Multiple Layers Of Complexity Research Articles

Identifying and testing adaptive management options to increase river catchment system resilience using a Bayesian Network model

AbstractThe cumulative impacts of future climatic and socioeconomic change threaten the ability of freshwater catchments to provide essential ecosystem services. Stakeholders who manage freshwaters require decision-support tools that increase their understanding of catchment system resilience and support the appraisal of adaptive management options to inform decision-making. Our research aims to test the ability of a Bayesian Network model to identify adaptive management scenarios and test their effectiveness across future pathways to 2050. Using the predominantly arable river Eden catchment (320 km2) in eastern Scotland as a case study, we invited stakeholders from multiple sectors to participate in a series of workshops aimed at addressing water quality issues and achieving good ecological status in the catchment both now and in the future. Our participatory methods helped stakeholders overcome multiple layers of complexity and uncertainty associated with future-focused water management. Outputs of a Bayesian Network model simulated both current and future catchment resilience to inform the identification of six management scenarios. The effectiveness of each management scenario was tested using the Bayesian Network model. Two adaptive management scenarios increased catchment resilience and helped achieve good ecological status; a ‘Best Available Technology’ scenario, including aerobic granular sludge treatment, and a management scenario focused on ‘Resource Centre’, including phosphorus recovery from wastewater treatment works and constructed lagoons for crop irrigation. Stakeholders were interested in a 'Nature Based' management scenario including options such as wetland wastewater treatment methods and rural sustainable drainage systems, which improved water quality in the catchment, but had lower certainty in achieving desired outcome. Findings led to a recognition that innovative and collaborative action was required to improve current and future freshwater conditions.

Identifying cell states in single-cell RNA-seq data at statistically maximal resolution.

Single-cell RNA sequencing (scRNA-seq) has become a popular experimental method to study variation of gene expression within a population of cells. However, obtaining an accurate picture of the diversity of distinct gene expression states that are present in a given dataset is highly challenging because of the sparsity of the scRNA-seq data and its inhomogeneous measurement noise properties. Although a vast number of different methods is applied in the literature for clustering cells into subsets with 'similar' expression profiles, these methods generally lack rigorously specified objectives, involve multiple complex layers of normalization, filtering, feature selection, dimensionality-reduction, employ ad hoc measures of distance or similarity between cells, often ignore the known measurement noise properties of scRNA-seq measurements, and include a large number of tunable parameters. Consequently, it is virtually impossible to assign concrete biophysical meaning to the clusterings that result from these methods. Here we address the following problem: Given raw unique molecule identifier (UMI) counts of an scRNA-seq dataset, partition the cells into subsets such that the gene expression states of the cells in each subset are statistically indistinguishable, and each subset corresponds to a distinct gene expression state. That is, we aim to partition cells so as to maximally reduce the complexity of the dataset without removing any of its meaningful structure. We show that, given the known measurement noise structure of scRNA-seq data, this problem is mathematically well-defined and derive its unique solution from first principles. We have implemented this solution in a tool called Cellstates which operates directly on the raw data and automatically determines the optimal partition and cluster number, with zero tunable parameters. We show that, on synthetic datasets, Cellstates almost perfectly recovers optimal partitions. On real data, Cellstates robustly identifies subtle substructure within groups of cells that are traditionally annotated as a common cell type. Moreover, we show that the diversity of gene expression states that Cellstates identifies systematically depends on the tissue of origin and not on technical features of the experiments such as the total number of cells and total UMI count per cell. In addition to the Cellstates tool we also provide a small toolbox of software to place the identified cellstates into a hierarchical tree of higher-order clusters, to identify the most important differentially expressed genes at each branch of this hierarchy, and to visualize these results.

A beginner's guide to study extracellular vesicles in human blood plasma and serum.

Blood is the most commonly used body fluid for obtaining and studying extracellular vesicles (EVs). While blood is a standard choice for clinical analysis, using blood as a source of EVs introduces multiple layers of complexity. At the Blood Extracellular Vesicle Workshop organized by the International Society for Extracellular Vesicles in Helsinki (2022), it became evident that beginner researchers lack trustworthy information on how to initiate their research and avoid common pitfalls. This educational guide explains the composition and frequently used terminology of blood, provides guidelines for blood collection, and the preparation of plasma and serum. It also introduces the basic principles of isolating and detecting blood EVs while considering blood-related factors. The goal of this guide is to assist beginners by offering a concise and evidence-based introduction to the current knowledge and available resources to study blood EVs.

Phenotyping the obesities: reality or utopia?

In this thematic issue on phenotyping the obesities, prominent international experts offer an insightful and comprehensive collection of articles covering the current knowledge in the field. In order to actually capture all the polyhedral determinants of the diverse types of obesity, the granularity of the phenotypic information acquired must be expanded in the context of a personalized approach. Whilst the use of precision medicine has been successfully implemented in areas like cancer and other diseases, health care providers are more reluctant to embrace detailed phenotyping to guide diagnosis, treatment and prevention in obesity. Given its multiple complex layers, phenotyping necessarily needs to go beyond the multi-omics approach and incorporate all the diverse spheres that conform the reality of people living with obesity. Potential barriers, difficulties, roadblocks and opportunities together with their interaction in a syndemic context are analyzed. Plausible lacunae are also highlighted in addition to pointing to the need of redefining new conceptual frameworks. Therefore, this extraordinary collection of state-ofthe-art reviews provides useful information to both experienced clinicians and trainees as well as academics to steer clinical practice and research in the management of people living with obesity irrespective of practice setting or career stage.

Yolkala Gumurrlili? with Whom Towards the Chest? A Relational Portrait of Yolŋu Social Organisation

ABSTRACT Much has been written about Yolŋu social organisation since Lloyd Warner’s early ethnography (1937). Debates within this literature have predominantly focused on the relative independence of bäpurru groups, a significant social unit within Yolŋu society, and whether these can accurately be described as ‘corporate descent groups’. To develop a fresh perspective on Yolŋu social organisation, this paper presents an exploration of five drawings by Dhambiŋ Burarrwaŋa and her waku (daughters, sister’s daughters), a novel methodology which has allowed us to recast well-known anthropological tropes within a setting of relational growth and cross-cultural communication. Rather than outlining a structural model, themes of raki’ (strings), luku (foot, footprint, anchor, root of a tree), gamunuŋgu (white clay), and lirrwi (ashes, shade) are explored in detail, as they reveal multiple layers of complexity and connection within otherwise abstract notions like ‘clan’. The drawings and accompanying exegesis situate Yolngu identity within living social connections. What emerges is a relational portrait that embeds the ‘clan debate’ within those relationships that make understanding possible in the first place.

Beyond the adjacent possible: On the irreducibility of human creativity to biology and physics

In this article, the problem of understanding multiple layers of complexity in our universe is addressed, with particular emphasis on explaining creative evolutions in the material, biological, and psycho-social layers. Perspectives from physics, biology, psychology, and philosophy are utilized in the discussion. Process philosophy is used to justify the theoretical foundation of the dynamic universal creativity process. The concepts of unified and final theories are discussed from a position that criticizes reductionism. The concept of the adjacent possible is reviewed as introduced by Kauffman to exclude the possibility that a theory from physics could be extended to explain the biological layer. In a similar way, the adjacent possible is shown to be useful but insufficient to explain the psycho-social layer of complexity, missing fundamental human abilities such as thinking of long-term futures, wisdom, and dynamic creativity leaps that use the impossible as an inspiration.

Multiple Layers of Complexity in O-Glycosylation Illustrated With the Urinary Glycoproteome

While N-glycopeptides are relatively easy to characterize, O-glycosylation analysis is more complex. In this article, we illustrate the multiple layers of O-glycopeptide characterization that make this task so challenging. We believe our carefully curated dataset represents perhaps the largest intact human glycopeptide mixture derived from individuals, not from cell lines. The samples were collected from healthy individuals, patients with superficial or advanced bladder cancer (three of each group), and a single bladder inflammation patient. The data were scrutinized manually and interpreted using three different search engines: Byonic, Protein Prospector, and O-Pair, and the tool MS-Filter. Despite all the recent advances, reliable automatic O-glycopeptide assignment has not been solved yet. Our data reveal such diversity of site-specific O-glycosylation that has not been presented before. In addition to the potential biological implications, this dataset should be a valuable resource for software developers in the same way as some of our previously released data has been used in the development of O-Pair and O-Glycoproteome Analyzer. Based on the manual evaluation of the performance of the existing tools with our data, we lined up a series of recommendations that if implemented could significantly improve the reliability of glycopeptide assignments.

Integrative genomics important to understand host-pathogen interactions.

Infectious diseases are the leading cause of morbidity and mortality worldwide. Causative pathogenic microbes readily mutate their genome and lead to outbreaks, challenging the healthcare and the medical support. Understanding how certain symptoms manifest clinically is integral for therapeutic decisions and vaccination efficacy/protection. Notably, the interaction between infecting pathogens, host response and co-presence of microbes influence the trajectories of disease progression and clinical outcome. The spectrum of observed symptomatic patients (mild, moderate and severe) and the asymptomatic infections highlight the challenges and the potential for understanding the factors driving protection/susceptibility. With the increasing repertoire of high-throughput tools, such as cutting-edge multi-omics profiling and next-generation sequencing, genetic drivers of factors linked to heterogeneous disease presentations can be investigated in tandem. However, such strategies are not without limits in terms of effectively integrating host-pathogen interactions. Nonetheless, an integrative genomics method (for example, RNA sequencing data) for exploring multiple layers of complexity in host-pathogen interactions could be another way to incorporate findings from high-throughput data. We further propose that a Holo-transcriptome-based technique to capture transcriptionally active microbial units can be used to elucidate functional microbiomes. Thus, we provide holistic perspective on investigative methodologies that can harness the same genomic data to investigate multiple seemingly independent but deeply interconnected functional domains of host-pathogen interaction that modulate disease severity and clinical outcomes.

WNT Signalling in Osteoarthritis and Its Pharmacological Targeting.

Osteoarthritis (OA) is a highly disabling musculoskeletal condition affecting millions of people worldwide. OA is characterised by progressive destruction and irreversible morphological changes of joint tissues and architecture. At molecular level, de-regulation of several pathways contributes to the disruption of tissue homeostasis in the joint. Overactivation of the WNT/β-catenin signalling pathway has been associated with degenerative processes in OA. However, the multiple layers of complexity in the modulation of the signalling and the still insufficient knowledge of the specific molecular drivers of pathogenetic mechanisms have made difficult the pharmacological targeting of this pathway for therapeutic purposes. This review aims to provide an overview of the WNT/β-catenin signalling in OA with a particular focus on its role in the articular cartilage. Pathway components whose targeting showed therapeutic potential will be highlighted and described. A specific section will be dedicated to Lorecivivint, the first inhibitor of the β-catenin-dependent pathway currently in phase III clinical trial as OA-modifying agent.

Tumor-on-a-chip platforms to study cancer-immune system crosstalk in the era of immunotherapy.

Immunotherapy is a powerful therapeutic approach able to re-educate the immune system to fight cancer. A key player in this process is the tumor microenvironment (TME), which is a dynamic entity characterized by a complex array of tumor and stromal cells as well as immune cell populations trafficking to the tumor site through the endothelial barrier. Recapitulating these multifaceted dynamics is critical for studying the intimate interactions between cancer and the immune system and to assess the efficacy of emerging immunotherapies, such as immune checkpoint inhibitors (ICIs) and adoptive cell-based products. Microfluidic devices offer a unique technological approach to build tumor-on-a-chip reproducing the multiple layers of complexity of cancer-immune system crosstalk. Here, we seek to review the most important biological and engineering developments of microfluidic platforms for studying cancer-immune system interactions, in both solid and hematological tumors, highlighting the role of the vascular component in immune trafficking. Emphasis is given to image processing and related algorithms for real-time monitoring and quantitative evaluation of the cellular response to microenvironmental dynamic changes. The described approaches represent a valuable tool for preclinical evaluation of immunotherapeutic strategies.

Understanding the multiple layers of complexity associated with hoarding and children

Consideration of prevalence estimates, age of onset, social and economic impairment and safety risks highlight that youth may be negatively impacted by hoarding through personal attachment, difficulty letting go and engagement in hoarding behaviour, and/or living in a home with a hoarding parent/caregiver Dr Soreni and colleagues’ paper provides a comprehensive review of the literature on the phenomenology of hoarding in childhood, including clinical features and other factors (e g , symptoms, development, attachment, information processing, comorbidity, family, social functioning) as well as a brief client vignette [ ]a commentary and personal account by Ms Crawford provides a picture of what it is like to be the child of someone with a hoarding problem who subsequently has had a professional career in the management and response to animal hoarding

90 YEARS OF PROGESTERONE: Progesterone receptor signaling in the normal breast and its implications for cancer.

Progesterone is considered as the pregnancy hormone and acts on many different target tissues. Progesterone receptor (PR) signaling is important for normal development and the physiologic function of the breast and impinges on breast carcinogenesis. Both systemically and locally, in the breast epithelium, there are multiple layers of complexity to progesterone action, many of which have been revealed through experiments in mice. The hormone acts via its receptor expressed in a subset of cells, the sensor cells, in the breast epithelium with different signaling outcomes in individual cells eliciting distinct cell-intrinsic and paracrine signaling involving different mediators for different intercellular interactions. PR expression itself is developmentally regulated and the biological outcome of PR signaling depends on the developmental stage of the mammary gland and the endocrine context. During both puberty and adulthood PR activates stem and progenitor cells through Wnt4-driven activation of the myoepithelium with downstream Adamts18-induced changes in extracellualr matrix (ECM) / basal membrane (BM). During estrous cycling and pregnancy, the hormone drives a major cell expansion through Rankl. At all stages, PR signaling is closely tied to estrogen receptor α (ER) signaling. As the PR itself is a target gene of ER, the complex interactions are experimentally difficult to dissect and still poorly understood. Ex vivo models of the human breast and studies on biopsy samples show that major signaling axes are conserved across species. New intraductal xenograft models hold promise to provide a better understanding of PR signaling in the normal breast epithelium and in breast cancer development in the near future.

Grounding History in Cheju Islanders' Travel Literature

Cheju kihaeng, a small yet growing genre of academicized travel writing, looks at Cheju Island as existing in a liminal time and space or as a position. Writing amidst as well as against tourism's dominance on Cheju, kihaeng writers emphasize engagement with localities as vantage points from which one can not only recover long-ignored or suppressed subjectivities but also reject notions of Korean homogeneity. This article examines the books of Cheju historian and high school teacher Yi Yŏngkwŏn, journalist Kim Hyŏnghun, and former Provincial Office of Education director Mun Yŏngt'aek. Although these three authors share the overall objective of writing kihaeng literature from a Cheju islander's perspective, their scope and interests demonstrate overlapping and sometimes divergent approaches to grounding history in the island's geography as they respond to or criticize trends in Cheju cultural tourism since the early 2000s. These three authors' treatment of local history and what it means to identify as a Cheju person reveals multiple complex layers and anxieties about how to begin to define as well as interrogate a notion of the Chejudodaun (Cheju-esque).

Multiple Ways of Reflecting: Teacher Candidates’ Introspective use of the Arts in a Clinically Rich Field Experience

In this arts-based inquiry, we studied how 50 teacher candidates at seven after-school program sites used the arts, along with traditional written reflections, to examine their teaching beliefs and represent their field experiences. Data were collected throughout the 6-week course semester and analyzed using a three-stage process of thematic coding. Resonant themes included teacher candidates reflecting through multiple layers of complexity on teacher identity (assumptions and beliefs), knowing students, and embedding differentiation in practice. Implications, including the need for pre-service teachers to have differentiated opportunities for assessment and expression, are addressed.

Minimally invasive mitral valve surgery

Minimally invasive mitral valve surgery is one of the most difficult procedures to learn. The learning curve is steep. This steep learning curve has “partially” to do with the fact that the operation is done with long-shafted instruments and that there are multiple layers of complexity to this procedure.

Ejection of Double Knots from the Radio Core of PKS 1510–089 during the Strong Gamma-Ray Flares in 2015

Abstract PKS 1510–089 is a bright and active γ-ray source that showed strong and complex γ-ray flares in mid-2015 during which the Major Atmospheric Gamma Imaging Cerenkov telescopes detected variable very high energy (photon energies >100 GeV) emission. We present long-term multifrequency radio, optical, and γ-ray light curves of PKS 1510–089 from 2013 to 2018, and results of an analysis of the jet kinematics and linear polarization using 43 GHz Very Long Baseline Array data observed between late 2015 and mid-2017. We find that a strong radio flare trails the γ-ray flares in 2015, showing an optically thick spectrum at the beginning and becoming optically thin over time. Two laterally separated knots of emission are observed to emerge from the radio core nearly simultaneously during the γ-ray flares. We detect an edge-brightened linear polarization near the core in the active jet state in 2016, similar to the quiescent jet state in 2008–2013. These observations indicate that the γ-ray flares may originate from compression of the knots by a standing shock in the core and the jet might consist of multiple complex layers showing time-dependent behavior, rather than of a simple structure of a fast jet spine and a slow jet sheath.

Giraffe social preferences are context dependent

The dynamic nature of animal societies often hides multiple layers of complexity. The field of animal behaviour is rapidly advancing with the development of increasingly sophisticated analytical methods that allow scientists to identify complex and nuanced drivers of social patterns. The resurgent interest in giraffe sociality illustrates this by challenging the early view that individuals interact at random; it became clear that, instead, giraffes can be organized into multilevel societies, apparently founded on preferred associations. However, it is unclear whether such enduring associations result from active choice for specific individuals. The extent to which other social and asocial factors can contribute to an individual's inclusion in groups remains underexplored. Here we assess how context affects social preferences at the individual level by evaluating grouping patterns of giraffes in different behavioural states, habitats and levels of disturbance. When we controlled for potential class-based (as opposed to individual-based) assortment of individuals by sex, age and gregariousness, we found that giraffes only exhibited individual social preferences when foraging, with minor influence of habitat complexity or level of disturbance. Our results indicate that behavioural context is a major driver of giraffe social association. This strengthens recent evidence of complex social systems in giraffes and suggests that classic metrics of social relationships (such as association indices) may be too coarse, concealing true social preferences in wild populations.

Simulating Troublesome Contexts: How Multiple Roles within Ward-Based Simulations Promote Professional Nursing Competence

Nursing care is multifaceted and is practised within complex healthcare environments. Although the concept of competence itself is tenuous ( Watson et al. 2002 ), achievement of nursing competencies remains an essential prerequisite for nurse registration in Ireland. The domains of nursing competence are: professional/ethical practice; holistic approaches to care and the integration of knowledge; organization and management of care; personal and professional development; and interpersonal relationships ( An Bord Altranais 2005 ). At a conceptual level, these can be likened, somewhat, to threshold concepts insofar as they represent important transitions of practice and understanding. In this article, we illustrate how a ward-based simulation exercise with evolving scenarios and multiple role performances mimics ‘troublesome contexts’. We find that this exercise successfully promotes both nurse competence and understanding of threshold concepts through the embodiment of multiple identities (e.g. nurse, patient, relative, observer, etc.). Evaluations of this activity amongst a cohort of final year nursing students have consistently identified the transformative nature of this activity, particularly when acting in the ‘patient’ role. In this article, we describe the processes inherent in this simulation exercise and how the multiple layers of complexity are achieved. The very act of performing multiple identities and roles within an evolving complex environment we suggest, results in a consequential, transformed view ( Meyer and Land 2003 ) of values, attitudes and behaviours in addition to enhancing nursing competence. Evidence of this is demonstrated in evaluations of the debriefing exercise undertaken immediately following simulation.

Blending customisation, context-awareness and adaptivity for personalised tangible interaction in cultural heritage

Shaping personalization in a scenario of tangible, embedded and embodied interaction for cultural heritage involves challenges that go well beyond the requirements of implementing content personalization for portable mobile guides. Content is coupled with the physical experience of the objects, the space, and the facets of the context – being those personal or social – acquire a more prominent role. This paper presents a personalization framework to support complex scenarios that combine the physical, the digital, and the social dimensions of a visit. It is based on our experience in collaborating with curators and museum experts to understand and shape personalization in a way that is meaningful to them and to visitors alike, that is sustainable to implement and effective in managing the complexity of context-awareness. The pro posed approach features a decomposition of personalization into multiple layers of complexity that involve a blend of customization on the visitor’s initiative or according to the visitor’s profile, system context-awareness, and automatic adaptivity computed by the system based on the visitor’s behaviour model. We use a number of case studies of implemented exhibitions where this approach was used to illustrate its many facets and how adaptive techniques can be effectively complemented with interaction design, rich narratives and visitors’ choice to create deeply personal experiences. Overarching reflections spanning case studies and prototypes provide evidence of the viability of the proposed frame work, and illustrate the final effect of the user experience.

The multilayer nature of ecological networks.

Although networks provide a powerful approach to study a large variety of ecological systems, their formulation does not typically account for multiple interaction types, interactions that vary in space and time, and interconnected systems such as networks of networks. The emergent field of 'multilayer networks' provides a natural framework for extending analyses of ecological systems to include such multiple layers of complexity, as it specifically allows one to differentiate and model 'intralayer' and 'interlayer' connectivity. The framework provides a set of concepts and tools that can be adapted and applied to ecology, facilitating research on high-dimensional, heterogeneous systems in nature. Here, we formally define ecological multilayer networks based on a review of previous, related approaches; illustrate their application and potential with analyses of existing data; and discuss limitations, challenges, and future applications. The integration of multilayer network theory into ecology offers largely untapped potential to investigate ecological complexity and provide new theoretical and empirical insights into the architecture and dynamics of ecological systems.