bluuebunny/crossref_metadata_2025 huggingface dataset:
Dealing with software estimates distortions from the perspective of negotiation theories
Authors: Fernandes Matsubara Patrícia Gomes
Published: November 2019

Software estimation is a critical task in software projects, and the accuracy of software estimates has been a concern for researchers and practitioners. Researchers have already identified some factors that impact estimates accuracy, like cognitive biases, that ultimately lead to unintentional distortions of software estimates. However, there is evidence that intentional distortions of software estimates are also part of the reality of estimation in software projects. The goal of this research project is to investigate whether negotiation theories can be effective to aid software engineers in defending their estimates and, therefore, reduce distortions. To achieve this, we apply the Design Science Research (DSR) approach by defining and evaluating negotiation guidelines adapted to the context of software project estimation. The problem addressed in this project is investigated through a systematic literature mapping (SLM) and a case study. Additionally, the guidelines are going to be applied in real scenarios in software companies. The expected contributions in this project are (i) the negotiation guidelines aiming at reducing software estimate distortions, (ii) empirical evidence about whether negotiation theories are effective to aid software engineers to deal with estimate distortions, and (iii) a set of technological rules about the use of these guidelines.
Model-driven Game Development
Authors: Zhu Meng , Wang Alf Inge
Published: November 2019

Model-driven game development (MDGD) introduces model-driven methodology to the computer game domain, shifting the focus of game development from coding to modeling to make game development faster and easier. The research on MDGD is concerned with both the general model-driven software development methodology and the particular characteristics of game development. People in the MDGD community have proposed several approaches in the past decades, addressing both the technology and the development process in the context of MDGD. This article presents the state-of-art of MDGD research based on a literature review of 26 approaches in the field. The review is structured around five perspectives: target game domains, domain frameworks, modelling languages, tooling, and evaluation methods. The article also includes reflections and a discussion of the challenges within MDGD.
Malware Dynamic Analysis Evasion Techniques
Authors: Afianian Amir , Niksefat Salman , Sadeghiyan Babak , Baptiste David
Published: November 2019

The cyber world is plagued with ever-evolving malware that readily infiltrate all defense mechanisms, operate viciously unbeknownst to the user, and surreptitiously exfiltrate sensitive data. Understanding the inner workings of such malware provides a leverage to effectively combat them. This understanding is pursued often through dynamic analysis which is conducted manually or automatically. Malware authors accordingly, have devised and advanced evasion techniques to thwart or evade these analyses. In this article, we present a comprehensive survey on malware dynamic analysis evasion techniques. In addition, we propose a detailed classification of these techniques and further demonstrate how their efficacy holds against different types of detection and analysis approaches.

Our observations attest that evasive behavior is mostly concerned with detecting and evading sandboxes. The primary tactic of such malware we argue is fingerprinting followed by new trends for reverse Turing test tactic which aims at detecting human interaction. Furthermore, we will posit that the current defensive strategies, beginning with reactive methods to endeavors for more transparent analysis systems, are readily foiled by zero-day fingerprinting techniques or other evasion tactics such as stalling. Accordingly, we would recommend the pursuit of more generic defensive strategies with an emphasis on path exploration techniques that has the potential to thwart all the evasive tactics.
The Role of Toll-Like Receptors in Skin Host Defense, Psoriasis, and Atopic Dermatitis
Authors: Sun Lixiang , Liu Wenjie , Zhang Ling-juan
Published: November 2019

As the key defense molecules originally identified in Drosophila, Toll-like receptor (TLR) superfamily members play a fundamental role in detecting invading pathogens or damage and initiating the innate immune system of mammalian cells. The skin, the largest organ of the human body, protects the human body by providing a critical physical and immunological active multilayered barrier against invading pathogens and environmental factors. At the first line of defense, the skin is constantly exposed to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), and TLRs, expressed in a cell type-specific manner by various skin cells, serve as key molecules to recognize PAMPs and DAMPs and to initiate downstream innate immune host responses. While TLR-initiated inflammatory responses are necessary for pathogen clearance and tissue repair, aberrant activation of TLRs will exaggerate T cell-mediated autoimmune activation, leading to unwanted inflammation, and the development of several skin diseases, including psoriasis, atopic dermatitis, systemic lupus erythematosus, diabetic foot ulcers, fibrotic skin diseases, and skin cancers. Together, TLRs are at the interface between innate immunity and adaptive immunity. In this review, we will describe current understanding of the role of TLRs in skin defense and in the pathogenesis of psoriasis and atopic dermatitis, and we will also discuss the development and therapeutic effect of TLR-targeted therapies.
ViPar: High-Level Design Space Exploration for Parallel Video Processing Architectures
Authors: Ali Karim M. A. , Ben Atitallah Rabie , Ait El Cadi Abdessamad , Fakhfakh Nizar , Dekeyser Jean-Luc
Published: November 2019

Embedded video applications are now involved in sophisticated transportation systems like autonomous vehicles and driver assistance systems. As silicon capacity increases, the design productivity gap grows up for the current available design tools. Hence, high-level synthesis (HLS) tools emerged in order to reduce that gap by shifting the design efforts to higher abstraction levels. In this paper, we present ViPar as a tool for exploring different video processing architectures at higher design level. First, we proposed a parametrizable parallel architectural model dedicated for video applications. Second, targeting this architectural model, we developed ViPar tool with two main features: (1) An empirical model was introduced to estimate the power consumption based on hardware utilization and operating frequency. In addition to that, we derived the equations for estimating the hardware utilization and execution time for each design point during the space exploration process. (2) By defining the main characteristics of the parallel video architecture like parallelism level, the number of input/output ports, the pixel distribution pattern, and so on, ViPar tool can automatically generate the dedicated architecture for hardware implementation. In the experimental validation, we used ViPar tool to generate automatically an efficient hardware implementation for a Multiwindow Sum of Absolute Difference stereo matching algorithm on Xilinx Zynq ZC706 board. We succeeded to increase the design productivity by converging rapidly to the appropriate designs that fit with our system constraints in terms of power consumption, hardware utilization, and frame execution time.
Enhanced Endothelin A and B Receptor Expression and Receptor-Mediated Vasoconstriction in Rat Mesenteric arteries after Lipopolysaccharide Challenge
Authors: Zhang Wei , Zhang Shan-Shan , Huang Hong-Lang , Song Bing-Jie , Liu Xiao , Qi Zhi
Published: November 2019

During organ culture of intact vessels, endothelin receptors (ETRs) were upregulated in vascular smooth muscle cells (VSMCs) by various stimuli, but whether inflammation alters ETR expression in vivo remains unclear. We aimed to explore the effects of lipopolysaccharide (LPS) challenge on ETR expression in the VSMC in vivo. Male Sprague-Dawley rats received a single intraperitoneal injection of LPS (5 mg/kg body weight) or normal saline (NS) for 6 hrs. The function and expression of ETR type A (ETA) and type B (ETB) were evaluated in the mesenteric arteries without endothelium, by using myograph system, real-time quantitative PCR, Western blot, and immunohistochemical staining, respectively. Serum tumor necrosis factor-α (TNF-α) level was assessed by using enzyme-linked immunosorbent assay. The results showed that, compared to control (NS) group, LPS treatment potently enhanced the vasoconstriction mediated by ETA or ETB in rat mesenteric artery, with elevated maximum effects. ETA and ETB expressions in the VSMC were increased at both mRNA and protein levels after LPS treatment, paralleled with activation of the NF-κB pathway and augmented serum TNF-α level. Conclusively, in the rat model of immediate systemic inflammation induced by LPS, ETA and ETB expressions were increased in the mesenteric arterial VSMC, paralleled with enhanced receptor-mediated vasoconstriction and activation of the NF-κB pathway. Our data has for the first time demonstrated the upregulation of ETRs in VSMCs by LPS-induced immediate inflammation in vivo.
Endoscopic Necrosectomy of Walled-Off Necrosis following Severe Pancreatitis Using a Hot AxiosTM Stent – A Case Series
Authors: Weigand Kilian , Mehrl Alexander , Goessmann Holger , Mueller Martina , Kandulski Arne
Published: November 2019

Background: Walled-off necrosis is a common complication of severe pancreatitis. Guidelines recommend endoscopic transgastric necrosectomy as therapy of choice. Different endoscopic approaches are possible. Methods: We retrospectively analyzed our series of 9 patients where necrosectomy was performed after application of a lumen-apposing metal stent (LAMS) delivered using a Hot AxiosTM Stent device. Results: In all 9 cases, the walled-off necrosis resolved completely. Necrosectomy was performed through the LAMS (mean: 5.7 times). Endoscopic necrosectomy was repeated every 3rd–7th day using 10- or 15-mm snares. There were no major complications. Especially, no early or delayed bleeding was seen. Conclusion: The Hot AxiosTM Stent device is a safe method for necrosectomy of walled-off necrosis. It enables puncture, drainage, and LAMS insertion in a single delivery, followed by several courses of necrosectomy if needed without stent exchange.
Long-Term Occupational Sleep Loss and Post-Retirement Cognitive Decline or Dementia
Authors: Thomas Jana , Overeem Sebastiaan , Claassen Jurgen A.H.R.
Published: November 2019

Introduction: Recent evidence suggests that poor sleep is a risk factor that contributes to the development of Alzheimer’s disease (AD). Most studies have focused on short-term effects of sleep deprivation on cognitive function, whereas longitudinal studies are limited to self-reported sleep and the risk of later-life dementia. Because sleep loss could be an early manifestation of neurodegenerative disease, reverse causality in these studies cannot be excluded. Objective: In this explorative, observational study, we investigated the effects of extended periods of extrinsically (work-related) caused sleep loss on later-life cognitive function, early dementia symptoms, and current sleep quality. Methods: We approached a community of retired male maritime pilots (approx. n = 500) through a newsletter. We investigated 50 respondents (mean age 71.7 years ± 7.7), with a history of >25 years of work on irregular schedules, which resulted in extended periods of sleep loss. Validated questionnaires on cognitive complaints (Cognitive Failure Questionnaire [CFQ]), early dementia symptoms (Early Dementia Questionnaire [EDQ]), current sleep quality (Pittsburgh Sleep Quality Index [PSQI] and sleep-wake diaries), quality of life (QoL, EQ-5D), and mood (Hospital Anxiety and Depression Scale [HADS]) were administered by a single investigator (J.T.), who also completed an observer rating of cognitive function. Results: Scores on the CFQ, EDQ, PSQI, EQ-5D, and HADS were within normal ranges adjusted for age, sex, and education. The observer rating was not indicative of cognitive decline. Conclusion: We found no evidence that long-term exposure to work-related sleep loss had resulted in cognitive decline or early dementia symptoms in this sample of retired maritime pilots.
Arrhythmia Mechanisms and Outcomes of Ablation in Pediatric Patients With Congenital Heart Disease
Authors: Houck Charlotte A. , Chandler Stephanie F. , Bogers Ad J.J.C. , Triedman John K. , Walsh Edward P. , de Groot Natasja M.S. , Abrams Dominic J.
Published: November 2019

Background:

In contrast to the adult population with congenital heart disease (CHD), arrhythmia mechanisms and outcomes of ablation in pediatric patients with CHD in recent era have not been studied in detail. Aims of this study were to determine arrhythmia mechanisms and to evaluate procedural and long-term outcomes in pediatric patients with CHD undergoing catheter ablation.

Methods:

Consecutive patients <18 years of age with CHD undergoing catheter ablation over an 11-year period (2007–2018) were included. Procedural outcome included complete or partial success, failure or empirical ablation. Long-term outcome included arrhythmia recurrence and burden according to a 12-point clinical arrhythmia severity score.

Results:

The study population consisted of 232 patients (11.7 years [0.01–17.8], 33.5 kg [2.2–130.1]). The most common diagnoses were Ebstein’s anomaly (n=44), septal defects (n=39), and single ventricle (n=36). Arrhythmia mechanisms included atrioventricular reentry tachycardia (n=104, 90 patients), atrioventricular nodal reentry tachycardia (n=33, 29 patients), twin atrioventricular nodal tachycardia (n=3, 2 patients), macroreentrant atrial tachycardia (n=59, 56 patients), focal atrial tachycardia (n=33, 25 patients), ventricular ectopy (n=10, 8 patients), and ventricular tachycardia (n=15, 13 patients). Fifty-six arrhythmias (39 patients) were undefined. Outcomes included complete success (n=189, 81%), partial success (n=7, 3%), failure (n=16, 7%), or empirical ablation (n=20, 9%). Over 3.6 years (0.3–10.7) arrhythmia recurred in 49%. Independent of arrhythmia recurrence, arrhythmia scores decreased from 4 (0–10) at baseline to 0.5 (0–8) at 4 years follow-up (
P
<0.001). In 23/51 repeat procedures (45%), a different arrhythmia substrate was found. Overall adverse event rate was 9.4%, although only 1.6% (n=4) were of major severity and 0.8% (n=2) of moderate severity.

Conclusions:

Pediatric patients with CHD demonstrate a broad spectrum of arrhythmia mechanisms. Despite recurrence and emergence of novel mechanisms after a successful procedure, ablation can be performed safely and successfully resulting in decreased arrhythmia burden.
Rethinking Cultural Evolutionary Psychology
Authors: Nichols Ryan , Moll Henrike , Mackey Jacob L.
Published: November 2019

This essay discusses Cecilia Heyes’ groundbreaking new book Cognitive Gadgets: The Cultural Evolution of Thinking. Heyes’ point of departure is the claim that current theories of cultural evolution fail adequately to make a place for the mind. Heyes articulates a cognitive psychology of cultural evolution by explaining how eponymous “cognitive gadgets,” such as imitation, mindreading and language, mental technologies, are “tuned” and “assembled” through social interaction and cultural learning. After recapitulating her explanations for the cultural and psychological origins of these gadgets, we turn to criticisms. Among those, we find Heyes’ use of evolutionary theory confusing on several points of importance; alternative theories of cultural evolution, especially those of the Tomasello group and of Boyd, Richerson and Henrich, are misrepresented; the book neglects joint attention and other forms of intersubjectivity in its explanation of the origins of cognitive gadgets; and, whereas Heyes accuses other theories of being “mindblind,” we find her theory ironically other-blind and autistic in character.
The Technological Utopia: Mimamori Care and Family Separation in Japan
Authors: van der Veere Anoma P.
Published: November 2019

Japan is undergoing a significant demographic upheaval, and the Japanese government is formulating policies for stimulating technological advances based on the assumption that they will solve issues such as labour shortages and elder care. The government argues through policy initiatives that technology will decrease the care burden on Japan’s workers, families, and itself. Although the domestic media show awareness of changing family patterns in Japan, newspapers are following a similar pattern of technological utopianism. However, this article posits that the proposed policy reforms rely on a conservative ideal of the extended family that ignores changing patterns in Japanese households. Moreover, it argues that, rather than facilitating a return to the ideal of an extended family, technology is exacerbating separation among families that have been growing apart for some time.
Cell Phone City: Reinventing Tokyo’s Urban Space for Social Use
Authors: Sneep Deirdre
Published: November 2019

Although the growth of the mobile internet is a global phenomenon, several urban agglomerations are in East Asian countries that rank particularly high in mobile internet use. Among them is Tokyo, the cradle of mobile internet technology. The constant connectedness to the internet transforms the city and its communities, making them interesting case studies for research on smart communities. In line with Goggin and McLelland’s 2017 call for a more localized perspective on (mobile) internet use, this article critically re-visits the existing theoretical framework on how virtual space influences the city, and it compares findings with anthropological fieldwork the author conducted in Tokyo. The article looks at how mobile phones can be used to interact with established contacts over a distance, connect strangers by forming ‘mobile phone hubs’, and even disconnect the user when the device is used to ‘shield’ oneself from those in the vicinity.
The Vertical Structure of Open-Ocean Submesoscale Variability during a Full Seasonal Cycle
Authors: Erickson Zachary K. , Thompson Andrew F. , Callies Jörn , Yu Xiaolong , Garabato Alberto Naveira , Klein Patrice
Published: November 2019

Submesoscale dynamics are typically intensified at boundaries and assumed to weaken below the mixed layer in the open ocean. Here, we assess both the seasonality and the vertical distribution of submesoscale motions in an open-ocean region of the northeast Atlantic. Second-order structure functions, or variance in properties separated by distance, are calculated from submesoscale-resolving ocean glider and mooring observations, as well as a 1/48° numerical ocean model. This dataset combines a temporal coverage that extends through a full seasonal cycle, a horizontal resolution that captures spatial scales as small as 1 km, and vertical sampling that provides near-continuous coverage over the upper 1000 m. While kinetic and potential energies undergo a seasonal cycle, being largest during the winter, structure function slopes, influenced by dynamical characteristics, do not exhibit a strong seasonality. Furthermore, structure function slopes show weak vertical variations; there is not a strong change in properties across the base of the mixed layer. Additionally, we compare the observations to output from a high-resolution numerical model. The model does not represent variability associated with superinertial motions and does not capture an observed reduction in submesoscale kinetic energy that occurs throughout the water column in spring. Overall, these results suggest that the transfer of mixed layer submesoscale variability down to depths below the traditionally defined mixed layer is important throughout the weakly stratified subpolar mode waters.
A Multiattribute Benefits-Based Choice Model with Multiple Mediators: New Insights for Positioning
Authors: Burke Paul F. , Eckert Christine , Sethi Srishti
Published: November 2019

Previous research has demonstrated that consumers evaluate products according to their perceived benefits when making a choice. This article extends prior work by proposing a method that evaluates the degree to which multiple a priori defined benefits mediate product choices. The model is the first to consider process heterogeneity—that is, heterogeneity in how consumers perceive multiple attributes to positively or negatively affect multiple benefits simultaneously and the contribution of each benefit to product utility. The authors propose discrete choice experiments to holistically measure the link between attributes and benefits, as well as between attributes and choice, resulting in data that can be analyzed with a generalized probit model. The approach contributes to mediation research by offering an alternative method of handling multiple multinomial mediators and dichotomous outcome variables. An empirical illustration of bread choices shows how consumer judgments about health and value perceptions of products mediate purchase decisions. The authors demonstrate how the method can help managers (1) confirm and test existing knowledge about latent benefits, including whether they explain all the variation in choice, and (2) consider process heterogeneity to inform market segmentation strategies.
The American Democratic Deficit in Assisted Reproductive Technology Innovation
Authors: Lewis Myrisha S.
Published: November 2019

In many areas of innovation, the United States is a leader, but this characterization does not apply to the United States' position in assisted reproductive technology innovation and clinical use. This article uses a political science concept, the idea of the “democratic deficit” to examine the lack of American public discourse on innovations in ART. In doing so, the article focuses on America's missing public consultation in health care innovation. This missing discourse is significant, as political and ethical considerations may impact regulatory decisions. Thus, to the extent that these considerations are influencing the decisions of federal agency employees, namely those who work within the U.S. Food and Drug Administration, the public is unable to participate in the decision-making process. This lack of a public discourse undermines the goals of the administrative state, which include democratic participation, transparency, and accountability.

The United Kingdom, on the other hand, has had a markedly divergent experience with assisted reproductive technology innovation. Instead of ignoring the various ethical, social, and legal issues surrounding assisted reproductive technology innovation, the United Kingdom engaged in a five-strand public consultation on the topic of mitochondrial transfer, a form of assisted reproductive technology that uses genetic modification in order to prevent disease transmission. This article argues that after a multi-decade standstill in terms of the public discourse related to ethical issues associated with assisted reproductive technology and germline modification, it is time for the United States to institute a more democratic inquiry into the scientific, ethical, and social implications of new forms of assisted reproductive technology and ultimately, forthcoming medical innovations that involve genetic modification.
Challenges in Building Robust Interventions in Contexts of Poverty: Insights from an NGO-driven multi-stakeholder network in Ethiopia
Authors: van Wijk Jakomijn , van Wijk Jeroen , Drost Sarah , Stam Wouter
Published: November 2019

We examine the demise of a multi-stakeholder network that was launched to promote an inclusive dairy market in Ethiopia to better understand why nongovernmental organizations (NGOs) may develop interventions in contexts of poverty that fail to endure after they exit. We identify organizational reflexivity – the capacity to recognize and understand the recursive interplay between an intervention and the local environment – as a key explanatory mechanism for this intervention outcome. Limited reflexivity not only prevented the NGO we studied from properly aligning the intervention with the context ( design failures), but also prevented the organization from adjusting its intervention when negative feedback emerged ( orchestration failures), which eventually evolved into the demise of the network ( maintenance failure). While our study confirms the theoretical premise that NGOs need to contextualize their interventions, we expand current knowledge by highlighting the role of organizational reflexivity in this process. Moreover, by showing how reflexivity deficits can trigger a cascade of failure, especially when intervening in voids where incumbent firms have interests in maintaining the void, our study calls attention to the politicized nature of institutional voids.
The Gender Gap in Market Work Hours Among Canadians: Examining Essential(ist) Linkages to Parenting Time and Household Labour Hours
Authors: Buchanan Tom , McFarlane Adian , Das Anupam
Published: November 2019

Using 2015 Canadian time diary data, we analyse how the gender gap in market work hours is linked to gender inequality in parenting time and household labour hours (N = 2,296). Among Canadians who are 15–34 years of age, we examine three family groupings, single without children, married without children and married with children. For the married with children group, we focus on respondents with at least one child aged 0–4 years. We find that the gender gap in market work is not significant for those single and married without children. For the married without children group, a gender gap exists for household labour. This suggests that a gender gap in household labour exists prior to the onset of children. As expected, a large gender gap in market work presents itself for married/common law respondents with young children. Half of the gender gap in market work is explained by household labour hours and parenting time. Our study demonstrates that time allocations contribute substantively to gender inequality in market work. Yet, the large unexplained part of the gap suggests that this issue is larger and more complex than mere bargaining decisions about domestic and market time.

JEL: I24, J13, J16, C10
Looking at the Figures: Visual Adaptation as a Mechanism for Body-Size and -Shape Misperception
Authors: Brooks Kevin R. , Mond Jonathan , Mitchison Deborah , Stevenson Richard J. , Challinor Kirsten L. , Stephen Ian D.
Published: November 2019

Many individuals experience body-size and -shape misperception (BSSM). Body-size overestimation is associated with body dissatisfaction, anxiety, depression, and the development of eating disorders in individuals who desire to be thinner. Similar symptoms have been noted for those who underestimate their muscularity. Conversely, individuals with high body mass indices (BMI) who underestimate their adiposity may not recognize the risks of or seek help for obesity-related medical issues. Although social scientists have examined whether media representations of idealized bodies contribute to the overestimation of fat or underestimation of muscle, other scientists suggest that increases in the prevalence of obesity could explain body-fat underestimation as a form of renormalization. However, these disparate approaches have not advanced our understanding of the perceptual underpinnings of BSSM. Recently, a new unifying account of BSSM has emerged that is based on the long-established phenomenon of visual adaptation, employing psychophysical measurements of perceived size and shape following exposure to “extreme” body stimuli. By inducing BSSM in the laboratory as an aftereffect, this technique is rapidly advancing our understanding of the underlying mental representation of human bodies. This nascent approach provides insight into real-world BSSM and may inform the development of therapeutic and public-health interventions designed to address such perceptual errors.
Noninvasive ventilation failure in patients with hypoxemic respiratory failure: the role of sepsis and septic shock
Authors: Duan Jun , Chen Lijuan , Liang Guopeng , Shu Weiwei , Li Liucun , Wang Ke , Wang Shengyu , Liu Xiaoyi , He Chunfeng , He Dehua , Chen Qimin , Wei Bilin , Chen Baixu , Shu Yuzhen , Tian Yao , Fan Liping , Han Xiaoli , Zhang Rui , Yang Xiangmei , Peng Yan , Wan Dong , Chen Xiaoying , Ye Lin , Tian Shijing , Huang Qiong , Jiang Lei , Bai Linfu , Zhou Lintong
Published: November 2019

Background:

Sepsis and septic shock are common in noninvasive ventilation (NIV) patients. However, studies on the association between sepsis and NIV failure are lacking.

Methods:

A prospective multi-center observational study was performed in 16 Chinese intensive care units (ICUs). Patients who used NIV due to hypoxemic respiratory failure were enrolled. Sepsis and septic shock were diagnosed according to the guideline of sepsis-3.

Results:

A total of 519 patients were enrolled. Sepsis developed in 365 patients (70%) and septic shock developed in 79 patients (15%). However, 75 patients (14%) had no sepsis. NIV failure was 23%, 38%, and 61% in patients, with no sepsis, sepsis, and septic shock, respectively. Multivariate analysis found that sepsis [odds ratio (OR) = 1.95, 95% confidence interval (CI): 1.06–3.61] and septic shock (OR = 2.47, 95% CI: 1.12–5.45) were independently associated with NIV failure. In sepsis and septic shock population, the NIV failure was 13%, 31%, 37%, 53%, and 67% in patients with sequential organ failure assessment (SOFA) scores of ⩽2, 3–4, 5–6, 7–8, and ⩾9, respectively. Patients with nonpulmonary induced sepsis had similar NIV failure rate compared with those with pulmonary induced sepsis, but had higher proportion of septic shock (37% versus 10%, p ⩽ 0.01) and lower ICU mortality (10% versus 22%, p ⩽ 0.01).

Conclusions:

Sepsis was associated with NIV failure in patients with hypoxemic respiratory failure, and the association was stronger in septic shock patients. NIV failure increased with the increase of organ dysfunction caused by sepsis. The reviews of this paper are available via the supplemental material section.
Sport-Specific Associations of Specialization and Sex With Overuse Injury in Youth Athletes
Authors: Post Eric G. , Biese Kevin M. , Schaefer Daniel A. , Watson Andrew M. , McGuine Timothy A. , Brooks M. Alison , Bell David R.
Published: November 2019

Background:

Significant evidence has emerged that sport specialization is associated with an increased risk of overuse injury in youth athletes. Several recommendations exist to reduce the risk of overuse injury in youth sports, but the risk of overuse injuries may be dependent on specific movements required by a given sport.

Hypotheses:

Associations between specialized sport participation and overuse injury will exist in volleyball athletes but not soccer or basketball athletes. Female athletes will be more likely to report an overuse injury in the previous year, regardless of sport.

Study Design:

Cross-sectional study.

Level of Evidence:

Level 3.

Methods:

Youth athletes between the ages of 12 and 18 years were recruited in-person at club team tournaments, competitions, and events around the state of Wisconsin during the 2016-2017 school year. Participants were asked to complete an anonymous questionnaire that consisted of (1) participant demographics, (2) sport specialization status, (3) monthly and weekly sport volume, and (4) sport-related injury history in the previous year.

Results:

A total of 716 youth athletes completed the questionnaire (70.8% female; mean age, 14.21 ± 1.50 years; 43.2% basketball, 19.4% soccer, 37.4% volleyball; 41.8% highly specialized; 32.3% reported overuse injury in the previous year). Sex was associated with overuse injury among basketball athletes, with female basketball athletes nearly 4 times more likely to report an overuse injury compared with male basketball athletes (odds ratio, [OR], 3.7; 95% CI, 2.1-6.6; P < 0.001). High specialization (OR, 2.3; 95% CI, 1.1-4.9; P = 0.02) and participating in a single sport for more than 8 months per year (OR, 2.0; 95% CI, 1.1-3.5; P < 0.05) were associated with overuse injury only among volleyball athletes.

Conclusion:

Specialization and exceeding 8 months per year in a single sport was associated with overuse injury in volleyball, which is one of the most popular youth sports for female athletes. Specialization was not associated with overuse injury in basketball or soccer athletes. Female basketball athletes were nearly 4 times more likely to report a history of overuse injury compared with male basketball athletes. The sex of a youth athlete and the sport that he or she plays may influence the risk of overuse injury associated with sport specialization.

Clinical Relevance:

Youth athletes, parents, and clinicians should be aware that the potential risks of specialization might vary based on the athlete’s sport and sex.
Management of patients with type 2 diabetes in cardiovascular rehabilitation
Authors: Hansen Dominique , Kraenkel Nicolle , Kemps Hareld , Wilhelm Matthias , Abreu Ana , Pfeiffer Andreas FH , Jordão Alda , Cornelissen Veronique , Völler Heinz
Published: November 2019

The clinical benefits of rehabilitation in cardiovascular disease are well established. Among cardiovascular disease patients, however, patients with type 2 diabetes mellitus require a distinct approach. Specific challenges to clinicians and healthcare professionals in patients with type 2 diabetes include the prevalence of peripheral and autonomic neuropathy, retinopathy, nephropathy, but also the intake of glucose-lowering medication. In addition, the psychosocial wellbeing, driving ability and/or occupational status can be affected by type 2 diabetes. As a result, the target parameters of cardiovascular rehabilitation and the characteristics of the cardiovascular rehabilitation programme in patients with type 2 diabetes often require significant reconsideration and a multidisciplinary approach. This review explains how to deal with diabetes-associated comorbidities in the intake screening of patients with type 2 diabetes entering a cardiovascular rehabilitation programme. Furthermore, we discuss diabetes-specific target parameters and characteristics of cardiovascular rehabilitation programmes for patients with type 2 diabetes in a multidisciplinary context, including the implementation of guideline-directed medical therapy.
Couple-Level Minority Stress and Mental Health among People in Same-Sex Relationships: Extending Minority Stress Theory
Authors: LeBlanc Allen J. , Frost David M.
Published: November 2019

We simultaneously examined the effects of individual- and couple-level minority stressors on mental health among people in same-sex relationships. Individual-level minority stressors emerge from the stigmatization of sexual minority individuals; couple-level minority stressors emerge from the stigmatization of same-sex relationships. Dyadic data from 100 same-sex couples from across the United States were analyzed with actor–partner interdependence models. Couple-level stigma was uniquely associated with nonspecific psychological distress, depressive symptomatology, and problematic drinking, net the effects of individual-level stigma and relevant sociodemographic controls. Analyses also show that couple-level minority stress played unique roles in critical stress processes of minority stress proliferation: minority stress expansion and minority stress contagion. The inclusion of couple-level stress constructs represents a useful extension of minority stress theory, enriching our capacity to deepen understandings of minority stress experience and its application in the study of well-being and health inequalities faced by vulnerable populations.
Bedside examination of the vestibular and ocular motor system in patients with acute vertigo or dizziness
Authors: Tarnutzer Alexander A , Dieterich Marianne
Published: November 2019

In the initial assessment of the patient with acute vertigo or dizziness, both structured history-taking and a targeted bedside neuro-otological examination are essential for distinguishing potentially life-threatening central vestibular causes from those of benign, self-limited peripheral labyrinthine origin and thus for deciding on further diagnostic testing. In this article, the key elements of the vestibular and ocular motor examination, which should be obtained at the bedside in these acutely dizzy patients, will be discussed. Specifically, this will include the following five domains: ocular stability for (I) nystagmus and for (II) eye position (skew deviation), (III) the head-impulse test (HIT), (IV) postural stability, and (V) ocular motor deficits of saccades, smooth pursuit eye movements, and optokinetic nystagmus. We will also discuss the diagnostic accuracy of specific combinations of these bedside tests (i.e. HIT, testing for nystagmus and vertical divergence, referred to as the H.I.N.T.S. three-step examination), emphasizing that the targeted neuro-otological bedside examination is more sensitive for identifying central causes in acute prolonged vertigo and dizziness than early MRI of the brain.
Biology and Application of Genome Editing
Authors: Zhang Feng
Published: November 2019

Precision genome editing, which can be used to alter specific DNA sequences, is a powerful tool for understanding the molecular circuitry underlying cellular processes. Over the past several years, we and others have harnessed microbial CRISPR-Cas systems for use as platforms for a range of genome manipulations, including single and multiplex gene knockout, gene activation, and large-scale screening applications. Recently, we discovered and characterized several novel CRISPR systems that target RNA, including the CRISPR-Cas13 family. We developed a toolbox for RNA modulation based on Cas13, including methods for highly specific RNA knockdown, transcript imaging, and precision base editing. During our initial characterization of Cas13, we observed that Cas13 also exhibits so-called non-specific "collateral" RNase activity in vitro, which we capitalized on to create SHERLOCK, a highly sensitive and specific CRISPR diagnostic platform. We are continuing to refine and extend CRISPR-based technologies as well as explore microbial diversity to find new enzymes and systems that can be adapted for use as molecular biology tools and novel therapeutics.

Disclosures

Zhang: Arbor Biotechnologies: Consultancy, Equity Ownership; Sherlock Biosciences: Consultancy, Equity Ownership; Pairwise Plants: Consultancy, Equity Ownership; Beam Therapeutics: Consultancy, Equity Ownership; Editas Medicine: Consultancy, Equity Ownership.
A Complicated Neighborhood: Insights into the Hodgkin Lymphoma Microenvironment
Authors: Gandhi Maher K.
Published: November 2019

Classical Hodgkin Lymphoma (cHL) is a heterogenous and complex biological entity. Whereas early studies focussed on characterization of the Reed-Sternberg (RS) cell, there is now increasing recognition of the importance of the tumor microenvironment (TME). This critical but only partially understood component of cHL biology is likely to impact pathogenesis, chemo-sensitivity and long-term outcome. Here, the non-malignant infiltrate is variably comprised of macrophages, regulatory T cells, and stroma, with the relative composition varying by histological sub-type. Notably, relative to other B cell lymphomas, cHL expresses high levels of immune checkpoint receptors such as PD-1 and LAG3, and immune checkpoint ligands such as PD-L1, PD-L2, the latter of which are frequently the subject of genetic amplifications. Hence the bi-directional relationship between the microenvironment and the malignant cell is now a valid target. Breakthroughs in our understanding of the TME in cHL have contributed to its status as the 'poster-child' for how checkpoint blockade can de-activate tumor-tolerance to induce meaningful clinical benefit. A further layer of complexity within the TME is the potential aetiological relationship between cHL and the Epstein-Barr virus, a ubiquitous virus found to reside within the RS cells in 40% of cases, particularly in those cases that have mixed cellularity. Unlike benign EBV-infected B cells, within RS cells the virus is in a highly aberrant latency state with expression of the viral oncoprotein LMP1, a virus that is known to induce immunosuppression and drive PD-L1 expression through the NFkB and the JAK-STAT pathways. But numerous unanswered mechanistic questions remain, not least in the light of the frequent genetically driven deficiencies in antigen presentation present in RS cells, particularly in cases of nodular sclerosing disease. This has reignited debate about the relative roles of adaptive and innate immunity in this disease. Remaining questions that need to be addressed include the evolution of the interaction between the TME and the malignant compartment during the course of cHL, the role of other immune checkpoints and their impact on combinatorial immune based strategies, and the contribution to immune-evasion played by stromal cells. Further understanding will assist the rational development of new immune-based strategies, and potentially one day a chemo-free regimen that is as clinically efficacious but less toxic than current chemotherapies.

Disclosures

Gandhi: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Research Funding; Roche: Honoraria, Other: Travel Support; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria.
Analyzing How Elderly Acute Myeloid Leukemia Patients Are Treated, an Institutional Experience
Authors: Willner Christopher Allen , Chisti Mohammad Muhsin , Soriano Michaela , Huang James
Published: November 2019

Rationale: Treatment of acute myelogenous leukemia (AML) remains a challenge in elderly populations, those with comorbid conditions, and patients with poor performance status indices. The optimal choice for induction therapy as well as further agent selection is unclear, and current guidelines recommend enrollment in a controlled clinical trial.

Methods: Institutional cases of AML via an electronic medical record query performed in November 2017 containing cases of AML in patients 65 years of age or greater from 01/01/2000 to 06/21/2017 were extracted. Instances of acute myelogenous leukemia were identified by ICD codes. Age, gender, induction therapy, cytogenetics, molecular analyses, and overall survival were collected.

Results: A total of 61 cases of AML in patients aged 65 or greater were identified, with those having incomplete data being excluded from analysis. The mean age of included patients was 78.9 years of age, 35 were male and 26 were female. 60 confirmed deaths were recorded. 26 patients received conventional 7+3 (42.6%), 22 received a hypomethylating agent (HMA) (31.1%), 16 (26.2%) did not receive treatment.

Conclusion: Our institutional data showed overall survival was significantly longer when treated with 7+3, 354 days (95% CI [93, 614]), vs. 61 days (95% CI [15, 107]). Similarly, OS was significantly longer when treated with HMA, 303 days (95% CI [23, 583]). Risk of death, accordingly, was as follows: 7+3 HR .347 (.179-.672), HMA HR .348 (.173-.703). Our institutional mortality data reasonably reflected SEER data analysis reported by Medeiros et al concerning untreated patients, but trended toward a greater OS for those treated with 7+3 or HMA. Registry data, as well as our institutional data, demonstrate a survival benefit to intensive chemotherapy and palliative chemotherapy, while controlled trials have not shown this benefit consistently in elderly populations. Practices regarding induction therapy vary greatly between institutions. Determination of which elderly patients to treat with intensive therapy remains difficult.

References:

Almeida AM, Ramos F. Acute myeloid leukemia in the older adults. Leuk Res Rep. 2016;6:1-7.

Eleni LD, Nicholas ZC, Alexandros S. Challenges in treating older patients with acute myeloid leukemia. J Oncol. 2010;2010:943823.

Medeiros BC, Satram-hoang S, Hurst D, Hoang KQ, Momin F, Reyes C. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015;94(7):1127-38.

Disclosures

Chisti: Eli Lilly: Speakers Bureau; Medscape: Honoraria; UpToDate: Honoraria.
Hereditary Hemolytic Anemias Other Than Thalassemia: Single Center Experience
Authors: Ozdemir Gul Nihal , Kilic Mehmet Akif
Published: November 2019

Aim: The aim of this study was to evaluate the demographic information, clinical and hematologic findings and treatment response of patients diagnosed with hereditary hemolytic anemias other than thalassemia at a single center.

Materials and Methods: A total of 157 children with a diagnosis of hereditary hemolytic anemia except thalassemia were included. Patients' files were reviewed retrospectively. Demographic, clinical and laboratory characteristics, family history, complications, history of splenectomy and cholecystectomy, splenectomy response, use of chelating agents and other treatments, first transfusion age and transfusion frequency of patients were evaluated. Mean, standard deviation, median and 25-75 percentile values were used when descriptive analysis were presented. Mann Whitney U and Kruskal Wallis Tests were used for nonparametric groups. Pearson Chi Square and Fisher Tests were used when categorical comparisons were made. A value of P <0.05 was considered statistically significant.

Results: Of the 157 patients , 101 patients (64,3%) had hereditary spherocytosis, 39 patients had (24,8%) glucose-6 phosphate dehydrogenase deficiency (G6PD), 15 patients had (9,6%) sickle cell anemia and 2 patients had (1.3%) pyruvate kinase deficiency. Sixty-one patients (38,9%) were girls and 96 were boys (61,1%). Median age of diagnosis was 10 months (range 1-188 months). Of 97 patients whom family history was questioned, 63 (64.9%) had family history. Most common complaint at diagnosis was paleness. Eighty-two patients had splenomegaly. Twenty-two patients (14%) had cholecystectomy and 56 patients (35.7%) had splenectomy on follow-up. The most frequent indication for splenectomy was hereditary spherocytosis. Fifty-eight (36.9%) patients required regular transfusion. Mean ferritin level of all was 506.3±1175.0. Patients with pyruvate kinase had the highest ferritin levels. Erythropoietin was used for 1 patient with hereditary spherocytosis in infancy without a response. Ten of 15 patients with sickle cell anemia were using hydroxyurea. Thirteen percent of all were using chelating agents.

Conclusion: Hereditary spherocytosis and G6PD deficiency were the most common hereditary hemolytic anemias except thalassemia in our center. Family history was more frequent in hereditary spherocytosis compared to other hereditary hemolytic anemias. Patients with G6PD deficiency were diagnosed earlier than other hereditary hemolytic anemias. Hereditary spherocytosis was the most common indication for splenectomy and eliminated/decreased transfusion requirement in 96%. Patients with other hemolytic anemias had lower iron load compared to thalassemia except pyruvate kinase deficiency patients.

Disclosures

No relevant conflicts of interest to declare.