An observational time-series study on the behavioral effects of adjunctive artisanal cannabidiol use by adults with treatment resistant epilepsies.

BACKGROUND: For approximately 30% of people with epilepsy, seizures are not well-controlled by anti-seizure medication (ASM). This condition, called treatment resistant epilepsy (TRE), is associated with increased morbidity and mortality, and substantially impacts the quality of life of both the individual and their family. Non-responsiveness to ASMs leads many people with TRE to seek alternative therapies, such as cannabinoid-based medication, particularly cannabidiol (CBD), with or without medical or professional advice. This is due in part to widespread reporting in the media about the benefits of CBD for seizures in some forms of epilepsy. METHODS: Adults with TRE, opting to add CBD to their existing treatment regime, completed this prospective, observational, longitudinal, quasi-experimental, time-series study. We hypothesized that adjunctive CBD use would positively impact participants' quality of life and psychological well-being in comparison to a baseline period without CBD use. Participants were followed for a period of approximately six months - for approximately one month of baseline prior to the initiation of CBD use and approximately five months after the initiation of CBD use. Participants provided urine samples and completed behavioral questionnaires that assessed quality of life, anxiety/depression, and adverse events during baseline and at two times during CBD use. RESULTS: Complete case analyses (n = 10) showed a statistically significant improvement in quality of life, a statistically significant decrease in anxiety symptoms, and a statistically significant decrease in the experience of adverse events over time (p < 0.05). Improvements noted in the experience of depression symptoms did not reach statistical significance. Urinalysis revealed the majority of participants had no CBD/metabolites in their system at the beginning of the study, and confirmed the presence of CBD/metabolites in participants' urine after CBD was added to their treatment regime. Analysis of missing data using multiple imputation supported the findings of the complete case analysis. INTERPRETATION: For a small group of individuals with TRE of varying etiologies, adjunctive use of artisanal CBD was associated with improvements in the behavioral and psychological symptoms of TRE, as well as improved medication tolerability.

Empathy, better patient care, and how interprofessional education can help.

Interprofessional education (IPE) has been promoted as one way to prepare healthcare students for interprofessional encounters they might experience in the workplace. However, the link between IPE, interprofessional care in the workforce, and better patient outcomes is tenuous, perhaps in part due to the inability of IPE programs to adequately address barriers associated with interprofessional care (e.g., power differentials, role disputes). Empathy, or understanding the experiences of others, has emerged as a critical tool to breaking down barriers inherent to working in teams. Given the evidence connecting empathy to stronger team collaboration and better patient care, researchers significantly revamped programming from a prior training called Interprofessional Education for Complex Neurological Cases (IPE Neuro) to enhance empathy, foster stronger team collaboration, and improve information integration among participants. In this improved three-session program, participants from seven different professions were grouped into teams, assessed a patient volunteer with neurological disorder, and created and presented an integrated, patient-centric treatment plan. Students (N = 31) were asked to report general empathy levels, as well as attitudes, team skills, and readiness toward interprofessional care, before and after the program. We conducted paired samples t-tests and thematic analysis to analyze the data. Results showed that participants reported higher empathy levels, more positive attitudes, and greater team skills pre- to posttest with moderate to large effects. Results bolster IPE Neuro programming as one approach to prepare students for interprofessional care while underscoring the potential implications of IPE to improve empathy levels of healthcare professionals.

Protected area, easement, and rental contract data reveal five communities of land protection in the United States.

Land protection efforts represent large societal investments and are critical to biodiversity conservation. Land protection involves a complex mosaic of areas managed by multiple organizations, using a variety of mechanisms to achieve different levels of protection. We develop an approach to synthesize, describe, and map this land protection diversity over large spatial scales. We use cluster analysis to find distinct "communities" of land protection based on the organizations involved, the strictness of land protection, and the protection mechanisms used. We also associate identified land protection communities with socioenvironmental variables. Applying these methods to describe land protection communities in counties across the coterminous United States, we recognize five different land protection communities. Two land protection communities occur in areas with low human population size at higher elevations and include a large amount of protected land primarily under federal management. These two community types are differentiated from one another by the particular federal agencies involved, the relative contributions of smaller actors, and the amount of protection by designations vs. conservation easements or covenants. Three remaining land protection communities have less overall protection. Land in one community is primarily protected by federally managed rental contracts and government managed easements; another is managed by a diversity of non-federal actors through fee-ownership and easements; and the third stands out for having the lowest amount of formally recorded protection overall. High elevation and poor quality soils are over-represented in U.S. protected lands. Rental contracts help fill in gaps in counties with high productivity soil while the U.S. Fish and Wildlife Service fills in gaps in low-elevation counties. Counties with large numbers of threatened species have more and stricter protection, particularly by regional entities like water management districts. The ability to synthesize and map land protection communities can help conservation planners tailor interventions to local contexts, position local agencies to approach collaborations more strategically, and suggest new hypotheses for researchers regarding interactions among different protection mechanisms.

Cross-sectional and longitudinal evaluation of cannabidiol (CBD) product use and health among people with epilepsy.

Recent approval of Epidiolex® (pharmaceutical cannabidiol/CBD) for the treatment of Lennox Gastaut syndrome (LGS) and Dravet syndrome highlights a therapeutic efficacy of CBD in the treatment of epilepsy. However, a large number of patients with epilepsy elect to use alternative artisanal CBD products due to cost or access constraints. Despite widespread availability and variety of these artisanal CBD products, studies evaluating their safety or efficacy are rare, making conclusions about clinical utility uncertain. The purpose of the present study was to evaluate cross-sectional and longitudinal associations of artisanal CBD product use with quality of life, mental health, healthcare utilization, and epilepsy-specific outcomes within a large, observational cohort of people with epilepsy. Participants who reported using artisanal CBD products at baseline (Artisanal CBD Users; n = 280) and participants who used no cannabis-based products (Controls; n = 138) completed web-based assessments evaluating psychiatric symptoms, healthcare utilization, and epilepsy-specific factors. Follow-up surveys were collected in a subset of participants (n = 190) following baseline assessment for longitudinal comparison. Cross-sectionally, higher quality of life, lower psychiatric symptom severity, and improved sleep were observed among Artisanal CBD Users at baseline compared with Controls. Initiation of artisanal CBD product use was also related to improved health outcomes longitudinally. No group differences were observed for seizure control, but both groups included a high number of individuals with no past month seizures. Artisanal CBD Users reported significantly better epilepsy medication tolerability, use of fewer prescription medications overall, and reduced healthcare utilization compared with Controls. These findings are consistent with research indicating that practitioners recommending CBD in clinical care for epilepsy report integrating the use of CBD both as a means to improve patient quality of life as well as for seizure control.

Feasibility of auricular acupressure as an adjunct treatment for neonatal opioid withdrawal syndrome (NOWS).

BACKGROUND: The opioid epidemic in the United States continues to threaten public health. As a result of this crisis, neonatal opioid withdrawal syndrome (NOWS) has risen exponentially and requires a multitude of non-pharmacologic treatments to ensure healthy neonatal outcomes. Methods: This feasibility study implemented an acupressure protocol as informed by the Near-Term Infant (NTI) conceptual framework for the treatment of NOWS. Aims of this study were to assess provider training, effective integration of acupressure within the standard of care, and acceptance of this treatment by mothers and healthcare providers. Results: With maternal consent, a total of 12 participants were enrolled and underwent auricular acupressure. Nurse Practitioners were credentialed (75%) and effectively administered neonatal acupressure (100%) in accordance with the study protocol. Mothers were very satisfied with acupressure for the treatment of NOWS (Client Satisfaction Questionaire-8 mean scores 3.8-4.0 of a possible 4.0), and the majority of healthcare providers were supportive (66%, mean scores 3.6 to 4.0 out of possible 5). Conclusions: Auricular acupressure was successfully implemented within the standard of care for NOWS. Future studies should incorporate outlined suggestions and include qualitative measures of acceptance as well as randomized controlled trials to evaluate efficacy.

Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles.

The aetiology of Kawasaki disease (KD), an acute inflammatory disorder of childhood, remains unknown despite various triggers of KD having been proposed. Host 'omic profiles offer insights into the host response to infection and inflammation, with the interrogation of multiple 'omic levels in parallel providing a more comprehensive picture. We used differential abundance analysis, pathway analysis, clustering, and classification techniques to explore whether the host response in KD is more similar to the response to bacterial or viral infections at the transcriptomic and proteomic levels through comparison of 'omic profiles from children with KD to those with bacterial and viral infections. Pathways activated in patients with KD included those involved in anti-viral and anti-bacterial responses. Unsupervised clustering showed that the majority of KD patients clustered with bacterial patients on both 'omic levels, whilst application of diagnostic signatures specific for bacterial and viral infections revealed that many transcriptomic KD samples had low probabilities of having bacterial or viral infections, suggesting that KD may be triggered by a different process not typical of either common bacterial or viral infections. Clustering based on the transcriptomic and proteomic responses during KD revealed three clusters of KD patients on both 'omic levels, suggesting heterogeneity within the inflammatory response during KD. The observed heterogeneity may reflect differences in the host response to a common trigger, or variation dependent on different triggers of the condition.

Allocating resources for land protection using continuous optimization: biodiversity conservation in the United States.

Spatial optimization approaches that were originally developed to help conservation organizations determine protection decisions over small spatial scales are now used to inform global or continental scale priority setting. However, the different decision contexts involved in large-scale resource allocation need to be considered. We present a continuous optimization approach in which a decision-maker allocates funding to regional offices. Local decision-makers then use these funds to implement habitat protection efforts with varying effectiveness when evaluated in terms of the funder's goals. We illustrate this continuous formulation by examining the relative priority that should be given to different counties in the coterminous United States when acquiring land to establish new protected areas. If weighting all species equally, counties in the southwest United States, where large areas can be bought cheaply, are priorities for protection. If focusing only on species of conservation concern, priorities shift to locations rich in such species, particularly near expanding exurban areas facing high rates of future habitat conversion (e.g., south-central Texas). Priorities for protection are sensitive to what is assumed about local ecological and decision-making processes. For example, decision-makers who doubt the efficacy of local land protection efforts should focus on a few key areas, while optimistic decision-makers should disperse funding more widely. Efforts to inform large-scale conservation priorities should reflect better the types of choice that decision-makers actually face when working over these scales. They also need to report the sensitivity of recommended priorities to what are often unstated assumptions about local processes affecting conservation outcomes.

Optometry Compensation Study: Narrowing Down the Unexplained Gender Wage Gap in Optometry.

SIGNIFICANCE: Men earn at least 6.5% more than women in their first full-time jobs as optometrists. For current salaries, the gender wage gap is more than 13%. This study details the gender wage gap that remains after controlling for practice ownership, residency training, and employer-defined full-time work. PURPOSE: The purpose of this study was to measure the gender wage gap by region and practice type for full-time optometrists who did not complete a residency and do not own their practice. METHODS: Participants completed an online survey, providing data for their first and current optometry positions and demographic information. Respondents who reported full-time employment in the United States, not completing a residency, and not owning their practice were selected for further analysis by census region and practice type. In each category, the gender wage gap was calculated. RESULTS: In all regions and practice types, men were paid higher starting salaries than women. For current salaries, men were paid higher in almost all regions and practice types. The wage gap increased from starting salary to current salary, although not in all regions and practice types. CONCLUSIONS: When practice ownership, residency completion, and full-time work are controlled for, there remains a difference in the pay received by men and women in optometry. The salary data presented in this study may help optometrists narrow the wage gap.

Timely linkage of individuals to substance use disorder treatment: development, implementation, and evaluation of FindHelpNowKY.org.

BACKGROUND: Substance use disorders (SUD) have steadily increased over the last two decades. Seeking SUD treatment involves searching SUD treatment facility types (inpatient, outpatient and intensive outpatient, residential and family residential, and detoxification facilities) that offer specialized SUD treatment depending on individual needs and preferences. Referrals to SUD treatment require innovative strategies that rapidly link individuals to SUD treatment when they are at the critical stage of readiness. The aim of this study was to develop, implement, and evaluate a user-friendly SUD treatment facility opening availability website called FindHelpNowKY.org. The objectives of the study were to 1) recruit SUD treatment facility and partner participation; 2) develop platform, content, and analytics for the FindHelpNowKY.org website intervention with an information repository; 3) assess barriers and facilitators to implementation; and 4) evaluate the development and implementation of FindHelpNowKY.org. METHODS: Website development stakeholders were identified and the website concept was developed. The logic model for FindHelpNowKY.org outlined resources, activities, and outputs as well as the associated short-term, medium-term, and long-term objectives, along with a website evaluation plan. Website usability and focus group testing was conducted. Information repository resource documents were compiled and categorized. An inventory of Kentucky-based SUD treatment facilities was compiled using various state and federal resources. RESULTS: Development/implementation barriers were addressed, facilitators were identified, and the website was implemented; 83% of SUD treatment facilities were indexed on the website, and average website user time was 7 min. From February to October 2018, there were 29,000 visitors, and 30,000 unique searches. The most common website query was a friend or family member seeking long-term residential or outpatient treatment facilities accepting Medicaid or Medicare. CONCLUSIONS: FindHelpNowKY.org has the potential to fill a critical need for timely access to available SUD treatment in the state. The website may be a valuable resource for health professionals that can enhance clinical workflow and reduce staff time conducting phone and website searches for available SUD treatment. The website is a promising tool for assessing current SUD treatment capacity vs. SUD treatment need. The FindHelpNow model can be used by other states to increase timely access to SUD treatment.

Neonatal Abstinence Syndrome: An Integrative Review of Neonatal Acupuncture to Inform a Protocol for Adjunctive Treatment.

BACKGROUND: The current opioid epidemic in the United States has given rise to a growing incidence of neonatal abstinence syndrome (NAS). Treatments for this condition optimize nonpharmacologic therapies in an effort to improve withdrawal symptoms and reduce or eliminate the need for opioid medications, thereby reducing hospital length of stay and improving healthy neonatal outcomes. PURPOSE: The purpose of this review was to evaluate the current evidence for neonatal acupuncture treatments and identify essential characteristics that must be included in a treatment protocol for NAS. METHODS/SEARCH STRATEGY: An integrative review was conducted under the guidance of the Whittemore and Knafl methodology and near-term infant conceptual framework. An evaluation of the quality and levels of evidence was also included. FINDINGS/RESULTS: A total of 10 studies were identified in this review. Four of these studies were randomized controlled trials, and utilized acupuncture in the neonatal population to evaluate impact on pain, NAS, and weight gain. IMPLICATIONS FOR PRACTICE: This review provided the essential elements for the development of a complementary acupuncture treatment protocol for the management of NAS. IMPLICATIONS FOR RESEARCH: Future research should include the identified essential characteristics in high-quality, blinded, randomized controlled trials to assess the treatment effect of acupuncture on neonates experiencing withdrawal symptoms.

Low-dose cyclophosphamide enhances antigen-specific CD4(+) T cell responses to NY-ESO-1/ISCOMATRIX™ vaccine in patients with advanced melanoma.

Clinical outcomes from cancer vaccine trials in patients with advanced melanoma have so far been disappointing. This appears at least partially due to a state of immunosuppression in these patients induced by an expansion of regulatory cell populations including regulatory T cells (Tregs). We have previously demonstrated potent immunogenicity of the NY-ESO-1/ISCOMATRIX™ vaccine in patients with resected melanoma (study LUD99-08); however, the same vaccine induced only a few vaccine antigen-specific immune responses in patients with advanced disease (study LUD2002-013). Pre-clinical models suggest that the alkylating agent cyclophosphamide can enhance immune responses by depleting Tregs. Therefore, we have enrolled a second cohort of patients with advanced melanoma in the clinical trial LUD2002-013 to investigate whether pre-treatment with cyclophosphamide could improve the immunogenicity of the NY-ESO-1/ISCOMATRIX™ vaccine. The combination treatment led to a significant increase in vaccine-induced NY-ESO-1-specific CD4(+) T cell responses compared with the first trial cohort treated with vaccine alone. We could not detect a significant decline in regulatory T cells in peripheral blood of patients 14 days after cyclophosphamide administration, although a decline at an earlier time point cannot be excluded. Our observations support the inclusion of cyclophosphamide in combination trials with vaccines and other immune-modulatory agents.

Navigating the pathway to advanced practice: A grounded theory of nurse practitioner role transition in a fellowship.

BACKGROUND: Greater attention to the transitional period for advanced practice nurses has urged health care organizations and employers to implement fellowships. Currently, the theoretical process of nurse practitioner (NP) role transition from the essential perspectives of NP fellows does not exist. PURPOSE: The purpose of this study was to construct a middle-range theory grounded in reality of an NP fellowship environment that explains how NPs transition to their new role. METHODOLOGY: Following Charmaz's constructivist methodology, 11 NPs who transitioned to practice in a fellowship were interviewed. RESULTS: "Navigating the Pathway to Advanced Practice: A Grounded Theory of Nurse Practitioner Role Transition in a Fellowship" emerged from the data and is composed of through five phases: (1) mapping a path, (2) stepping onto the trailhead, (3) navigating the trailway, (4) gaining traction, and (5) summiting. CONCLUSIONS: The resulting middle-range theory is the first in the nursing literature that conceptualizes meaning about NP role transition in a fellowship. This process occurs in the contextual factor of a realm of support that includes growth, value, lifelong learning, and readiness. Throughout this process, NPs build competence and confidence that advances them to summit, or transition, to their NP role at the completion of an NP fellowship. IMPLICATIONS: This discovery will fill the research gap pertaining to best practice interventions in support of NPs during role transition in fellowships. Understanding how NPs transition to their new advanced practice roles may inform organizations on how to structure fellowships that support learning, encourage confidence, and enhance competence.

Integration of a nurse practitioner and physician associate leadership structure within an academic cancer center.

BACKGROUND: Nurse practitioners and physician associates are an essential part of the multidisciplinary cancer care team with expanding and evolving roles within cancer specialties. LOCAL PROBLEM: As these clinicians flourish, a parallel need for leadership rises to optimize scope of practice, mentor, and retain this crucial workforce. The purpose of this quality improvement project was to development a nurse practitioner and physician associate leadership structure within an academic cancer center. METHODS: Development of this nurse practitioner and physician associate leadership structure was guided by transformational leadership theory. In collaboration with nursing, business, and physician leadership, a quad structure was supported. INTERVENTIONS: Implementation of a leadership structure included the establishment of eight team leaders and two managers. These leaders identified multiple opportunities for improvement including improved communications, offload of nonbillable work, development of incentive programs, provision of equipment, specialty practice alignment, hematology/oncology fellowship, and professional development. RESULTS: Overall, a nurse practitioner and physician associate leadership structure allowed for representation across the cancer center. Such inclusion supported multiple quality improvement projects developed in partnership with nursing, business, and physician leaders. Cumulatively, these interventions yielded efficient workflows and expansion of services. Consistent with reported evidence, these efforts contributed to nurse practitioner and physician associate retention as well as improved job satisfaction. CONCLUSIONS: Advanced practice leadership is essential to recruiting, developing, supporting, and retaining nurse practitioner and physician assistant colleagues in cancer care.

Long-term benefits to psychological health and well-being after ceremonial use of Ayahuasca in Middle Eastern and North African immigrants and refugees.

Background: Refugees and immigrants can experience complex stressors from the process of immigration that can have lasting and severe long-term mental health consequences. Experiences after ayahuasca ingestion are shown to produce positive effects on psychological wellbeing and mental health, including anecdotal reports of improved symptoms of trauma and related disorders. However, data on the longitudinal health impact of naturalistic ayahuasca use in Middle Eastern and North African (MENA) immigrant and refugee populations is limited. Aims: The current longitudinal online survey study was conducted to gather prospective data on ceremonial ayahuasca use in a group (N = 15) of primarily female MENA immigrants and refugees and to provide further insight into the patterns and outcomes surrounding that use. The study sought to assess self-reported changes in physical and mental health, well-being, and psychological functioning, examine relationships between aspects of individual mindset (e.g., psychedelic preparedness) prior to ayahuasca use and observed outcomes during (e.g., subjective drug effects) and afterwards (i.e., persisting effects), characterize risks and negative experiences, and describe trauma exposure and personal history. Results/Outcomes: Our findings revealed ceremonial use of ayahuasca is associated with significant improvements in mental health, well-being, and psychological functioning, including reductions in depression, anxiety, and shame, and increases in cognitive reappraisal and self-compassion. Most participants reported no lasting adverse effects and experienced notable positive behavioral changes persisting months after ingestion. Conclusion/Interpretation: While preliminary, results suggest naturalistic ayahuasca use might hold therapeutic potential for MENA populations exposed to trauma prior to and during the process of migration.

A computational framework to improve cross-platform implementation of transcriptomics signatures.

The emergence of next-generation sequencing technologies and computational advances have expanded our understanding of gene expression regulation (i.e., the transcriptome). This has also led to an increased interest in using transcriptomic biomarkers to improve disease diagnosis and stratification, to assess prognosis and predict the response to treatment. Significant progress in identifying transcriptomic signatures for various clinical needs has been made, with large discovery studies accounting for challenges such as patient variability, unwanted batch effects, and data complexities; however, obstacles related to the technical aspects of cross-platform implementation still hinder the successful integration of transcriptomic technologies into standard diagnostic workflows. In this article, we discuss the challenges associated with integrating transcriptomic signatures derived using high-throughput technologies (such as RNA-sequencing) into clinical diagnostic tools using nucleic acid amplification (NAA) techniques. The novelty of the proposed approach lies in our aim to embed constraints related to cross-platform implementation in the process of signature discovery. These constraints could include technical limitations of amplification platform and chemistry, the maximal number of targets imposed by the chosen multiplexing strategy, and the genomic context of identified RNA biomarkers. Finally, we propose to build a computational framework that would integrate these constraints in combination with existing statistical and machine learning models used for signature identification. We envision that this could accelerate the integration of RNA signatures discovered by high-throughput technologies into NAA-based approaches suitable for clinical applications.

Psychedelic Experiences Increase Mind Perception but do not Change Atheist-Believer Status: A Prospective Longitudinal Study.

Recent studies suggest psychedelic use may be associated with changes in a variety of beliefs or belief-like states, including increased 1) mind perception, 2) non-naturalistic beliefs, and 3) Atheist-Believer status (e.g. believer, agnostic, or nonbeliever). We conducted a prospective longitudinal study among participants (N = 657) who planned to have a psilocybin experience outside a laboratory setting. We asked participants about their beliefs concerning mind perception of various entities, specific metaphysical positions, and Atheist-Believer status both before (and after their experience. Replicating previous findings, we observed increases in mind perception across a variety of living and non-living targets (e.g. plants, rocks). However, we found little to no change in metaphysical beliefs (e.g. dualism) or Atheist-Believer status. Taken together, these findings contrast with those from cross-sectional studies that psilocybin experiences result in changes to Atheist-Believer status and non-naturalistic beliefs but support the relevance of mind perception and mentalization.

Impact of isotype on the mechanism of action of agonist anti-OX40 antibodies in cancer: implications for therapeutic combinations.

BACKGROUND: OX40 has been widely studied as a target for immunotherapy with agonist antibodies taken forward into clinical trials for cancer where they are yet to show substantial efficacy. Here, we investigated potential mechanisms of action of anti-mouse (m) OX40 and anti-human (h) OX40 antibodies, including a clinically relevant monoclonal antibody (mAb) (GSK3174998) and evaluated how isotype can alter those mechanisms with the aim to develop improved antibodies for use in rational combination treatments for cancer. METHODS: Anti-mOX40 and anti-hOX40 mAbs were evaluated in a number of in vivo models, including an OT-I adoptive transfer immunization model in hOX40 knock-in (KI) mice and syngeneic tumor models. The impact of FcγR engagement was evaluated in hOX40 KI mice deficient for Fc gamma receptors (FcγR). Additionally, combination studies using anti-mouse programmed cell death protein-1 (mPD-1) were assessed. In vitro experiments using peripheral blood mononuclear cells (PBMCs) examining possible anti-hOX40 mAb mechanisms of action were also performed. RESULTS: Isotype variants of the clinically relevant mAb GSK3174998 showed immunomodulatory effects that differed in mechanism; mIgG1 mediated direct T-cell agonism while mIgG2a acted indirectly, likely through depletion of regulatory T cells (Tregs) via activating FcγRs. In both the OT-I and EG.7-OVA models, hIgG1 was the most effective human isotype, capable of acting both directly and through Treg depletion. The anti-hOX40 hIgG1 synergized with anti-mPD-1 to improve therapeutic outcomes in the EG.7-OVA model. Finally, in vitro assays with human peripheral blood mononuclear cells (hPBMCs), anti-hOX40 hIgG1 also showed the potential for T-cell stimulation and Treg depletion. CONCLUSIONS: These findings underline the importance of understanding the role of isotype in the mechanism of action of therapeutic mAbs. As an hIgG1, the anti-hOX40 mAb can elicit multiple mechanisms of action that could aid or hinder therapeutic outcomes, dependent on the microenvironment. This should be considered when designing potential combinatorial partners and their FcγR requirements to achieve maximal benefit and improvement of patient outcomes.

Plasma Protein Biomarkers Distinguish Multisystem Inflammatory Syndrome in Children From Other Pediatric Infectious and Inflammatory Diseases.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious hyperinflammatory complication following infection with severe acute respiratory syndrome coronavirus 2. The mechanisms underpinning the pathophysiology of MIS-C are poorly understood. Moreover, clinically distinguishing MIS-C from other childhood infectious and inflammatory conditions, such as Kawasaki disease or severe bacterial and viral infections, is challenging due to overlapping clinical and laboratory features. We aimed to determine a set of plasma protein biomarkers that could discriminate MIS-C from those other diseases. METHODS: Seven candidate protein biomarkers for MIS-C were selected based on literature and from whole blood RNA sequencing data from patients with MIS-C and other diseases. Plasma concentrations of ARG1, CCL20, CD163, CORIN, CXCL9, PCSK9 and ADAMTS2 were quantified in MIS-C (n = 22), Kawasaki disease (n = 23), definite bacterial (n = 28) and viral (n = 27) disease and healthy controls (n = 8). Logistic regression models were used to determine the discriminatory ability of individual proteins and protein combinations to identify MIS-C and association with severity of illness. RESULTS: Plasma levels of CD163, CXCL9 and PCSK9 were significantly elevated in MIS-C with a combined area under the receiver operating characteristic curve of 85.7% (95% confidence interval: 76.6%-94.8%) for discriminating MIS-C from other childhood diseases. Lower ARG1 and CORIN plasma levels were significantly associated with severe MIS-C cases requiring inotropes, pediatric intensive care unit admission or with shock. CONCLUSION: Our findings demonstrate the feasibility of a host protein biomarker signature for MIS-C and may provide new insight into its pathophysiology.

Mechanisms driving the density-area relationship in a saproxylic beetle.

Mechanisms underlying density-area relationships (correlations between population density and patch size) have rarely been tested experimentally. It is often assumed that higher density on large patches is evidence that large patches are high quality (i.e. have greater survival and reproduction), but the same pattern could result from disproportionate movement from small to large patches. Movement-based and within-patch processes must be experimentally separated to show that large patches are indeed of higher quality, but few studies have done so. We experimentally tested movement-based and within-patch hypotheses to explain the positive density-area relationship observed for a saproxylic (decayed wood-dependent) beetle, Odontotaenius disjunctus Illiger (Coleoptera: Passalidae). In separate experiments we quantified (1) immigration into and (2) finite growth rate within logs (=patches) that varied in size and density of conspecific beetles. A log was 11.7-fold [95 % confidence interval (CI) 3.4-40.8) and 10.5-fold (95 % CI 2.7-40.9) more likely to contain a new immigrant if it was large or contained a conspecific pair of beetles, respectively. Neither log size nor conspecific density was associated with changes in finite growth rate that would lead to higher density: decreased log size and increased conspecific density reduced finite growth rate in direct proportion to the loss in available resources per mating pair. We conclude that movement behavior rather than habitat quality is responsible for the positive density-area relationship for O. disjunctus. An important implication of our results is that population density is an imperfect indicator of habitat quality.