Conceptual Advances Research Articles

Separating generalizable from source-specific preference heterogeneity in the fusion of revealed and stated preferences

Preference heterogeneity is one of the central behavioral concepts in applied econometrics. Its centrality is particularly evident in the choice modeling literature, notably in its widespread application to environmental and health economics, marketing, and transport. Despite conceptual and empirical advances in modeling preference heterogeneity, the generalizability of preference heterogeneity to different decision contexts and different data generation processes remains an open question. The basic premise of this paper is that latent sources of preference heterogeneity can be decomposed into components general to decision contexts and others specific to them. We study the structure of preference heterogeneity in different data generation processes with the goal of reliably identifying common (presumably generalizable) and specific (presumably not generalizable) sources of preference heterogeneity. The contribution of the paper is both conceptual and methodological, leading to the testing of five rival model specifications which together elucidate the heterogeneity structure present in two preference data sources of the same choice behavior. In the empirical application, we find that the multitrait-multimethod model of preference heterogeneity has the best fit and most sensible interpretations, indicating that while each data source contributes uniquely to certain heterogeneity components, both data sources contribute also to common (generalizable) preference heterogeneity. Recognition of the separability of the common versus source-specific preference heterogeneity will lead to more reliable and accurate demand model forecasts and assessments of welfare impacts.

Evaluation of Therapies for Peripheral and Neuraxial Opioid-induced Pruritus based on Molecular and Cellular Discoveries.

Opioids are a mainstay of treatment for pain worldwide. Pruritus, a common side effect of opioids, is a patient dissatisfier that limits their use in many clinical settings. Both parenteral and neuraxial administration of opioids frequently evoke pruritus. The ability of opioids to suppress pain while causing itch continues to perplex clinicians and researchers alike. Several mechanisms have been proposed to explain how opioids can give rise to pruritus, but specific knowledge gaps perpetuate debate. This review summarizes the clinical burden of opioid-induced pruritus and emphasizes recent discoveries of peripheral and central mechanisms for opioid-induced pruritus, particularly with respect to scientific and conceptual advances in spinal cord circuitry and mast cell biology. The mechanisms and effectiveness of existing medications used for clinical management of pruritus will be evaluated, and we will highlight the emerging preclinical utility of selective κ-opioid receptor agonists, such as nalfurafine, for the management of opioid-induced pruritus.

My life with the Red Queen in fishery genetics

AbstractI had the privilege of being a part of fishery genetics from its start in the 1970s, when protein electrophoresis was first used to identify stocks of commercially important fishes and shellfishes. Research questions in fishery genetics have evolved tremendously over the past few decades, as new molecular techniques changed the nature of the questions that could be posed. The development of new DNA methods spurred the development of new theoretical models, new statistical methods and an unending stream of computer programs. These developments have led to conceptual shifts in the understanding of natural populations and how to manage them. Twists and turns in the history of fishery genetics parallel the story of the Red Queen in Lewis Carroll's Through the Looking Glass. I have had to “run in place” during my career to learn new techniques and ideas that, in turn, have been replaced with yet newer ones. However, my personal challenge throughout my career has been to develop “scientific intuition” to find underlying causes in datasets. Even though we now have the ability to sequence entire genomes, it is premature to announce the “end of history” for technical and conceptual advances in fishery genetics.

Challenges and prospects for a potential allohexaploid Brassica crop.

The production of a new allohexaploid Brassica crop (2n = AABBCC) is increasingly attracting international interest: a new allohexaploid crop could benefit from several major advantages over the existing Brassica diploid and allotetraploid species, combining genetic diversity and traits from all six crop species with additional allelic heterosis from the extra genome. Although early attempts to produce allohexaploids showed mixed results, recent technological and conceptual advances have provided promising leads to follow. However, there are still major challenges which exist before this new crop type can be realized: (1) incorporation of sufficient genetic diversity to form a basis for breeding and improvement of this potential crop species; (2) restoration of regular meiosis, as most allohexaploids are genetically unstable after formation; and (3) improvement of agronomic traits to the level of "elite" breeding material in the diploid and allotetraploid crop species. In this review, we outline these major prospects and challenges and propose possible plans to produce a stable, diverse and agronomically viable allohexaploid Brassica crop.

TFP Extended: Development and Recent Advances

Recent advances in the understanding of personality pathology have contributed to an emphasis on the core of personality pathology as deficits in self-functioning and interpersonal functioning at different levels of severity that must be assessed for clinical intervention. In concert with these conceptual and empirical advances, transference-focused psychotherapy (TFP), an empirically supported psychodynamic treatment for borderline personality disorder, has been in constant development with extensive clinical use. This article describes an object relations model for conceptualizing and assessing levels of personality organization, a transdiagnostic approach to personality pathology, and related treatment modifications, thus expanding the utilization of TFP beyond borderline personality disorder to the full range of personality dysfunction. The core of this treatment approach is a sequential interpretive process between patient and therapist. This process takes place within the context of a structured treatment frame tailored to the unique individual with problems in self-functioning and interpersonal functioning in his/her particular environment.

Revisiting the epistemic gap: It’s not the thought that counts

ABSTRACT This paper revisits the longstanding observation that children produce modal verbs (e.g., must, could) with their root meanings (e.g., abilities, obligations) by age 2, typically a year or more earlier than with their epistemic meanings (e.g., inferences). Established explanations for this “Epistemic Gap” argue that epistemic language production is delayed because small children can only reason about root meanings. However, root and epistemic uses of modal verbs also differ syntactically and in input representation. We present a corpus study on 17 English-learning children and their input, exploring early productions with both epistemic modal verbs and grammatically simpler and more frequent epistemic adverbs (e.g., maybe, probably). Results show that children use remarkably adult-like epistemic adverb sentences from even before age 2, when they are only producing modal verbs with root meanings. The Epistemic Gap is not well explained by general conceptual advancements. Instead, our data suggest input attestation and ease of form-to-meaning mapping may influence early child epistemic language. These findings are furthermore consistent with cross-linguistic differences in the timing of first epistemic uses of modal verbs, and with recent advancements in our understanding of infant and toddler modal reasoning abilities.

Fifteen years later: moving forward Heller's heritage on fiscal space for health.

Economist Peter Heller, writing a seminal paper published in Health, Policy and Planning in 2006, identified five opportunities for expanding fiscal space for health: raising revenue, reprioritizing expenditure, borrowing, using seigniorage and mobilizing external grants. The development of the initial framework marked a significant conceptual advancement in health financing, by situating health reforms within a broader macro-fiscal context. Fifteen years later, fiscal space for health is not viewed simply as a question of finding additional revenues but also as a matter of improving public financial management (PFM) in the health sector, specifically for publicly funded health systems. This paper advances the concept of budgetary space for health, which explores available resources generated through greater overall public expenditure, prioritized budget allocations, and improved PFM. The paper adds a critical component, unpacking the ways through which PFM improvements can maximize budgetary space for health. The approach fits the realities of public finances in the era of the Sustainable Development Goals. The key implication is that PFM aspects should be systematically included in assessments of budgetary space to inform more effective country dialogues between the finance and health sectors.

Targeting Pyrimidine Metabolism in the Era of Precision Cancer Medicine.

Metabolic rewiring is considered as a primary feature of cancer. Malignant cells reprogram metabolism pathway in response to various intrinsic and extrinsic drawback to fuel cell survival and growth. Among the complex metabolic pathways, pyrimidine biosynthesis is conserved in all living organism and is necessary to maintain cellular fundamental function (i.e. DNA and RNA biosynthesis). A wealth of evidence has demonstrated that dysfunction of pyrimidine metabolism is closely related to cancer progression and numerous drugs targeting pyrimidine metabolism have been approved for multiple types of cancer. However, the non-negligible side effects and limited efficacy warrants a better strategy for negating pyrimidine metabolism in cancer. In recent years, increased studies have evidenced the interplay of oncogenic signaling and pyrimidine synthesis in tumorigenesis. Here, we review the recent conceptual advances on pyrimidine metabolism, especially dihydroorotate dehydrogenase (DHODH), in the framework of precision oncology medicine and prospect how this would guide the development of new drug precisely targeting the pyrimidine metabolism in cancer.

Dimensions of invasiveness: Links between local abundance, geographic range size, and habitat breadth in Europe’s alien and native floras

Understanding drivers of success for alien species can inform on potential future invasions. Recent conceptual advances highlight that species may achieve invasiveness via performance along at least three distinct dimensions: 1) local abundance, 2) geographic range size, and 3) habitat breadth in naturalized distributions. Associations among these dimensions and the factors that determine success in each have yet to be assessed at large geographic scales. Here, we combine data from over one million vegetation plots covering the extent of Europe and its habitat diversity with databases on species' distributions, traits, and historical origins to provide a comprehensive assessment of invasiveness dimensions for the European alien seed plant flora. Invasiveness dimensions are linked in alien distributions, leading to a continuum from overall poor invaders to super invaders-abundant, widespread aliens that invade diverse habitats. This pattern echoes relationships among analogous dimensions measured for native European species. Success along invasiveness dimensions was associated with details of alien species' introduction histories: earlier introduction dates were positively associated with all three dimensions, and consistent with theory-based expectations, species originating from other continents, particularly acquisitive growth strategists, were among the most successful invaders in Europe. Despite general correlations among invasiveness dimensions, we identified habitats and traits associated with atypical patterns of success in only one or two dimensions-for example, the role of disturbed habitats in facilitating widespread specialists. We conclude that considering invasiveness within a multidimensional framework can provide insights into invasion processes while also informing general understanding of the dynamics of species distributions.

Path Formation and Reformation: Studying the Variegated Consequences of Path Creation for Regional Development

The emergence of new regional paths is a key topic in economic geography. While new paths are largely associated with positive regional economic outcomes, little is known about how the formation of a new industry affects other parts of the regional economy. By linking recent conceptual advancements on early path formation and interpath relationships, this article develops a framework for studying how path creation, as a result of diverse resource formation processes, can cause reformation processes of existing industries. The value of the framework is illustrated in a case study on the tourism path formation process in the Zambezi region (Namibia) and its impacts on the agricultural sector. The findings reveal how the path formation has caused new forms of intraregional inequalities as well as novel opportunities for the existing agricultural sector depending on the interpath relationship. Beyond these case study–specific findings, the results emphasize the importance of a broader perspective that goes beyond a single new path and includes nonparticipating regional actors in the analysis. Only in this way can we understand how new path creation translates into regional economic development.

Fate and State of Vascular Smooth Muscle Cells in Atherosclerosis

Vascular smooth muscle cells (VSMCs) have long been associated with phenotypic modulation/plasticity or dedifferentiation. Innovative technologies in cell lineage tracing, single-cell RNA sequencing, and human genomics have been integrated to gain unprecedented insights into the molecular reprogramming of VSMCs to other cell phenotypes in experimental and clinical atherosclerosis. The current thinking is that an apparently small subset of contractile VSMCs undergoes a fate switch to transitional, multipotential cells that can adopt plaque-destabilizing (inflammation, ossification) or plaque-stabilizing (collagen matrix deposition) cell states. Several candidate mediators of such VSMC fate and state changes are coming to light with intriguing implications for understanding coronary artery disease risk and the development of new treatment modalities. Here, we briefly summarize some technical and conceptual advancements derived from 2 publications in Circulation and another in Nature Medicine that, collectively, illuminate new research directions to further explore the role of VSMCs in atherosclerotic disease.

Visualising and understanding cGMP signals in the cardiovascular system.

cGMP is an important signalling molecule in humans. Fluorescent cGMP biosensors have emerged as powerful tools for the sensitive analysis of cGMP pathways at the single-cell level. Here, we briefly outline cGMP's multifaceted role in (patho)physiology and pharmacotherapy. Then we summarise what new insights cGMP imaging has provided into endogenous cGMP signalling and drug action, with a focus on the cardiovascular system. Indeed, the use of cGMP biosensors has led to several conceptual advances, such as the discovery of local, intercellular and mechanosensitive cGMP signals. Importantly, single-cell imaging can provide valuable information about the heterogeneity of cGMP signals within and between individual cells of an isolated cell population or tissue. We also discuss current challenges and future directions of cGMP imaging, such as the direct visualisation of cGMP microdomains, simultaneous monitoring of cGMP and other signalling molecules and, ultimately, cGMP imaging in tissues and animals under close-to-native conditions. LINKED ARTICLES: This article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc.

Physiologia: A Progressive Open Access Journal Publishing New Horizons in the Physiology of Life

Physiologia (the Latin origins of Physiology, ISSN 2673-6772), is a new journal aimed at publishing original and review articles demonstrating conceptual advances across the realms of physiology [...]

Accessibility and the Capabilities Approach: a review of the literature and proposal for conceptual advancements

ABSTRACT The Capability Approach, developed by Sen and Nussbaum, has recently gained increasing attention in the transport literature. This paper adds to this growing body of literature by investigating how the approach can generate consistent evaluative approaches to inform (urban) transport planning. The paper reviews the mobility literature that has investigated the Capabilities Approach and identifies the opportunities and challenges of employing the approach as a basis for transport planning. The review highlights the different, and sometimes patchy, ways in which the key notions of the approach have been conceptualised and operationalised. Discussing this growing but scattered literature, the paper embraces the emerging direction that understands accessibility as the capability that transport planning and policy should consider. Further refining this understanding, the paper proposes a twofold evaluative approach combining a top-down and a bottom-up component to capture the myriad of conversion factors shaping people’s accessibility-as-capability and functioning. By systematically adopting the Capabilities Approach, transport planning and mobility policies will be directed to enhancing each person’s freedom to pursue the life they have reason to value in contemporary societies.

Native to designed: microbial -amylases for industrial applications.

Background-amylases catalyze the endo-hydrolysis of -1,4-D-glycosidic bonds in starch into smaller moieties. While industrial processes are usually performed at harsh conditions, -amylases from mainly the bacteria, fungi and yeasts are preferred for their stabilities (thermal, pH and oxidative) and specificities (substrate and product). Microbial -amylases can be purified and characterized for industrial applications. While exploring novel enzymes with these properties in the nature is time-costly, the advancements in protein engineering techniques including rational design, directed evolution and others have privileged their modifications to exhibit industrially ideal traits. However, the commentary on the strategies and preferably mutated residues are lacking, hindering the design of new mutants especially for enhanced substrate specificity and oxidative stability. Thus, our review ensures wider accessibility of the previously reported experimental findings to facilitate the future engineering work.Survey methodology and objectivesA traditional review approach was taken to focus on the engineering of microbial -amylases to enhance industrially favoured characteristics. The action mechanisms of - and -amylases were compared to avoid any bias in the research background. This review aimed to discuss the advances in modifying microbial -amylases via protein engineering to achieve longer half-life in high temperature, improved resistance (acidic, alkaline and oxidative) and enhanced specificities (substrate and product). Captivating results were discussed in depth, including the extended half-life at 100C, pH 3.5 and 10, 1.8 M hydrogen peroxide as well as enhanced substrate (65.3%) and product (42.4%) specificities. These shed light to the future microbial -amylase engineering in achieving paramount biochemical traits ameliorations to apt in the industries.ConclusionsMicrobial -amylases can be tailored for specific industrial applications through protein engineering (rational design and directed evolution). While the critical mutation points are dependent on respective enzymes, formation of disulfide bridge between cysteine residues after mutations is crucial for elevated thermostability. Amino acids conversion to basic residues was reported for enhanced acidic resistance while hydrophobic interaction resulted from mutated hydrophobic residues in carbohydrate-binding module or surface-binding sites is pivotal for improved substrate specificity. Substitution of oxidation-prone methionine residues with non-polar residues increases the enzyme oxidative stability. Hence, this review provides conceptual advances for the future microbial -amylases designs to exhibit industrially significant characteristics. However, more attention is needed to enhance substrate specificity and oxidative stability since they are least reported.

Enhancing the Responsiveness of Family-Based CBT Through Culturally Informed Case Conceptualization and Treatment Planning

Family-based CBT has been shown to be effective in controlled settings for an array of youth mental health difficulties, yet disparities in treatment engagement and outcomes across culturally diverse groups remain. In practice, cultural minority families are less likely to reap the demonstrated benefits of supported programs. Although there have been tremendous advances in case conceptualization, leading models have largely ignored cultural factors, contributing to observed disparities. The present paper reviews recent advances in science-informed case conceptualization and highlights how such advances nonetheless have failed to provide guidance on systematically incorporating cultural formulation into assessment and treatment planning. We then build upon Christon et al. (2015) useful 5-stage model of science-based case conceptualization in an effort to move the field toward culturally informed case conceptualization. We highlight how leveraging cultural assessment—such as with the use of the Cultural Formulation Interview (CFI)—can facilitate the incorporation of cultural factors into each of the five stages of science-based case conceptualization. A case example is utilized to illustrate key opportunities for strategically incorporating relevant information gleaned from the CFI into culturally responsive care with youth and families.

Materials Design and Optimization for Next-Generation Solar Cell and Light-Emitting Technologies.

We review some of the most potent directions in the design of materials for next-generation solar cell and light-emitting technologies that go beyond traditional solid-state inorganic semiconductor-based devices, from both the experimental and computational standpoints. We focus on selected recent conceptual advances in tackling issues which are expected to significantly impact applied literature in the coming years. Specifically, we consider solution processability, design of dopant-free charge transport materials, two-dimensional conjugated polymeric semiconductors, and colloidal quantum dot assemblies in the fields of experimental synthesis, characterization, and device fabrication. Key modeling issues that we consider are calculations of optical properties and of effects of aggregation, including recent advances in methods beyond linear-response time-dependent density functional theory and recent insights into the effects of correlation when going beyond the single-particle ansatz as well as in the context of modeling of thermally activated fluorescence.

Hypothesis-Driven Palladium-Catalyzed Transformations for the Construction of New Molecular Architectures.

The development of new synthetic protocols to access diverse molecular scaffolds from readily available starting compounds is of significance in both academia and industry. Towards this, the catalysis by transition metals has been employed as a powerful tool to access molecules with broad structural and functional diversity. An overview of the recent literature manifested the tremendous potential of transition metal-catalyzed processes in advancing organic synthesis in a new direction. This account compiles new conceptual advancements in the palladium-catalyzed Alder-ene type cycloisomerization reactions, C-H functionalizations, and one-pot multicatalytic processes, which have become essential tools to access new classes of molecules.

Value chain partnerships and farmer entrepreneurship as balancing ecosystem services: Implications for agri-food systems resilience

Both in the European Union (EU) and worldwide, the resilience of agri-food systems depends on the human ability to balance between socio-economic and ecological trade-offs. Recent ecosystem services literature acknowledges that smallholder farmers’ participation to stakeholder partnerships and continuous learning influences their balancing ability. Yet, little research has so far focused on how smallholders’ participation in partnerships with other value chain actors - such as companies supplying or procuring from them - shape their learning processes and, in turn, how their mindset and behavioral change influences agri-food systems resilience outcomes. To address this gap, this conceptual paper advances a framework suggesting plausible linkages between: the organization of value chain partnerships; smallholder farmer entrepreneurship (meant as the ability to redeploy resources innovatively in and around farms); and agri-food systems resilience outcomes (such as stabilizing rural livelihoods, supporting ecological services and enhancing socio-cultural services). This framework suggests that value chain partnerships are more effective in supporting the smallholder farmers’ entrepreneurial learning: when they pool more resources (both tangible, like financial or physical assets, and intangible as knowledge or market information) among partners; when they distribute decision-making rights over their use more evenly; and when they balance between formal and informal coordination mechanisms. On the basis of empirical examples, these conceptual arguments suggest that policy incentives – such as the new Common Agricultural Policy (CAP) in the EU – should be directed towards resource pooling, experimentation and learning to effectively support smallholder farmer entrepreneurship and their contribution to the achievement of agri-food systems resilience outcomes.

A holistic framework integrating plant-microbe-mineral regulation of soil bioavailable nitrogen

Soil organic nitrogen (N) is a critical resource for plants and microbes, but the processes that govern its cycle are not well-described. To promote a holistic understanding of soil N dynamics, we need an integrated model that links soil organic matter (SOM) cycling to bioavailable N in both unmanaged and managed landscapes, including agroecosystems. We present a framework that unifies recent conceptual advances in our understanding of three critical steps in bioavailable N cycling: organic N (ON) depolymerization and solubilization; bioavailable N sorption and desorption on mineral surfaces; and microbial ON turnover including assimilation, mineralization, and the recycling of microbial products. Consideration of the balance between these processes provides insight into the sources, sinks, and flux rates of bioavailable N. By accounting for interactions among the biological, physical, and chemical controls over ON and its availability to plants and microbes, our conceptual model unifies complex mechanisms of ON transformation in a concrete conceptual framework that is amenable to experimental testing and translates into ideas for new management practices. This framework will allow researchers and practitioners to use common measurements of particulate organic matter (POM) and mineral-associated organic matter (MAOM) to design strategic organic N-cycle interventions that optimize ecosystem productivity and minimize environmental N loss.