Systems-level Approach Research Articles

Rethinking the Overwork Culture: Practical Strategies for Creating Sustainable Change

This article provides organizational leaders seeking to disrupt entrenched cultures of overwork with practical strategies drawn from academic literature and consulting experiences. It explores key drivers of overwork at both the organizational level, such as a lack of boundaries between work and personal time, perceptions of overwork as a requirement, pressure from leadership, and lack of alternative policies, and at the societal level. Concrete steps are then outlined for establishing sustainable change, like setting clear boundaries on availability and working hours, empowering employees with flexible arrangements, disconnecting from technology after hours, shifting perceptions of productivity away from face time, increasing transparency from leadership, and building in recovery periods. Case studies from Buffer and Mailchimp demonstrate success. The article advocates a holistic, systems-level approach led by committed executives to alter cultural norms and mindsets over the long run through fostering autonomy, flexibility and trust in order to enhance both performance and well-being. Leaders are encouraged to customize strategies to their contexts while continuously measuring impact and refining approaches, with the ultimate goal of empowering employees to bring their full selves each day.

Ex vivo and in vitro methods as a platform for studying anthropogenic effects on marine mammals: four challenges and how to meet them

Marine mammals are integral to global biodiversity and marine health through their roles in coastal, benthic, and pelagic ecosystems. Marine mammals face escalating threats from climate change, pollution, and human activities, which perturb their oceanic environment. The diverse biology and extreme adaptations evolved by marine mammals make them important study subjects for understanding anthropogenic pressures on marine ecosystems. However, ethical and logistical constraints restrict the tractability of experimental research with live marine mammals. Additionally, studies on the effects of changing ocean environments are further complicated by intricate gene-environment interactions across populations and species. These obstacles can be overcome with a comprehensive strategy that involves a systems-level approach integrating genotype to phenotype using rigorously defined experimental conditions in vitro and ex vivo. A thorough analysis of the interactions between the genetics of marine mammals and their exposure to anthropogenic pressures will enable robust predictions about how global environmental changes will affect their health and populations. In this perspective, we discuss four challenges of implementing such non-invasive approaches across scientific fields and international borders: 1) practical and ethical limitations of in vivo experimentation with marine mammals, 2) accessibility to relevant tissue samples and cell cultures; 3) open access to harmonized methods and datasets and 4) ethical and equitable research practices. Successful implementation of the proposed approach has the potential impact to inspire new solutions and strategies for marine conservation.

Humoral signatures of Caspr2-antibody spectrum disorder track with clinical phenotypes and outcomes.

Immunoglobulin (Ig) G4 auto-antibodies (Abs) against contactin-associated protein-like 2 (Caspr2), a transmembrane cell adhesion protein expressed in the central and peripheral nervous system, are found in patients with a broad spectrum of neurological symptoms. While the adoptive transfer of Caspr2-specific IgG induces brain pathology in susceptible rodents, the mechanisms by which Caspr2-Abs mediate neuronal dysfunction and translate into clinical syndromes are incompletely understood. We use a systems-level approach combined with high-dimensional characterization of Ab-associated immune features to deeply profile humoral biosignatures in patients with Caspr2-Ab-associated neurological syndromes. We identify two signatures strongly associated with two major clinical phenotypes, limbic encephalitis (LE) and predominant peripheral nerve hyperexcitability without LE (non-LE). Caspr2-IgG Fc-driven pro-inflammatory features, characterized by increased binding affinities for activating Fcγ receptors (FcγRs) and C1q, along with a higher prevalence of IgG1-class Abs, in addition to IgG4, are strongly associated with LE. Both the occurrence of Caspr2-specific IgG1 and higher serum levels of interleukin (IL)-6 and IL-15, along with increased concentrations of biomarkers reflecting neuronal damage and glial cell activation, are associated with poorer clinical outcomes at 1-year follow-up. The presence of IgG1 isotypes and Fc-mediated effector functions control the pathogenicity of Caspr2-specific Abs to induce LE. Biologics targeting FcR function might potentially restrain Caspr2-Ab-induced pathology and improve clinical outcomes. This study was funded by a German-French joint research program supported by the German Research Foundation (DFG) and the Agence Nationale de la Recherche (ANR) and by the Interdisciplinary Centre for Clinical Research (IZKF) Münster.

301 Leveraging genomics to advance the breeding of Canadian livestock

Abstract Implementing breeding strategies for a more sustainable food system is one of the most pressing topics for livestock industries. Although different species face different challenges, large-scale research projects can pave the way for future opportunities in these key sectors. Herein, we present two examples (dairy and poultry) of how research projects can result in meaningful changes to commercial breeding programs. The first example is an international large-scale dairy project, which will deliver a roadmap for greenhouse gas (GHG) management using genomics and nutrition. The project aims to facilitate a 55% reduction in GHG emissions from Canadian dairy at an estimated value of $338M CAD. This systems-level approach will leverage resources developed through previous and current large-scale projects to produce accurate multi-level emission estimates and identify opportunities to mitigate enteric GHG emissions. The results of this project will provide accurate, reliable, and robust data for industry stakeholders, national policy, and GHG inventories. The second example is a research collaboration with a commercial turkey breeding company that will enable breeding strategies for long-term and sustainable genetic improvement in health traits. This project aims to reduce preslaughter mortality by 5% and condemnations due to myopathies and health issues. This reduction alone is expected to result in 7.5M kg more turkey meat at a value of $19.8M CAD. Furthermore, there is also an expected reduction of 2.3M kg of CO2 equivalent per year for each 1% livability improvement due to production efficiencies and reduced inputs wasted for more sustainable and ethical meat production. Overall, ongoing and future research initiatives will continue to deliver solutions for key Canadian livestock sectors to improve animal health and welfare as well as efficiency and sustainability. The strides made in these ongoing collaborative projects are imperative for enhancing the sustainability of animal agriculture to feed the growing population.

How Early Career Family Medicine Women Physicians Negotiate Their First Job After Residency.

Nested within a growing body of evidence of a gender pay gap in medicine are more alarming recent findings from family medicine: a gender pay gap of 16% can be detected at a very early career stage. This article explores qualitative evidence of women's experiences negotiating for their first job out of residency to ascertain women's engagement with and approach to the negotiation process. We recruited family physicians who graduated residency in 2019 and responded to the American Board of Family Medicine 2022 graduate survey. We developed a semistructured interview guide following a modified life history approach to uncover women's experiences through the transitory stages from residency to workforce. A qualitative researcher used Zoom to interview 19 geographically and racially diverse early career women physicians. Interviews were transcribed verbatim and analyzed using NVivo software following an Inductive Content Analysis approach. Three main themes emerged from the data. First, salary was found to be nonnegotiable, exemplified by participants' inability to change initial salary offers. Second, the role of peer support throughout residency and early career was crucial to uncovering and rectifying salary inequity. Third, a pay expectation gap was identified among women from minority and low-income households. To rectify the gender pay gap in medicine, a systems-level approach is required. This can be achieved through various levels of interventions: societally expanding the use of and removing the stigma around parental leave, recognizing the importance of contributions not currently valued by productivity-based payment models, examining assumptions about leadership; and institutionally moving away from fee-for-service systems, encouraging flexible schedules, increasing salary transparency, and improving advancement transparency.

Bridging health self-efficacy and patient engagement with patient-centered culturally sensitive health care for Black American adults.

This study investigates whether systems-level interventions, specifically patient-centered culturally sensitive health care (PC-CSHC) from healthcare providers, office staff, and the clinic environment, moderate the relationship between health self-efficacy and patient engagement among Black American adults. An online survey was completed by 198 Black American adults. PC-CSHC from healthcare providers, office staff, and the clinic environment did not mitigate the adverse effects of low health self-efficacy on patient engagement. However, PC-CSHC from healthcare providers (b = 0.38) was as significant as health self-efficacy (b = 0.37) in predicting patient engagement, R2 = 0.47, F(9, 177) = 19.61, p < 0.001. Provider-delivered PC-CSHC can enhance patient engagement among Black American adults. This systems-level approach has the potential to reach more patients than intrapersonal interventions alone and alleviates the undue burden placed on Black Americans to leverage intrapersonal strengths in the face of health disparities rooted in structural racism.

Multi-scale reactor designs extend the physical limits of fixation.

valorization is a promising strategy for climate adaptation and transitioning towards a circular carbon economy. Here, we present a multi-scale, integrated systems approach for designing biomanufacturing systems that can utilize as a feedstock, focusing on the Wood-Ljungdahl and reductive glycine pathways. This approach relies on first principles, coupling the optimization of pathway and process variables. We examine the -fixation capacity of both pathways in single- and multi-compartment reactor systems, demonstrating that the reductive glycine pathway has the potential to fix at significantly higher rates than photosynthetic organisms. We show that small differences in the energy-dissipative and stoichiometric structures of carbon-fixation pathways could significantly impact optimal designs and feasible design spaces. Our first-principle, systems-level approach quantifies these differences and uncovers strategies to expand the design space and extend the physical limits of carbon fixation, offering insights into pathway selection and process configurations for efficient biomanufacturing.

Systems-Informed PERMA + 4: Measuring Well-being and Performance at the Employee, Team, and Supervisor Levels

Past research has relied on employees to self-report their levels of well-being and performance in the workplace. Systems-informed positive psychology has been proposed to understand the dynamic interrelationships of the employee in their social and environmental context. PERMA + 4 is a comprehensive framework designed to measure the building blocks of well-being at work. Using an international sample of employees (N=2000), this study developed a systems-informed (i.e., at the individual (I), team (T), and supervisor (S) levels) PERMA + 4 measure and examined the associations with well-being and work performance. Full-time employees who worked on a team of two or more individuals, and had a direct supervisor were recruited to take an online survey assessing their work-related well-being and performance. Findings supported convergent, discriminant, and incremental validity of individual, team, and supervisor PERMA + 4 with well-being and work performance outcomes. Scholars and practitioners may consider using a systems-informed PERMA + 4 approach to measure and evaluate workplace programs and interventions that target the well-being of individuals, teams, and leaders. Such a systems-level approach may contribute to improved work performance.

Harnessing peer mentorship as a tool to turn human resource for health brain drain into brain gain: a case study of a Nigerian peer-mentored research group

BackgroundPeer mentorship can be a potential tool to reduce the disparities in health research capacity between high- and low- and middle-income countries. This case study describes the potential of peer mentorship to tackle two critical issues: bridging health research capacity of doctors from low- and middle-income countries (LMICs) and the transformation of human resource for health brain drain into "brain gain".Case presentationIn 2021, a virtual peer mentorship group was established by 16 alumni of the University of Benin College of Medical Sciences' 2008 graduating class, residing across three continents. This program aimed to facilitate research collaboration and skill development among colleagues with diverse research experience levels, fostering a supportive environment for career development in research. The group relied heavily on digital technology to carry out its activities due to the different geographical locations of the group members. Led by experienced peer leaders, the group fostered a collaborative learning environment where members leveraged each other's expertise. Within 18 months, we published two research papers in high-impact peer-reviewed global health journals, launched a mixed-methods research study, and conducted training sessions on research design and implementation. Findings from our work were presented at conferences and workshops. However, logistical hurdles, competing priorities, structural constraints, and uneven participation presented challenges.ConclusionThe peer mentorship collaboration has achieved some successes so far, and this model can be emulated by other cohorts of medical professionals across LMICs. Despite the group's success at a micro- or individual level, there remain significant structural barriers to research capacity building in LMICs that can only be addressed at the meso- and macro-levels by institutions and government, respectively. A systems-level approach is required to develop and support research capacity building and foster global research collaboration and effectively turn brain drain into brain gain.

ASPECTS OF FOOD SAFETY ISSUES IN MODERN AGRICULTURE

Foodborne illnesses remain a persistent public health threat, with thousands of outbreaks each year caused by contaminated produce, meat, and dairy. The study analyzed food safety risks associated with traditional industrial farming practices, including concentrated animal feeding operations (CAFOs), large-scale produce production, and nationwide processing and distribution networks. Quantitative analysis of outbreak data reveals hot spots of contamination in commodities and the food system. Qualitative research and interviews contextualize the complex contamination pathways and challenges of preventing the spread of pathogens in modern agriculture. The main risks include inappropriate manure use, contaminated irrigation water, undersized buffer zones and inadequate sanitation at processing facilities. Policy improvements related to livestock density, water treatment, and implementation of protection plans may help reduce future threats. Ultimately, enhancing food safety in a way that does not compromise productivity and affordability requires a comprehensive, systems-level approach across the farm, processing facility, and regulatory agency. KEYWORDS: food safety, foodborne illness, industrial agriculture, commodities, contamination, pathogens, policy

Failure to Rescue as a Quality Measure in Sepsis

This Viewpoint discusses the limitations of current tools to improve sepsis outcomes and proposes that these tools be supplemented with “failure to rescue,” a systems-level approach for recognizing and addressing complications and managing sepsis throughout the hospitalization period.

Impact of novel methods and research approaches in plant pathology: Are individual advances sufficient to meet the wider challenges of disease management?

AbstractAdvances continue to be made by plant pathologists on topics in plant health, environmental protection and food security. Many advances have been made for individual crops, pathogens and diseases that in many cases have led to their successful management. A wider impact of research depends on recognition of the multifaceted challenges posed by plant diseases and the need to integrate studies in a systems level approach. The adoption of high‐throughput sequencing for diagnosis and detection is widespread but impact depends upon the agricultural and ecological context combined with improved surveillance. Deployment of host resistance in the field needs to be aligned with a greater appreciation of plant genetic diversity and the complementary contribution made by tolerance of disease. Epidemiological understanding of the spatiotemporal spread of plant diseases has improved through population dynamic and genetic analyses. Research emphasis on the plant microbiome has invigorated soil microbial studies, especially for disease complexes and declines, but the challenge is to move to interventions that benefit plant health. Analysis of the impacts of climate change has been made for single‐crop disease studies, but seldom have these been placed in the context of pathogen adaptation, new crops, wild plants, vectors and soil microbes. Advances in informatic analysis illustrate not only the global impacts of plant disease introductions, but also the challenges inherent in marshalling and integrating information. Advances have been made in applying artificial intelligence technologies across many areas of plant pathology but have yet to be integrated within any coordinated research agenda.

Change, Adversity, and Adaptation: Young People's Experience of the COVID-19 Pandemic Expressed through Artwork and Semi-Structured Interviews.

This study explores how young people's mental health was affected by the COVID-19 pandemic using artwork and semi-structured interviews. The mental health impacts of the pandemic are important to understand so that policy and practice professionals can support those affected, prepare and respond to future crises, and support young people who are isolated and restricted in other contexts. Co-designed participatory art workshops and interviews were conducted with 16-18-year-olds (n = 21, 62% female) from the London-based Longitudinal cohort Study of Cognition, Adolescents and Mobile Phones (SCAMP). Artworks and interview transcripts were qualitatively co-and analysed with young people. From interviews, six themes were identified: adaptation, restriction, change, challenges, overcoming adversity, and lockdown life. From the artwork, four themes were identified: trapped, negative mental wellbeing, positive emotions, and technology. Everyday factors such as home environment, social support, hobbies, habits, and online education were key determinants of how challenged and restricted participants felt, and their capacity to overcome this. This demonstrates the importance of wider (social and environmental) determinants and supports a systems-level public health approach to young people's mental health. For example, young people's mental health services should collaborate with other sectors to address such determinants in a holistic way. Clearer guidance and support with occupation, relationships, environment, routine and activities could mitigate the negative mental health impacts of major environmental changes on young people.

The relationship between justice system non-involvement and the social and emotional wellbeing of young Aboriginal and Torres Strait Islander people

Aboriginal and Torres Strait Islander young people are highly overrepresented within the Australian justice system. Despite an increase in research and policies, it is still unclear which interventions, programs and policies are most effective. The aim of the current study was to investigate the relationship between the Social and Emotional Wellbeing (SEWB) of Aboriginal young people and justice system non-involvement from a strengths-based perspective. The sample consisted of 725 Aboriginal adolescents aged 10–15 years who completed The Next Generation Project’s Youth Well-Being Study survey. Logistic regression was conducted to assess the SEWB factors associated with justice system non-involvement. It was found that self-rated good health, positive scores on the Prosocial Scale of the Strengths and Difficulties Questionnaire and younger age were significant predictors of justice system non-involvement. Policies and programs focusing on systems level approaches to support wellbeing in young Aboriginal people are likely to be beneficial.

Abstract Wrk2-02: Modelling the effects of cell-cell interactions in the tumor microenvironment from single cell variability

Abstract Multicellular programs underly emergent phenotypes in health and disease. Yet, deciphering the functional effects of interactions amongst cell types remains a major challenge. Cells typically send messages to their microenvironment by emitting ligands, which bind to complimentary receptors on the surfaced of target cells; then triggering a change in the behavior of the target cell. Complimentary ligand-receptor-pairs are well annotated and methods have been developed to infer cell-cell interactions from single cell expression data based on their mutual expression. However, these methods do not assess the effect of ligand-receptor-mediated interactions on the microenvironment. Thus, we developed ContactTracing – a fundamentally new, systems level approach that exploits inter- and intra-sample variability to infer ligand effects on gene expression in target (receptor-expressing) cells without prior knowledge of downstream signaling (Nature, 2023). Foundational work towards benchmarking and validation of this method was performed in isogenic breast cancer models distinguished by tumor cell-intrinsic rates of chromosome missegregation (a cellular process called chromosomal instability, or CIN). Through this, we identified tumor ligands emanating from an endoplasmic reticulum (ER)-stress response as potential mediators of immune suppression in chromosomally unstable tumors. Indeed, CIN-induced chronic STING activation led to rapid interferon-selective desensitization and a switch to ER-stress-dependent transcription. Moreover, inhibition of chronic STING - or key mediators of its unfolded protein response to ER-stress - suppressed metastasis in syngeneic models of melanoma, breast and colorectal cancer; validating this innovative methodology and identifying a targetable mediator of cancer metastasis. Citation Format: A. Laughney. Modelling the effects of cell-cell interactions in the tumor microenvironment from single cell variability [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr Wrk2-02.

P3LS: Partial Least Squares under privacy preservation

Modern manufacturing value chains require intelligent orchestration of processes across company borders in order to maximize profits while fostering social and environmental sustainability. However, the implementation of integrated, systems-level approaches for data-informed decision-making along value chains is currently hampered by privacy concerns associated with cross-organizational data exchange and integration. We here propose Privacy-Preserving Partial Least Squares (P3LS) regression, a novel federated learning technique that enables cross-organizational data integration and process modeling with privacy guarantees. P3LS involves a singular value decomposition (SVD) based PLS algorithm and employs removable, random masks generated by a trusted authority in order to protect the privacy of the data contributed by each data holder. We demonstrate the capability of P3LS to vertically integrate process data along a hypothetical value chain consisting of three parties and to improve the prediction performance on several process-related key performance indicators. Furthermore, we show the numerical equivalence of P3LS and PLS model components on both a synthetic and a real-world dataset and provide a thorough privacy analysis of the former. Moreover, we propose privacy-preserving explained X- and Y-block variance computations for determining the contribution of each data holder to the federated process model as a basis to incentivize data federation and fair profit-sharing.

Exploring Scoring Function Space: Developing Computational Models for Drug Discovery.

The idea of scoring function space established a systems-level approach to address the development of models to predict the affinity of drug molecules by those interested in drug discovery. Our goal here is to review the concept of scoring function space and how to explore it to develop machine learning models to address protein-ligand binding affinity. We searched the articles available in PubMed related to the scoring function space. We also utilized crystallographic structures found in the protein data bank (PDB) to represent the protein space. The application of systems-level approaches to address receptor-drug interactions allows us to have a holistic view of the process of drug discovery. The scoring function space adds flexibility to the process since it makes it possible to see drug discovery as a relationship involving mathematical spaces. The application of the concept of scoring function space has provided us with an integrated view of drug discovery methods. This concept is useful during drug discovery, where we see the process as a computational search of the scoring function space to find an adequate model to predict receptor-drug binding affinity.

Exploring GPCR signaling pathway networks as cancer therapeutic targets

GPCR signaling can contribute to establishing the tumor microenvironment and influence the progression and metabolism of tumors. Arora etal.1 describe a systems-level approach to investigate the patterns of co-expression of GPCR signaling pathway networks across diverse tumors and identify network components that correlate with patient-survival data across different cancer types.

A COMPREHENSIVE REVIEW ON UNRAVELLING THE INTRICACIES OF MOLECULAR NEUROSCIENCE

Molecular neuroscience is a multidisciplinary field dedicated to unravelling the molecular mechanisms underlying brain function and dysfunction. This comprehensive review provides an overview of recent advancements in molecular neuroscience, spanning from neuronal signalling pathways to the genetic basis of neurological disorders covered encompass synaptic plasticity and learning, neurodevelopment and synaptogenesis, neurotransmitter systems, and the genetic underpinnings of neurological disorders. Advances in techniques such as optogenetics, calcium imaging, and genomic technologies have revolutionized our understanding of the brain at the molecular level. Moreover, emerging technologies such as single-cell RNA sequencing and CRISPR/Cas9 genome editing hold promise for further elucidating the complexities of the nervous system. By integrating molecular, cellular, and systems-level approaches, molecular neuroscience continues to pave the way for novel insights into brain function and the development of targeted therapeutics for neurological diseases.

"I'm dealing with a health care system that doesn't get it": Barriers and facilitators to inclusive healthcare for autistic adults.

Research has suggested that autistic adults may have a bigger chance of having mental health and physical health conditions such as depression, anxiety, sleep disorders, diabetes, obesity, and heart problems than adults without autism. Unfortunately, the unique healthcare needs of autistic adults are often overlooked, so it is not clear why autistic adults have worse health or what can be done to improve it. This study wants to find out the challenges autistic adults experience in taking care of their health and in going to different doctors. Researchers interviewed autistic adults across the country about their healthcare experiences. The interviewed autistic adults told the researchers about the barriers (things that did not help) and facilitators (things that did help) that impacted whether they received the care they needed. The researchers then organized what they learned from the autistic adults into a model called the Systems Engineering Initiative for Patient Safety model of work system and patient safety. This model explains how different parts of a healthcare system (person, tasks, technology and tools, environment, and organization) interact with one another and impact the healthcare experiences and outcomes of the patients in their care, like autistic adults. Overall, this study advocates for a systems-level approach to improving the healthcare experiences of autistic adults and their health outcomes.