Conceptual Advances Research Articles

Theory of oil fouling for microfiltration and ultrafiltration membranes in produced water treatment

Due to the complexity of oil-in-water emulsions, the existing literature is still missing a mathematical tool that can describe membrane fouling in a fully quantitative manner on the basis of relevant fouling mechanisms. HypothesisIn this work, a quantitative model that successfully describes cake layer formation and pore blocking is presented. We propose that the degree of pore blocking is determined by the membrane contact angle and the resulting surface coverage, while the cake layer is described by a mass balance and a cake erosion flux. ValidationThe model is validated by comparison to experimental data from previous works (Dickhout et al. 2019; Virga et al., 2020) where membrane type, surfactant type and salinity were varied. Most input parameters could be directly taken from the experimental conditions, while four fitting parameters were required. FindingsThe experimental data can be well described by the model which was developed to provide insight into the dominant fouling mechanisms. Moreover, where existing models usually assume that pore blocking precedes cake layer formation, here we find that cake layer formation can start and occur while the degree of pore blocking is still increasing, in line with the more dynamic nature of oil droplets filtration. These new conceptual advances in the field of colloid and interface science open up new pathways for membrane fouling understanding, prevention and control.

Protecting Youth from Racism and Prejudice: Contexts, Interventions, and Future Directions

In the first half of the 21st century, it is clear that racism and prejudice are prevalent worldwide and begin in childhood—as children can be perpetrators, victims, and bystanders of racism and prejudice. Reducing racism in youth is a critical step toward improving the society we all live in. This special issue reviews and synthesizes the latest research on racism and prejudice in childhood and adolescence, examining the role of families, schools, media, and friendships in reducing prejudice in youth and highlighting how to enhance collective well-being. By focusing on research over the past two decades, and including a range of international perspectives, this special section helps make theoretical, conceptual, and methodological advances on the topic of reducing and protecting children from racism.

New-fangled conceptual perspectives and advances in the world of salivary gland

Understanding the pathogenesis and being familiar with diagnostic and management methods is critical in order to provide effective oral health care for patients. The current knowledge of the pathogenesis of each cancer subtype has made it possible to classify and define salivary gland tumors better. Specific treatment regimens for salivary gland tumors can be developed by studying molecular biology. Using immunohistochemistry in conjunction with gene analysis using PCR, specific defects can be identified, which provides insight into the most promising therapies. Hypofunctional salivary glands may benefit from organ replacement regenerative therapy using human adult stem cells.

Role of the duodenal microbiota in functional dyspepsia.

Functional dyspepsia (FD) is a common and debilitating gastrointestinal disorder attributed to altered gut-brain interactions. While the etiology of FD remains unknown, emerging research suggests the mechanisms are likely multifactorial and heterogenous among patient subgroups. Small bowel motor disturbances, visceral hypersensitivity, chronic microinflammation, and increased intestinal tract permeability have all been linked to the pathogenesis of FD. Recently, alterations to the gut microbiome have also been implicated to play an important role in the disease. Changes to the duodenal microbiota may either trigger or be a consequence of immune and neuronal disturbances observed in the disease, but the mechanisms of influence of small intestinal flora on gastrointestinal function and symptomatology are unknown. This review summarizes and synthesizes the literature on the link between the microbiota, low-grade inflammatory changes in the duodenum and FD. This review is not intended to provide a complete overview of FD or the small intestinal microbiota, but instead outline some of the key conceptual advances in understanding the interactions between altered gastrointestinal bacterial communities; dietary factors; host immune activation; and stimulation of the gut-brain axes in patients with FD versus controls. Current and emerging treatment approaches such as dietary interventions and antibiotic or probiotic use that have demonstrated symptom benefits for patients are reviewed, and their role in modulating the host-microbiota is discussed. Finally, suggested opportunities for diagnostic and therapeutic improvements for patients with this condition are presented.

Regulation of ZEB1 Function and Molecular Associations in Tumor Progression and Metastasis.

Simple SummaryGiven the importance of the epithelial-to-mesenchymal transition in tumor progression and the pivotal role of ZEB1 as a transcriptional repressor during this process, the regulation of ZEB1-targeted gene expression is an active area of investigation. Diverse signaling pathways converge to induce ZEB1 activity, but few studies have focused on the enzyme-dependent modifications of ZEB1 that occur after its translation from mRNA (i.e., post-translational modifications, PTM). In addition to outlining the current knowledge in the field, we outline several questions regarding the PTM-mediated regulation of ZEB1 that remain unanswered. Thus, the areas of research covered in this review paper will provide a noteworthy conceptual advancement in our understanding of ZEB1′s biological function, as well as its post-transcriptional and post-translational regulation. Furthermore, the review will enhance the development of treatment strategies by identifying knowledge gaps in ZEB1′s regulatory mechanisms that could potentially be targeted to prevent and treat metastasis in cancer patients.Zinc finger E-box binding homeobox 1 (ZEB1) is a pleiotropic transcription factor frequently expressed in carcinomas. ZEB1 orchestrates the transcription of genes in the control of several key developmental processes and tumor metastasis via the epithelial-to-mesenchymal transition (EMT). The biological function of ZEB1 is regulated through pathways that influence its transcription and post-transcriptional mechanisms. Diverse signaling pathways converge to induce ZEB1 activity; however, only a few studies have focused on the molecular associations or functional changes of ZEB1 by post-translational modifications (PTMs). Due to the robust effect of ZEB1 as a transcription repressor of epithelial genes during EMT, the contribution of PTMs in the regulation of ZEB1-targeted gene expression is an active area of investigation. Herein, we review the pivotal roles that phosphorylation, acetylation, ubiquitination, sumoylation, and other modifications have in regulating the molecular associations and behavior of ZEB1. We also outline several questions regarding the PTM-mediated regulation of ZEB1 that remain unanswered. The areas of research covered in this review are contributing to new treatment strategies for cancer by improving our mechanistic understanding of ZEB1-mediated EMT.

Small mammal personalities generate context dependence in the seed dispersal mutualism

Mutualisms are foundational components of ecosystems with the capacity to generate biodiversity through adaptation and coevolution and give rise to essential services such as pollination and seed dispersal. To understand how mutualistic interactions shape communities and ecosystems, we must identify the mechanisms that underlie their functioning. One mechanism that may drive mutualisms to vary in space and time is the unique behavioral types, or personalities, of the individuals involved. Here, our goal was to examine interindividual variation in the seed dispersal mutualism and identify the role that different personalities play. In a field experiment, we observed individual deer mice (Peromyscus maniculatus) with known personality traits predating and dispersing seeds in a natural environment and classified all observed interactions made by individuals as either positive or negative. We then scored mice on a continuum from antagonistic to mutualistic and found that within a population of scatter hoarders, some individuals are more mutualistic than others and that one factor driving this distinction is animal personality. Through this empirical work, we provide a conceptual advancement to the study of mutualism by integrating it with the study of intraspecific behavioral variation. These findings indicate that animal personality is a previously overlooked mechanism generating context dependence in plant–animal interactions and suggest that behavioral diversity may have important consequences for the functioning of mutualisms.

Recent developments in fetal lung ultrasound

Fetal ultrasound has been employed for years to help evaluate fetal growth and development and to monitor pregnancy. Furthermore, fetal lung maturity has been assessed pre-natally by examination of the amniotic fluid, usually obtained by transabdominal amniocentesis, for lecithin, lecithin/sphingomyelin ratio, or “P” factor (fluorescent polarization measurement for lipids.) Quantitative ultrasound texture analysis of fetal lung has been proposed in previous studies as a promising noninvasive method to predict fetal lung maturity, fetal lung hypoplasia, and neonatal respiratory morbidity. This technique utilizes standard fetal lung images, which are easily obtained by sonographers during routine ultrasound examinations. Additional information then can be extracted from these images by applying quantitative processing methods that characterize the tissue. This presentation discusses how to differentiate preterm (<37 weeks of gestation) from term (≥37 weeks of gestation) fetal lungs by quantitative texture analysis of ultrasound images. This quantification is based on the extent of heterogeneity associated with lung maturity by employing a unique, novel noninvasive technique to determine the Heterogeneity Index (HI) in ultrasound images. The HI values are then compared in sonograms of immature lungs with mature lungs. Conceptual advances for the possibility of integrating this technology in handheld ultraportable systems for point-of-care ultrasound (POCUS) are also presented.

Genetics of Normotension Preventing Hypertension Leads to a Novel Physiological Paradigm.

Possessing blood pressure in normal ranges is considered healthy, and does not warrant medical attention for obvious clinical reasons. However, to realize normotension and then maintain it even when confronted with a hypertensive threat must have its biological 'shield of armour'. While sensitivity to hypertension has been widely recognized and studied, inherent mechanisms that enable a physiological resistance to hypertension to occur have received little attention. Recent advances in normotension genetics have produced unexpected insights. A hypertension 'suppressor' likely inhabits the normotensive genome of inbred Lewis rats. This suppressor behaves as a 'master' control capable of functionally abrogating the effects of hypertension-promoting alleles from multiple quantitative trait loci. This conceptual advancement lays the foundation for uncovering an anti-hypertension gene. Discovering its identity will assist our attempts at developing innovative diagnostic and therapeutic strategies for circumventing and treating hypertension. This new domain of suppressing hypertension goes beyond the conventional pharmacological treatments of hypertension before symptoms appear. For this purpose, a valid theoretical basis and framework is needed that can interpret the experimental data and produce testable predictions for authenticating, enriching or amending the normotension paradigm in the future.

Mass movements

AbstractIn this chapter, we consider key advances in the understanding of mass movements betweenc.1965 andc.2000. This period saw a burgeoning need for a greater level of understanding of mass-movement processes in response to a series of high-impact mass-movement events, and because of the need to develop infrastructure safely. A series of step changes were enabled through hillslope geomorphology (broadly defined) being open to overarching and consolidating concepts, methods and models from cognate disciplines, whilst seizing opportunities to gain insight from rapidly advancing methods increasingly focused at a scale of investigation relevant to landsliding. Byc.2000, geomorphologists had made significant contributions to our understanding of mass-movement processes and ultimately led many key conceptual advances, notably relating to: bridging across scales of hillslope investigation; linking and developing understanding of process, form and mechanisms of slope stability; and articulating the temporal characteristics of slope stability and mass movement.

Adapting Common Resource Management to Under-Use Contexts: The Case of Common Pasture Organizations in the Black Forest Biosphere Reserve

Commonly used pastures have provided great socio-cultural, economic and ecological values across European mountain ranges. Since the last century, under-use is threatening these socio-ecological systems. Preserving common pastures as an integral part of cultural landscapes is the principal objective of the recently established Black Forest Biosphere Reserve in south-western Germany. We use the example of Black Forest common pasture organizations to scrutinize organisational arrangements, challenges and support of common resource sustenance in under-use contexts by drawing on Ostrom’s Design Principles, the Socio-Ecological-Systems Framework and resilience theory. To this end, we use mixed methods for data collection (semi-structured interviews, expert survey, focus group discussion) rooted in qualitative empirical social-ecological science. The suggested tripartite framework offers insights for conceptual and theoretical advancements in under-use contexts. As such, this research shows that design principles for under-use should (1) consider broader social boundaries to include all actors benefiting from the resources, (2) achieve congruence of provision, appropriation and local conditions that focus on sufficient levels of landscape stewardship services involving new beneficiaries for burden sharing, (3) match appropriators’ rights and duties as well as incentives for and motivations of pasture management. Concerning practical aspects, measures to support common pasture organizations’ adaptation need to incorporate multi-level governance and to increase connectivity.

Fast-decaying plant litter enhances soil carbon in temperate forests but not through microbial physiological traits

Conceptual and empirical advances in soil biogeochemistry have challenged long-held assumptions about the role of soil micro-organisms in soil organic carbon (SOC) dynamics; yet, rigorous tests of emerging concepts remain sparse. Recent hypotheses suggest that microbial necromass production links plant inputs to SOC accumulation, with high-quality (i.e., rapidly decomposing) plant litter promoting microbial carbon use efficiency, growth, and turnover leading to more mineral stabilization of necromass. We test this hypothesis experimentally and with observations across six eastern US forests, using stable isotopes to measure microbial traits and SOC dynamics. Here we show, in both studies, that microbial growth, efficiency, and turnover are negatively (not positively) related to mineral-associated SOC. In the experiment, stimulation of microbial growth by high-quality litter enhances SOC decomposition, offsetting the positive effect of litter quality on SOC stabilization. We suggest that microbial necromass production is not the primary driver of SOC persistence in temperate forests. Factors such as microbial necromass origin, alternative SOC formation pathways, priming effects, and soil abiotic properties can strongly decouple microbial growth, efficiency, and turnover from mineral-associated SOC.

Design of a Service for Hospital Internal Transport of Urgent Pharmaceuticals via Drones

The internal transport of medical goods in a hospital heavily relies on human resources that carry the materials on foot. Such mode of transport may be affected by inefficiencies, e.g., due to bottlenecks, and other logistic challenges. Thus, it may benefit from the use of unmanned aircraft systems in several aspects. Such a scenario introduces specific criticalities for healthcare organizations in densely populated areas and below congested airspace, such as the Milan metropolitan area. The authors applied a co-creation methodology to design a highly automated drone service for the delivery of pharmaceuticals at San Raffaele Hospital, Milan, Italy. The needs of the main users were identified by means of semi-structured interviews and visualization material. Based on those outcomes, a drone service was designed and validated with the main users. It emerged that the main gain point of such a service would be increasing hospital logistics efficiency. The risks tied to the operations (e.g., tampering of the delivery container) were evaluated and appropriate mitigations were identified (e.g., use of tamper-evident seals or mechatronic locks). The information required by the digital system offering the needed logistics functions was analyzed for future development. Recent conceptual and regulatory advancements in the field of Urban Air Mobility (UAM) in Europe were elaborated to outline the digital ecosystem in which aviation and non-aviation actors would exchange information to ensure operations’ efficiency, safety and regulatory compliance.

E-Learning Research Trends in Higher Education in Light of COVID-19: A Bibliometric Analysis.

This paper provides a broad bibliometric overview of the important conceptual advances that have been published during COVID-19 within “e-learning in higher education.” E-learning as a concept has been widely used in the academic and professional communities and has been approved as an educational approach during COVID-19. This article starts with a literature review of e-learning. Diverse subjects have appeared on the topic of e-learning, which is indicative of the dynamic and multidisciplinary nature of the field. These include analyses of the most influential authors, of models and networks for bibliometric analysis, and progress towards the current research within the most critical areas. A bibliometric review analyzes data of 602 studies published (2020–2021) in the Web of Science (WoS) database to fully understand this field. The data were examined using VOSviewer, CiteSpace, and KnowledgeMatrix Plus to extract networks and bibliometric indicators about keywords, authors, organizations, and countries. The study concluded with several results within higher education. Many converging words or sub-fields of e-learning in higher education included distance learning, distance learning, interactive learning, online learning, virtual learning, computer-based learning, digital learning, and blended learning (hybrid learning). This research is mainly focused on pedagogical techniques, particularly e-learning and collaborative learning, but these are not the only trends developing in this area. The sub-fields of artificial intelligence, machine learning, and deep learning constitute new research directions for e-learning in light of COVID-19 and are suggestive of new approaches for further analysis.

Theorising painkiller (mis)use in football using Bourdieu's practice theory and physical capital

This conceptual article advances the value of Bourdieu's practice theory and physical capital as a tool to understand the various types of painkiller (mis)use in sport. Consuming painkillers to manage injury and fatigue is a common practice among male professional footballers and misuse can exacerbate existing injuries and contribute to chronic physical and mental health conditions. In order to highlight the interaction between micro and macro-level factors we conceptualise painkiller use in professional football as a relational process between habitus, capital, and field position wherein variation in use is a result of social trajectory and field experiences. The analysis elaborates upon Bourdieu's practice theory in sport. It shows that the importance of protecting physical capital stems from internalised dispositions about how the body is viewed, which legitimise the use of painkillers within the social field of football despite the damaging potential outcomes for players. The article extends Bourdieu's practice theory to managing painkiller (mis)use, provides recommendations towards a future research programme, and identifies potential interventions for improving athlete welfare.

‘Societal Relationships with Nature’: A framework for understanding nature‐related conflicts and multiple values

Abstract In this paper, we operationalize the concept of Societal Relationships with Nature (SRN) as a framework for understanding nature‐related conflicts and multiple values. Based on three dimensions knowledgescape, interactions and identity, we propose a set of questions for the empirical analysis of conflict situations. We use two case studies—designation of a biosphere reserve in southern Chile and the return of the wolf in Germany—to illustrate how the SRN framework can reveal and structure the complexity of human–nature relationships. From the conceptual advances and the academic debate on multiple values of nature, we derive four requirements for approaches to analyse nature‐related conflicts and how different stakeholders attribute importance to nature. These should (a) cover the relevant aspects and reveal the critical issues underlying a conflict, (b) enable an understanding of differences and commonalities in people’s perspectives and positions, (c) be comprehensive enough to uncover important issues in complex situations without losing empirical practicability and (d) take power relations into account. We discuss whether and how the SRN framework meets these requirements. We present the SRN framework in particular to the academic community working at the interface with policy and practice on multiple values of nature and nature‐related conflicts. SRN analysis can also be applied to complement valuation approaches by specifying and explaining differences in people’s attributions of value to nature. Read the free Plain Language Summary for this article on the Journal blog.

Games researchers play: conceptual advancement versus validation strategies

Conceptual advances and validation are critical to research, yet at odds. Using a game theoretical perspective, we show that a mixed strategy combining advances and validation, leads to increases in both individual researchers' and societal gains. This win-win outcome can be used to design new research strategies, funding, and recognition standards.

Striving towards sustainable development: how environmental degradation and energy efficiency interact with health expenditures in SAARC countries.

The previous studies focused on environmental issues, identifying their root causes, urging prompt action to reduce environmental degradation. In this context, the current article extends the literature by incorporating the ecological impacts on the health sector and the role of sustainable development. The present study adds to the body of knowledge by examining the relationship between CO2 emissions, sustainable development, energy efficiency, energy intensity, and health expenditures for SAARC countries from 2000 to 2020. Fully modified OLS (FMOLS) and dynamic OLS (DOLS) are used and diagnostic tests to check the association between the variables. The empirical analysis validated the long-run impact of the examined factors on health expenditures. The results show that energy efficiency and sustainable development have a statistically significant negative effect on health expenditures, vice-versa for CO2 emission. Energy efficiency, energy intensity, and CO2 emissions have been shown to have a one-way causative relationship with health expenditures, but sustainable development and economic growth have a two-way causation relationship. The better health status of the SAARC economies necessitates the establishment of long-term development strategies, environmental sustainability, and an examination of the energy sector. This work’s conceptual and empirical advances have significant policy ramifications for this part of the globe and its efforts to improve sustainability.

The Maturational Naturalness of Original Sin

A doctrine of original sin or of the human condition generally requires an account of how that sin or condition is transmitted. One would think there are two options for thinking about this. Either original sin is innate or it is acquired. Both would seem to be problematic, the former because all the available options involve untoward metaphysical commitments or implicate God in unacceptable ways; the latter because of the uniformity of the human condition the doctrine requires. In this article, I use conceptual advances within the cognitive science of religion and empirical research to advance a plausible model of what the human condition consists in and how it is passed down.

Abstract P5-13-04: NF1 mutations render HER2+ breast cancer highly sensitive to T-DM1 by altering microtubule dynamics

Abstract Background: Despite major technological and conceptual advancements, treatment decisions in HER2+ metastatic breast cancer (mBC) remain largely based on clinical evidence, with no established predictive biomarkers to direct treatment for individual patients. The tumour suppressor Neurofibromatosis 1 (NF1) has been implicated in endocrine resistance but its role remains incompletely characterized in mBC. NF1 is best known as a GTPase-activating protein (GAP) that attenuates RAS signalling. However, the GAP function is likely not limited to RAS, and NF1 has been involved in other GTP-dependent processes including cytoskeletal dynamics. Data mining and analysis of public mutational registries revealed NF1 mutations as particularly enriched in HER2+ mBC compared to other molecular subtypes. Methods: To investigate the biological consequences of NF1 loss, we generated NF1 KO HER2+ mBC cell lines (BT474 and SKBR3) by CRISPR-Cas9 and both 2D and 3D proliferations assays were used for drug sensitivity profiling; live-cell imaging, high-resolution confocal microscopy and an ad-hoc computational algorithm were employed to study cell fate and microtubule conformational changes. Patient data were obtained from the Northwestern University through a prospective observational study in mBC patients. Results: Screening of several compounds approved for HER2+ mBC showed that response was generally equal or reduced in NF1 KO vs WT cells. However, response to trastuzumab-emtansine (T-DM1) was significantly increased in NF1 KO cells (IC50 ~0,3 vs 1,6 μg/mL in NF1WT). This sensitization was not observed with other antibody drug conjugates (ADCs) like DS-8201 and was reproducible with maytansine alone, suggesting a pharmacologically relevant NF1 activity on microtubules. Using the FUCCI(Ca) reporter, which tracks cell cycle progression at single-cell level, we saw a more prominent G2/M phase arrest and cell death upon T-DM1 treatment in NF1 KO compared to WT cells. Notably, NF1 KO cells exhibited a higher frequency of aberrant mitotic figures (chromosome alignment defects and multipolar spindle formation) and stronger β-galactosidase activity, an established marker of senescence. Collectively, these results suggest that NF1 KO cells become particularly subject to T-DM1-triggered mitotic catastrophe. Dephosphorylation of GTP-bound tubulin is required for appropriate microtubular dynamics; so-called “GTP islands” within the inner microtubule region are prone to rapid repolymerization and are normally kept at low levels. We hypothesize that expanded GTP-tubulin islands generated by the loss of NF1 GAP activity is a major cause of microtubular instability in NF1 KO cells. Preliminary evidence in support of this model was obtained by quantification of GTP-tubulin with a specific antibody. Finally, we assessed the predictive role of NF1 as a biomarker for T-DM1 response in a cohort of 300 mBC patients with mutational data in circulating tumour DNA (Guardant 360); we identified 13 heavily pretreated patients (>4 prior lines) who received T-DM1, of which 3 had loss-of-function NF1 mutations and 10 were NF1 WT. Median progression-free survival was higher in NF1-mutated than WT patients (334 vs 80 days); given the small sample size, these results cannot yet be considered significant (p=0.14). Conclusions: These results provide preliminary mechanistic and clinical evidence supporting the use of NF1 loss to guide treatment in HER2+ mBC. As novel HER2-specific agents are being rapidly added to the therapeutic arsenal, we propose biology-driven criteria to identify patients that may benefit specifically from T-DM1. In addition, NF1 dependence for correct microtubular dynamics may be exploited by other inhibitors of microtubular polymerization in use as ADC payloads, further extending the potential usefulness of NF1 determination. Citation Format: Bruno A Duso, Elena Gavilán Dorronzoro, Giulia Tini, Maria R de Filippo, Emanuele Bonetti, Maria R Ippolito, Chiara Soriani, Paolo D'Amico, Simona Rodighiero, Giuseppe Curigliano, Stefano Santaguida, Massimo Cristofanilli, Pier Giuseppe Pelicci, Luca Mazzarella. NF1 mutations render HER2+ breast cancer highly sensitive to T-DM1 by altering microtubule dynamics [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-04.

Probiotics in the Intensive Care Unit.

The understanding of the gut microbiome in health and disease has shown tremendous progress in the last decade. Shaped and balanced throughout life, the gut microbiome is intricately related to the local and systemic immune system and a multitude of mechanisms through which the gut microbiome contributes to the host’s defense against pathogens have been revealed. Similarly, a plethora of negative consequences, such as superinfections and an increased rate of hospital re-admissions, have been identified when the gut microbiome is disturbed by disease or by the iatrogenic effects of antibiotic treatment and other interventions. In this review, we describe the role that probiotics may play in the intensive care unit (ICU). We discuss what is known about the gut microbiome of the critically ill, and the concept of probiotic intervention to positively modulate the gut microbiome. We summarize the evidence derived from randomized clinical trials in this context, with a focus on the prevention of ventilator-associated pneumonia. Finally, we consider what lessons we can learn in terms of the current challenges, efficacy and safety of probiotics in the ICU and what we may expect from the future. Throughout the review, we highlight studies that have provided conceptual advances to the field or have revealed a specific mechanism; this narrative review is not intended as a comprehensive summary of the literature.