , Sirois Caroline , Roy Élise
Published: October 2018

Background:

Canada leads in opioid prescription and consumption rates, and this has resulted in high levels of opioid-related morbidity and mortality. Pharmacists’ input could contribute significantly to understanding the disadvantages of opioid prescribing and dispensing and improving the service. This study aimed to examine the experiences of community pharmacists in relation to opioid prescribing and dispensing, with a focus on optimizing collaboration and communication.

Methods:

An online survey was performed among pharmacists from the province of Quebec, Canada, in 2016. Pharmacists were eligible if registered and working in community pharmacies.

Results:

In all, 542 questionnaires were analyzed (participation rate of 8.1%). Pharmacotherapy-related problems were reported in at least 50% of opioid prescriptions: additional drug(s) required (reported by 30% of pharmacists), interaction(s) between opioid(s) and other drug(s) (16%), physician did not meet the general issuing standards for opioid prescriptions (26%) and patient had mild to moderate pain that was easily managed by a nonopioid analgesic (20%). Half of the patients were reported as requesting anticipated refills, possibly indicating abuse or poor pain control. Most pharmacists (89.6%) reported needing to contact physicians in 1 to 3 out of 10 opioid prescriptions, but many pharmacists (71.8%, often or very often) reported difficulties communicating with physicians.

Conclusions:

Pharmacists’ observations of pharmacotherapy-related problems and patients’ unusual behaviours reveal a significant number of issues related to opioid prescribing and dispensing in an outpatient setting. Improved collaboration between physicians and pharmacists appears mandatory to address the issues reported in this study.
Novel Bluetooth-Enabled Tubeless Insulin Pump: A User Experience Design Approach for a Connected Digital Diabetes Management Platform
Authors: Pillalamarri Sandhya S. , Huyett Lauren M. , Abdel-Malek Aiman
Published: October 2018

Background:

Medical device technology is evolving at a rapid pace, with increasing patient expectations to use modern technologies for diabetes management. With the significant expansion of the use of wireless technology and complex, securely connected digital platforms in medical devices, end user needs and behaviors have become essential areas of focus.

Methods:

This article provides a detailed description of the user-centered design approach implemented in developing the Omnipod DASH™ Insulin Management System (Insulet Corp., Billerica, MA) Bluetooth®-enabled locked-down Android device handheld controller (Personal Diabetes Manager, PDM). Key methodologies used in the PDM design are described, including how the science of user experience (UX) was integrated into new agile product development. UX methods employed included heuristic evaluations of insulin pumps, iterative formative usability testing, information architecture studies, in-home ethnographic visits, participatory design activities, and interviews.

Results:

Over 343 users participated in UX research and testing. Key design choices informed by UX research included updating the layout of critical data on the PDM home page, providing access to requested contextual information while a bolus is in progress, and creating an easy-to-understand visual of a 24-hour basal program. Task completion rates for comprehending information on the PDM home page were 87% or greater. The System Usability Scale result for the design prior to limited market release was 84.4 ± 13.4 (out of 100; n = 37).

Conclusions:

The UX process described in this article can serve as a blueprint for medical device manufacturers seeking to enhance product development. Adopting UX research methodologies will help ensure that new diabetes devices are safe, easy-to-use, and meet the needs of users.
Islam and the Question of Confessional Religious Identity: The Islamic State, Apostasy, and the Making of a Theology of Violence
Authors: Kumar H. M. Sanjeev
Published: October 2018

The Islamic State (ISIS) has sought to realign the role of public religion in the modern secular space by proclaiming to contest all forms of apostasy and re-interrogate the conceptual formulations of belief/unbelief in Islam. Through such quests for realignment, it has sought to revive the medieval debate on the question of confessional religious identity which involved definitional disputations concerning true Muslims. The debate surfaced during the formative phase of the Muslim society and led to the engendering of competing sectarian religiosities. For the Islamic State, its urge for reviving this medieval discourse on confessional religious identity of Muslims is embedded in a romantic vision of the abode of pure Islam, to be inhabited only by true Muslims. However, such a geopolitical imaginary is deeply grounded in a sectarian Sunni political ontology coupled with a prejudicial interpretation of jihad. To accomplish its objectives and for enunciating the attributes of the land of pure Islam, the organization has transformed the Qur’an, which is in the intransitive form, into a transitive form so as to theologize the sacred text into a radical instrument of violence. It has also attempted to transfigure the spiritual character of Islam, referred to as the deen (a pluralistic system), into a cult.
Does Violent Protest Backfire? Testing a Theory of Public Reactions to Activist Violence
Authors: Simpson Brent , Willer Robb , Feinberg Matthew
Published: October 2018

How do people respond to violent political protest? The authors present a theory proposing that the use of violence leads the general public to view a protest group as less reasonable, a perception that reduces identification with the group. This reduced identification in turn reduces public support for the violent group. Furthermore, the authors argue that violence also leads to more support for groups that are perceived as opposing the violent group. The authors test this theory using a large ( n = 800) Internet-based survey experiment with a politically diverse sample. Participants responded to an experimental scenario based on recent violent confrontations between white nationalist protesters and antiracist counter-protesters, allowing the authors to study whether violent protest would reduce public support even when used against a widely reviled group. The authors found that the use of violence by an antiracist group against white nationalists led to decreased support for the antiracist group and increased support for the white nationalist group. Furthermore, the results were consistent with the theorized causal process: violence led to perceptions of unreasonableness, which reduced identification with and support for the protest group. Importantly, the results revealed a striking asymmetry: although acts of violence eroded support for an antiracist group, support for white nationalist groups was not reduced by the use of violence, perhaps because the public already perceives these groups as very unreasonable and identifies with them at low levels. Consistent with this interpretation, the authors found that self-identified Republicans, a subset of the sample that reported less extremely negative views of white nationalists, showed reduced support for white nationalists when they engaged in violence.
Phycobiliproteins and phycocyanin of Arthrospira maxima (Spirulina) reduce apoptosis promoters and glomerular dysfunction in mercury-related acute kidney injury
Authors: Rojas-Franco Placido , Franco-Colín Margarita , Camargo María Estela Meléndez , Carmona María Mirian Estévez , Ortíz-Butrón María del Rocío Elizabeth , Blas-Valdivia Vanessa , Cano-Europa Edgar
Published: October 2018

Arthrospira maxima ( Spirulina) is considered a nutraceutical or functional food because it provides health benefits and it is used as nephroprotector because it contains nucleophilic compounds as phycobiliproteins and phycocyanin that prevent oxidative stress and cellular damage process. Also, it is known that inorganic mercury is bioaccumulated and exerted kidney toxicity. Despite the nephroprotective effect of Spirulina and its components, there is not enough information about the effect of them on renal function as well as the apoptosis process inhibition. This work aimed to investigate whether phycobiliproteins and phycocyanin of Spirulina can improve HgCl2-related glomerular and tubular renal dysfunction as well as the Bax, Bcl2, and effectors caspases alterations. Male mice were administrated with Spirulina, phycobiliproteins or phycocyanin 30 min before 5 mg/Kg HgCl2 administration. The nutraceuticals were administrated for the next 5 days. Then, the mice were euthanized. The renal function, caspases 3 and 9 activities, as well as Bax and Bcl2 expression were evaluated. Spirulina and its components prevent HgCl2-related apoptosis induction and glomerular dysfunction. We concluded that phycobiliproteins and phycocyanin of Spirulina reduce glomerular damage but not the tubular dysfunction in a mercury-related acute kidney injury.
Chronic immune response dysregulation in MDS pathogenesis
Authors: Barreyro Laura , Chlon Timothy M. , Starczynowski Daniel T.
Published: October 2018

Chronic innate immune signaling in hematopoietic cells is widely described in myelodysplastic syndromes (MDS), and innate immune pathway activation, predominantly via pattern recognition receptors, increases the risk of developing MDS. An inflammatory component to MDS has been reported for many years, but only recently has evidence supported a more direct role of chronic innate immune signaling and associated inflammatory pathways in the pathogenesis of MDS. Here we review recent findings and discuss relevant questions related to chronic immune response dysregulation in MDS.
Polyreactive IgM initiates complement activation by PF4/heparin complexes through the classical pathway
Authors: Khandelwal Sanjay , Ravi Joann , Rauova Lubica , Johnson Alexandra , Lee Grace M. , Gilner Jennifer B. , Gunti Sreenivasulu , Notkins Abner L. , Kuchibhatla Maragatha , Frank Michael , Poncz Mortimer , Cines Douglas B. , Arepally Gowthami M.
Published: October 2018

The mechanisms by which exposure to heparin initiates antibody responses in many, if not most, recipients are poorly understood. We recently demonstrated that antigenic platelet factor 4 (PF4)/heparin complexes activate complement in plasma and bind to B cells. Here, we describe how this process is initiated. We observed wide stable variation in complement activation when PF4/heparin was added to plasma of healthy donors, indicating a responder “phenotype” (high, intermediate, or low). Proteomic analysis of plasma from these healthy donors showed a strong correlation between complement activation and plasma immunoglobulin M (IgM) levels (r = 0.898; P < .005), but not other Ig isotypes. Complement activation response to PF4/heparin in plasma displaying the low donor phenotype was enhanced by adding pooled IgM from healthy donors, but not monoclonal IgM. Depletion of IgM from plasma abrogated C3c generation by PF4/heparin. The complement-activating features of IgM are likely mediated by nonimmune, or natural, IgM, as cord blood and a monoclonal polyreactive IgM generate C3c in the presence of PF4/heparin. IgM facilitates complement and antigen deposition on B cells in vitro and in patients receiving heparin. Anti-C1q antibody prevents IgM-mediated complement activation by PF4/heparin complexes, indicating classical pathway involvement. These studies demonstrate that variability in plasma IgM levels correlates with functional complement responses to PF4/heparin. Polyreactive IgM binds PF4/heparin, triggers activation of the classical complement pathway, and promotes antigen and complement deposition on B cells. These studies provide new insights into the evolution of the heparin-induced thrombocytopenia immune response and may provide a biomarker of risk.
BH3-mimetic toolkit guides the respective use of BCL2 and MCL1 BH3-mimetics in myeloma treatment
Authors: Gomez-Bougie Patricia , Maiga Sophie , Tessoulin Benoît , Bourcier Jessie , Bonnet Antoine , Rodriguez Manuel S. , Le Gouill Steven , Touzeau Cyrille , Moreau Philippe , Pellat-Deceunynck Catherine , Amiot Martine
Published: October 2018

BH3 mimetics are promising drugs for hematologic malignancies that trigger cell death by promoting the release of proapoptotic BCL2 family members from antiapoptotic proteins. Multiple myeloma is considered to be a disease dependent mainly on MCL1 for survival, based mostly on studies using cell lines. We used a BH3-mimetic toolkit to study the dependency on BCL2, BCLXL, or MCL1 in malignant plasma cells from 60 patients. Dependencies were analyzed using an unbiased BH3 mimetics cell-death clustering by k-means. In the whole cohort of patients, BCL2 dependency was mostly found in the CCND1 subgroup (83%). Of note, MCL1 dependence significantly increased from 33% at diagnosis to 69% at relapse, suggesting a plasticity of the cellular dependency favoring MCL1 dependencies at relapse. In addition, 35% of overall patient samples showed codependencies on either BCL2/MCL1 or BCLXL/MCL1. Finally, we identified a group of patients not targeted by any of the BH3 mimetics, predominantly at diagnosis in patients not presenting the common recurrent translocations. Mechanistically, we demonstrated that BAK is crucial for cell death induced by MCL1 mimetic A1210477, according to the protection from cell death observed by BAK knock-down, as well as the complete and early disruption of MCL1/BAK complexes on A1210477 treatment. Interestingly, this complex was also dissociated in A1210477-resistant cells, but free BAK was simultaneously recaptured by BCLXL, supporting the role of BCLXL in A1210477 resistance. In conclusion, our study opens the way to rationally use venetoclax and/or MCL1 BH3 mimetics for clinical evaluation in myeloma at both diagnosis and relapse.
Next-generation sequencing–based posttransplant monitoring of acute myeloid leukemia identifies patients at high risk of relapse
Authors: Kim TaeHyung , Moon Joon Ho , Ahn Jae-Sook , Kim Yeo-Kyeoung , Lee Seung-Shin , Ahn Seo-Yeon , Jung Sung-Hoon , Yang Deok-Hwan , Lee Je-Jung , Choi Seung Hyun , Lee Ja-yeon , Tyndel Marc S. , Shin Myung-Geun , Lee Yoo Jin , Sohn Sang Kyun , Park Seong-Kyu , Zhang Zhaolei , Kim Hyeoung-Joon , Kim Dennis Dong Hwan
Published: October 2018

Key Points

Higher allelic burden at day 21 of post-HCT is associated with higher risk of relapse and mortality. Longitudinal tracking of AML patients receiving HCT is feasible and provides clinically relevant information.
Reversing anti–factor Xa agents and the unmet needs in trauma patients
Authors: Hunt Beverley J. , Neal Matthew D. , Stensballe Jakob
Published: October 2018

Andexanet alfa, a reversing agent for anticoagulants that inhibit factor Xa, has recently been licensed in the United States. We discuss the impact of this licensure on current practice and review in detail the problems of a neglected and growing clinical area: reversing the anticoagulation effect of factor Xa inhibitors in bleeding trauma patients. We identify areas of practice that need research so that care of bleeding trauma patients receiving direct factor Xa inhibitors can be improved.
Humanized Mcl-1 mice enable accurate preclinical evaluation of MCL-1 inhibitors destined for clinical use
Authors: Brennan Margs S. , Chang Catherine , Tai Lin , Lessene Guillaume , Strasser Andreas , Dewson Grant , Kelly Gemma L. , Herold Marco J.
Published: October 2018

Key Points

Due to the higher affinity of current MCL-1 inhibitors, huMcl-1 mice have been established. A therapeutic window for S63845 can be established in huMcl-1 mice transplanted with huMcl-1;Eµ-Myc lymphomas.
A multi-hop graph-based approach for an energy-efficient routing protocol in wireless sensor networks
Authors: Rhim Hana , Tamine Karim , Abassi Ryma , Sauveron Damien , Guemara Sihem
Published: October 2018

Emerging technological advances in wireless communication and networking have led to the design of large scale networks and small sensor units with minimal power requirements and multifunctional processing. Though energy harvesting technologies are improving, the energy of sensors remains a scarce resource when designing routing protocols between sensor nodes and base station. This paper proposes a multi-hop graph-based approach for an energy-efficient routing (MH-GEER) protocol in wireless sensor networks which aims to distribute energy consumption between clusters at a balanced rate and thus extend networks’ lifespans. MH-GEER deals with node clustering and inter-cluster multi-hop routing selection. The clustering phase is built upon the centralized formation of clusters and the distributed selection of cluster heads similar to that of low-energy adaptive clustering hierarchy (LEACH). The routing phase builds a dynamic multi-hop path between cluster heads and the base station. Our strategy is about exploring the energy levels in the entire network and using these to select the next hop in a probabilistic, intelligent way. Performance evaluation shows that MH-GEER minimizes energy depletion in distant clusters and ensures load balancing in a network, thus improving the network’s lifetime and stability compared with single-hop conventional LEACH protocol.
Surface area wiped, product type, and target strain impact bactericidal efficacy of ready-to-use disinfectant Towelettes
Authors: West Alyssa M , Nkemngong Carine A , Voorn Maxwell G , Wu Tongyu , Li Xiaobao , Teska Peter J , Oliver Haley F
Published: October 2018

Background

Disinfectant products are often used on environmental surfaces (e.g. countertops, patient beds) and patient care equipment in healthcare facilities to help prevent the transmission of healthcare-associated infections. Ready-to-use (RTU) disinfectants in the form of pre-wetted towelettes are increasingly popular among healthcare facilities. Currently, the EPA does not require disinfectant manufacturers to include a recommended maximum surface area per towelette on their product labels. The objective of this study was to investigate the efficacy of disinfectant towelette products on a hard non-porous surface across different coverage areas using a quantitative EPA method. We hypothesized that there would be significant differences in the efficacy of disinfectant towelette products, and that the greater surface area(s) wiped would result in reduced bactericidal efficacy.

Methods

This study tested ten disinfectant towelette products against Staphylococcus aureus strain ATCC CRM-6538 and Pseudomonas aeruginosa strain ATCC 15442 on Formica surfaces. Defined surface areas were wiped and the towelette weighed before and after wiping to determine the amount of liquid released. Bactericidal efficacy testing was also performed after wiping following standard EPA protocols.

Results

We found that disinfectant product, area of surface wiped, and strain impacted the bactericidal efficacy achieved. Disinfectant product type and area of surface wiped significantly impacted the percent of liquid released per ft2from the towelette.

Conclusion

Overall, bactericidal efficacy varied by towelette product, surface area wiped, and strain. This study also found that wiping larger surface areas may lead to decreased bactericidal efficacy. Further research is needed to test its implication.
Optimizing Outcome Prediction in Diffuse Large B-Cell Lymphoma by Use of Machine Learning and Nationwide Lymphoma Registries: A Nordic Lymphoma Group Study
Authors: Biccler Jorne L. , Eloranta Sandra , de Nully Brown Peter , Frederiksen Henrik , Jerkeman Mats , Jørgensen Judit , Jakobsen Lasse Hjort , Smedby Karin E. , Bøgsted Martin , El-Galaly Tarec C.
Published: October 2018

Purpose

Prognostic models for diffuse large B-cell lymphoma (DLBCL), such as the International Prognostic Index (IPI) are widely used in clinical practice. The models are typically developed with simplicity in mind and thus do not exploit the full potential of detailed clinical data. This study investigated whether nationwide lymphoma registries containing clinical data and machine learning techniques could prove to be useful for building modern prognostic tools.

Patients and Methods

This study was based on nationwide lymphoma registries from Denmark and Sweden, which include large amounts of clinicopathologic data. Using the Danish DLBCL cohort, a stacking approach was used to build a new prognostic model that leverages the strengths of different survival models. To compare the performance of the stacking approach with established prognostic models, cross-validation was used to estimate the concordance index (C-index), time-varying area under the curve, and integrated Brier score. Finally, the generalizability was tested by applying the new model to the Swedish cohort.

Results

In total, 2,759 and 2,414 patients were included from the Danish and Swedish cohorts, respectively. In the Danish cohort, the stacking approach led to the lowest integrated Brier score, indicating that the survival curves obtained from the stacking model fitted the observed survival the best. The C-index and time-varying area under the curve indicated that the stacked model (C-index: Denmark [DK], 0.756; Sweden [SE], 0.744) had good discriminative capabilities compared with the other considered prognostic models (IPI: DK, 0.662; SE, 0.661; and National Comprehensive Cancer Network–IPI: DK, 0.681; SE, 0.681). Furthermore, these results were reproducible in the independent Swedish cohort.

Conclusion

A new prognostic model based on machine learning techniques was developed and was shown to significantly outperform established prognostic indices for DLBCL. The model is available at https://lymphomapredictor.org .
Please allow me to introduce myself
Authors: Briscoe James
Published: October 2018

Summary: New Editor-in-Chief James Briscoe discusses his future plans for Development, announces some changes to the editorial team and calls on the community's support to ensure the journal continues to flourish.
Apobec1 complementation factor (A1CF) and RBM47 interact in tissue-specific regulation of C to U RNA editing in mouse intestine and liver
Authors: Blanc Valerie , Xie Yan , Kennedy Susan , Riordan Jesse D. , Rubin Deborah C. , Madison Blair B. , Mills Jason C. , Nadeau Joseph H. , Davidson Nicholas O.
Published: October 2018

Mammalian C to U RNA is mediated by APOBEC1, the catalytic deaminase, together with RNA binding cofactors (including A1CF and RBM47) whose relative physiological requirements are unresolved. Although A1CF complements APOBEC1 for in vitro RNA editing, A1cf–/– mice exhibited no change in apolipoproteinB (apoB) RNA editing, while Rbm47 mutant mice exhibited impaired intestinal RNA editing of apoB as well as other targets. Here we examined the role of A1CF and RBM47 in adult mouse liver and intestine, following deletion of either one or both gene products and also following forced (liver or intestinal) transgenic A1CF expression. There were minimal changes in hepatic and intestinal apoB RNA editing in A1cf–/– mice and no changes in either liver- or intestine-specific A1CF transgenic mice. Rbm47 liver-specific knockout (Rbm47LKO) mice demonstrated reduced editing in a subset (11 of 20) of RNA targets, including apoB. By contrast, apoB RNA editing was virtually eliminated (<6% activity) in intestine-specific (Rbm47IKO) mice with only five of 53 targets exhibiting C-to-U RNA editing. Double knockout of A1cf and Rbm47 in liver (ARLKO) eliminated apoB RNA editing and reduced editing in the majority of other targets, with no changes following adenoviral APOBEC1 administration. Intestinal double knockout mice (ARIKO) demonstrated further reduced editing (<10% activity) in four of five of the residual APOBEC1 targets identified in ARIKO mice. These data suggest that A1CF and RBM47 each function independently, yet interact in a tissue-specific manner, to regulate the activity and site selection of APOBEC1 dependent C-to-U RNA editing.