Large Gray Area Research Articles

Real-world applicability of differentiated thyroid cancer guidelines.

Thyroid cancer (TC) is the most common endocrine malignancy with constantly growing incidence. Radioiodine ablation is a safe and effective method for managing TC. Recently various Guidelines (GL) have been published on whom should be ablated, when and under which circumstances. Our study compares 6 GL with a given patient cohort. Additionally, we evaluated each GL's quality via an independent tool. We compared six Guidelines (GL) for TC ablation on a cohort of 336 patients, implementing GL retrospectively: 2009 and 2016 American Thyroid Association (ATA), European Thyroid Association's (ETA) Consensus Statement, UK's National Institute for Health and Care Excellence (NICE), German position paper from Surgery and Nuclear Medicine (German) and European Association of Nuclear Medicine and Society of Nuclear Medicine and Molecular Image (EANM/SNMMI). Quality assessment was conducted using the Appraisal of Guidelines, Research and Evaluation instrument II (AGREE II). Results showed significant variability among GL. American Thyroid Association 2016, a clear improvement of the ATA 2009, presents a large grey area of "probable ablation candidates". European Thyroid Association and NICE agree that only a small portion of our ablated patients would benefit from it and the AGREE II tool shows a lack of applicability, but very good scores elsewhere. German and EANM/SNMMI GL agree that most of our clinical decisions to ablate were correct and their AGREE II scores are the highest in all six domains. Considering that dynamic risk classification plays a major role in determining the most appropriate treatment, it appears that the guidelines should be updated in order to support individualized patient management. However, it is the experience of the individual physician that will determine the final decision.

P-388 Is access to egg freezing equitable and fair? A comparison between policies in Belgium and France

Abstract Study question What underlying norms and values are the inclusion and exclusion criteria for egg freezing in Belgium and France based on? Are they equitable and fair? Summary answer Exclusion criteria are desirable from a distributive justice viewpoint. While age limits are justifiable, criteria such as oncological vs non-oncological and gender are not equitable. What is known already In 2018, the Belgian federal institute for health insurance (RIZIV or ENAMI) decided on health insurance coverage for the retrieval, freezing and storing of gametes and gonadal tissues for fertility preservation. This coverage is however not available to all candidates for egg freezing, but strongly directed towards oncology patients. France took a different approach. Since the French Law on Bioethics was passed in August 2021, egg freezing is available to all women between their 29th and 37th birthday. Egg harvesting is covered by public health insurance, but not the storage costs. Study design, size, duration This is a normative analysis in which the different inclusion and exclusion criteria from the Belgian and French system are critically analysed in light of existing ethical scholarship on access to egg freezing from the past decade. Special attention is paid to arguments relating to justice as fairness. Participants/materials, setting, methods Literature research; normative analysis The method that is used to bring empirical data (as found in literature research) and normative ethics together is the ‘Wide Reflective Equilibrium’, the most commonly used method in bioethics. Main results and the role of chance While the French system, allowing access to a great range of people, appears to be the most fair, the opportunity costs involved plead for the implementation of inclusion and exclusion criteria to make sure that resources are allocated in a more equitable manner. These criteria should be based on effectiveness and social justice. Looking at the currently implemented criteria, the distinction between medical and non-medical or between oncological and non-oncological conditions is difficult to justify given the large grey area where these categories overlap. For example, in Belgium several categories of people at risk of losing their fertility are excluded: transmen receiving gender-confirming therapy, people needing a stem cell transplant for other than hematopoietic reasons (e.g. sickle cell anaemia) or women nearing the end of their reproductive lifespan (also if due to previous cancer treatment). Arguments in favour of age limits are effectiveness and the avoidance of false hope for people of advanced reproductive age. Arguments against are founded on concerns of ageism and social injustice. Of the potential arguments arguing for gender limits – specifically the exclusion of transmen – none appear convincing, while access for transmen is problematic both in Belgium and France. Limitations, reasons for caution This analysis is a case study of two countries, not a comprehensive or representative analysis of European policies. Wider implications of the findings Countries that are considering implementing systems for coverage of egg freezing by public funding, can learn from these case studies to better finetune their inclusion and exclusion criteria. Trial registration number N/A

Touchdown Jesus? Analyzing Establishment Clause Concerns in Public University College Football

This research explores the history and evolution of the Establishment Clause from the Everson v. Board of Education (1947) separation of church and state framework, to the newly anointed accommodationist approach preferred in the Kennedy v. Bremerton School District (2022), within the context of college football at public universities. Player-led prayers, coach-led prayers, PA system-led prayer, the use of team chaplains, and other acts of religious expression are thoroughly discussed. College football coaches have a unique relationship with the student-athletes on their team, which includes examination of the Establishment Clause and the role of coercion (Chaudhuri v. Tennessee (1997); Lee v. Weisman, (1992); Mellen v. Bunting (2003). Similarly, the Supreme Court’s decision in Kennedy v. Bremerton (2022) to cast aside the Lemon Test analysis in favor of an approach that accommodates the traditional aspects of prayer applies the precedent from Marsh v. Chambers (1983) and Town of Greece v. Galloway (2014). While it is clear the use of team chaplains, coaches who actively proselytize at public institutions, and the use of the PA system for prayer at public institutions violates the Establishment Clause, coaches who engage in quiet, private prayer do not under the precedent established in Kennedy v. Bremerton (2022). However, this recent Supreme Court ruling leaves a large gray area of unanswered application relative to player-led team prayers, having a team prayer, coach-led prayer that is not quiet and private, and the role of coercion in the legal analysis.

Role of miRNA-145, 148, and 185 and Stem Cells in Prostate Cancer.

MicroRNAs (miRNAs) are small non-coding RNA molecules that play a role in cancer linked to the regulation of important cellular processes and pathways involving tumorigenesis, cell proliferation, differentiation, and apoptosis. A lot of human miRNA sequences have been identified which are linked to cancer pathogenesis. MicroRNAs, in prostate cancer (PC), play a relevant role as biomarkers, show a specific profile, and have been used as therapeutic targets. Prostate cancer (PC) is the most frequently diagnosed cancer in men. Clinical diagnoses among the gold standards for PC diagnosis and monitoring are prostate-specific antigen (PSA) testing, digital rectal examination, and prostate needle biopsies. PSA screening still has a large grey area of patients, which leads to overdiagnosis. Therefore, new biomarkers are needed to improve existing diagnostic tools. The miRNA expression profiles from tumour versus normal tissues are helpful and exhibit significant differences not only between cancerous and non-cancerous tissues, but also between different cancer types and subtypes. In this review, we focus on the role of miRNAs-145, 148, and 185 and their correlation with stem cells in prostate cancer pathogenesis. MiR-145, by modulating multiple oncogenes, regulates different cellular processes in PC, which are involved in the transition from localised to metastatic disease. MiR-148 is downregulated in high-grade tumours, suggesting that the miR-148-3 family might act as tumour suppressors in PC as a potential biomarker for detecting this disease. MiR-185 regulation is still unclear in being able to regulate tumour processes in PC. Nevertheless, other authors confirm the role of this miRNA as a tumour suppressor, suggesting its potential use as a suitable biomarker in disease prognosis. These three miRNAs are all involved in the regulation of prostate cancer stem cell behaviour (PCSCs). Within this contest, PCSCs are often involved in the onset of chemo-resistance in PC, therefore strategies for targeting this subset of cells are strongly required to control the disease. Hence, the relationship between these two players is interesting and important in prostate cancer pathogenesis and in PCSC stemness regulation, in the attempt to pave the way for novel therapeutic targets in prostate cancer.

Early Irish Lexicography ‒ A Research Survey

This article is primarily concerned with lexicographic resources, i.e. glossaries, word-lists, dictionaries, and lexica of various shapes and form, for Early Irish. Early Irish comprises of several distinct stages of the Irish language: Primitive Irish (c. 4th–6th centuries A.D.), almost solely attested in Ogam inscriptions, Early or Archaic Old Irish (c. 7th century), Old Irish (c. 8th–9th centuries), and Middle Irish (c. 10th–12thcenturies), the latter three transmitted through manuscripts. A large grey area exists between lexicographic resources in the strict sense and monographs that treat subsec-tions of the Early Irish lexicon under particular phonological, morphological, or other grammatical perspectives. However, examples of the latter, unless they contain sub-stantial lexicon-like portions, will not be considered here.

The large grey area between ‘bona fide’ and ‘rogue’ stem cell interventions — Ethical acceptability and the need to include local variability

This article aims to put into perspective the binary opposition between ‘scientific’ clinical research trials and ‘rogue’ experimental stem cell therapies, and to show why the ethics criteria used by the dominant science community are not suitable for distinguishing between adequate and inadequate treatments. By focusing on the grey area between clinical stem cell trials and stem cell experimentation, the experimental space where patients, medical professionals and life scientists negotiate for diverging reasons and aims, I show why idealised notions of ethics are not feasible for many stem cell scientists in low- and middle-income countries.Drawing on fieldwork in China from 2012 to 2013, the article asks why ‘the unethical’ according to some is acceptable to Chinese life scientists. The case study of stem cell service provider Beike Biotech illustrates how stem cell interventions take place in a large grey area, where narrow notions of ethics are blurred with and supplanted by broader notions of ethics, co-determined by estimations of socio-economic, political and cultural understandings of risk, opportunity and benefit.I borrow the term ‘bionetworking’, understood as the entrepreneurial aspects of scientific networks that engage in creating biomedical products, to analyse various forms of medical experimentation. I speak of the ‘externalisation’ and ‘internalisation’ of local factors to elucidate how features of patient populations and their environments are subsumed in clinical research applications. Compared to polarised views of stem cell therapy, this approach increases the transparency of clinical interventions and broadens our understanding of why ‘stem cell tourism’ to some is ‘stem cell therapy’ to others.

Comparing national home-keeping and the regulation of translational stem cell applications: An international perspective

A very large grey area exists between translational stem cell research and applications that comply with the ideals of randomised control trials and good laboratory and clinical practice and what is often referred to as snake-oil trade. We identify a discrepancy between international research and ethics regulation and the ways in which regulatory instruments in the stem cell field are developed in practice. We examine this discrepancy using the notion of ‘national home-keeping’, referring to the way governments articulate international standards and regulation with conflicting demands on local players at home.Identifying particular dimensions of regulatory tools – authority, permissions, space and acceleration – as crucial to national home-keeping in Asia, Europe and the USA, we show how local regulation works to enable development of the field, notwithstanding international (i.e. principally ‘western’) regulation. Triangulating regulation with empirical data and archival research between 2012 and 2015 has helped us to shed light on how countries and organisations adapt and resist internationally dominant regulation through the manipulation of regulatory tools (contingent upon country size, the state's ability to accumulate resources, healthcare demands, established traditions of scientific governance, and economic and scientific ambitions).

Design of piezoelectric microtransducers based on the topology optimization method

In this work, a systematic procedure based on the topology optimization method to design piezoelectric transducers in a static in-plane and out-of-plane framework is presented. The layout of the host structure and the electrode profile of the piezoelectric material are optimized simultaneously. Our numerical approach shows a significant improvement by using simultaneous optimization rather than optimizing separately the host structure and the electrode profile. Two important issues in this problem are the appearance of large gray areas (a mixture of solid and void material) in the optimized designs for the in-plane case and branches (disconnected areas) for the out-of-plane one, that actually distort the real performance of such transducers. To solve these problems and in order to obtain efficient and really close to 0---1 designs, a new interpolation function, appearing in the objective function for the sensor and in the source term for the actuator, is required. Thanks to the reciprocity of the piezoelectric effect, we get to prove analytically and to corroborate numerically how such a fact leads to the same optimized designs for sensors and actuators. A similar approach has shown quite good performance in the design of modal sensors/actuators, although restricted to the design of the electrode layout for a given structure. Finally, some of the optimized designs for the in-plane case have been fabricated. In several cases passive pieces are included to study movement into fluids.

Design of piezoelectric modal filters by simultaneously optimizing the structure layout and the electrode profile

Modal transducers can be designed by optimizing the polarity of the electrode which covers the piezoelectric layers bonded to the host structure. This paper is intended as a continuation of our previous work (Donoso and Bellido J Appl Mech 57:434---441, 2009a) to make better the performance of such piezoelectric devices by simultaneously optimizing the structure layout and the electrode profile. As the host structure is not longer fixed, the typical drawbacks in eigenproblem optimization such as spurious modes, mode tracking and switching or repeated eigenvalues soon appear. Further, our model has the novel issue that both cost and constraints explicitly depend on mode shapes. Moreover, due to the physics of the problem, the appearance of large gray areas is another pitfall to be solved. Our proposed approach overcomes all these difficulties with success and let obtain nearly 0-1 designs that improve the existing optimal electrode profiles over a homogeneous plate.

Caenorhabditis elegans: What We Can and Cannot Learn from Aging Worms.

The nematode Caenorhabditis elegans is a widely used model organism for research into aging. However, nematodes diverged from other animals between 600 and 1300 million years ago. Beyond the intuitive impression that some aspects of aging appear to be universal, is there evidence that insights into the aging process of nematodes may be applicable to humans? There have been a number of results in nematodes that appear to contradict long-held beliefs about mechanisms and causes of aging. For example, ablation of several key antioxidant systems has often failed to result in lifespan shortening in C. elegans. While it is clear that some central signaling pathways controlling lifespan are broadly conserved across large evolutionary distances, it is less clear to what extent downstream molecular mechanisms of aging are conserved. In this review we discuss the biology of C. elegans and mammals in the context of aging and age-dependent diseases. We consider evidence from studies that attempt to investigate basic, possibly conserved mechanisms of aging especially in the context of the free radical theory of aging. Practical points, such as the need for blinding of lifespan studies and for appropriate biomarkers, are also considered. As data on the aging process(es) in different organisms increase, it is becoming increasingly clear that there are both conserved (public) and private aspects to aging. It is important to explore the dividing lines between these two aspects and to be aware of the large gray areas in-between.

My Experience with Direct to Consumer Genetic Testing.

My Experience with Direct to Consumer Genetic Testing.

Contornos del derecho procesal contemporáneo

Un cambio de época significa ruptura de paradigmas, cambio de ideas y también de perspectivas. Pero un cambio de época es lento y está acompañado de una amplia zona gris, el ejemplo más cercano se vivió cuando la edad media entra al renacimiento, posteriormente a la ilustración para finalmente nacer la edad moderna o era de la razón. En esta línea evolutiva, la constitucionalización del derecho a partir de la adopción de las Constituciones materiales de postguerra, el reconocimiento de la pluralidad jurídica como coexistencia de diversos sistemas que interactúan, el acercamiento del common law y del civil law, y las formas de fusión que se empiezan a concretar a partir de teorías ius naturalistas -ius positivistas, son un síntoma claro de que se vive actualmente un cambio de época. En esta transformación las distintas áreas del derecho han empezado a migrar, no en vano actualmente al constitucionalismo se le denomina neoconstitucionalismo, el derecho laboral discute como prioridad el principio de realidad y la filosofia del derecho en su dimensión privada empieza a preguntarse por la moral y la justicia social. Y esta transformación hoy no le es indiferente al derecho procesal. De esto trata este artículo de establecer algunos lineamientos del cambio que se debe producir, especialmente a partir de la academia.

Infectious Disease: A Geographic Guide and Atlas of Human Infectious Diseases

Infectious Disease: A Geographic Guide and Atlas of Human Infectious Diseases

Interpretation of drinking water quality guidelines – The case of arsenic

Drinking water quality guidelines are often interpreted by the non-expert as make or break cut-off values below which drinking water is absolutely safe, and above which it is totally unacceptable. In reality there is no such knifelike cut-off limit, and there is a large grey area between safe water and undrinkable water. The uncertainty of the boundaries of the grey area for each constituent presents a serious problem, both in the creation of sound drinking water quality guidelines or standards, and in the problem of how to interpret the risk to human health when guideline values are exceeded. In this paper this problem is discussed using the case of arsenic, where the definition of the boundaries of the grey area is particularly uncertain.

Klinischer Verdacht auf Kindesmisshandlung

Violence against children has many faces. Child physical abuse, neglect, sexual abuse and interparental violence can cause acute and permanent damage and affect children's development and their life plans in the long term. In industrialized nations almost 1 child in 10 is affected. Up to 10% of child physical abuse cases involve the central nervous system with 80% of these cases occurring during the first year of life. Worldwide more than 50,000 children die as a result of violence, abuse and neglect every year, according to the United Nations Children's Fund UNICEF. In Germany, there are about 120 cases of non-accidental head injury per year. In addition to the officially known cases there is a large grey area for all forms of violence. Recognition of these cases and the provision of help for the victims require an appropriate suspicion and understanding of the pertinent pathophysiology. Suspicion must be based on a well-documented medical history and multidisciplinary diagnostic assessment. Medical confidentiality prevents the disclosure of such information making early detection networks and guidelines for collaboration absolutely indispensable.

Betwixt and Between: The Spectrum of Formality Revealed in the Labor Market Experiences of Mexican Migrant Workers in the United States

Interviews with Mexican migrant workers in Portland, Oregon, reveal the inadequacy of the conception of informality to capture the complexity of their labor market experiences in the United States. We propose the term “semi-formal” to describe the large gray area between formal and informal employment, and a spectrum of formality with which to think about the degree of formality present in any particular employment situation.

Operationalizing the essential role of the information technology artifact in information systems research

In this paper we argue that a large gray area of information systems research exists, whose relevance to the information technology artifact is subject to significant debate even among IS scholars ...

Operationalizing the Essential Role of the Information Technology Artifact in Information Systems Research: Gray Area, Pitfalls, and the Importance of Strategic Ambiguity

In this paper we argue that a large gray area of information systems research exists, whose relevance to the information technology artifact is subject to significant debate even among IS scholars who support the essential role of the IT artifact. As we explain, not explicitly addressing this gray area can have negative, although often inadvertent, effects on the innovative nature of IS research; we explore this danger through three pitfalls. We then propose a stance of strategic ambiguity to deal with the gray area. Strategic ambiguity calls for deliberately withholding judgment on the relevance of research in the gray area and acceptance of gray-area research provided it meets the excellence required by professional journals. We believe that strategic ambiguity benefits innovative IS research without harming the essential role of the IT artifact.

Can User Agents Accurately Represent Privacy Policies?

The Platform for Privacy Preferences (P3P) is a W3C specification that provides a standard computer-readable language for web sites to encode their privacy policies. This standardization allows for the creation of web browsers and other user agents that can display privacy warnings and signals that are meaningful to users or that automate actions in accordance with user instructions. This paper shows that P3P user agents will necessarily include judgmental design decisions and that the accuracy of the P3P user agent interactions becomes a critical matter. The accuracy of P3P user agents raises significant legal concerns about privacy agreements, inadvertent deception, and liability. The technological mediation designed to make it easier for users to understand the privacy practices of web sites risks adding ambiguity, confusion and legal uncertainty. This paper argues that one way to avoid having privacy practices represented inaccurately by P3P user agents is to certify P3P user agents for the accuracy of their representations of web site P3P policies. While there are some things that P3P user agents might do that would be readily identified as inaccurate or misleading, there is a large gray area in which user agents might present factual information side-by-side with subjective judgments. These judgments may be deemed misleading by some people but not others. Many of the issues raised here are new, but this is not likely to be the last time that these issues arise. As work progresses on computer-mediated search and negotiation technologies with a wide variety of applications, these issues are likely to surface repeatedly. In this paper we explore these issues and suggest some possible solutions, as well as a number of open questions.

Growth cone interactions with purified cell and substrate adhesion molecules visualized by interference reflection microscopy

The migration of growth cones on substrates consisting of naturally occurring cell adhesion molecules has been extensively studied in cell culture. However, relatively little is known about how growth cones contact the substrate or how the patterns of contact change as growth cones move forward. We have examined the interactions of chick retinal ganglion cell growth cones with laminin, merosin, N-cadherin, L1 and poly- l-lysine by time-lapse interference reflection microscopy (IRM) using a laser scanning confocal microscope. In images obtained by IRM, areas of a cell that are closely apposed to the substrate appear dark whereas areas that are farther away appear light. Growth cones on laminin and merosin were almost uniformly light, indicating that very little of the membrane was in close contact with the substrate. Growth cones on N-cadherin had a mottled appearance with some relatively large dark gray areas. The proximal portions of filopodia often were dark, in contrast to those on laminin and merosin which were light. In addition, growth cones on N-cadherin had numerous dark gray punctate regions of close association with the substrate. Growth cones on L1 had darker regions than growth cones on other substrates and these comprised a larger fraction of their area. There also were differences in the temporal dynamics of growth cone interactions with different substrates and these differences correlated with differences in rates of growth. None of the contacts observed in growth cones were as dark or stable as focal contacts of fibroblasts.