bluuebunny/crossref_metadata_2025 huggingface dataset:
Principles of epistemic logic I: Knowledge
Authors: Rosenkranz Sven
Published: April 2021

All epistemic logics come with some idealizations. Not all such idealizations seem acceptable. A large family of epistemic logics assume that if ⌜φ‎⌝ and ⌜ψ‎⌝ are logically equivalent, so are ⌜One knows that φ‎⌝ and ⌜One knows that ψ‎⌝. This assumption, characteristic of normal epistemic logics but also of many non-normal ones, is acceptable only if the objects of knowledge can be construed as sets of possible worlds known under some mode of presentation or other, where knowledge-ascriptions do not yet make those modes explicit. Unlike fine-grained conceptions that reject the assumption, such coarse-grained conceptions of the objects of knowledge have the untoward consequence that failures of logical omniscience are no longer expressible in the logic. But even on coarse-grained conceptions, epistemic logic cannot be expected to be normal. Fine-grained conceptions allow for failures of logical omniscience to be expressible in the logic. On balance, fine-grained conceptions are to be preferred. Against this backdrop, candidate principles for inclusion in the logic of knowledge are critically reviewed in the light of general epistemological considerations. Very few survive closer scrutiny.
Grounds for justification
Authors: Rosenkranz Sven
Published: April 2021

We must distinguish between the condition of a proposition’s being justified in one’s situation and the metaphysical grounds determining that this condition obtains. While the former is luminous, the latter need not be. It is argued that knowing is a strict full ground for doxastic justification, and being in a position to know is a strict full ground for propositional justification. It follows that facts about one’s evidence that serve as strict partial grounds for knowing are strict partial grounds for doxastic justification, and facts about one’s evidence that serve as strict partial grounds for being in a position to know are strict partial grounds for propositional justification. Even if only partial, such evidential grounds can only be assumed to be available in some, but not all, cases in which one has doxastic justification without knowing, and propositional justification without being in a position to know. A more comprehensive account identifies facts about evidential probabilities as facts that yield strict full grounds for justification. While one’s evidence is the totality of what one is in a position to know, the evidential probability of p equals the probability of p conditional on one’s evidence. The account requires taking the notion of evidential probability as primitive. It uniformly applies to all cases of justification, including the bad cases envisaged by radical scepticism. Degrees of strength of justification are explained in terms of facts about evidential probabilities. Just as their grounds, degrees of strength of justification are not luminous, even if justification is.
Placing Contemporary Sovereign Debt
Authors: Datz Giselle
Published: April 2021

Since 2003, the battle between holdout creditors and the Argentine government in US courts has inspired a number of judicious studies on its legal underpinnings and repercussions. It has also prompted so-called ‘anti-vulture funds’ laws in countries like the UK, Belgium, and France. Despite these developments, the role of place in debt restructurings has remained relatively neglected. The paper analyses domestic laws protecting foreign debtors from minority holdout litigation and injunctive orders in federal courts that incite contractual changes as part of a fragmented landscape of local, and at times overlapping, spheres of sovereign debt governance, paradoxically embedded in a deeply integrated global financial system. A key finding of this analysis is that while contracts ground debt dynamics in specific jurisdictions (financial centres), they do not reduce uncertainty in the outcomes of sovereign debt restructurings. Moreover, financial centres have functioned not only as sites for private market-making, but also for public experimentation in international debt processes.
Contract Provisions, Default Risk, and Bond Prices
Authors: Chari Anusha , Leary Ryan
Published: April 2021

This chapter presents a case study that investigates the pricing of key contract provisions in Puerto Rican debt. It contributes to a body of research that asks whether investors price contract provisions and, if so, whether the pricing varies with credit risk. Contract provisions across different types of Puerto Rican bonds contain multiple sources of variation. Specifically, the chapter examines investor pricing of three key legal provisions of Puerto Rican debt; general obligation debt versus the secured bonds issued by the Puerto Rico Sales Tax Financing Corporation; debt issued under New York law versus Puerto Rican law; and finally impact of the Puerto Rico Oversight, Management, and Economic Stability Act (PROMESA) which retroactively enacted collective action clauses for Puerto Rican debt. In each instance, we find evidence consistent with the hypothesis that investors value specific contract provisions and legal protections and more so when credit risk is high, and restructuring becomes likely.
Deliberative Peace Referendums
Authors: Levy Ron , O'Flynn Ian , Kong Hoi L.
Published: April 2021

‘Peace referendums’, which seek to manage armed conflict, are increasingly common around the world. Yet such referendums remain erratic forces—liable as often to aggravate as to resolve tensions. In this book we consider when, despite their risks, referendums can play useful roles amid conflict. We argue that this largely depends on a referendum’s design, including how well it incorporates contemporary lessons from the theory and practice of deliberative democracy. Deliberative democracy seeks to channel disagreement into reasoned forms of decision-making—for instance, by identifying certain ‘public’ values around which disparate groups may find a measure of common ground. As yet, however, few deliberative democracy scholars have advanced arguments for referendums in conflict societies. This is unsurprising: while designing a referendum to be deliberative is a challenge even in the most peaceable of societies, in a conflict society it is harder still. Nevertheless, discounting deliberative institutional schemes because deliberation appears too difficult, and a society too conflictual, overlooks the possibility that some armed conflict can be traced to scarce opportunities to deliberate in the first place. Using a distinctive combination of deliberative democratic and constitutional theory, and also drawing from the field of conflict studies, we develop what we call the Deliberative Peace Referendum—a referendum held under conditions of conflict and designed to be deliberative. This kind of referendum has two broad objectives: to assist a peace settlement to be achieved, and to secure the settlement’s long-term resilience. After scaffolding a tenuous agreement, the referendum may help to concretize an agreement as a durable constitutional settlement by drawing on deliberative democracy’s perceived legitimacy. A Deliberative Peace Referendum thus takes aim at the standard pathologies of referendums—pathologies that must be addressed if referendums are to avoid repeating the problems of peace referendums in the past. Our purpose with this book is to rescue peace referendums from their habitual under-theorization and poor design, and to rehabilitate them as genuine tools of conflict management.
Settlement Achievement
Authors: O’Flynn. Levy
Published: April 2021

This chapter focuses on the first of two principal rationales supporting the use of peace referendums, namely settlement achievement. The chapter starts by locating the argument of the book in the public reason tradition, and specifically in the work of John Rawls. The chapter identifies how public values often feature in crucial, if generally under-appreciated, ways in peace agreements—not just as lofty aspirations but as powerful normative constraints on the content of particular constitutional clauses. The chapter then defends the claim that non-elites may be as, or even more, adept than some classes of elites (such as governmental, ethnic, or secessionist leaders) at deliberating about those values. We accept that constitutional settlements often contain a great deal of institutional detail; and we also accept that elites are usually better placed to deliberate about that detail. Yet we explain why the comparative advantage may rest with non-elites when it comes to deliberating about general public values. All of this is contingent on robust deliberative institutional supports being in place, both through the course of the referendum campaign and at the final vote.
Loosening the Need-Concept Tie
Authors: Queloz Matthieu
Published: April 2021

This chapter on E. J. Craig’s genealogy of the concept of knowledge aims to bring out four attractive features of the method. First, by examining its alleged incompatibility with knowledge-first epistemology, it is shown how genealogy allows one to treat as arising separately what in reality has to arise together, so that one can isolate a concept’s practical contribution even when it could not have arisen in isolation. Second, genealogy allows one to consider a concept’s development out of prior forms that more clearly display its relation to human needs even when these prior forms could not have been realized in history, for reasons that the genealogy itself brings out. Third, genealogy reveals practical pressures driving the de-instrumentalization of concepts, the process whereby concepts shed the traces of their origins in the needs of individual concept-users. And finally, the method allows one to assess and reconcile competing accounts of concepts.
The Zuiderzee Commission
Authors: Kox A. J. , Schatz H. F.
Published: April 2021

Chapter 10 deals with Lorentz’s very important role as the chairman of the State Commission for the enclosure and reclamation of the Zuiderzee and the inordinate amount of time he spent on this. He almost single-handedly designed and executed the hydrological calculations needed for the successful construction of the enclosure dam of this large inland body of water. It includes a detailed description of the Commission’s work, the difficulties that needed to be overcome, as well as the theoretical framework, recommendations, and predictions.
International cooperation in crisis
Authors: Kox A. J. , Schatz H. F.
Published: April 2021

Chapter 11 deals with the slow process of restoring international scientific cooperation after the end of the World War, highlighting the Dutch role and Lorentz’s untiring efforts in the various, at first unsuccessful attempts to include German scientists in international scientific cooperative bodies. In particular, his important role as member and later chairman of the commission for international intellectual cooperation of the League of Nations (CICI) is discussed.
Mutuality and Concepts of Responsible Business
Authors: Colin-Jones Alastair , Murthy Sudhir Rama
Published: April 2021

Chapter 6 places Economics of Mutuality in the context of a wider set of responsible business concepts, such as stakeholder theory. It considers whether these ideas represent fundamental ‘paradigm’ shifts in business or whether they are essentially modifications of existing theories It concludes that stakeholder theory was a significant shift away from shareholder-centric views of the firm, and, in line with stakeholder theory, Economics of Mutuality places corporate purposes other than shareholder value at the heart of the firm and derives business practices on the basis of that. But it differs from stakeholder theories in emphasizing the importance of relations with stakeholders in delivering corporate purposes not the interests of stakeholders themselves. It also differs from existing models in looking at the boundaries of the firm beyond traditional ownership rights and contractual arrangements. It is therefore a problem-solving view of the firm as against a financially or stakeholder-driven concept that embraces shareholders and stakeholders but does not put corporate purpose at the heart of either of them.
Delivering on Purpose
Authors: Ouarzazi Yassine El
Published: April 2021

Chapter 8 describes the process of ecosystem orchestration in more detail. It sets out an eight-step process around: (a) establishing a purpose, (b) designing metrics that measure the purpose, (c) identifying the relevant stakeholders, (d) mapping their objectives, capabilities, relationships, and pain points (i.e. problems), (e) selecting the pain points in the ecosystem that the organization should address, (f) measuring the baseline performance metrics before the intervention, (g) identifying, testing, and implementing the interventions to address the pain points, and (h) measuring the impact of the interventions on purpose and performance. The chapter emphasizes that the process of ecosystem orchestration involves the company placing the interests of the ecosystem and the ecosystem’s purpose against the company’s own self-interest at the centre of its own purpose. In so doing, the company should embrace the creation of mutuality of benefits not for enlightened self-interest but on a commitment to delivering the ecosystem purpose.
Mondragon
Authors: Ellis Justine , Colin-Jones Alastair , Zugasti Ibon
Published: April 2021

Mondragon is a federation of industrial cooperative associations with over 260 companies subsidiaries in thirty-five countries, founded in 1959 in Spain’s Basque Region. Today it employs seventy-five thousand workers producing revenues of approximately $14 billion. Membership of the cooperative gives employees equal rights to vote and ownership; management boards consist of employees from all levels of the organization; the highest managers earn no more than six times the salary of the lowest paid workers; no more than 20 per cent of workers can be temporary contractors; and the general assembly of worker-owners decides how to distribute 70 per cent of profits after tax. An illustration of the effect of the structure came with the collapse of the white-goods manufacturer and one of Mondragon’s largest cooperatives, Fagor. With 1,800 jobs at risk, Mondragon invested in cross-training employees to take on different roles at other cooperatives, transferred capital from stable to vulnerable cooperatives and placed 1,500 people in other cooperatives in the group.
Novo Nordisk
Authors: Jackson Ben , Ouarzazi Yassine El
Published: April 2021

Novo Nordisk, the Danish multinational pharmaceutical company, has taken an innovative approach to addressing diabetes around the world in a programme known as ‘Cities Changing Diabetes’. This involves partnering with patients, policymakers, health-care professionals and non-government organizations to find policies based on life-style changes that help people living in urban environments to avoid, manage, and treat the onset of type 2 diabetes. Community engagement with health, health-promoting policies, and health-system strengthening were the types of initiatives that were trialled, and impact measurements were undertaken to evaluate the performance of the programme.
Education
Authors: Casserley Catherine
Published: April 2021

This chapter looks at Part 6 of the Equality Act 2010, which sets out what is unlawful conduct in relation to education. Chapter 1 of Part 6 deals with schools; Chapter 2 with further and higher education; and Chapter 3 with general qualifications bodies. At the time of writing, there is no statutory code of practice in relation to either pre-16 education or further and higher education. The Equality and Human Rights Commission has produced non-statutory guidance, referred to as technical guidance, however, for schools and for further and higher education. There has been relatively little case law in the education field though what there has been has either been brought in the First-tier Tribunal (where disability discrimination cases in schools must be brought) or has tended to focus on race and religious discrimination and been litigated by way of judicial review.
Equality of Terms
Authors: McDonald Rhodri , Buckley Sophie
Published: April 2021

This chapter explores Part 5, Chapter 3 of the Equality Act 2010, which deals with equality in contractual terms and conditions of employment and occupational pension scheme rules. It deals with all aspects of equal pay law, i.e. the rules requiring that men and women doing equal work should have equal contractual and pension benefits. The chapter begins by briefly setting these provisions in context, addressing their relationship with discrimination law and EU law. It then looks at the sex equality clause (contract terms) and sex equality rule (pensions). Finally, the chapter concludes with a consideration of the maternity equality clause and maternity equality rule.
Patent Examination of Artificial Intelligence-related Inventions
Authors: Liu Jianchen , Liu Ming
Published: April 2021

To date, artificial intelligence (AI) has caused fundamental changes in inventing processes, and many issues are arising therefrom, especially whether and in what way inventions implemented by AI are patent-eligible under the current patent regime. To deal with the issue of patentability, some countries have adjusted their patent regime to AI-related inventions. As a major economy with a world-leading AI industry, China has accumulated abundant experience in examining applications with respect to AI-related inventions. This chapter focuses on China’s experience in the examination of AI-related inventions and its latest regulatory movements in this regard. More specifically, it revolves around China’s practice of modifying its Guidelines for Patent Examination (‘Guidelines’) to clear the way for AI-generated inventions in April 2017, reaching consensus on applying the Patent Law, Implementing Rules of the Patent Law, and the Guidelines to examining the applications of AI-generated inventions, and further revising the Guidelines in December 2019 to make them more suitable for AI-related inventions. This chapter argues that these experiences can be a useful benchmark for other jurisdictions to grant patent rights to AI-related inventions.
The signatures of organellar calcium
Authors: Resentini Francesca , Ruberti Cristina , Grenzi Matteo , Bonza Maria Cristina , Costa Alex
Published: April 2021

Recent insights about the transport mechanisms involved in the in and out of calcium ions in plant organelles, and their role in the regulation of cytosolic calcium homeostasis in different signaling pathways.
Stock Return Extrapolation, Option Prices, and Variance Risk Premium
Authors: Atmaz Adem
Published: April 2021

This paper presents a tractable dynamic equilibrium model of stock return extrapolation in the presence of stochastic volatility. In the model, consistent with survey evidence, investors expect future returns to be higher (lower) but also less (more) volatile following positive (negative) stock returns. The biased volatility expectation introduces a new channel through which past returns and investor sentiment affect derivative prices. In particular, through this novel channel, the model reconciles the otherwise puzzling evidence of past returns affecting option prices and the evidence of variance risk premium predicting future stock market returns even after controlling for the realized variance.
Framing disruption: how a regulatory capture frame legitimized the deregulation of Boston’s ride-for-hire industry
Authors: Adler Laura
Published: April 2021

The theory of regulatory capture has long been used to make the case for deregulation by questioning the legitimacy of government’s regulatory function. How do government officials, who are tasked with regulating, embrace deregulation? This article explores that question in the context of Boston’s debate over regulating transportation network companies (TNCs). Analyzing media coverage, I identify two types of frames that emerged as stakeholders attempted to influence TNC regulation: issue frames aimed to shape the interpretation of the ride-for-hire industry, while meta-frames shifted the focus of debate from TNCs to regulation itself. Specifically, a meta-frame invoking the theory of regulatory capture became central. Supplementing media coverage with in-depth interviews, I show that government officials did not refute the capture frame but rather used this frame to draw a distinction between legitimate and illegitimate regulation. I propose that these distinctions are central to legitimizing a deregulatory agenda, as officials condemn specific types of regulation in order to shore up the broader category of regulation. The case sheds light on how the idea of government as an impediment to innovation is embraced by government officials themselves, paving the way for new market configurations.
Sensitivity and threshold dynamics ofPinus strobusandQuercusspp. in response to experimental and naturally occurring severe droughts
Authors: Asbjornsen Heidi , McIntire Cameron D , Vadeboncoeur Matthew A , Jennings Katie A , Coble Adam P , Berry Z Carter
Published: April 2021

Increased drought frequency and severity are a pervasive global threat, yet the capacity of mesic temperate forests to maintain resilience in response to drought remains poorly understood. We deployed a throughfall removal experiment to simulate a once in a century drought in New Hampshire, USA, which coupled with the region-wide 2016 drought, intensified moisture stress beyond that experienced in the lifetimes of our study trees. To assess the sensitivity and threshold dynamics of two dominant northeastern tree genera (Quercus and Pinus), we monitored sap flux density (Js), leaf water potential and gas exchange, growth and intrinsic water-use efficiency (iWUE) for one pretreatment year (2015) and two treatment years (2016–17). Results showed that Js in pine (Pinus strobus L.) declined abruptly at a soil moisture threshold of 0.15 m3 m−3, whereas oak’s (Quercus rubra L. and Quercus velutina Lam.) threshold was 0.11 m3 m−3—a finding consistent with pine’s more isohydric strategy. Nevertheless, once oaks’ moisture threshold was surpassed, Js declined abruptly, suggesting that while oaks are well adapted to moderate drought, they are highly susceptible to extreme drought. The radial growth reduction in response to the 2016 drought was more than twice as great for pine as for oaks (50 vs 18%, respectively). Despite relatively high precipitation in 2017, the oaks’ growth continued to decline (low recovery), whereas pine showed neutral (treatment) or improved (control) growth. The iWUE increased in 2016 for both treatment and control pines, but only in treatment oaks. Notably, pines exhibited a significant linear relationship between iWUE and precipitation across years, whereas the oaks only showed a response during the driest conditions, further underscoring the different sensitivity thresholds for these species. Our results provide new insights into how interactions between temperate forest tree species’ contrasting physiologies and soil moisture thresholds influence their responses and resilience to extreme drought.
Physicians Leading Physicians
Authors: Ruiz Colón Gabriela , Yang Jingkun , Svec David , Heidenreich Paul , Britt Patricia , Smith Margaret , Sharp Christopher , Shieh Lisa
Published: April 2021

Following the adoption of an acuity-adaptable unit model in an academic medical center, a $13M increase in cost of intermediate intensive care unit (IICU) accommodations was observed. The authors followed A3 methodology to determine the root cause of this increase and developed a 3-prong intervention centered on physician engagement, given that physicians have the ability to order a patient’s level of care. This intervention consisted of: (1) identifying physician champions to promote appropriate IICU use, (2) visual changes to essential electronic medical record tools, and (3) data-driven feedback to physician champions. In the year following intervention deployment, average IICU length of stay decreased from 1.08 to 0.62 days and average IICU use decreased from 21.4% to 12.3%, corresponding to ~$5.7M cost savings with no significant change in balancing measures observed. Together, these results demonstrate that a multicomponent intervention aimed at engaging physicians reduced inappropriate IICU use with no increase in adverse events.
Prevalence of Anxiety in Smoking Cessation: A Worldwide Systematic Review and Meta-analysis
Authors: Amiri Sohrab
Published: April 2021

Objectives:

Smoking cessation can have a significant impact on mental health, so this study aimed to investigate the prevalence of anxiety after smoking cessation by a worldwide systematic review and meta-analysis.

Methods:

PubMed and Scopus were selected for the study and these were systematically searched until October 2020 based on a syntax of keywords. This search in these 2 databases is limited to English. The event and sample size were used to assess the prevalence of anxiety. The prevalence of anxiety was also assessed based on anxiety disorders and continents. The odds ratio (OR) was used to compare the odd of anxiety in smoking cessation versus nonsmokers and smokers as reference groups based on a random-effects method. Heterogeneity and publication bias were assessed.

Results:

The prevalence of anxiety after smoking cessation is 19% with a confidence interval (CI) of 14%-24%. Among anxiety disorders, it was the highest prevalence for social anxiety with 29% prevalence. The prevalence of anxiety after smoking cessation in America is 15% and in Europe is 29%. Smoking cessation has a higher odd of anxiety than nonsmokers (OR=1.20; CI: 1.12-1.29). Smoking cessation has a lower odd of anxiety than smokers (OR=0.77; CI: 0.66-0.89).

Discussion:

Since smoking cessation is a factor that reduces anxiety, so in studies in this area as well as therapeutic interventions, it is necessary to consider this issue.
Therapeutic Implications of NLRP3-Mediated Inflammation in Coronary Artery Disease
Authors: Hemenway Gregory , Frishman William H.
Published: April 2021

Atherosclerosis is considered a chronic, inflammatory disease responsible for more than 15% of all global deaths, secondary to its complications of myocardial infarction, vascular disease, and stroke. Current treatment regimens consist of lipid-lowering pharmaceuticals, control of risk factors, and prevention of plaque rupture and thrombosis with antiplatelet agents. However, a significant burden on society remains due to the morbidity and mortality of coronary artery disease despite our best practices. In addition to dyslipidemia and hemostasis, inflammation has now moved to the proverbial forefront as the remaining obstacle to appropriate management of atherosclerosis. A complex dance of endothelial dysfunction, complement activation, and immune cell-mediated cytokine release underlie the pathogenesis of atherosclerotic plaque development, destabilization, and rupture. Cholesterol-induced sterile inflammation is thought to be central to this process via activation of a protein complex called the nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) inflammasome. The focus of this review article will be to examine the NLRP3 inflammasome, which directs the release of interleukin-1, leading to downstream pro-inflammatory effects, and its potential for therapeutic targeting using currently available and future tools in our pharmacologic arsenal. In particular, we focus on the results of several large, recently concluded clinical trials including the Canakinumab Antiinflammatory Thrombosis Outcome Study, Colchicine Cardiovascular Outcomes Trial, and the Low-Dose Colchicine Study, examining the efficacy of direct inhibition of interleukin-1 with canakinumab or a multimodal approach to inhibiting the NLRP3 inflammasome using colchicine, as well as an overview of novel small molecule inhibitors that are still in development.
A Systematic Review of Nurse-Led Antiretroviral Medication Adherence Intervention Trials: How Nurses Have Advanced the Science
Authors: Lambert Crystal Chapman , Galland Brooke , Enriquez Maithe , Reynolds Nancy R.
Published: April 2021

Antiretroviral therapy (ART) is essential to achieving viral suppression and improving health and clinical outcomes in persons living with HIV. Despite the effectiveness of ART and many promising evidence-based ART adherence interventions, viral suppression rates continue to be less than optimal. Nurses play pivotal roles in HIV care management, yet their role in the development and delivery of evidence-based adherence interventions has received little attention. Therefore, this review examined the contributions of nurses to ART adherence research and delivery. We found that nurse-led and nurse-facilitated interventions can be effective in fostering ART adherence in persons living with HIV. Considering the role nurses play in HIV care management and the effectiveness of interventions involving nurses, more nurse-led and nurse-facilitated interventions to address ART adherence are indicated. However, there is a need for further research to examine multilevel interventions and comparative cost and effectiveness of nurse-delivered ART interventions with other forms of delivery.
Work From Home During the COVID-19 Outbreak
Authors: Galanti Teresa , Guidetti Gloria , Mazzei Elisabetta , Zappalà Salvatore , Toscano Ferdinando
Published: April 2021

Objective:

The COVID-19 pandemic made working from home (WFH) the new way of working. This study investigates the impact that family-work conflict, social isolation, distracting environment, job autonomy, and self-leadership have on employees’ productivity, work engagement, and stress experienced when WFH during the pandemic.

Methods:

This cross-sectional study analyzed data collected through an online questionnaire completed by 209 employees WFH during the pandemic. The assumptions were tested using hierarchical linear regression.

Results:

Employees’ family-work conflict and social isolation were negatively related, while self-leadership and autonomy were positively related, to WFH productivity and WFH engagement. Family-work conflict and social isolation were negatively related to WFH stress, which was not affected by autonomy and self-leadership.

Conclusion:

Individual- and work-related aspects both hinder and facilitate WFH during the COVID-19 outbreak.
OpenEar Image Data Enables Case Variation in High Fidelity Virtual Reality Ear Surgery
Authors: Sieber Daniel Manuel , Andersen Steven Arild Wuyts , Sørensen Mads Sølvsten , Mikkelsen Peter Trier
Published: April 2021

Background:

Virtual reality (VR) simulation is an established option for temporal bone surgical training. Most VR simulators are based on computed tomography imaging, whereas the Visible Ear Simulator (VES) is based on high-fidelity cryosections of a single temporal bone specimen. Recently published OpenEar datasets combine cone-beam computed tomography (CBCT) and micro-slicing to achieve similar model quality. This study explores integration of OpenEar datasets into VES to enable case variation in simulation with implications for patient-specific modeling based on CBCT.

Methods:

The OpenEar dataset consists of segmented, coregistered, multimodal imaging sets of human temporal bones. We derived drillable bone segments from the dataset as well as triangulated surface models of critical structures such as facial nerve or dura. Realistic visualization was achieved using coloring from micro-slicing, custom tinting, and texture maps. Resulting models were validated by clinical experts.

Results:

Six of the eight OpenEar datasets could be integrated in VES complete with instructional guides for various temporal bone surgical procedures. Resulting models were of high quality because of postprocessing steps taken to increase realism including colorization and imaging artifact removal. Bone artifacts were common in CBCT, resulting in dehiscences that most often could not be found in the ground truth micro-slicing data.

Conclusion:

New anatomy models are included in VES version 3.5 freeware and provide case variation for training which could help trainees to learn more quickly and transferably under variable practice conditions. The use of CBCT for VR simulation models without postprocessing results in bone artifacts, which should be considered when using clinical imaging for patient-specific simulation, surgical rehearsal, and planning.
Progression Toward Decompensated Right Ventricular Failure in the Ovine Pulmonary Hypertension Model
Authors: Ukita Rei , Tumen Andrew , Stokes John W. , Pinelli Christopher , Finnie Kelsey R. , Talackine Jennifer , Cardwell Nancy L. , Wu W. Kelly , Patel Yatrik , Tsai Emily J. , Rosenzweig Erika B. , Cook Keith E. , Bacchetta Matthew
Published: April 2021

Decompensated right ventricular failure (RVF) in patients with pulmonary hypertension (PH) is fatal, with limited treatment options. Novel mechanical circulatory support systems have therapeutic potential for RVF, but the development of these devices requires a large animal disease model that replicates the pathophysiology observed in humans. We previously reported an effective disease model of PH in sheep through ligation of the left pulmonary artery (PA) and progressive occlusion of the main PA. Herein, we report a case of acute decompensation with this model of chronic RVF. Gradual PA banding raised the RV pressure (maximum RV systolic/mean pressure = 95 mmHg/56 mmHg). Clinical findings and laboratory serum parameters suggested appropriate physiologic compensation for 7 weeks. However, mixed venous saturation declined precipitously on week 7, and creatinine increased markedly on week 9. By the 10th week, the animal developed dependent, subcutaneous edema. Subsequently, the animal expired during the induction of general anesthesia. Post-mortem evaluation revealed several liters of pleural effusion and ascites, RV dilatation, eccentric RV hypertrophy, and myocardial fibrosis. The presented case supports this model’s relevance to the human pathophysiology of RVF secondary to PH and its value in the development of novel devices, therapeutics, and interventions.
Exploring Popular Social Media Networks for Patients With Inflammatory Bowel Diseases
Authors: Goren Idan , Sharvit Gal , Godny Lihi , Fatal Sarine E. , Barkan Revital , Hag Ola , Ollech Jacob E. , Ziv-Baran Tomer , Leshno Moshe , Turner Dan , Dotan Iris , Yanai Henit
Published: April 2021

Goal:

The aim was to assess topics of interest and concerns among patients with inflammatory bowel diseases (IBD) who are active online.

Background:

Social media (SM) networks are a major communication tool for patients with IBD and health care professionals.

Patients and Methods:

We performed an anonymized investigation of SM networks for IBD patients; I-a thematic analysis of patients’ posts, II-an online survey advertised through Facebook and other popular SM networks throughout November 2019.

Results:

Analyzing 2133 posts (2014 to 2019) revealed 18 topics of interest. The online survey was completed by 534 respondents [63%-Crohn’s disease, 56%-female, median age-38 years (interquartile range: 28.7 to 51.0)]. Most respondents (70%) were followed in referral centers, and 45% were receiving biological therapy. Respondents reported high satisfaction with IBD care and health care provider professionalism. The top 5 topics of interest were diet, lifestyle, complementary and alternative medicine, diagnostic test interpretation, and specialist referrals and reviews. Cluster analysis demonstrated that gender, income, and education level were associated with specific interest and concerns.

Conclusion:

Patients’ activity on SM is independent of their satisfaction with formal IBD care and rather reflects an ongoing need for information and support. These needs may be addressed both in clinical settings and through online tools.
Alcohol and Breast Cancer
Authors: Balaam Sarah , Bailey Tom G. , Anderson Debra , Retell James , McCarthy Alexandra L.
Published: April 2021

Background

There is evidence that drinking alcohol increases the risk of recurrent breast cancer. It is unclear whether Australian women with breast cancer are aware of this evidence or modify their alcohol intake accordingly.

Objective

This article reports a secondary analysis of data from the Women's Wellness after Cancer Program (WWACP) randomized controlled trial (N = 351). The WWACP aimed to enhance quality of life and reduce chronic disease risk in women previously treated for cancer through lifestyle modification. Here we provide the alcohol-related data from the study's breast cancer participants (n = 269). We analyzed baseline alcohol consumption, the variables associated with alcohol intake, and intervention effect on intake at weeks 12 (end of intervention) and 24 (to determine sustainability).

Interventions/Methods

Measures included the Dietary Questionnaire for Epidemiological Studies, Short Form-36, International Physical Activity Questionnaire, Green Climacteric Scale, Pittsburgh Sleep Quality Index, and Center for Epidemiologic Studies Depression Scale.

Results

Most participants practiced safe alcohol consumption. Among drinkers, drinking caffeine, smoking, emotional and physical role limitations, and greater discomfort with vasomotor symptoms were associated with increased intake. Relative to baseline, alcohol consumption decreased from 5.22 g/d to 4.18 g/d in the intervention group, whereas consumption increased among control subjects at 12 weeks. No difference between groups was observed at week 24.

Conclusion

The intervention was associated with less alcohol intake at week 12 among drinkers, but this reduction was not sustained at the 24-week follow-up.

Implications for Practice

Future iterations of the WWACP will emphasize stronger messaging and supports regarding alcohol consumption after breast cancer treatment.
Sustaining a Concept-Based Curriculum
Authors: Solheim Karen , Mittelstadt Karen , Muehrer Rebecca , Pinekenstein Barbara , Willis Danny
Published: April 2021

Background

Many schools of nursing are transitioning to a concept-based curriculum (CBC) to better prepare students to practice across complex practice settings.

Problem

Current literature focused on transitioning to a CBC lacks discussion on how to sustain a CBC once it is implemented.

Approach

In this article, the authors emphasize the importance of intentionally sustaining a dynamic CBC and provide strategies to accomplish this aspect of the curriculum trajectory.

Conclusion

The authors recommend a multipronged approach to sustainability that takes into account the dynamic nature of curricular change, implementation, and evaluation. Strategies are centered around themes of promoting effective use of a dynamic curricular model, stakeholder engagement, and leadership.
Augmentation of Perforator Flap Blood Supply with Vascular Supercharge or Flap Prefabrication: Evaluation in a Rat Model
Authors: Huang Xin , Liu Daiming , Gu Shuchen , Pu Lee L. Q. , Xu Xiangwen , Khoong Yimin , Wang Zi , Zhao Yixuan , Gao Yashan , Zan Tao
Published: April 2021

Background:

Vascular supercharge and flap prefabrication are two surgical maneuvers to improve flap blood supply. Although these techniques have been studied intensively, few studies have focused on the differences between supercharge and prefabricated flaps regarding their flap survival areas, vasculatures, and hemodynamics.

Methods:

In this study, 21 male Sprague-Dawley rats were divided into three groups as follows: group A, single perforator flap; group B, supercharge flap; and group C, prefabricated flap. Flap survival was measured 1 week after flap elevation. Indocyanine green angiography was applied to visualize flap vascularity and to analyze flap hemodynamics. Von Willebrand factor immunohistochemical staining was applied to assess the number of microvessels in the choke zone of the abdominal wall.

Results:

The flap survival areas were expanded significantly in the arteriovenous supercharge group and the vascular bundle prefabricated group compared with that in the single-perforator group (81.34 ± 8.12 percent and 75.51 ± 8.08 percent versus 46.27 ± 10.01 percent, respectively; p < 0.05). Hemodynamic analysis suggested that although a significant increase in arterial infusion could be achieved with flap prefabrication, the venous effusion of the prefabricated flap was the worst among the three groups, indicating greater susceptibility to compromised venous return. Active neovascularization was confirmed by an increased number of microvessels in group C. Specifically, the dilatation of choke vessels and the newly formed vessels of the prefabricated pedicle could be appreciated by indocyanine green angiographic mapping.

Conclusions:

Both vascular supercharge and flap prefabrication can augment the blood supply of the perforator flap but by means of different mechanisms. Because a supercharge flap is less susceptible to venous compromise, it is suggested to first consider the use of vascular supercharging when feasible.
Effect of Reduction Mammoplasty on Pulmonary Function Tests
Authors: Guliyeva Gunel , Cheung Joseph Y. , Avila Francisco R. , Huayllani Maria T. , Boczar Daniel , Broer Peter N. , Forte Antonio Jorge
Published: April 2021

In patients with breast hypertrophy, excessive breast weight applies pressure on the thorax, which may disrupt the normal breathing. The purpose of this study is to evaluate the impact of the breast hypertrophy and reduction mammoplasty on respiratory function. A comprehensive search of 3 databases, PubMed, Ovid, and Scopus databases, was performed. “Mammoplasty” and “respiration or pulmonary function tests” were the keywords used to search for relevant articles. Ten studies involving 280 patients with breast hypertrophy were included in the final review. Seven articles demonstrated an increase in at least 1 pulmonary function test value after the surgery. This systematic review revealed that, preoperatively, pulmonary function test values of the patients are usually in the normal range. Nonetheless, reduction mammoplasty still improves lung function parameters. Additionally, patients with respiratory complaints felt improvement in their symptoms after the surgery. However, future studies are needed, as heterogeneity among studies was observed.
Outcomes of Living Kidney Donor Candidate Evaluations in the Living Donor Collective Pilot Registry
Authors: Kasiske Bertram L. , Ahn Yoon Son , Conboy Michael , Dew Mary Amanda , Folken Christian , Levan Macey , Israni Ajay K. , Lentine Krista L. , Matas Arthur J. , Newell Kenneth A. , LaPointe Rudow Dianne , Massie Allan B. , Musgrove Donald , Snyder Jon J. , Taler Sandra J. , Wang Jeffrey , Waterman Amy D.
Published: April 2021

Background.

Gaps in our knowledge of long-term outcomes affect decision making for potential living kidney donors.

Methods.

The Scientific Registry of Transplant Recipients was asked to determine the feasibility of a candidate registry.

Results.

Ten living kidney donor programs evaluated 2107 consecutive kidney donor candidates; 2099 of 2107 (99.6%) completed evaluations, 1578 of 2099 (75.2%) had a decision, and 790 of 1578 (50.1%) were approved to donate as of March 12, 2020. By logistic regression, candidates most likely to be approved were married or had attended college or technical school; those least likely to be approved had ≥1 of the following characteristics: Black race, history of cigarette smoking, and higher blood pressure, higher triglycerides, or higher urine albumin-to-creatinine ratios. Reasons for 617 candidates not being approved included medical issues other than chronic kidney disease risk (25.3%), chronic kidney disease risk (18.5%), candidate withdrawal (15.2%), recipient reason (13.6%), anatomical risk to the recipient (10.3%), noneconomic psychosocial (10.3%), economic (0.5%), and other reasons (6.4%).

Conclusions.

These results suggest that a comprehensive living donor registry is both feasible and necessary to assess long-term outcomes that may inform decision making for future living donor candidates. There may be socioeconomic barriers to donation that require more granular identification so that active measures can address inequities. Some candidates who did not donate may be suitable controls for discerning the appropriateness of acceptance decisions and the long-term outcomes attributable to donation. We anticipate that these issues will be better identified with modifications to the data collection and expansion of the registry to all centers over the next several years.
Integrative molecular and clinical profiling of acral melanoma identifies LZTR1 as a key tumor promoter and therapeutic target
Authors: Farshidfar Farshad , Peng Cong , Levovitz Chaya , Knight James , Bacchiocchi Antonella , Su Juan , Rhrissorrakrai Kahn , Yin Mingzhu , Sznol Mario , Ariyan Stephan , Clune James , Olino Kelly , Parida Laxmi , Nikolaus Joerg , Zhang Meiling , Zhao Shuang , Wang Yan , Huang Gang , Wan Miaojian , Li Xianan , Cao Jian , Yan Qin , Chen Xiang , Newman Aaron M. , Halaban Ruth
Published: April 2021

Acral melanoma, the most common melanoma subtype among non-Caucasian individuals, is associated with poor prognosis. However, its key molecular drivers remain obscure. Here, we performed integrative genomic and clinical profiling of acral melanomas from a cohort of 104 patients treated in North America or China. We found that recurrent, late-arising amplifications of cytoband chr22q11.21 are a leading determinant of inferior survival, strongly associated with metastasis, and linked to downregulation of immunomodulatory genes associated with response to immune checkpoint blockade. Unexpectedly, LZTR1 – a known tumor suppressor in other cancers – is a key candidate oncogene in this cytoband. Silencing of LZTR1 in melanoma cell lines caused apoptotic cell death independent of major hotspot mutations or melanoma subtypes. Conversely, overexpression of LZTR1 in normal human melanocytes initiated processes associated with metastasis, including anchorage-independent growth, formation of spheroids, and increased levels of MAPK and SRC activities. Our results provide new insights into the etiology of acral melanoma and implicate LZTR1 as a key tumor promoter and therapeutic target.
Early immune pressure imposed by tissue resident memory T cells sculpts tumour evolution in non-small cell lung cancer
Authors: Weeden Clare E , Gayevskiy Velimir , Trussart Marie , Marceaux Claire , Ribera Nina Tubau , Batey Daniel , Teh Charis E , Mitchell Andrew J , Antippa Phillip , Leong Tracy , Steinfort Daniel , Irving Louis , Gordon Claire L , Swanton Charles , Speed Terence P , Gray Daniel HD , Asselin-Labat Marie-Liesse
Published: April 2021

Tissue-resident memory T cells (TRM) provide immune defence against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts TRMactivation and how the immune pressure exerted by TRMaffects developing tumours in humans. We performed deep profiling of lung cancers arising in never-smokers (NS) and ever-smokers (ES), finding evidence of enhanced TRMimmunosurveillance in ES lung. Only tumours arising in ES patients underwent clonal immune escape, even when evaluating cancers with similar tumour mutational burden to NS patients, suggesting that the timing of immune pressure exerted by TRMis a critical factor in the evolution of tumour immune evasion. Tumours grown in T cell quiescent NS lungs displayed little evidence of immune evasion and had fewer neoantigens with low diversity, paradoxically making them amenable to treatment with agonist of the costimulatory molecule, ICOS. These data demonstrate local environmental insults enhance TRMimmunosurveillance of human tissue, shape the evolution of tumour immunogenicity and that this interplay informs effective immunotherapeutic modalities.