Towards the Holy Grail: combining system dynamics and discrete-event simulation in healthcare

The idea of combining discrete-event simulation and system dynamics has been a topic of debate in theoperations research community for over a decade. Many authors have considered the potential benefits ofsuch an approach from a methodological or practical standpoint. However, despite numerous examples ofmodels with both discrete and continuous parameters in the computer science and engineering literature,nobody in the OR field has yet succeeded in developing a genuinely hybrid approach which truly integratesthe philosophical approach and technical merits of both DES and SD in a single model. In this paperwe consider some of the reasons for this and describe two practical healthcare examples of combinedDES/SD models, which nevertheless fall short of the “holy grail” which has been so widely discussed inthe literature over the past decade

Resurrecting the interval of need concept to improve dialogue between researchers, policymakers, and social care practitioners

Academics, social care practitioners, and policymakers speak different languages. If academic research is to have an impact on society, it must be understandable and convincing to the end users. We argue that the conceptualisation of social care ‘need’ is different among these stakeholders, leading to poor communication between them. Academics should use concepts that have more meaning to practitioners. We propose resurrecting a little-used concept from the 1970s, ‘interval of need’, to help to bridge this gap. The interval of need concept identifies how often people require help, supplementing the usual data about types of tasks where assistance is needed. The history of the concept is described, followed by a test of its usefulness for today’s researchers by applying it to data from the English Longitudinal Study of Ageing. An updated version of interval of need is proposed. Validation checks were conducted against mortality data, and through conceptual validation from a social work practitioner. The nature of the dataset limited comparability with previous studies. However, we conclude that the interval of need concept has promising scope to enhance communication of research findings, potentially leading to improved outcomes for service users. This paper strives to mark a turning point in the language and analysis of social care, ensuring that academic investigation in this field is convincing and clear to practitioners and policymakers

Genome-wide DNA methylation meta-analysis in the brains of suicide completers

Suicide is the second leading cause of death globally among young people representing a significant global health burden. Although the molecular correlates of suicide remains poorly understood, it has been hypothesised that epigenomic processes may play a role. The objective of this study was to identify suicide-associated DNA methylation changes in the human brain by utilising previously published and unpublished methylomic datasets. We analysed prefrontal cortex (PFC, n = 211) and cerebellum (CER, n = 114) DNA methylation profiles from suicide completers and non-psychiatric, sudden-death controls, meta-analysing data from independent cohorts for each brain region separately. We report evidence for altered DNA methylation at several genetic loci in suicide cases compared to controls in both brain regions with suicide-associated differentially methylated positions enriched among functional pathways relevant to psychiatric phenotypes and suicidality, including nervous system development (PFC) and regulation of long-term synaptic depression (CER). In addition, we examined the functional consequences of variable DNA methylation within a PFC suicide-associated differentially methylated region (PSORS1C3 DMR) using a dual luciferase assay and examined expression of nearby genes. DNA methylation within this region was associated with decreased expression of firefly luciferase but was not associated with expression of nearby genes, PSORS1C3 and POU5F1. Our data suggest that suicide is associated with DNA methylation, offering novel insights into the molecular pathology associated with suicidality.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.NA/Fondation Brain Canada (Fondation Neuro Canada) MR/K013807/1/MRC_/Medical Research Council/United Kingdom NIMH 1R21MH094771/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) MR/K013807/1/Brain and Behavior Research Foundation (Brain & Behavior Research Foundation) MR/K013807/1/RCUK | MRC | Medical Research Foundation NA/Fonds de Recherche du Québec-Société et Culture (FRQSC) R21 MH094771/MH/NIMH NIH HHS/United Statespublished version, accepted version, submitted versio

Integrated patient-to-room and nurse-to-patient assignment in hospital wards

Assigning patients to rooms and nurses to patients are critical tasks within hospitals that directly affect patient and staff satisfaction, quality of care, and hospital efficiency. Both patient-to-room assignments and nurse-to-patient assignments are typically agreed upon at the ward level, and they interact in several ways such as jointly determining the walking distances nurses must cover between different patient rooms. This motivates to consider both problems jointly in an integrated fashion. This paper presents the first optimization models and algorithms for the integrated patient-to-room and nurse-to-patient assignment problem. We provide a mixed integer programming formulation of the integrated problem that considers the typical objectives from the single problems as well as additional objectives that can only be properly evaluated when integrating both problems. Moreover, motivated by the inherent complexity that results from integrating these two NP-hard and already computationally challenging problems, we devise an efficient heuristic for the integrated patient-to-room and nurse-to-patient assignment problem. To evaluate the running time and quality of the solution obtained with the heuristic, we conduct extensive computational experiments on both artificial and real-world instances. The artificial instances are generated by a parameterized instance generator for the integrated problem that is made freely available

Genome-wide DNA Methylation Meta-Analysis in the Brains of Suicide Completers

Suicide is the second leading cause of death globally among young people representing a significant global health burden. Although the molecular correlates of suicide remains poorly understood, it has been hypothesised that epigenomic processes may play a role. The objective of this study was to identify suicide-associated DNA methylation changes in the human brain by utilising previously published and unpublished methylomic datasets. We analysed prefrontal cortex (PFC, n = 211) and cerebellum (CER, n = 114) DNA methylation profiles from suicide completers and non-psychiatric, sudden-death controls, meta-analysing data from independent cohorts for each brain region separately. We report evidence for altered DNA methylation at several genetic loci in suicide cases compared to controls in both brain regions with suicide-associated differentially methylated positions enriched among functional pathways relevant to psychiatric phenotypes and suicidality, including nervous system development (PFC) and regulation of long-term synaptic depression (CER). In addition, we examined the functional consequences of variable DNA methylation within a PFC suicide-associated differentially methylated region (PSORS1C3 DMR) using a dual luciferase assay and examined expression of nearby genes. DNA methylation within this region was associated with decreased expression of firefly luciferase but was not associated with expression of nearby genes, PSORS1C3 and POU5F1. Our data suggest that suicide is associated with DNA methylation, offering novel insights into the molecular pathology associated with suicidality

Genome-wide DNA Methylation Meta-analysis in the Brains of Suicide Completers

Suicide is the second leading cause of death globally among young people representing a significant global health burden. Although the molecular correlates of suicide remains poorly understood, it has been hypothesised that epigenomic processes may play a role. The objective of this study was to identify suicide-associated DNA methylation changes in the human brain by utilising previously published and unpublished methylomic datasets. We analysed prefrontal cortex (PFC, n = 211) and cerebellum (CER, n = 114) DNA methylation profiles from suicide completers and non-psychiatric, sudden-death controls, meta-analysing data from independent cohorts for each brain region separately. We report evidence for altered DNA methylation at several genetic loci in suicide cases compared to controls in both brain regions with suicide-associated differentially methylated positions enriched among functional pathways relevant to psychiatric phenotypes and suicidality, including nervous system development (PFC) and regulation of long-term synaptic depression (CER). In addition, we examined the functional consequences of variable DNA methylation within a PFC suicide-associated differentially methylated region (PSORS1C3 DMR) using a dual luciferase assay and examined expression of nearby genes. DNA methylation within this region was associated with decreased expression of firefly luciferase but was not associated with expression of nearby genes, PSORS1C3 and POU5F1. Our data suggest that suicide is associated with DNA methylation, offering novel insights into the molecular pathology associated with suicidality

Supply chain risk management strategies in normal and abnormal times:Policymakers’ role in reducing generic medicine shortages

Purpose – This paper links supply chain risk management to medicine supply chains to explore the role ofpolicymakers in employing supply chain risk management strategies (SCRMS) to reduce generic medicineshortages.Design/methodology/approach – Using secondary data supplemented with primary data, the authors mapand compare seven countries’ SCRMS for handling shortage risks in their paracetamol supply chains beforeand during the first two waves of the COVID-19 pandemic.Findings – Consistent with recent research, the study finds that policymakers had implemented few SCRMSspecifically for responding to disruptions caused by COVID-19. However, shortages were largely avoided sincemultiple strategies for coping with business-as-usual disruptions had been implemented prior to the pandemic.The authors did find that SCRMS implemented during COVID-19 were not always aligned with thoseimplemented pre-pandemic. The authors also found that policymakers played both direct and indirect roles.Research limitations/implications – Combining longitudinal secondary data with interviews sheds lighton how, regardless of the level of preparedness during normal times, SCRMS can be leveraged to avertshortages in abnormal times. However, the problem is highly complex, which warrants further research.Practical implications – Supply chain professionals and policymakers in the healthcare sector can use thefindings when developing preparedness and response plans.Social implications – The insights developed can help policymakers improve the availability of high-volumegeneric medicines in (ab)normal times.Originality/value – The authors contribute to prior SCRM research in two ways. First, the authorsoperationalize SCRMS in the medicine supply chain context in (ab)normal times, thereby opening avenues forfuture research on SCRM in this context. Second, the authors develop insights on the role policymakers playand how they directly implement and indirectly influence the adoption of SCRMS. Based on the study findings,the authors develop a framework that captures the diverse roles of policymakers in SCRM

Methylation QTLs in the developing brain and their enrichment in schizophrenia risk loci

We characterized DNA methylation quantitative trait loci (mQTLs) in a large collection (n = 166) of human fetal brain samples spanning 56-166 d post-conception, identifying >16,000 fetal brain mQTLs. Fetal brain mQTLs were primarily cis-acting, enriched in regulatory chromatin domains and transcription factor binding sites, and showed substantial overlap with genetic variants that were also associated with gene expression in the brain. Using tissue from three distinct regions of the adult brain (prefrontal cortex, striatum and cerebellum), we found that most fetal brain mQTLs were developmentally stable, although a subset was characterized by fetal-specific effects. Fetal brain mQTLs were enriched amongst risk loci identified in a recent large-scale genome-wide association study (GWAS) of schizophrenia, a severe psychiatric disorder with a hypothesized neurodevelopmental component. Finally, we found that mQTLs can be used to refine GWAS loci through the identification of discrete sites of variable fetal brain methylation associated with schizophrenia risk variants