Safe and just Earth system boundaries.

The stability and resilience of the Earth system and human well-being are inseparably linked1-3, yet their interdependencies are generally under-recognized; consequently, they are often treated independently4,5. Here, we use modelling and literature assessment to quantify safe and just Earth system boundaries (ESBs) for climate, the biosphere, water and nutrient cycles, and aerosols at global and subglobal scales. We propose ESBs for maintaining the resilience and stability of the Earth system (safe ESBs) and minimizing exposure to significant harm to humans from Earth system change (a necessary but not sufficient condition for justice)4. The stricter of the safe or just boundaries sets the integrated safe and just ESB. Our findings show that justice considerations constrain the integrated ESBs more than safety considerations for climate and atmospheric aerosol loading. Seven of eight globally quantified safe and just ESBs and at least two regional safe and just ESBs in over half of global land area are already exceeded. We propose that our assessment provides a quantitative foundation for safeguarding the global commons for all people now and into the future.

Inequalities in Life Expectancy Across North Carolina: A Spatial Analysis of the Social Determinants of Health and the Index of Concentration at Extremes.

Health inequalities are characterized by spatial patterns of social, economic, and political factors. Life expectancy (LE) is a commonly used indicator of overall population health and health inequalities that allows for comparison across different spatial and temporal regions. The objective of this study was to examine geographic inequalities in LE across North Carolina census tracts by comparing the performance of 2 popular geospatial health indices: Social Determinants of Health (SDoH) and the Index of Concentration at Extremes (ICE). A principal components analysis (PCA) was used to address multicollinearity among variables and aggregate data into components to examine SDoH, while the ICE was constructed using the simple subtraction of geospatial variables. Spatial regression models were employed to compare both indices in relation to LE to evaluate their predictability for population health. For individual SDoH and ICE components, poverty and income had the strongest positive correlation with LE. However, the common spatial techniques of adding PCA components together for a final SDoH aggregate measure resulted in a poor relationship with LE. Results indicated that both metrics can be used to determine spatial patterns of inequities in LE and that the ICE metric has similar success to the more computationally complex SDoH metric. Public health practitioners may find the ICE metric's high predictability matched with lower data requirements to be more feasible to implement in population health monitoring.

The impact and feasibility of a brief, virtual, educational intervention for home healthcare professionals on Parkinson's Disease and Related Disorders: pilot study of I SEE PD Home.

BACKGROUND: Individuals with advanced Parkinson's Disease (PD) and Parkinson-related disorders (PRD) are frequently referred for home allied therapies and nursing care, yet home healthcare professionals have limited training in PD/PRD. While recognizing the need for such care, patients and families report home healthcare professionals are unfamiliar with these conditions, which may be driven by neurophobia and may contribute to suboptimal care and early termination of services. We sought to determine the feasibility and effects of a virtual, multimodal educational intervention on PD knowledge, confidence, and empathy among home health professionals. METHODS: Home health nurses, occupational therapists, physical therapists and physical therapy assistants, and speech-language pathologists participated in a daylong, virtual symposium on advanced PD/PRD, combining focused lectures, discipline-specific breakout sessions, immersive virtual reality vignettes, and interactive panels with both patients and families, and movement disorders and home healthcare experts. Participants completed online pre- and post-symposium surveys including: demographics; PD/PRD knowledge (0-10 points possible); empathy (Interpersonal Reactivity Index); and 10-point scales of confidence with and attitudes towards individuals with PD/PRD, respectively. Pre-post intervention changes and effect sizes were evaluated with paired t-tests and Cohen's d. We performed qualitative analyses of post-symposium free-text feedback using a grounded theory approach to identify participants' intentions to change their practice. RESULTS: Participants had a mean improvement of 3.1 points on the PD/PRD knowledge test (p < 0.001, d = 1.97), and improvement in confidence managing individuals with PD/PRD (p = 0.0003, d = .36), and no change in empathy. The interactive, virtual format was rated as effective by 95%. Common themes regarding symposium-motivated practice change included: interdisciplinary collaboration; greater involvement and weighting of the patient and caregiver voice in care plans; attention to visit scheduling in relation to patient function; recognition and practical management of the causes of sudden change in PD/PRD, including infections and orthostatic hypotension. CONCLUSIONS: A virtual, multimodal, brief educational pilot intervention improved PD/PRD-specific knowledge and confidence among home healthcare nurses and allied health professionals. Future studies are necessary to test the short- and long-term effects of this intervention more broadly and to investigate the impact of this education on patient and caregiver outcomes.

Crisis response among essential workers and their children during the COVID-19 pandemic.

Limited research has been conducted on the mental health concerns of frontline and essential workers and their children during the COVID-19 pandemic in the United States (U.S.). This study examined the association between working on the frontlines in the U.S. during the COVID-19 pandemic (March to July 2020) and personal crisis text concerns (e.g., self-harm, suicidal thoughts, anxiety/stress, and substance abuse) for frontline essential workers and the children of frontline workers. We used a novel data set from a crisis texting service, Crisis Text Line (CTL), that is widely used throughout the U.S. Generalized Estimating Equations examined the individual association between eight specific crisis types (Depression, Stress/Anxiety, Self-Harm, Suicidal Thoughts, Substance Abuse, Isolation, Relationship Issues, and Abuse) and being in frontline work or being a child of a frontline worker during the early phase of the pandemic. Using CTL concerns as a proxy for the prevalence of mental health issues, we found that children of workers, specifically the youngest demographic (13 years and under), females, and non-conforming youth had a higher risk of specific crisis events during the COVID-19 pandemic. Additionally, Hispanic children of workers reported higher rates of stress/anxiety, whereas African American children of workers had higher rates of abuse and depression. Frontline workers had a higher risk of suicidal thoughts, and the risk of crisis events was generally highest for non-binary, transgender, and male users. Increases in CTL usage among frontline workers were noted across 7-28 days after spikes in local COVID-19 cases. The research to date has focused on the mental health of frontline essential workers, but our study highlights troubling trends in psychological stress among children of these workers. Supportive interventions and mental health resources are needed not only for frontline essential workers, but for their children too.

Clinical Surveillance and Evaluation of Suspected Ebola Cases in a Vaccine Trial During an Ebola Epidemic: The Sierra Leone Trial to Introduce a Vaccine Against Ebola.

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens.

Influenza virus encodes only 11 viral proteins but replicates in a broad range of avian and mammalian species by exploiting host cell functions. Genome-wide RNA interference (RNAi) has proven to be a powerful tool for identifying the host molecules that participate in each step of virus replication. Meta-analysis of findings from genome-wide RNAi screens has shown influenza virus to be dependent on functional nodes in host cell pathways, requiring a wide variety of molecules and cellular proteins for replication. Because rapid evolution of the influenza A viruses persistently complicates the effectiveness of vaccines and therapeutics, a further understanding of the complex host cell pathways coopted by influenza virus for replication may provide new targets and strategies for antiviral therapy. RNAi genome screening technologies together with bioinformatics can provide the ability to rapidly identify specific host factors involved in resistance and susceptibility to influenza virus, allowing for novel disease intervention strategies.

Exploring Place-Based Differences in Suicide and Suicide-Related Outcomes Among North Carolina Adolescents and Young Adults.

PURPOSE: Suicide is an ongoing public health crisis among youth and adolescents, and few studies have investigated the spatial patterning in the United States among this subpopulation. Potential precursors to suicide in this vulnerable group are also on the rise, including nonfatal self-injury. METHODS: This study uses emergency department data, death certificates, and violent death reporting system data for North Carolina from 2009 to 2018 to investigate spatial clusters of self-injury and suicide. RESULTS: Findings show that the demographic characteristics of individuals committing fatal and nonfatal self-injury are quite different. Self-injury and completed suicides exhibited different geographical patterns. Area-level measures like micropolitan status and measures of racial and income segregation predicted the presence of high-risk suicide clusters. Suicides among Native Americans and veteran status/military personnel also were associated with higher risk suicide clusters. DISCUSSION: Future interventions should target these specific high-risk locations for immediate reductions in adolescent and youth suicides.

Analyzing the spatial determinants of local Covid-19 transmission in the United States.

The Coronavirus Disease 19 (COVID-19) has quickly spread across the United States (U.S.) since community transmission was first identified in January 2020. While a number of studies have examined individual-level risk factors for COVID-19, few studies have examined geographic hotspots and community drivers associated with spatial patterns in local transmission. The objective of the study is to understand the spatial determinants of the pandemic in counties across the U.S. by comparing socioeconomic variables to case and death data from January 22nd to June 30th 2020. A cluster analysis was performed to examine areas of high-risk, followed by a three-stage regression to examine contextual factors associated with elevated risk patterns for morbidity and mortality. The factors associated with community-level vulnerability included age, disability, language, race, occupation, and urban status. We recommend that cluster detection and spatial analysis be included in population-based surveillance strategies to better inform early case detection and prioritize healthcare resources.

Performance of the Trioplex real-time RT-PCR assay for detection of Zika, dengue, and chikungunya viruses.

The emergence and spread of Zika virus (ZIKV) presented a challenge to the diagnosis of ZIKV infections in areas with transmission of dengue (DENV) and chikungunya (CHIKV) viruses. To facilitate detection of ZIKV infections, and differentiate these infections from DENV and CHIKV, we developed the Trioplex real-time RT-PCR assay (Trioplex assay). Here, we describe the optimization of multiplex and singleplex formats of the assay for a variety of chemistries and instruments to facilitate global standardization and implementation. We evaluated the analytical performance of all Trioplex modalities for detection of these three pathogens in serum and whole blood, and for ZIKV in urine. The limit of detection for the three viruses and in different RNA-extraction modalities is near 103 genome copy equivalents per milliliter (GCE/mL). Simultaneous testing of more than one specimen type from each patient provides a 6.4% additional diagnostic sensitivity. Overall, the high sensitivity of the Trioplex assay demonstrates the utility of this assay ascertaining Zika cases.

Identification of Host Kinase Genes Required for Influenza Virus Replication and the Regulatory Role of MicroRNAs.

Human protein kinases (HPKs) have profound effects on cellular responses. To better understand the role of HPKs and the signaling networks that influence influenza virus replication, a small interfering RNA (siRNA) screen of 720 HPKs was performed. From the screen, 17 HPKs (NPR2, MAP3K1, DYRK3, EPHA6, TPK1, PDK2, EXOSC10, NEK8, PLK4, SGK3, NEK3, PANK4, ITPKB, CDC2L5 (CDK13), CALM2, PKN3, and HK2) were validated as essential for A/WSN/33 influenza virus replication, and 6 HPKs (CDK13, HK2, NEK8, PANK4, PLK4 and SGK3) were identified as vital for both A/WSN/33 and A/New Caledonia/20/99 influenza virus replication. These HPKs were found to affect multiple host pathways and regulated by miRNAs induced during infection. Using a panel of miRNA agonists and antagonists, miR-149* was found to regulate NEK8 expression, miR-548d-3p was found to regulate MAPK1 transcript expression, and miRs -1228 and -138 to regulate CDK13 expression. Up-regulation of miR-34c induced PLK4 transcript and protein expression and enhanced influenza virus replication, while miR-34c inhibition reduced viral replication. These findings identify HPKs important for influenza viral replication and show the miRNAs that govern their expression.

MicroRNA regulation of human protease genes essential for influenza virus replication.

Influenza A virus causes seasonal epidemics and periodic pandemics threatening the health of millions of people each year. Vaccination is an effective strategy for reducing morbidity and mortality, and in the absence of drug resistance, the efficacy of chemoprophylaxis is comparable to that of vaccines. However, the rapid emergence of drug resistance has emphasized the need for new drug targets. Knowledge of the host cell components required for influenza replication has been an area targeted for disease intervention. In this study, the human protease genes required for influenza virus replication were determined and validated using RNA interference approaches. The genes validated as critical for influenza virus replication were ADAMTS7, CPE, DPP3, MST1, and PRSS12, and pathway analysis showed these genes were in global host cell pathways governing inflammation (NF-κB), cAMP/calcium signaling (CRE/CREB), and apoptosis. Analyses of host microRNAs predicted to govern expression of these genes showed that eight miRNAs regulated gene expression during virus replication. These findings identify unique host genes and microRNAs important for influenza replication providing potential new targets for disease intervention strategies.