Assessing the impact of recovery housing on healthcare utilization in Portland, Oregon.

Introduction: Central City Concern (CCC) operates several recovery housing sites in the Portland, Oregon metropolitan region, including the Blackburn Center (Blackburn) and the Richard L. Harris Building (Harris). This retrospective, observational study was designed to assess recovery housing's impact on inpatient detoxification readmission rates and healthcare utilization patterns. Methods: Our study population consisted of individuals discharged from CCC's Hooper Detox Stabilization Center from June 2019 to September 2020. A total of 75 clients housed at Blackburn, 63 clients housed at Harris, and 57 clients discharged as unhoused were included in the study sample. Using logistic regression for each of the two recovery housing groups relative to the unhoused group, we examined differences in readmissions to inpatient detoxification after their qualifying discharge. We then used Difference-In-Difference model to compare the per member per year (PMPY) use of different domains of health care before and after their qualifying discharge. Results: Compared to clients discharged as unhoused, Blackburn and Harris residents had lower risk of readmissions to inpatient detoxification treatment at 90- and 180-days post-discharge. Additionally, while the mean number of PMPY emergency department visits increased for clients discharged as unhoused in the post period, the average number of emergency department visits decreased for clients who obtained recovery housing at Blackburn (DiD=-3.65 PMPY, p-value=0.02) and at Harris (DiD=-3.87 PMPY, p-value=0.01). Conclusion: Findings highlight the impact and importance of recovery housing for individuals managing a substance use disorder and the value of healthcare system and public sector investment housing like Blackburn and Harris.

Evaluation of an Integrated Intervention to Address Clinical Care and Social Needs Among Patients with Type 2 Diabetes.

BACKGROUND: The Providence Diabetes Collective Impact Initiative (DCII) was designed to address the clinical challenges of type 2 diabetes and the social determinants of health (SDoH) challenges that exacerbate disease impact. OBJECTIVE: We assessed the impact of the DCII, a multifaceted intervention approach to diabetes treatment that employed both clinical and SDoH strategies, on access to medical and social services. DESIGN: The evaluation employed a cohort design and used an adjusted difference-in-difference model to compare treatment and control groups. PARTICIPANTS: Our study population consisted of 1220 people (740 treatment, 480 control), aged 18-65 years old with a pre-existing type 2 diabetes diagnosis who visited one of the seven Providence clinics (three treatment and four control) in the tri-county area of Portland, Oregon, between August 2019 and November 2020. INTERVENTIONS: The DCII threaded together clinical approaches such as outreach, standardized protocols, and diabetes self-management education and SDoH strategies including social needs screening, referral to a community resource desk, and social needs support (e.g., transportation) to create a comprehensive, multi-sector intervention. MAIN MEASURES: Outcome measures included SDoH screens, diabetes education participation, HbA1c, blood pressure, and virtual and in-person primary care utilization, as well as inpatient and emergency department hospitalization. KEY RESULTS: Compared to patients at the control clinics, patients at DCII clinics saw an increase in diabetes education (15.5%, p<0.001), were modestly more likely to receive SDoH screening (4.4%, p<0.087), and had an increase in the average number of virtual primary care visits of 0.35 per member, per year (p<0.001). No differences in HbA1c, blood pressure, or hospitalization were observed. CONCLUSIONS: DCII participation was associated with improvements in diabetes education use, SDoH screening, and some measures of care utilization.

Cellular and molecular responses to ethyl-parathion in undifferentiated SH-SY5Y cells provide neurotoxicity pathway indicators for organophosphorus impacts.

High-fidelity nonanimal screening methods are needed that can rapidly and accurately characterize organophosphorus compound (OP)-induced neurotoxicity. Herein, the efficacy of human neuroblastoma cell line (SH-SY5Y) to provide molecular and cellular responses characteristic of the OP neurotoxicity pathway was investigated in response to the OP-model compound, ethyl-parathion. Undifferentiated SH-SY5Y cells were exposed to ethyl-parathion for 30 min at 0 (control), 0.5, 2.5, 5, 10, and 25 µg/ml. Dose-responsive reductions in cell viability were observed with significant reductions at ≥10 µg/ml. From these results, ethyl-parathion exposures of 0 (control), 5, and 10 µg/ml were selected to examine bioindicators underlying the OP neurotoxicity pathway including: reactive oxygen species (ROS), cell membrane peroxidation, mitochondrial membrane potential (MMP), and apoptosis. Ethyl-parathion elicited highly significant increases in ROS relative to controls (p < .01) at both exposure concentrations, confirmed using N-acetyl cysteine (NAC) as a ROS quencher which alleviated ROS increases. A response characteristic of increased ROS exposure, cell membrane-lipid peroxidation, significantly increased (p < .05) at the highest ethyl-parathion exposure (10 µg/ml). As a likely consequence of membrane-lipid peroxidation, ethyl-parathion-induced reductions in MMP were observed with significant effects at 10 µg/ml, reducing MMP by 58.2%. As a culmination of these cellular-damage indicators, apoptosis progression was investigated by phosphatidylserine translocation where ethyl-parathion-induced dose-responsive, highly significant (p < .01) increases at both 5 and 10 µg/ml. Overall, the mechanistic responses observed in undifferentiated SH-SY5Y cells corresponded with in vivo mammalian results demonstrating potential for this nonanimal model to provide accurate OP neurotoxicology screening.

Patient experience and healthcare utilization for a COVID-19 telemedicine home monitoring program offered in English and Spanish.

BACKGROUND: Telemedicine is a vital component of the healthcare system's response to COVID-19. In March of 2020, Providence health system rapidly implemented a telemedicine home monitoring program (HMP) for COVID-19 patients that included use of at-home pulse oximeters and thermometers and text-based surveys to monitor symptoms. By June 2020, Providence updated the HMP to be offered in Spanish. This program was implemented before COVID-19 testing was readily available and therefore was offered to all patients suspected of having COVID-19. This study examines engagement, experience, and utilization patterns for English and Spanish-speaking patients engaged in the COVID-19 HMP. METHODS: A retrospective review of program data was used to understand HMP patient engagement (responsiveness to three daily text to monitor symptoms), satisfaction with the program (likelihood to recommend the program) as well as comfort using home monitoring devices and comfort recovering from home. To understand impact on care for COVID-19 confirmed cases, we used electronic health records to measure patterns in healthcare use for COVID-19 positive HMP participants and non-HMP propensity weighted controls. All patients enrolled in the COVID-19 HMP from March-October 2020 were included in the study. Patients tested for COVID-19 during the time window and not enrolled in HMP were included in the propensity-weighted comparison group. Descriptive and regression analyses were performed overall and stratified by English and Spanish speakers. RESULTS: Of the 4,358 HMP participants, 75.5% identified as English speakers and 18.2% identified as Spanish speakers. There was high level of responsiveness to three daily text-based surveys monitoring symptoms engagement (>80%) and a high level of comfort using the home monitoring devices (thermometers and pulse oximeters) for English- and Spanish-speaking participants (97.3% and 99.6%, respectively). The majority of English (95.7%) and Spanish-speaking (100%) patients felt safe monitoring their condition from home and had high satisfaction with the HMP (76.5% and 83.6%, respectively). English and Spanish-speaking COVID-19 positive HMP participants had more outpatient and emergency departments (ED) encounters than non-participants 7 and 30 days after their positive test. CONCLUSION: This widely implemented HMP provided participants with a sense of safety and satisfaction and its use was associated with more outpatient care and ED encounters. These outcomes were comparable across English and Spanish-speakers, highlighting the importance and potential impact of language-concordant telemedicine.

Local Housing Choice Voucher Distribution Policies Impact Healthcare Utilization: a Randomized Natural Experiment.

While associations between obtaining affordable housing and improved health care are well documented, insufficient funding often forces housing authorities to prioritize limited housing vouchers to specific populations. We assessed the impact of obtaining housing on health care utilization at two urban housing authorities with different distribution policies: Housing Authority A prioritized seniors and people with disabilities, while Housing Authority B prioritized medically complex individuals and families with school-aged children. Both housing authorities used random selection to distribute vouchers, allowing us to conduct a randomized natural experiment of cases and waitlisted controls. No significant demographic differences were present between those receiving vouchers and waitlisted controls. Housing Authority A vouchers were associated with increased outpatient visits (OR = 1.19; P = 0.051). Housing Authority B vouchers decreased the likelihood of emergency department visits (OR = 0.61; P = 0.042). This study provides evidence that, while obtaining housing can result in better health care outcomes overall, local prioritization policies can influence that impact.

Plasma Metabolite Signature Classifies Male LRRK2 Parkinson's Disease Patients.

Parkinson's disease (PD) is a progressive neurodegenerative disease, causing loss of motor and nonmotor function. Diagnosis is based on clinical symptoms that do not develop until late in the disease progression, at which point the majority of the patients' dopaminergic neurons are already destroyed. While many PD cases are idiopathic, hereditable genetic risks have been identified, including mutations in the gene for LRRK2, a multidomain kinase with roles in autophagy, mitochondrial function, transcription, molecular structural integrity, the endo-lysosomal system, and the immune response. A definitive PD diagnosis can only be made post-mortem, and no noninvasive or blood-based disease biomarkers are currently available. Alterations in metabolites have been identified in PD patients, suggesting that metabolomics may hold promise for PD diagnostic tools. In this study, we sought to identify metabolic markers of PD in plasma. Using a 1H-13C heteronuclear single quantum coherence spectroscopy (HSQC) NMR spectroscopy metabolomics platform coupled with machine learning (ML), we measured plasma metabolites from approximately age/sex-matched PD patients with G2019S LRRK2 mutations and non-PD controls. Based on the differential level of known and unknown metabolites, we were able to build a ML model and develop a Biomarker of Response (BoR) score, which classified male LRRK2 PD patients with 79.7% accuracy, 81.3% sensitivity, and 78.6% specificity. The high accuracy of the BoR score suggests that the metabolomics/ML workflow described here could be further utilized in the development of a confirmatory diagnostic for PD in larger patient cohorts. A diagnostic assay for PD will aid clinicians and their patients to quickly move toward a definitive diagnosis, and ultimately empower future clinical trials and treatment options.

Treatment patterns and health care costs among patients with psoriatic arthritis treated with biologic or targeted synthetic disease-modifying antirheumatic drugs.

BACKGROUND: Biologic and targeted synthetic disease-modifying antirheumatic drug (tsDMARD) therapies are used in management of psoriatic arthritis (PsA). Although previous studies have demonstrated that rates of adherence, persistence, discontinuation, and switching, as well as health care costs, are variable among treatments, limited published data exist on more recently approved therapies. OBJECTIVE: To describe adherence, persistence, discontinuation, reinitiation, switching, dosing patterns, and health care costs among PsA patients treated with biologics and tsDMARDs. METHODS: This was a real-world, retrospective administrative claims study. Adult PsA patients with at least 1 claim for an approved PsA biologic (adalimumab, certolizumab, etanercept, golimumab, infliximab, secukinumab, or ustekinumab) or tsDMARD (apremilast or tofacitinib) between January 1, 2015, and June 30, 2019, were selected from the IBM MarketScan administrative claims databases. The first claim for one of the study treatments determined the index date and drug cohort. Patients were required to be continuously enrolled in their health plans for 12 months before and after the index date and to have at least 1 claim with a diagnosis of PsA in the 12 months before or on the index date. Adherence (measured by proportion of days covered [PDC] and medication possession ratio [MPR]), persistence (< 60-day gap in treatment), discontinuation (> 90-day gap), reinitiation of index drug, switching, and dosing patterns for each index drug were assessed during the 12-month follow-up period. Health care costs were reported per patient per month (PPPM) during the 12-month follow-up and assessed after adjusting PsA treatment costs by the Institute for Clinical and Economic Review discount factors to account for discounts and rebates not usually reflected in claims data and by adherence. RESULTS: Overall, 6,674 patients met the selection criteria. The top 3 index drugs were adalimumab (37%), apremilast (26%), and etanercept (18%). Over 12 months of follow-up, 31%-59% of patients remained persistent on the index drug, whereas 35%-56% discontinued, 13%-29% switched to a different biologic or tsDMARD, and 3%-15% reinitiated the index therapy, depending on the index drug. The mean PDC ranged from 0.51 to 0.69 during the 12-month follow-up and 0.80 to 0.93 during the follow-up period before discontinuation. Dose values were largely consistent with prescribing information, with the exception of secukinumab. Index drug costs PPPM ranged from $2,361 (apremilast) to $6,528 for ustekinumab after adjustment for discounts and adherence. CONCLUSIONS: Results from this real-world analysis suggest that there is substantial variability in persistence, discontinuation, adherence, reinitiating, and switching patterns among the different biologic and tsDMARD treatment options for PsA patients. In addition, this study provides real-world cost data for biologics and tsDMARDs among patients with PsA. DISCLOSURES: This study was funded by Eli Lilly Inc., which participated in analysis and interpretation of data, drafting, reviewing, and approving the publication. All authors contributed to the development of the publication and maintained control over the final content. Murage, Malatestinic, Zhu, Atiya, Kern, Stenger, and Sprabery are employees and stockholders of Eli Lilly Inc. Princic and Park are employed by IBM Watson Health, which received funding from Eli Lilly Inc. to conduct this study. Ogdie has received consulting fees from Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Corrona, Janssen, Lilly, Novartis, and Pfizer and has also received grant support from Pfizer, Novartis, and Amgen. Portions of these data have been presented in poster form at the virtual International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2020 and Congress of Clinical Rheumatology (CCR) West 2020 conferences.

Health and Health Care Use Strongly Associated with Cumulative Burden of Social Determinants of Health.

Understanding health outcomes and patterns of health care utilization associated with patients' cumulative social determinant of health (SDOH) risk is essential to supporting better health care. This study compared mental and physical health outcomes and health care utilization by increasing number of social needs among a clinical adult population. Surveys were sent to 6000 patients with recent visits to 7 primary care clinics in Portland, Oregon in 2018. The final study sample included respondents who matched to medical claims data, N = 1748. The authors used a modified logistic regression model to estimate risk ratios for the relationship between cumulative SDOH factors and self-reported chronic conditions, and a 2-part model to estimate the effects of cumulative SDOH risk on health care utilization. Increased SDOH need was associated with increasing likelihood of worse self-reported health outcomes, especially mental health. Compared with those with no SDOH need, having 1-2 SDOH need(s) (adjusted risk ratio [aRR] 1.25; 95% confidence interval [CI]: 1.06-1.46) and 3 or more SDOH needs (aRR 1.45; 95% CI: 1.22-1.73) had a greater risk of reporting any behavioral health condition. However, the number of SDOH had a graded but inverse impact on use of mental health care services where fewer visits were observed among those using care. Having SDOH was associated with increased likelihood of having an emergency department visit and increased number of primary care visits. This study demonstrates the compounding impact of SDOH on health and health care use. This highlights the importance of collecting SDOH, including the total number of SDOH needs, when considering a patient's health and health care.

Real-World Treatment Patterns and Healthcare Costs in Patients with Psoriatic Arthritis Treated with Ixekizumab: A Retrospective Study.

OBJECTIVE: To describe adherence, persistence, discontinuation, restarting, switching, dosing, and health care costs among patients with psoriatic arthritis (PsA) treated with ixekizumab (IXE). METHODS: MarketScan administrative claims databases were used to select adults (≥18 years) initiating IXE between January 1, 2016, and June 30, 2019, for this retrospective study (earliest IXE claim = index). Eligible patients had one or more PsA diagnoses during the 12 months preceding the index and had 12 months of follow-up time after the index. Adherence (measured by proportion of days covered [PDC]) persistence (<60-day gap), discontinuation (≥90-day gap), switching, and dosing patterns were reported. Health care costs were reported per patient per month (PPPM) during follow-up and were assessed after adjusting PsA treatment costs for discount rates reported by the Institute for Clinical and Economic Review (ICER). RESULTS: A total of 496 patients met the selection criteria (mean age, 51.1 years; 50.4% female). Over the 12-month follow-up, 52.8% remained persistent, 38.7% discontinued, 13.5% had no other treatment, 4.6% restarted, and 20.6% switched to a new biologic/traditional synthetic disease-modifying antirheumatic drug. 70.6%of patients were identified as highly adherent (i.e. PDC > 0.80)to IXE prior to discontinuation. Dose values were consistent with prescribing information for patients with and without comorbid psoriasis. Although IXE costs ($5233 [SD = $2497]) accounted for 85.6% of PsA-related health care costs, only 3.5% of IXE costs were patient out-of-pocket expenses. Adjusting for the ICER discounts decreased all-cause and PsA-related costs by $2509 PPPM. CONCLUSION: Results from this real-world analysis suggest that treatment patterns and costs among patients with PsA initiating IXE are consistent with prior literature for other biologics.

Evaluation of the dimensional accuracy of thermoformed appliances taken from 3D printed models with varied shell thicknesses: An in vitro study.

OBJECTIVE: Clinicians make numerous decisions when 3D printing models for fabrication of thermoformed appliances, including printing solid or hollow models. While hollow models can reduce resin use, models intended for thermoformed appliance fabrication must be printed with sufficient thickness to withstand thermoforming. The aim of the study was to determine for hollow 3D printed orthodontic models if there is an effect of shell thickness on the dimensional accuracy of retainers thermoformed upon them as compared with solid models and, if so, to identify the minimum shell thickness that ensures dimensional accuracy of the thermoformed retainer under the conditions investigated. MATERIAL AND METHODS: Thermoformed appliances were fabricated on 3D printed models of six shell thicknesses: 1.0mm, 1.5mm, 2.0mm, 2.5mm, 3.0mm, and solid (n=10/group). The models were scanned before and after thermoforming. Thermoformed appliances were captured by two methods: scanning a polyvinylsiloxane casting of the appliance and scanning the appliance interior surface (intaglio surface). Each model-appliance pair was compared using superimposition software. A generalized linear model and post-hoc Tukey contrasts (α=0.05) were applied to compare each thickness. RESULTS: Model thickness has a statistically significant effect on dimensional accuracy of thermoformed appliances. Appliances fabricated on 1.0mm and 1.5mm models displayed poor accuracy, with a statistically significantly lower percentage of data points within tolerance (±0.250mm) than appliances fabricated on models printed at 2.0mm thickness and greater. CONCLUSIONS: 3D printed model thickness affects the dimensional accuracy of a thermoformed retainer. To ensure minimal deformation and promote clinical utility of the thermoformed appliance, models should be printed with a minimum shell thickness of 2.0mm for the materials investigated.

Effect of a Health System-Sponsored Mobile App on Perinatal Health Behaviors: Retrospective Cohort Study.

BACKGROUND: Pregnancy mobile apps are becoming increasingly popular, with parents-to-be seeking information related to their pregnancy and their baby through mobile technology. This increase raises the need for prenatal apps with evidence-based content that is personalized and reliable. Previous studies have looked at whether prenatal apps impact health and behavior outcomes among pregnant and postpartum individuals; however, research has been limited. OBJECTIVE: The primary objective of this study is to assess whether the use of a health system-sponsored mobile app-Circle by Providence-aimed at providing personalized and reliable health information on pregnancy, postpartum recovery, and infant care is associated with improved health outcomes and increased healthy behaviors and knowledge among users. METHODS: This observational study compared app users and app nonusers using a self-reported survey and electronic medical records. The study took place over 18 months and was conducted at Providence St. Joseph Health in Portland, Oregon. The sample included patients who received prenatal care at one of seven Providence clinics and had a live birth at a Providence hospital. Recruitment occurred on a rolling basis and only those who completed the survey were included. Survey respondents were separated into app users and app nonusers, and survey responses and clinical outcomes were compared across groups using univariate and adjusted multivariate logistic regression. RESULTS: A total of 567 participants were enrolled in the study-167 in the app user group and 400 in the nonuser group. We found statistically significant differences between the two groups for certain behavior outcomes: subjects who used the app had 75% greater odds of breastfeeding beyond 6 months postpartum (P=.012), were less likely to miss prenatal appointments (P=.046), and were 50% more likely to exercise 3 or more times a week during pregnancy (P=.04). There were no differences in nutritional measures, including whether they took prenatal vitamins, ate 5 fruits or vegetables a day, or drank caffeine. We found no differences in many of the infant care outcomes; however, there was an increase in awareness of "purple crying." Finally, there were no significant differences in measured clinical health outcomes, including cesarean births, length of hospital stays (in minutes), low birth weight infants, preterm births, small-for-gestational-age births, large-for-gestational-age births, and neonatal intensive care unit stays. CONCLUSIONS: The use of the Circle app, which provides access to personalized and evidence-based health information, was associated with an increase in certain healthy behaviors and health knowledge, although there was no impact on clinical health outcomes. More research is needed to determine the impact of mobile prenatal apps on healthy pregnancies, clinical health outcomes, and infant care.

Biochar Affects Essential Nutrients of Carrot Taproots and Lettuce Leaves.

Essential nutrient concentrations in crops can affect human health. While biochar has the potential as a soil amendment to improve crop yields, it may also affect the concentrations of nutrients such as Ca, Fe, K, Mg, Mn, and Zn in edible portions of crops. To better characterize effects of biochar on important human nutrients in food crops, we evaluated the effects of biochar on lettuce (Lactuca sativa L. cv. Black-Seeded Simpson) leaf and carrot [Daucus carota subsp. sativus (Hoffm.) Schübl. cv. Tendersweet] developing taproot nutrients. Plants were grown in pots in a greenhouse using sandy loam (Coxville, fine, kaolinitic, thermic Typic Paleaquults) and loamy sand (Norfolk, fine-loamy, kaolinitic, thermic Typic Kandiudults,) series soils, amended with biochar produced from four feedstocks: pine chips (PC), poultry litter (PL), swine solids (SS), and switchgrass (SG); and two blends of PC plus PL [Pc/PL, 50%/50% (55) and 80%/20% (82) by weight]. Biochar was produced at 350, 500, and 700 °C from each feedstock. Lettuce leaf and carrot taproot total nutrient concentrations were determined by inductively coupled plasma analysis. Biochar (especially at least in part manure-based, i.e., PL, SS, 55, and 82 at nearly all temperatures) primarily decreased nutrient concentrations in lettuce leaves, with Ca, Mg, and Zn affected most. Carrot taproot nutrient concentrations also deceased, but to a lesser extent. Some biochars increased leaf or taproot nutrient concentrations, especially K. This study indicated that biochar can both decrease and increase leaf and taproot nutrient concentrations important for human health. Thus, potential effects on nutrients in plants should be carefully considered when biochar is used as a soil amendment with vegetable crops.

Persistent Gut Microbial Dysbiosis in Children with Acute Lymphoblastic Leukemia (ALL) During Chemotherapy.

Prophylactic or therapeutic antibiotic use along with chemotherapy treatment potentially has a long-standing adverse effect on the resident gut microbiota. We have established a case-control cohort of 32 pediatric and adolescent acute lymphoblastic leukemia (ALL) patients and 25 healthy siblings (sibling controls) to assess the effect of chemotherapy as well as antibiotic prophylaxis on the gut microbiota. We observe that the microbiota diversity and richness of the ALL group is significantly lower than that of the control group at diagnosis and during chemotherapy. The microbiota diversity is even lower in antibiotics-exposed ALL patients. Although the gut microbial diversity tends to stabilize after 1-year post-chemotherapy, their abundances were altered because of chemotherapy and prophylactic antibiotic treatments. Specifically, the abundances of mucolytic gram-positive anaerobic bacteria, including Ruminococcus gnavus and Ruminococcus torques, tended to increase during the chemotherapy regimen and continued to be elevated 1 year beyond the initiation of chemotherapy. This dysbiosis may contribute to the development of gastrointestinal complications in ALL children following chemotherapy. These findings set the stage to further understand the role of the gut microbiome dynamics in ALL patients and their potential role in alleviating some of the adverse side effects of chemotherapy and antibiotics use in immunocompromised children.

Understanding the Socioeconomic and Health Challenges of the Medicaid Expansion Population in Oregon.

Following the Patient Protection and Affordable Care Act, Medicaid eligibility in the United States expanded to include low-income adults. One key challenge for organizations and providers serving the Medicaid population was predicting if and how this change would alter the composition of enrollees. This study characterized demographics, socioeconomic challenges, and health of the expansion and non-expansion Medicaid populations in a metropolitan area in Oregon using a survey and Medicaid claims. Results showed that the expansion population has more men and non-English speakers than the non-expansion population. They also have greater education and employment, but face similar socioeconomic challenges including struggling to meet basic needs and housing instability. This study also found comparable self-reported physical and mental health, but lower prevalence of physical or mental health diagnoses and several ambulatory care reactive conditions including hypertension, obesity, and type 2 diabetes. The authors concluded that expansion and non-expansion populations differ in sex, language, education, employment, and health, but they face similar socioeconomic challenges. This information is useful for organizations coordinating and providing care to Medicaid members so they can understand the needs of the population and set appropriate population health management strategies.

Comparative Tumor RNA Sequencing Analysis for Difficult-to-Treat Pediatric and Young Adult Patients With Cancer.

Importance: Pediatric cancers are epigenetic diseases; therefore, considering tumor gene expression information is necessary for a complete understanding of the tumorigenic processes. Objective: To evaluate the feasibility and utility of incorporating comparative gene expression information into the precision medicine framework for difficult-to-treat pediatric and young adult patients with cancer. Design, Setting, and Participants: This cohort study was conducted as a consortium between the University of California, Santa Cruz (UCSC) Treehouse Childhood Cancer Initiative and clinical genomic trials. RNA sequencing (RNA-Seq) data were obtained from the following 4 clinical sites and analyzed at UCSC: British Columbia Children's Hospital (n = 31), Lucile Packard Children's Hospital at Stanford University (n = 80), CHOC Children's Hospital and Hyundai Cancer Institute (n = 46), and the Pacific Pediatric Neuro-Oncology Consortium (n = 24). The study dates were January 1, 2016, to March 22, 2017. Exposures: Participants underwent tumor RNA-Seq profiling as part of 4 separate clinical trials at partner hospitals. The UCSC either downloaded RNA-Seq data from a partner institution for analysis in the cloud or provided a Docker pipeline that performed the same analysis at a partner institution. The UCSC then compared each participant's tumor RNA-Seq profile with more than 11 000 uniformly analyzed tumor profiles from pediatric and young adult patients with cancer, downloaded from public data repositories. These comparisons were used to identify genes and pathways that are significantly overexpressed in each patient's tumor. Results of the UCSC analysis were presented to clinical partners. Main Outcomes and Measures: Feasibility of a third-party institution (UCSC Treehouse Childhood Cancer Initiative) to obtain tumor RNA-Seq data from patients, conduct comparative analysis, and present analysis results to clinicians; and proportion of patients for whom comparative tumor gene expression analysis provided useful clinical and biological information. Results: Among 144 samples from children and young adults (median age at diagnosis, 9 years; range, 0-26 years; 72 of 118 [61.0%] male [26 patients sex unknown]) with a relapsed, refractory, or rare cancer treated on precision medicine protocols, RNA-Seq-derived gene expression was potentially useful for 99 of 144 samples (68.8%) compared with DNA mutation information that was potentially useful for only 34 of 74 samples (45.9%). Conclusions and Relevance: This study's findings suggest that tumor RNA-Seq comparisons may be feasible and highlight the potential clinical utility of incorporating such comparisons into the clinical genomic interpretation framework for difficult-to-treat pediatric and young adult patients with cancer. The study also highlights for the first time to date the potential clinical utility of harmonized publicly available genomic data sets.

Identifying underlying constructs of childhood adversity in a low-income population.

BACKGROUND: Extensive research has documented the association between adverse childhood experiences (ACEs) and poor outcomes later in life, as well as the high prevalence of ACEs in the American population. Studies consistently find that over half of American adults have experienced at least one ACE. Despite this, research on the long-term impacts of ACEs is challenging due to the complex nature of adversity. OBJECTIVE: Our study aimed to define underlying constructs of adversity, and explore how they changed throughout childhood, in a low-income population. PARTICIPANTS AND SETTING: We fielded a survey to Medicaid-enrolled adults in the Portland, OR metropolitan area. METHODS: Our survey captured different experiences in childhood, including relationships and support, educational challenges, housing and employment stability, neighborhood environment, discrimination, abuse, neglect, and household dysfunction; questions were asked for 6-12 and 13-18 years of age. We then used factor analysis to identify underlying constructs of adversity in the two age ranges. RESULTS: We identified two factors - Inadequate Emotional Support and Instability - in each age range. Inadequate Emotional Support remained consistent in both time periods while the Instability factor changed, expanding from household-centric experiences in childhood to a wider variety of experiences in adolescence. Additionally, a number of variables did not load on either factor in either age range. CONCLUSIONS: These results underscore the importance of expanding how we think about instability specifically, and childhood adversity in general.

Effects of human demand on conservation planning for biodiversity and ecosystem services.

Safeguarding ecosystem services and biodiversity is critical to achieving sustainable development. To date, ecosystem services quantification has focused on the biophysical supply of services with less emphasis on human beneficiaries (i.e., demand). Only when both occur do ecosystems benefit people, but demand may shift ecosystem service priorities toward human-dominated landscapes that support less biodiversity. We quantified how accounting for demand affects the efficiency of conservation in capturing both human benefits and biodiversity by comparing conservation priorities identified with and without accounting for demand. We mapped supply and benefit for 3 ecosystem services (flood mitigation, crop pollination, and nature-based recreation) by adapting existing ecosystem service models to include and exclude factors representing human demand. We then identified conservation priorities for each with the conservation planning program Marxan. Particularly for flood mitigation and crop pollination, supply served as a poor proxy for benefit because demand changed the spatial distribution of ecosystem service provision. Including demand when jointly targeting biodiversity and ecosystem service increased the efficiency of conservation efforts targeting ecosystem services without reducing biodiversity outcomes. Our results highlight the importance of incorporating demand when quantifying ecosystem services for conservation planning.

Efectos de la Demanda Humana sobre la Planeación de la Conservación para la Biodiversidad y los Servicios Ambientales Resumen La salvaguardia de los servicios ambientales y de la biodiversidad es muy importante para lograr el desarrollo sustentable. A la fecha, la cuantificación de los servicios ambientales se ha enfocado en el suministro biofísico de servicios con un menor énfasis en los beneficiarios humanos (es decir, la demanda). Es sólo cuando se considera a ambos que los ecosistemas benefician a las personas, pero la demanda puede cambiar las prioridades de los servicios ambientales hacia los paisajes dominados por humanos, los cuales mantienen una menor biodiversidad. Cuantificamos cómo afecta la consideración de la demanda a la eficiencia de la conservación en la captura de los beneficios humanos y de la biodiversidad al comparar las prioridades de conservación con y sin la consideración de la demanda. Mapeamos el suministro y el beneficio para tres servicios ambientales (mitigación de inundaciones, polinización de cultivos y actividades recreativas basadas en la naturaleza) al adaptar los modelos de servicios ambientales existentes para que incluyeran y excluyeran los factores que representan la demanda humana. Después identificamos las prioridades de conservación para cada uno con el programa de planeación de la conservación Marxan. En el caso particular de la mitigación de inundaciones y la polinización de cultivos, el suministro fue un sustituto pobre para el beneficio debido a que la demanda cambió la distribución espacial de la provisión de servicios ambientales. La inclusión de la demanda cuando nos enfocamos en la biodiversidad y en los servicios ambientales como conjunto incrementó la eficiencia de los esfuerzos de conservación enfocados en los servicios ambientales sin reducir los resultados para la biodiversidad. Nuestros resultados resaltan la importancia de la incorporación de la demanda cuando se cuantifican los servicios ambientales para la planeación de la conservación.

Comparative toxicogenomics of three insensitive munitions constituents 2,4-dinitroanisole, nitroguanidine and nitrotriazolone in the soil nematode Caenorhabditis elegans.

BACKGROUND: Ecotoxicological studies on the insensitive munitions formulation IMX-101 and its components 2,4-dinitroanisole (DNAN), nitroguanidine (NQ) and nitrotriazolone (NTO) in various organisms showed that DNAN was the main contributor to the overall toxicity of IMX-101 and suggested that the three compounds acted independently. These results motivated this toxicogenomics study to discern toxicological mechanisms for these compounds at the molecular level. METHODS: Here we used the soil nematode Caenorhabditis elegans, a well-characterized genomics model, as the test organism and a species-specific, transcriptome-wide 44 K-oligo probe microarray for gene expression analysis. In addition to the control treatment, C. elegans were exposed for 24 h to 6 concentrations of DNAN (1.95-62.5 ppm) or NQ (83-2667 ppm) or 5 concentrations of NTO (187-3000 ppm) with ten replicates per treatment. The nematodes were transferred to a clean environment after exposure. Reproduction endpoints (egg and larvae counts) were measured at three time points (i.e., 24-, 48- and 72-h). Gene expression profiling was performed immediately after 24-h exposure to each chemical at the lowest, medium and highest concentrations plus the control with four replicates per treatment. RESULTS: Statistical analyses indicated that chemical treatment did not significantly affect nematode reproduction but did induce 2175, 378, and 118 differentially expressed genes (DEGs) in NQ-, DNAN-, and NTO-treated nematodes, respectively. Bioinformatic analysis indicated that the three compounds shared both DEGs and DEG-mapped Reactome pathways. Gene set enrichment analysis further demonstrated that DNAN and NTO significantly altered 12 and 6 KEGG pathways, separately, with three pathways in common. NTO mainly affected carbohydrate, amino acid and xenobiotics metabolism while DNAN disrupted protein processing, ABC transporters and several signal transduction pathways. NQ-induced DEGs were mapped to a wide variety of metabolism, cell cycle, immune system and extracellular matrix organization pathways. CONCLUSION: Despite the absence of significant effects on apical reproduction endpoints, DNAN, NTO and NQ caused significant alterations in gene expression and pathways at 1.95 ppm, 187 ppm and 83 ppm, respectively. This study provided supporting evidence that the three chemicals may exert independent toxicity by acting on distinct molecular targets and pathways.

Disaggregating the evidence linking biodiversity and ecosystem services.

Ecosystem services (ES) are an increasingly popular policy framework for connecting biodiversity with human well-being. These efforts typically assume that biodiversity and ES covary, but the relationship between them remains remarkably unclear. Here we analyse >500 recent papers and show that reported relationships differ among ES, methods of measuring biodiversity and ES, and three different approaches to linking them (spatial correlations, management comparisons and functional experiments). For spatial correlations, biodiversity relates more strongly to measures of ES supply than to resulting human benefits. For management comparisons, biodiversity of 'service providers' predicts ES more often than biodiversity of functionally unrelated taxa, but the opposite is true for spatial correlations. Functional experiments occur at smaller spatial scales than management and spatial studies, which show contrasting responses to scale. Our results illuminate the varying dynamics relating biodiversity to ES, and show the importance of matching management efforts to the most relevant scientific evidence.

Spatial and Temporal Dynamics and Value of Nature-Based Recreation, Estimated via Social Media.

Conserved lands provide multiple ecosystem services, including opportunities for nature-based recreation. Managing this service requires understanding the landscape attributes underpinning its provision, and how changes in land management affect its contribution to human wellbeing over time. However, evidence from both spatially explicit and temporally dynamic analyses is scarce, often due to data limitations. In this study, we investigated nature-based recreation within conserved lands in Vermont, USA. We used geotagged photographs uploaded to the photo-sharing website Flickr to quantify visits by in-state and out-of-state visitors, and we multiplied visits by mean trip expenditures to show that conserved lands contributed US $1.8 billion (US $0.18-20.2 at 95% confidence) to Vermont's tourism industry between 2007 and 2014. We found eight landscape attributes explained the pattern of visits to conserved lands; visits were higher in larger conserved lands, with less forest cover, greater trail density and more opportunities for snow sports. Some of these attributes differed from those found in other locations, but all aligned with our understanding of recreation in Vermont. We also found that using temporally static models to inform conservation decisions may have perverse outcomes for nature-based recreation. For example, static models suggest conserved land with less forest cover receive more visits, but temporally dynamic models suggest clearing forests decreases, rather than increases, visits to these sites. Our results illustrate the importance of understanding both the spatial and temporal dynamics of ecosystem services for conservation decision-making.