Inherent Methodological Challenges Research Articles

Training radiomics-based CNNs for clinical outcome prediction: Challenges, strategies and findings

Radiological images play a central role in radiotherapy, especially in target volume delineation. Radiomic feature extraction has demonstrated its potential for predicting patient outcome and cancer risk assessment prior to treatment. However, inherent methodological challenges such as severe class imbalance, small training sample size, multi-centre data and weak correlation of image representations to outcomes are yet to be addressed adequately. Current radiomic analysis relies on segmented images (e.g., of tumours) for feature extraction, leading to loss of important context information in surrounding tissue. In this work, we examine the correlation between radiomics and clinical outcomes by combining two data modalities: pre-treatment computerized tomography (CT) imaging data and contours of segmented gross tumour volumes (GTVs). We focus on a clinical head & neck cancer dataset and design an efficient convolutional neural network (CNN) architecture together with appropriate machine learning strategies to cope with the challenges. During the training process on two cohorts, our algorithm learns to produce clinical outcome predictions by automatically extracting radiomic features. Test results on two other cohorts show state-of-the-art performance in predicting different clinical endpoints (i.e., distant metastasis: AUC = 0.91; loco-regional failure: AUC = 0.78; overall survival: AUC = 0.70 on segmented CT data) compared to prior studies. Furthermore, we also conduct extensive experiments both on the whole CT dataset and a combination of CT and GTV contours to investigate different learning strategies for this task. For example, further experiments indicate that overall survival prediction significantly improves to 0.83 AUC by combining CT and GTV contours as inputs, and the combination provides more intuitive visual explanations for patient outcome predictions.

Systematic review of prenatal exposure to endocrine disrupting chemicals and autism spectrum disorder in offspring.

Autism spectrum disorders comprise a complex group with many subtypes of behaviorally defined neurodevelopmental abnormalities in two core areas: deficits in social communication and fixated, restricted, repetitive, or stereotyped behaviors and interests each with potential unique risk factors and characteristics. The underlying mechanisms and the possible causes of autism spectrum disorder remain elusive and while increased prevalence is undoubtable, it is unclear if it is a reflection of diagnostic improvement or emerging risk factors such as endocrine disrupting chemicals. Epidemiological studies, which are used to study the relation between endocrine disrupting chemicals and autism spectrum disorder, can have inherent methodological challenges that limit the quality and strength of their findings. The objective of this work is to systematically review the treatment of these challenges and assess the quality and strength of the findings in the currently available literature. The overall quality and strength were "moderate" and "limited," respectively. Risk of bias due to the exclusion of potential confounding factors and the lack of accuracy of exposure assessment methods were the most prevalent. The omnipresence of endocrine disrupting chemicals and the biological plausibility of the association between prenatal exposure and later development of autism spectrum disorder highlight the need to carry out well-designed epidemiological studies that overcome the methodological challenges observed in the currently available literature in order to be able to inform public policy to prevent exposure to these potentially harmful chemicals and aid in the establishment of predictor variables to facilitate early diagnosis of autism spectrum disorder and improve long-term outcomes.

A Collaborative Methodology for Local Strategic Planning: Insights from Four Plans in Portugal

ABSTRACT Planning practitioners have been challenged by the demand for more open, effective, and transparent processes. But the collaborative practices that have tried to materialize these goals often yield unsatisfactory results. While this can partly be attributed to various forms of vertical coordination, achieving these different, and sometimes conflicting, goals also poses inherent methodological challenges. This paper discusses an innovative approach to these issues applied in four strategic plans in Portugal. It focusses on the way in which the methodology tried to give practical meaning to the so-called ‘communicative turn’ in planning, while addressing some of the shortcomings associated with it.

Ex vivo diffusion-weighted MRI tractography of the Göttingen minipig limbic system.

The limbic system encompasses a collection of brain areas primarily involved in higher cognitive and emotional processing. Altered function in the limbic circuitry may play a major role in various psychiatric disorders. This study aims to provide a high-quality ex vivo diffusion-weighted MRI (DWI) tractographic overview of the Göttingen minipig limbic system pathways, which are currently not well described. This may facilitate future translational large animal studies. The study used previously obtained post-mortem DWI scans in 3 female Göttingen minipigs aging 11-15months. The tractography performed on the DWI data set was made using a probabilistic algorithm, and regions of interest (ROIs) were defined in accordance with a histological atlas. The investigated pathways included the fornix, mammillothalamic tract, stria terminalis, stria medullaris, habenulo-interpeduncular tract, and cingulum. All the investigated limbic connections could be visualized with a high detail yielding a comprehensive three-dimensional overview, which was emphasized by the inclusion of video material. The minipig limbic system pathways displayed using tractography closely resembled what was previously described in both human studies and neuronal tracing studies from other mammalian species. We encountered well-known inherent methodological challenges of tractography, e.g., partial volume effects and complex white matter regions, which may have contributed to derouted false-positive streamlines and the failure to visualize some of the minor limbic pathway ramifications. This underlines the importance of preexisting anatomical knowledge. Conclusively, we have, for the first time, provided an overview and substantial insight of the Göttingen minipig limbic system.

Assessing Long-term Neurodevelopmental Outcome Following General Anesthesia in Early Childhood: Challenges and Opportunities.

Neurodegeneration has been reported in young animals after exposure to all commonly used general anesthetic agents. The brain may be particularly vulnerable to anesthetic toxicity during peak synaptogenesis (in gestation and infancy). Human studies of long-term neurodevelopmental outcome following general anesthesia in early childhood report contradictory findings. This review assesses the strengths and deficiencies in human research methodologies to inform future studies. We identified 76 studies, published between 1990 and 2017, of long-term neurodevelopmental outcome following early childhood or in utero general anesthesia exposure: 49 retrospective, 9 ambidirectional, 17 prospective cohort studies, and 1 randomized controlled trial. Forty-nine studies were explicitly concerned with anesthetic-induced neurotoxicity. Full texts were appraised for methodological challenges and possible solutions. Major challenges identified included delineating effects of anesthesia from surgery, defining the timing and duration of exposure, selection of a surgical cohort and intervention, addressing multiple confounding life course factors, detecting modest neurotoxic effects with small sample sizes (median, 131 children; interquartile range, 50–372), selection of sensitive neurodevelopmental outcomes at appropriate ages for different developmental domains, insufficient length of follow-up (median age, 6 years; interquartile range, 2–12 years), and sample attrition. We discuss potential solutions to these challenges. Further adequately powered, multicenter, prospective randomized controlled trials of anesthetic-induced neurotoxicity in children are required. However, we believe that the inherent methodological challenges of studying anesthetic-induced neurotoxicity necessitate the parallel use of well-designed observational cohort studies.

Breastfeeding and behavioural problems: Propensity score matching with a national cohort of infants in Chile

ImportancePotential effects of breast feeding on children’s behaviour remains an elusive debate given inherent methodological challenges. Propensity score matching affords benefits by ensuring greater equivalence on observable social and health...

Constructive realism: advantages of ontology and methodology

This article attempts to reveal and analyse the advantages of constructive realism as a methodological framework of contemporary science. Comparing realism and constructivism as two divergent positions in epistemology in their extreme forms, we mention their downsides. These are the epistemological component for extreme realism and the ontological component for radical constructivism. We indicate that the concept of our study is characterized with the best balance of ontology and gnoseology and it allows overcoming ontological and epistemological difficulties associated with constructivism and realism correspondingly. We conclude that constructive realism may facilitate the development of the scientific worldview pertinent to modern knowledge and ready to respond the inherent methodological challenges that science faces.

Resources Access Through International Alliances and Firm Value: A Test of Resource Effects in the International Airline Industry

The resource-based view argues that firm performance will be stronger when the resources available to the firm are simultaneously high in revenue enhancing or cost-reducing potential, rareness, and inimitability. However, this central prediction of the resource-based view itself has not been the target of rigorous empirical tests due to inherent methodological challenges. We present a framework to test the central argument by applying the event study method. We discuss the benefits of examining stock price reactions when firms access new resource increments, in particular through international alliances. Empirically, we analyze 225 international codesharing alliance announcements made by 23 international airlines between 1986 and 1998. We show that the market value of a focal firm increases significantly more when the resources available through its international alliance partner are simultaneously high in revenue/cost potential, rare and inimitable, than if the resources are deficient in any of the three characteristics.

Sustainable Companies: Possibilities and Barriers in Norwegian Company Law

Climate change is a case in point for the necessity of working towards a sustainable development; towards achieving economic development and social justice within the non-negotiable limits of our planet, as is the biodiversity crisis. Norway, home of Gro Harlem Brundtland, chair of the UN-appointed Commission that through its report “Our Common Future” put sustainable development on the global agenda, prides itself on being an environmentally-friendly nation. Although Norway does have a good international repute, its oil-based economy makes the challenge of achieving a smooth transition to a sustainable economy (in the environmental and social sense as well as the economic) no less for Norway than for other countries. In such a transition, business will inevitably need to play an important role. The vast impact that the operations of companies today, on an aggregated level, have on the global economy, on society in general and on the biosphere and the atmosphere, means that a critical analysis of the purpose of companies and the regulatory framework within which they operate is crucial to a deeper understanding of the correlation between society and sustainable development. The company is the most important private legal vehicle to gather capital, generate profits and redistribute income in the world. Companies are also the main contributors to anthropogenic greenhouse gas (GHG) emissions through their choices concerning research and development, their use of resources, their production and transportation, and their – and the end users' – use and recycling or discharge of products. In other words, companies are a major contributor to the problem. They can also become a key factor in finding the solution. The discussion of how to resolve this should rise above and go beyond the corporate social responsibility (CSR) debate. As a part of the work in the Oslo-based research project Sustainable Companies, this paper therefore maps the possibilities and barriers in the Norwegian legal framework for companies for promoting sustainable companies in the environmental sense. The aim of the project is to find out how to better integrate environmental concerns into the decision-making in companies. The core focus of the papers, as of the project itself, is the hither-to to a great extent ignored area of company law. This first section of the paper goes on to set out the backdrop: the Norwegian corporate scene and the legal sources and their inherent methodological challenges, for the guidance of the international reader. Section 2 analyses core company law issues relevant to the integration of environmental concerns in companies, including the purpose of the company and the company interest, and the competences of the various company organs. Section 3 analyses the important supportive area of reporting, accounting and auditing, which is the current compromise solution for those wishing companies to act more responsibly. Section 4 discusses liability and enforcement related to these rules and other means of promoting environmental sustainability in companies, while Section 5 briefly assesses other potential incentives and disincentives. Section 6 and 7 assesses the potential barriers and possibilities in the Norwegian regulation of groups of companies, while Section 8 concludes.

Addressing challenges of validity and internal consistency of mental health measures in a 27- year longitudinal cohort study - the Northern Swedish Cohort study.

BackgroundThere are inherent methodological challenges in the measurement of mental health problems in longitudinal research. There is constant development in definitions, taxonomies and demands concerning the properties of mental health measurements. The aim of this paper was to construct composite measures of mental health problems (according to today’s standard) from single questionnaire items devised in the early 1980s, and to evaluate their internal consistency and factorial invariance across the life course using the Northern Swedish Cohort.MethodsAll pupils in the last year of compulsory school in Luleå in 1981 (n = 1083) form a prospective cohort study where the participants have been followed with questionnaires from the age of 16 (in 1981) until the age of 43 (in 2008). We created and tested the following composite measures from self-reports at each follow-up: depressive symptoms, anxiety symptoms, functional somatic symptoms, modified GHQ and positive health. Validity and internal consistency were tested by confirmatory factor analysis, including tests of factorial invariance over time.ResultsAs an overall assessment, the results showed that the composite measures (based on more than 30-year-old single item questions) are likely to have acceptable factorial invariance as well as internal consistency over time.ConclusionsTesting the properties of the mental health measures used in older studies according to the standards of today is of great importance in longitudinal research. Our study demonstrates that composite measures of mental health problems can be constructed from single items which are more than 30 years old and that these measures seem to have the same factorial structure and internal consistency across a significant part of the life course. Thus, it can be possible to overcome some specific inherent methodological challenges in using historical data in longitudinal research.

Methodological Challenges in Examining the Impact of Healthcare Predictive Analytics on Nursing-Sensitive Patient Outcomes.

The expansion of real-time analytic abilities within current electronic health records has led to innovations in predictive modeling and clinical decision support systems. However, the ability of these systems to influence patient outcomes is currently unknown. Even though nurses are the largest profession within the healthcare workforce, little research has been performed to explore the impact of clinical decision support on their decisions and the patient outcomes associated with them. A scoping literature review explored the impact clinical decision support systems containing healthcare predictive analytics have on four nursing-sensitive patient outcomes (pressure ulcers, failure to rescue, falls, and infections). While many articles discussed variable selection and predictive model development/validation, only four articles examined the impact on patient outcomes. The novelty of predictive analytics and the inherent methodological challenges in studying clinical decision support impact are likely responsible for this paucity of literature. Major methodological challenges include (1) multilevel nature of intervention, (2) treatment fidelity, and (3) adequacy of clinicians' subsequent behavior. There is currently insufficient evidence to demonstrate efficacy of healthcare predictive analytics-enhanced clinical decision support systems on nursing-sensitive patient outcomes. Innovative research methods and a greater emphasis on studying this phenomenon are needed.

An Analytical Framework for Delirium Research in Palliative Care Settings: Integrated Epidemiologic, Clinician-Researcher, and Knowledge User Perspectives

ContextDelirium often presents difficult management challenges in the context of goals of care in palliative care settings. ObjectivesThe aim was to formulate an analytical framework for further research on delirium in palliative care settings, prioritize the associated research questions, discuss the inherent methodological challenges associated with relevant studies, and outline the next steps in a program of delirium research. MethodsWe combined multidisciplinary input from delirium researchers and knowledge users at an international delirium study planning meeting, relevant literature searches, focused input of epidemiologic expertise, and a meeting participant and coauthor survey to formulate a conceptual research framework and prioritize research questions. ResultsOur proposed framework incorporates three main groups of research questions: the first was predominantly epidemiologic, such as delirium occurrence rates, risk factor evaluation, screening, and diagnosis; the second covers pragmatic management questions; and the third relates to the development of predictive models for delirium outcomes. Based on aggregated survey responses to each research question or domain, the combined modal ratings of “very” or “extremely” important confirmed their priority. ConclusionUsing an analytical framework to represent the full clinical care pathway of delirium in palliative care settings, we identified multiple knowledge gaps in relation to the occurrence rates, assessment, management, and outcome prediction of delirium in this population. The knowledge synthesis generated from adequately powered, multicenter studies to answer the framework's research questions will inform decision making and policy development regarding delirium detection and management and thus help to achieve better outcomes for patients in palliative care settings.

Effects on DNA Damage and/or Repair Processes as Biological Mechanisms Linking Psychological Stress to Cancer Risk.

Considerable research effort in the past several decades has focused on the impact of psychological stress, and stress hormones, on cancer progression. Numerous studies have reported that stress hormone treatment or in vivo stress exposure can enhance the growth of tumor cell lines in vitro, as well as tumors in animal models, and have begun to explore molecular mechanisms. Comparatively little research has focused on the impact of psychological stress and stress hormones on cancer initiation, in part due to inherent methodological challenges, but also because potential underlying biological mechanisms have remained obscure. In this review, we present a testable theoretical model of pathways by which stress may result in cellular transformation and tumorigenesis. This model supports our overarching hypothesis that psychological stress, acting through increased levels of catecholamines and/or cortisol, can increase DNA damage and/or reduce repair mechanisms, resulting in increased risk of DNA mutations leading to carcinogenesis. A better understanding of molecular pathways by which psychological stress can increase the risk of cancer initiation would open new avenues of translational research, bringing together psychologists, neuroscientists, and molecular biologists, potentially resulting in the development of novel approaches for cancer risk reduction at the population level.

Impact of Participating in a Policy Debate Program on Academic Achievement: Evidence from the Chicago Urban Debate League.

Policy makers have advanced out-of-school time learning as a means to address far-reaching class and racial/ethnic disparities in high school achievement and college readiness, particularly in urban districts. However, limited data have hindered large-scale efforts to evaluate the influence of such activities on student achievement. Recent federal policy has encouraged the development of data systems that track students over the academic life course, and while these datasets hold great opportunity for research they pose inherent methodological challenges. This study applies a novel statistical approach in a comprehensive administrative dataset to evaluate the relationship between participating in a policy debate program and academic achievement in the Chicago Public School (CPS) district from 1997 to 2006 (N = 9145). Using multiple imputation to account for missing data and selective attrition, and propensity score matching to account for self-selection, we find that debaters were more likely to graduate, more likely to meet ACT college-readiness benchmarks, and had greater gains in cumulative grade point average (GPA) over the course of high school relative to comparable peers. This is the largest evaluation study of a debate program on achievement, and these findings suggest that debate programs may offer a means to extend learning time and promote engagement with scholastic materials in a manner that translates into academic performance. Key words: Education, out-of-school time learning, afterschool activities, achievement gap.

Europeanisation and Foreign and Security Policy – Undermining or Rescuing the Nation State?

The article aims to explore the utility of Europeanisation as a concept to grasp the interactions between national and European levels. The article illustrates how the EU impacts on the national level of policy, polity and the politics of Member States and assesses how the role of nation states within the European political system has changed as a result. First, the existing definitions of Europeanisation are critically assessed, contextualised and delimited. Initially developed for communitised policy areas in the first pillar, Europeanisation is defined as an interactive, ongoing and mutually constitutive process of ‘Europeanising’ and ‘Europeanised’ countries, linking national and European levels. Defining Europeanisation as ‘domestic change’, the article then discusses mechanisms, objects and forms, as well as the criteria and conditions of change. The article subsequently seeks to clarify the validity of the Europeanisation concept in capturing the increasing interwovenness of national and European spheres in intergovernmental policy fields situated in the second pillar of the EU, that is, foreign and security policy. Inherent methodological challenges, mainly due to the deficient delimitation of Europeanisation and the intergovernmental character of this policy field are discussed as well as the particularities of its applicability in this unique policy area.