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Background: Opioid agonist treatment (OAT) reduces many of the harms associated with opioid dependence. We use mathematical modelling to comprehensively evaluate the overall health benefits of OAT in people who inject drugs in Perry County (KY, USA), Kyiv (Ukraine), and Tehran (Iran)., Methods: We developed a dynamic model of HIV and hepatitis C virus (HCV) transmission, incarceration, and mortality through overdose, injury, suicide, disease-related and other causes. The model was calibrated to site-specific data using Bayesian methods. We evaluated preventable drug-related deaths (deaths due to HIV, HCV, overdose, suicide, or injury) averted over 2020-40 for four scenarios, added incrementally, compared with a scenario without OAT: existing OAT coverage (setting-dependent; community 4-11%; prison 0-40%); scaling up community OAT to 40% coverage; increasing average OAT duration from 4-14 months to 2 years; and scaling up prison-based OAT., Outcomes: Drug-related harms contributed differentially to mortality across settings: overdose contributed 27-47% (range of median projections) of preventable drug-related deaths over 2020-40, suicide 6-17%, injury 3-17%, HIV 0-59%, and HCV 2-18%. Existing OAT coverage in Tehran (31%) could have a substantial effect, averting 13% of preventable drug-related deaths, but will have negligible effect (averting <2% of preventable drug-related deaths) in Kyiv and Perry County due to low OAT coverage (<4%). Scaling up community OAT to 40% could avert 12-24% of preventable drug-related deaths, including 13-22% of overdose deaths, with greater effect in settings with significant HIV mortality (Tehran and Kyiv). Improving OAT retention and providing prison-based OAT would have a significant additional effect, averting 27-51% of preventable drug-related deaths., Interpretation: OAT can substantially reduce drug-related harms, particularly in settings with HIV epidemics in people who inject drugs. Maximising these effects requires research and investment into achieving higher coverage and provision and longer retention of OAT in prisons and the community., Funding: UK National Institute for Health Research, US National Institute on Drug Abuse., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

New HIV infections associated with injection drug use are of major concern in rural US communities. This study explores acceptability of, consent for, and uptake of free at-home HIV testing among people who use drugs (PWUD) in one of the nation's epicenters for drug-related harms and HIV vulnerability: Rural Central Appalachia. Eligible participants were 18-35 years old, lived in Appalachian Kentucky, and reported using opioids to get high in the previous 30 days. A majority reported being likely (63.6%, 96/151) to take a free at-home HIV tests and 66.9% (101/151) consented to receive one. Among those who were randomly selected to receive a Home Access HIV-1 test kit (n = 37), 37.8% mailed in blood spots and 21.6% called to receive results. This study provides evidence that PWUD may be willing to take an at-home test, but other barriers may inhibit actual completion.

Evergreen conifer forests are the most prevalent land cover type in North America. Seasonal changes in the color of evergreen forest canopies have been documented with near-surface remote sensing, but the physiological mechanisms underlying these changes, and the implications for photosynthetic uptake, have not been fully elucidated. Here, we integrate on-the-ground phenological observations, leaf-level physiological measurements, near surface hyperspectral remote sensing and digital camera imagery, tower-based CO 2 flux measurements, and a predictive model to simulate seasonal canopy color dynamics. We show that seasonal changes in canopy color occur independently of new leaf production, but track changes in chlorophyll fluorescence, the photochemical reflectance index, and leaf pigmentation. We demonstrate that at winter-dormant sites, seasonal changes in canopy color can be used to predict the onset of canopy-level photosynthesis in spring, and its cessation in autumn. Finally, we parameterize a simple temperature-based model to predict the seasonal cycle of canopy greenness, and we show that the model successfully simulates interannual variation in the timing of changes in canopy color. These results provide mechanistic insight into the factors driving seasonal changes in evergreen canopy color and provide opportunities to monitor and model seasonal variation in photosynthetic activity using color-based vegetation indices., (© 2020 The Authors New Phytologist © 2020 New Phytologist Foundation.)

Component ratios and kinetics are key to understanding and optimising novel formulations. This warrants investigation of valid methods. Attenuated Total Reflectance Fourier Transform Infra-Red (ATR)-FTIR spectra of separate primers/adhesives were modelled using summed spectra of solvents (water, ethanol), methacrylate monomers (HEMA (hydroxyethyl methacrylate), Bis-GMA (bisphenol A glycidyl methacrylate), and 10-MDP (10-methacryloyloxydecyl dihydrogen phosphate)), and fillers, multiplied by varying fractions. Filler loads were obtained following their separation from the adhesives, by analysing three repetitions ( n = 3). Spectral changes during light exposure at 37 °C (20 s, LED 1100-1330 mW/cm 2 ) were used to determine polymerisation kinetics ( n = 3). Independent samples T-test was used for statistical analysis (significance level of 5%). FTIR modelling suggested a primer solvent percentage of OBFL (Optibond FL) (30%) was half that of CFSE (Clearfil SE 2) (60%). OBFL included ethanol and water, while CFSE included only water. Monomer peaks were largely those of HEMA with lower levels of phosphate monomers. OBFL/CFSE adhesive model spectra suggested that both contained equal volumes of Bis-GMA/HEMA, with CFSE having 10-MDP. Filler levels and spectra from OBFL (48 wt.%) and CFSE (5 wt.%) were different. Both systems reached a 50% conversion rate within seconds of light exposure. The final conversion for OBFL (74 ± 1%) was lower compared to CFSE (79 ± 2%) ( p < 0.05). ATR-FTIR is a useful method to investigate relative levels of main components in bonding systems and their polymerisation kinetics. Such information is valuable to understanding such behaviour.

Background: People who inject drugs (PWID) experience high incarceration rates, with current/recent incarceration being associated with increased hepatitis C virus (HCV) transmission. We assess the contribution of incarceration to HCV transmission amongst PWID in Perry County (PC), Kentucky, USA, and the impact of scaling-up community and in-prison opioid substitution therapy (OST), including the potential for reducing incarceration., Methods: A dynamic model of incarceration and HCV transmission amongst PWID was calibrated in a Bayesian framework to epidemiological and incarceration data from PC, incorporating an empirically estimated 2.8-fold (95%CI: 1.36-5.77) elevated HCV acquisition risk amongst currently incarcerated or recently released (<6 months) PWID compared to other PWID. We projected the percentage of new HCV infections that would be prevented among PWID over 2020-2030 if incarceration no longer elevated HCV transmission risk, if needle and syringe programmes (NSP) and OST are scaled-up, and/or if drug use was decriminalized (incarceration/reincarceration rates are halved) with 50% of PWID that would have been imprisoned being diverted onto OST. We assume OST reduces reincarceration by 10-42%., Results: Over 2020-2030, removing the effect of incarceration on HCV transmission could prevent 42.7% (95% credibility interval: 15.0-67.4%) of new HCV infections amongst PWID. Conversely, scaling-up community OST and NSP to 50% coverage could prevent 28.5% (20.0-37.4%) of new infections, with this increasing to 32.7% (24.5-41.2%) if PWID are retained on OST upon incarceration, 36.4% (27.7-44.9%) if PWID initiate OST in prison, and 45.3% (35.9-54.1%) if PWID are retained on OST upon release. decriminalization (with diversion to OST) could further increase this impact, preventing 56.8% (45.3-64.5%) of new infections. The impact of these OST interventions decreases by 2.1-28.6% if OST does not reduce incarceration., Conclusion: Incarceration is likely to be an important contributor to HCV transmission amongst PWID in PC. Prison-based OST could be an important intervention for reducing this risk., Competing Interests: Declaration of Interests J.S. has received a conference attendance sponsorship from Gilead. P.V. has received unrestricted research grants from Gilead unrelated to this work and honorarium from Gilead and Abbvie unrelated to this work. H.F. has received an honorarium from MSD unrelated to this work. The other authors report no conflicts., (Copyright © 2020. Published by Elsevier B.V.)

Soybean ( Glycine max ) sudden death syndrome (SDS), caused by Fusarium virguliforme , is a key limitation in reaching soybean yield potential, stemming from incomplete disease management through cultural practices and partial host resistance. A fungicidal seed treatment was released in 2014 with the active ingredient fluopyram and was the first chemical management strategy to reduce soybean yield loss stemming from SDS. Although farm level studies have found fluopyram profitable, we were curious to discover whether fluopyram would be beneficial nationally if targeted to soybean fields at risk for SDS yield loss. To estimate economic benefits of fluopyram adoption in SDS at-risk acres, in the light of U.S. public research and outreach from a privately developed product, we applied an economic surplus approach, calculating ex ante net benefits from 2018 to 2032. Through this framework of logistic adoption of fluopyram for alleviation of SDS-associated yield losses, we projected a net benefit of $5.8 billion over 15 years, considering the costs of public seed treatment research and future extension communication. Although the sensitivity analysis indicates that overall net benefits from fluopyram adoption on SDS at-risk acres are highly dependent upon the market price of soybean, the incidence of SDS, the adoption path, and ceiling of this seed treatment, the net benefits still exceeded $407 million in the worst-case scenario.

Behavior courses face numerous challenges when moving to an online environment, as has been made necessary by the COVID-19 pandemic. These challenges occur largely because behavior courses, like most organismal biology courses, often stress experiential learning through laboratories that involve live animals, as well as a lecture component that emphasizes formative assessment, discussion, and critical thinking. Although online behavior courses may be remote, they can still be interactive and social, and designed with inclusive pedagogy. Here, we discuss some of the key decisions that instructors should consider, provide recommendations, and point out new opportunities for student learning that stem directly from the move to online instruction. Specific topics include challenges related to generating an inclusive and engaging online learning environment, synchronous versus asynchronous formats, assignments that enhance student learning, testing format and execution, grade schemes, design of laboratory experiences including opportunities for community science, design of synthetic student projects, and workload balance for students and instructors. We designed this primer both for animal behavior instructors who need to quickly transition to online teaching in the midst of a pandemic, and for those facing such transitions in upcoming terms. Much of the manuscript's content should also be of general interest and value to instructors from all areas of organismal biology who are attempting to quickly transition to online teaching., (© 2020 Wiley‐VCH GmbH.)

Objective: This study aimed to assess effects of emotional eating and stress on weight change among Black women in a culturally tailored weight-control program., Methods: SisterTalk, a cable-TV-delivered weight-control randomized trial, included 331 Black women (aged 18-75 years; BMI ≥ 25 kg/m 2 ) in Boston, Massachusetts. BMI and waist circumference (WC) were assessed at baseline and 3, 8, and 12 months post randomization. Frequency of "eating when depressed or sad" (EWD) and "eating to manage stress" (ETMS) (i.e., "emotional eating") and perceived stress were also assessed. Lagged analyses of data for intervention participants (n = 258) assessed associations of BMI and WC outcomes at each follow-up visit with EWD and ETMS frequency and stress measured at the most recent prior visit., Results: At 3 months (immediately post intervention), BMI decreased for women in all EWD and ETMS categories but increased at later follow-up for women reporting EWD and ETMS always/often. In addition, 8-month EWD and ETMS predicted 12-month BMI change (both P < 0.05). Higher perceived stress was associated with higher EWD and ETMS; however, stress was not associated with lagged BMI or WC at any time., Conclusions: Addressing emotional eating and related triggers may improve weight maintenance in interventions with Black women., (© 2020 The Obesity Society.)

Description The world is in the midst of a pandemic from COVID-19, a disease caused by the virus SARS-CoV-2. Despite broad mitigation efforts, new cases continue with 74 million cases and 1.6 million deaths worldwide. Regardless of previous research efforts, there is no commercially available vaccine for any coronavirus. Novel vaccine development has historically taken at least 10 years from discovery to availability with only a 6% market entry probability. With the global impact, there is an urgency to expedite a vaccine to protect the population. The U.S. government launched Operation Warp Speed with the goal to produce and deliver 300 million doses of safe and effective vaccines by January 2021. Efforts toward this goal have included coordinated government agency support, parallel clinical trial deployment, de-risking manufacturing earlier in the development process and real-time U.S. Food & Drug Administration evaluation of the safety and efficacy data. Safety is a priority and key analysis has not been eliminated during the compressed timeframe. The two frontrunner candidates show promising efficacy rates for preventing COVID-19 with Moderna reporting 94.1% efficacy and Pfizer reporting 95.0% efficacy. Despite the herculean efforts by scientists to develop an effective vaccine in such a short timeframe, several national surveys suggest that public confidence in these vaccines is low with less than 50% of the survey respondents willing to be vaccinated. According to experts, the U.S. needs the vaccine to be at least 70-80% effective and a 70-80% vaccination rate in order to return to normal. Significant education and promotion is planned in coordination with the Centers for Disease Control., Competing Interests: Conflicts of Interest The authors declare they have no conflicts of interest., (© 2020 HCA Physician Services, Inc. d/b/a Emerald Medical Education.)

Aim: Knowledge translation (KT) is a multistage process of implementing practice change to align with evidence-based practice. This study aimed to determine the confidence of allied health professionals (AHPs) to undertake KT., Methods: A quantitative questionnaire was disseminated to AHPs over a 4-week period. Awareness of and confidence with KT was assessed using a 100-mm visual analogue scale., Results: 374 AHPs responded from 12 metropolitan hospitals in Queensland, Australia. Moderate confidence was reported for identifying an evidence-practice gap (median 70 mm, interquartile range [IQR] 50-80 mm), finding relevant literature/evidence (67 mm, 40-84 mm), and sharing evidence with colleagues (70 mm, 50-85 mm). Clinicians were less confident in choosing a KT framework (20 mm, 3-50 mm), implementing a practice change (40 mm, 15-61 mm), assessing barriers and enablers (50 mm, 25-70 mm) and supporting less experienced clinicians undertaking KT (42 mm, 14-68 mm). There was a weak positive correlation between years of experience and confidence in implementing practice change (rho=0.127, p=0.017). A majority of respondents (89%, n=333) reported an interest in learning more about KT., Conclusions: AHPs were interested in KT but had low confidence in implementing research into practice. These findings identify opportunities to support the training and education needs of AHPs in KT.

Oncology nurses are at the heart of tackling the increasing global burden of cancer. Their contribution is unique because of the scale and the diversity of care roles and responsibilities in cancer care. In this Series paper, to celebrate the International Year of the Nurse and Midwife, we highlight the contribution and impact of oncology nurses along the cancer care continuum. Delivering people-centred integrated care and optimal communication are essential components of oncology nursing care, which are often played down. More oncology nurses using, doing, and leading research will further show the key nursing impact on care as part of a team. The oncology nurse influence in saving lives through prevention and early detection of cancer is noteworthy. Supportive care, the central pillar of oncology nursing, enables and empowers people to self-manage where possible. Globally, oncology nurses make a great positive difference to cancer care worldwide; their crucial contribution throughout the continuum of care warrants the inclusion and promotion of nursing in every country's cancer strategy. 2020 is the year of the nurse: let us take this learning to the future., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Obesity is costly, yet there have been few attempts to estimate the actual costs of providing hospital care to the obese inpatient. This study aimed to test the feasibility of measuring obesity-related health care costs and accuracy of coding data for acute inpatients. A prospective observational study was conducted over three weeks in June 2018 in a single orthopaedic ward of a metropolitan tertiary hospital in Queensland, Australia. Demographic data, anthropometric measurements, clinical characteristics, cost of hospital encounter and coding data were collected. Complete demographic, anthropometric and clinical data were collected for all 18 participants. Hospital costing reports and coding data were not available within the study timeframe. Participant recruitment and data collection were resource-intensive, with mobility assistance required to obtain anthropometric measurements in more than half of the participants. Greater staff time and costs were seen in participants with obesity compared to those without obesity (obesity: body mass index ≥ 30), though large standard deviations indicate wide variance. Data collected suggest that obesity-related cost and resource use amongst acute inpatients require further exploration. This study provides recommendations for protocol refinement to improve the accuracy of data collected for future studies measuring the actual cost of providing hospital care to obese inpatients.

Background: This analysis aims to assess whether injection drug use cessation among peers predicts injection drug use cessation among individuals and explores whether this association varies by relationship type and strength., Methods: Data were collected through baseline and 6-month assessments for the Social Networks among Appalachian People study (2008-2011). Interviewer-administered surveys collected sociodemographic and drug use behaviors (past 6 months and lifetime). Participants also listed sex, drug use, and social support partners (past 6 months). Listed names were cross-referenced with survey participants to identify relationships between study participants. The analytic sample was further restricted to include only those relationship pairs where both individuals reported a history of injection drug use at baseline (n = 244 unique individuals and 746 dyads). We fit a generalized estimating equations logistic regression model to (1) assess the relationship between peer injection cessation and individual injection cessation and (2) determine whether the strength of this association differs by relationship-level variables (i.e., relationship role, relationship type, relationship duration, frequency of interaction, residential proximity)., Results: Overall, those with a network member who ceased injection drug use were more likely to stop injecting over the following 6-month period (AOR=1.65). The magnitude of this association was greater for social support partners (AOR=2.95), family members (AOR=3.56), those with whom the participant interacted at least daily (AOR=2.17), and those who the participant knew longer (AOR=2.09). Further, among family members, the effect size was greater when relationships were further restricted to immediate family members (AOR=5.35)., Conclusion: Our findings suggest that in this rural community, closer, more supportive relationships, may be more influential for modeling injection cessation; however, relationship-types were not mutually exclusive so differences in effect size across strata may not be statistically significant. In this setting, social support through the recovery process (including cessation attempts with peers) may increase likelihood of injection cessation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Rural communities in the United States are increasingly becoming epicenters of substance use and related harms. However, best practices for recruiting rural people who use drugs (PWUD) for epidemiologic research are unknown, because such strategies were developed in cities. This study explores the feasibility of web- and community-based strategies to recruit rural, young adult PWUD into epidemiologic research., Materials and Methods: We recruited PWUD from rural Kentucky to participate in a web-based survey about opioid use using web-based peer referral and community-based strategies, including cookouts, flyers, street outreach, and invitations to PWUD enrolled in a concurrent substance use study. Staff members labeled recruitment materials with unique codes to enable tracking. We assessed eligibility and fraud through online eligibility screening and a fraud detection algorithm, respectively. Eligibility criteria included being aged 18-35, recently using opioids to get high, and residing in the study area., Results: Recruitment yielded 410 complete screening entries, of which 234 were eligible and 151 provided complete, nonfraudulent surveys (ie, surveys that passed a fraud-detection algorithm designed to identify duplicate, nonlocal, and/or bot-generated entries). Cookouts and subsequent web-based peer referrals accounted for the highest proportion of screening entries (37.1%, n = 152), but only 29.6% (n = 45) of entries from cookouts and subsequent web-based peer referrals resulted in eligible, nonfraudulent surveys. Recruitment and subsequent web-based peer referral from the concurrent study yielded the second most screening entries (27.8%, n = 114), 77.2% (n = 88) of which resulted in valid surveys. Other recruitment strategies combined to yield 35.1% (n = 144) of screening entries and 11.9% (n = 18) of valid surveys., Conclusions: Web-based methods need to be complemented by context-tailored, street-outreach activities to recruit rural PWUD.

Rural Appalachia remains an epicenter of the prescription opioid epidemic. In 2008, a cohort study was undertaken to examine longitudinal trends in nonmedical prescription opioid use (NMPOU). Eight waves of data (2008-2020) from the Social Networks among Appalachian People (SNAP) cohort were utilized for the current analysis. Only those who reported recent (past 6-month) NMPOU at baseline are included (n = 498, 99%). Mixed-effects logistic regression was used to model factors associated with NMPOU over time. Recent NMPOU declined significantly over the past decade (p < .001). However, 54.1% of participants still engaged in NMPOU at their most recent follow-up. Receipt of benefits for a physical or mental disability (adjusted odds ratio [aOR]: 3.11, 95% Confidence Interval [CI]: 1.98, 4.90) and self-described poor health status (aOR: 3.67, 95% CI: 1.61, 8.37) were both associated with NMPOU. All treatment modalities (methadone maintenance, residential, outpatient counseling) tested in the model, with the notable exception of detoxification, were associated with significantly lower odds of NMPOU. Although significant declines in prescription opioid misuse were observed in the cohort, more than half of all participants were engaged in NMPOU more than a decade after entering the study. Substance use disorder (SUD) treatment (excluding detoxification) was shown associated with reduced odds of continued NMPOU; therefore, increasing access to evidence-based treatments should be a priority in rural areas affected by the ongoing opioid epidemic., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Though overdose rates have been increasing in US rural areas for two decades, little is known about the rural risk environment for overdoses. This qualitative study explored the risk environment for overdoses among young adults in Eastern Kentucky, a rural epicenter of the US opioid epidemic., Methods: Participants were recruited via community-based outreach. Eligibility criteria included living in one of five rural Eastern Kentucky counties; being aged 18-35; and using opioids to get high in the past 30 days. Semi-structured interviews explored the rural risk environment, and strategies to prevent overdose and dying from an overdose. Interviews were transcribed verbatim and analyzed using constructivist grounded-theory methods., Results: In this sample (N = 19), participants reported using in a range of locations, including homes and outdoor settings; concerns about community stigma and law enforcement shaped the settings where participants used opioids and the strategies they deployed in these settings to prevent an overdose, and to survive an overdose. Almost half of participants reported using opioids in a "trap house" or other dealing locations, often to evade police after buying drugs, and reported that others present pressed them to use more than usual. If an overdose occurred in this setting, however, these same people might refuse to call EMS to protect themselves from arrest. Outdoor settings presented particular vulnerabilities to overdose and dying from an overdose. Most participants reported using opioids outdoors, where they skipped overdose prevention steps to reduce their risk of arrest; they worried that no one would find them if they overdosed, and that cell phone coverage would be too weak to summon EMS., Conclusion: Findings suggest that initiatives to reduce overdoses in Eastern Kentucky would be strengthened by de-escalating the War on Drugs and engaging law enforcement in initiatives to protect the health of people who use opioids., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Buprenorphine is a cornerstone to curbing opioid epidemics, but emerging data suggest that rural pharmacists in the US sometimes refuse to dispense this medication. We conducted a case study to explore buprenorphine dispensing practices in 12 rural Appalachian Kentucky counties, and analyze whether and how they were shaped by features of the rural risk environment., Methods: In this case study, we conducted one-on-one semi-structured interviews with 14 pharmacists operating 15 pharmacies in these counties to explore buprenorphine dispensing practices and perceived influences on these practices. Thematic analyses of the resulting transcripts revealed three features of the rural risk environment that shaped dispensing. To explore these three risk environment features, we analyzed policy documents (e.g., Attorney General lawsuits) and administrative databases (e.g., incarceration data). Textual documents were analyzed using thematic analyses and administrative data were analyzed using descriptive statistics; memoes explored relationships among risk environment features and dispensing practices., Results: Twelve of the 15 pharmacies limited dispensing, by refusing to serve new patients; limiting dispensing to known patients or prescribers; or refusing to dispense buprenorphine altogether. Concerns about exceeding a "Drug Enforcement Administration (DEA) cap" on opioid dispensing stifled dispensing. A legacy of aggressive and fraudulent marketing of opioid analgesics (OAs) by pharmaceutical companies and physician OA overprescribing undermined pharmacist trust in buprenorphine and in its prescribers. The escalating local war on drugs may have undermined dispensing by reinforcing stigma against people who use drugs., Conclusions: Initiatives to increase buprenorphine prescribing must be accompanied by policy changes to increase dispensing. Specifically, buprenorphine should be removed from opioid monitoring systems; efforts to de-escalate the war on drugs should be extended to encompass rural areas; initiatives to dismantle aggressive OA marketing should be strengthened; and efforts to re-build pharmacist trust in physicians are needed., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In acute myeloid leukemia (AML), TP53 mutations and dysregulation of wild-type p53 is common and supports an MDM2 antagonist as a therapy. RO6839921 is an inactive pegylated prodrug of the oral MDM2 antagonist idasanutlin (active principle [AP]) that allows for IV administration. This phase 1 monotherapy study evaluated the safety, pharmacokinetics, and pharmacodynamics of RO6839921 in patients with AML. Primary objectives identified dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Secondary objectives assessed pharmacokinetic, pharmacodynamic, and antileukemic activity. A total of 26 patients received 120-300 mg AP of idasanutlin. The MTD was 200 mg, with DLTs at 250 (2/8 patients) and 300 mg (2/5). Treatment-related adverse events in >20% of patients were diarrhea, nausea, vomiting, decreased appetite, and fatigue. Six deaths (23.1%) occurred, all unrelated to treatment. Pharmacokinetics showed rapid and near-complete conversion of the prodrug to AP and dose-proportional exposure across doses. Variability ranged from 30%-47% (22%-54% for idasanutlin). TP53 was 21 (87.5%) wild-type and 3 mutant (12.5%). The composite response rate (complete remission [CR], CR with incomplete hematologic recovery/morphological leukemia-free state [CRi/MLFS], or CR without platelet recovery [CRp]) was 7.7%. Antileukemic activity (CR, CRi/MLFS, partial response, hematologic improvement/stable disease) was observed in 11 patients (disease control rate, 42%): 10/11 were TP53 wild-type; 1 had no sample. p53 activation was demonstrated by MIC-1 induction and was associated with AP exposure. There was not sufficient differentiation or improvement in the biologic or safety profile compared with oral idasanutlin to support continued development of RO6839921. NCT02098967.

Background: The home food environment can shape the diets of young children. However, little is known about modifiable factors that influence home food availability and dietary intake., Objective: The purpose of this study was to examine the relationship between grocery shopping frequency with home- and individual-level diet quality., Design: This was a secondary, cross-sectional analyses of data from the Study on Children's Home Food Availability Using TechNology. Data were collected in the homes of participants from November 2014 through March 2016., Participants/settings: A purposive sample of 97 low-income African American and Hispanic or Latinx parent-child dyads residing in Chicago, IL, enrolled in the study., Main Outcome Measures: The main outcomes were home- and individual-level diet quality. Healthy Eating Index-2010 (HEI-2010) scores were calculated from home food inventory data collected in participants' homes to assess home-level diet quality. To assess individual-level diet quality, HEI-2010 scores were based on multiple 24-hour diet recalls from parent-child dyads., Statistical Analyses: Grocery shopping frequency was examined in relation to diet quality at the home and individual levels. Grocery shopping frequency was defined as the number of times households shopped on a monthly basis (ie, once a month, twice a month, 3 times a month, or 4 times or more a month). Multivariable linear regression analysis, controlling for covariates, tested the relationships between grocery shopping frequency and HEI-2010 total and component scores at the home and individual levels., Results: Grocery shopping frequency was positively associated with home-level HEI-2010 scores for total diet, whole grains, and empty calories (higher scores reflect better diet quality) and with individual-level HEI-2010 scores for total and whole fruit (parents only), vegetables (children only), and sodium (children only)., Conclusions: Grocery shopping frequency was associated with multiple dimensions of diet quality at the home and individual levels. These results offer a potential strategy to intervene on home food availability and individual dietary intake., (Copyright © 2020 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Direct oral anticoagulants (DOACs) are an emerging treatment option for patients with cancer and acute venous thromboembolism (VTE), but studies have reported inconsistent results. This systematic review and meta-analysis compared the efficacy and safety of DOACs and low-molecular-weight heparins (LMWHs) in these patients. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and conference proceedings were searched to identify relevant randomized controlled trials. Additional data were obtained from the original authors to homogenize definitions for all study outcomes. The primary efficacy and safety outcomes were recurrent VTE and major bleeding, respectively. Other outcomes included the composite of recurrent VTE and major bleeding, clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality. Summary relative risks (RRs) were calculated in a random effects meta-analysis. In the primary analysis comprising 2607 patients, the risk of recurrent VTE was nonsignificantly lower with DOACs than with LMWHs (RR, 0.68; 95% CI, 0.39-1.17). Conversely, the risks of major bleeding (RR, 1.36; 95% CI, 0.55-3.35) and CRNMB (RR, 1.63; 95% CI, 0.73-3.64) were nonsignificantly higher. The risk of the composite of recurrent VTE or major bleeding was nonsignificantly lower with DOACs than with LMWHs (RR, 0.86; 95% CI, 0.60-1.23). Mortality was comparable in both groups (RR, 0.96; 95% CI, 0.68-1.36). Findings were consistent during the on-treatment period and in those with incidental VTE. In conclusion, DOACs are an effective treatment option for patients with cancer and acute VTE, although caution is needed in patients at high risk of bleeding., (© 2020 by The American Society of Hematology.)

Human-wildlife conflict is difficult to measure, but the analysis of records from wildlife rehabilitation facilities has shown potential as a technique for characterizing human impacts on wildlife. To examine the value of wildlife rehabilitation records for characterizing local human-wildlife conflicts and prevalence of select wildlife diseases, we reviewed 45,668 records representing over 280 species admitted to a wildlife rehabilitation facility over a 10-year period (2005-2014). We identified the most frequently recorded causes of admission for commonly admitted species, and evaluated how causes of admission may vary across taxa throughout the year. Our analyses support the value of wildlife rehabilitation facility data for characterizing some pressures from human-wildlife conflict and select disease trends for certain taxa, as well as utility for informing topics to emphasize in local conservation education efforts. For example, orphaned neonatal wildlife accounted for the largest proportion of admissions to this facility, and highlights a opportunity for conservation education regarding when wildlife is truly orphaned and requires professional intervention. Additionally, domestic dog attack cases accounted for a proportion of admissions comparable to that of domestic cat attacks, demonstrating a need for the conversation surrounding the impact of domestic pets on local wildlife to expand to include dogs in addition to cats., Competing Interests: The authors have declared that no competing interests exist.

Despite its high prevalence, there is no systematic approach to documenting and coding obesity in hospitals. This study aimed to determine the prevalence of obesity among inpatients, the proportion of obese patients recognised as obese by hospital administration, and the cost associated with their admission. A cross-sectional study was undertaken in three hospitals in Queensland, Australia. Inpatients present on three audit days were included in this study. Data collected were age, sex, height, and weight. Body mass index (BMI) was calculated in accordance with the World Health Organization's definition. Administrative data were sourced from hospital records departments to determine the number of patients officially documented as obese. Total actual costing data were sourced from hospital finance departments. From a combined cohort of n = 1327 inpatients (57% male, mean (SD) age: 61 (19) years, BMI: 28 (9) kg/m 2 ), the prevalence of obesity was 32% ( n = 421). Only half of obese patients were recognised as obese by hospital administration. A large variation in the cost of admission across BMI categories prohibited any statistical determination of difference. Obesity is highly prevalent among hospital inpatients in Queensland, Australia. Current methods of identifying obesity for administrative/funding purposes are not accurate and would benefit from reforms to measure the true impact of healthcare costs from obesity.

Appalachian Kentucky is currently fighting two public health emergencies-COVID-19 and the opioid epidemic-leaving the area strapped for resources to care for these ongoing crises. During this time, people who use opioids (PWUO) have increased vulnerability to fatal overdoses and drug-related harms (e.g., HIV). Disruption of already limited services posed by COVID-19 could have an especially detrimental impact on the health of PWUO. Though the COVID-19 pandemic is jeopardizing hard-won progress in fighting the opioid epidemic, innovations in state policy and service delivery brought about by the pandemic may improve the health of PWUO long-term if they are retained.

Continuing cariogenic bacterial growth demineralizing dentine beneath a composite filling is the most common cause of tooth restoration failure. Novel composites with antibacterial polylysine (PLS) (0, 4, 6, or 8 wt%) in its filler phase were therefore produced. Remineralising monocalcium phosphate was also included at double the PLS weight. Antibacterial studies involved set composite disc placement in 1% sucrose-supplemented broth containing Streptococcus mutans (UA159). Relative surface bacterial biofilm mass ( n = 4) after 24 h was determined by crystal violet-binding. Live/dead bacteria and biofilm thickness ( n = 3) were assessed using confocal laser scanning microscopy (CLSM). To understand results and model possible in vivo benefits, cumulative PLS release from discs into water ( n = 3) was determined by a ninhydrin assay. Results showed biofilm mass and thickness decreased linearly by 28% and 33%, respectively, upon increasing PLS from 0% to 8%. With 4, 6, and 8 wt% PLS, respectively, biofilm dead bacterial percentages and PLS release at 24 h were 20%, 60%, and 80% and 85, 163, and 241 μg/disc. Furthermore, initial PLS release was proportional to the square root of time and levelled after 1, 2, and 3 months at 13%, 28%, and 42%. This suggested diffusion controlled release from water-exposed composite surface layers of 65, 140, and 210 μm thickness, respectively. In conclusion, increasing PLS release initially in any gaps under the restoration to kill residual bacteria or longer-term following composite/tooth interface damage might help prevent recurrent caries.

Purpose MDM2 is a negative regulator of the tumor suppressor p53. RO6839921 is an inactive pegylated prodrug of idasanutlin, an MDM2 antagonist, developed for intravenous administration. On cleavage by plasma esterases, the active principle (AP = idasanutlin) is released. This phase 1 study investigated the safety, pharmacokinetics, and pharmacodynamics of RO6839921 in patients with advanced solid tumors (NCT02098967). Methods Patients were evaluated on a 5-day dosing schedule every 28 days. Dose escalation used the Bayesian new continual reassessment model. Accelerated dose titration was permitted until grade ≥2 drug-related AEs were observed. The target DLT rate to define the MTD was 16-25%. p53 activation was assessed by measuring macrophage inhibitory cytokine-1 (MIC-1). Results Forty-one patients received 14-120 mg AP; 39 were DLT evaluable. The MTD was 110-mg AP (8% DLT rate), whereas 120-mg AP had a 44% DLT rate. DLTs were neutropenia, thrombocytopenia, and stridor. The most common treatment-related AEs (≥30%) were nausea, fatigue, vomiting, and thrombocytopenia. Pharmacokinetic analyses indicated rapid conversion of prodrug to AP and an approximately linear and dose-proportional dose-exposure relationship, with a 2-fold increase in exposure between Days 1 and 5 of AP. MIC-1 increases were exposure dependent. Stable disease was observed in 14 patients (34%). Conclusions RO6839921 showed reduced pharmacokinetic exposure variability and a safety profile comparable with that of oral idasanutlin. Although this study indicated that RO6839921 could be administered to patients, the results did not provide sufficient differentiation or improvement in the biologic or safety profile compared with oral idasanutlin to support continued development.

The study aim was to assess the effect of incorporating polylysine (PLS) filler at different mass fractions (0.5, 1 and 2 wt%) on PLS release and Streptococcus mutans planktonic growth. Composite containing PLS mass and volume change and PLS release upon water immersion were assessed gravimetrically and via high-performance liquid chromatography (HPLC), respectively. Disc effects on bacterial counts in broth initially containing 8 × 10 5 versus 8 × 10 6 CFU/mL Streptococcus mutans UA159 were determined after 24 h. Survival of sedimented bacteria after 72 h was determined following LIVE/DEAD staining of composite surfaces using confocal microscopy. Water sorption-induced mass change at two months increased from 0.7 to 1.7% with increasing PLS concentration. Average volume increases were 2.3% at two months whilst polylysine release levelled at 4% at 3 weeks irrespective of composite PLS level. Early percentage PLS release, however, was faster with higher composite content. With 0.5, 1 and 2% polylysine initially in the composite filler phase, 24-h PLS release into 1 mL of water yielded 8, 25 and 93 ppm respectively. With initial bacterial counts of 8 × 10 5 CFU/mL, this PLS release reduced 24-h bacterial counts from 10 9 down to 10 8 , 10 7 and 10 2 CFU/mL respectively. With a high initial inoculum, 24-h bacterial counts were 10 9 with 0, 0.5 or 1% PLS and 10 7 with 2% PLS. As the PLS composite content was raised, the ratio of dead to live sedimented bacteria increased. The antibacterial action of the experimental composites could reduce residual bacteria remaining following minimally invasive tooth restorations.

Nuclear membrane rupture during interphase occurs in a variety of cell contexts, both healthy and pathological. Membrane ruptures can be rapidly repaired, but these mechanisms are still unclear. Here we show barrier-to-autointegration factor (BAF), a nuclear envelope protein that shapes chromatin and recruits membrane proteins in mitosis, also facilitates nuclear membrane repair in interphase, in part through recruitment of the nuclear membrane proteins emerin and Lem-domain-containing protein 2 (LEMD2) to rupture sites. Characterization of GFP-BAF accumulation at nuclear membrane rupture sites confirmed BAF is a fast, accurate, and persistent mark of nucleus rupture whose kinetics are partially dictated by membrane resealing. BAF depletion significantly delayed nuclear membrane repair, with a larger effect on longer ruptures. This phenotype could be rescued by GFP-BAF, but not by a BAF mutant lacking the Lap2, emerin, Man1 (LEM)-protein binding domain. Depletion of the BAF interactors LEMD2 or emerin, and to a lesser extent lamin A/C, increased the duration of nucleus ruptures, consistent with LEM-protein binding being a key function of BAF during membrane repair. Overall our results suggest a model where BAF is critical for timely repair of large ruptures in the nuclear membrane, potentially by facilitating membrane attachment to the rupture site.

Nebulized fentanyl is well established for analgesia but its use for dyspnea requires further investigation. The aim of our study was to determine the effectiveness of nebulized fentanyl in treating patients with dyspnea and to determine if there were harmful side effects described by patients or their providers. We used a convenience sample of patients from July 1 2014 to July 1 2018 and performed a retrospective chart review. We found that 360 doses of nebulized fentanyl were given to 73 patients during that time period. Of the 73 patients evaluated, 32 patients (43.8%) were female and forty-one were male (56.1%). The median age was 67 and the median length of stay was 9 days. There were no documented findings of bronchospasm, hypotension, or allergic reaction in any of the medical records reviewed. Patients treated with nebulized fentanyl for dyspnea showed a mean decreased respiratory rate of 4.3 breaths/min and a mean increased oxygen saturation of 2.3%. Also, 71% of patients with documented responses experienced an improvement in their dyspnea. Our preliminary data suggest that nebulized fentanyl has limited side effects and may have a role in the treatment of dyspnea. Further research is necessary to determine its efficacy.

Geographic momentary assessments (GMA) collect real-time behavioral data in one's natural environment using a smartphone and could potentially increase the ecological validity of behavioral data. Several studies have evaluated the feasibility and acceptability of GMA among persons who use drugs (PWUD) and men who have sex with men (MSM), but fewer have discussed privacy, confidentiality, and safety concerns, particularly when illegal or stigmatized behavioral data were collected. This study explores perceptions regarding privacy, confidentiality, and safety of GMA research among PWUD and MSM recruited in three different settings (rural Appalachia, a mid-sized city in the South, and a mid-Atlantic city). Between November 2014 and April 2017, we recruited 35 PWUD from rural Appalachian Kentucky (N = 20) and Baltimore, Maryland (N = 15) and 20 MSM from Lexington, Kentucky to complete semi-structured qualitative interviews. Through thematic analyses, we identified and compared privacy, confidentiality, and safety concerns by demographic characteristics, risk behaviors, and setting. Privacy, confidentiality, and safety concerns varied by setting, age, smartphone ownership, use of illegal drugs, and history of drug-related arrests. Among those who used drugs, participants reported concerns with being tracked and burden associated with carrying and safeguarding study phones and responding to survey prompts. Privacy and confidentiality concerns were noted in each setting, but tracking concerns were greatest among Baltimore participants and led many to feel that they (or others) would be unwilling to participate or comply with study procedures. While locations considered to be sensitive varied by setting, participants in all settings said they would take measures to prevent sensitive information from being collected (i.e., intentionally disable devices, leave phones at home, alter response times). Privacy, confidentiality, and safety concerns may limit the accuracy of risk location information, study compliance, and participation. As concerns were often greatest among those engaging in illegal behaviors and with the highest risk behaviors, selection bias and non-response bias could negatively influence the representativeness and validity of study findings.

Background: The Anticoagulation Therapy in Selected Cancer Patients at Risk of Recurrence of Venous Thromboembolism (SELECT-D) trial demonstrated reduction in recurrent venous thromboembolism (VTE) but increased bleeding with rivaroxaban compared with dalteparin for treatment of acute VTE in cancer patients, at 6 months. Uncertainty remains around optimal duration of anticoagulation., Objectives: To assess VTE recurrence and bleeding, with anticoagulation or not, beyond 6 months., Patients/methods: In SELECT-D, after 6 months of trial treatment for VTE, patients with active cancer and residual deep vein thrombosis (RDVT) or index pulmonary embolism (PE) were eligible for randomization to a further 6 months of rivaroxaban or placebo. Patients with no RDVT stopped anticoagulation. Primary outcome was VTE recurrence at 12 months. The second randomization closed prematurely because of low recruitment when 92 of the planned 300 patients were recruited., Results: Ninety-two of 136 eligible patients were randomized to rivaroxaban or placebo. The cumulative VTE recurrence after 6 months from the second randomization was 14% with placebo and 4% with rivaroxaban (hazard ratio, 0.32; 95% confidence interval [CI], 0.06-1.58). The major and clinically relevant non-major bleeding rates were 0% and 0% with placebo; and 5% (95% CI, 1-18) and 4% (95% CI, 1-17) with rivaroxaban. In an exploratory analysis, 7 (15%) of 46 placebo patients with RDVT or an index PE experienced recurrent VTE compared to none in the 35 patients in the RDVT-negative cohort (P = .03)., Conclusion: The SELECT-D trial was underpowered to detect a statistically significant reduction in recurrent VTE with extended anticoagulation. The absence of RDVT and/or index PE, defined a population at low risk of recurrence., (© 2020 International Society on Thrombosis and Haemostasis.)

This study aimed to determine dietitians' familiarity with knowledge translation (KT), confidence in undertaking KT, and preferences for receiving KT training. An online questionnaire was designed and disseminated to all dietitians working across hospital and health services in Queensland, Australia, for completion over a 6-week period (April-May 2018). Of the 124 respondents, 69% (n = 85) reported being familiar with KT, but only 28% (n = 35) reported being confident in applying KT to their practice. Higher confidence was reported with problem identification, evidence appraisal, and adapting evidence to local context, compared with implementation, evaluation, and dissemination. Almost all respondents reported an interest in learning more about KT (n = 121, 98%), with a preference for easily accessible and short "snippets" of training aimed at beginner-intermediate level. Lack of management support, difficulty attending multi-day courses, cost, travel requirements, and lack of quarantined time were reported barriers to attending KT training. There is a high awareness and interest but low confidence in undertaking KT amongst dietitians. This highlights an opportunity for workforce development to prepare dietitians to be skilled and confident in KT. Training and support needs to be low-cost and multi-modal to meet diverse needs.

The noncanonical Wnt ligand Wnt5a is found in high concentrations in ascites of women with ovarian cancer. In this study, we elucidated the role of Wnt5a in ovarian cancer metastasis. Wnt5a promoted ovarian tumor cell adhesion to peritoneal mesothelial cells as well as migration and invasion, leading to colonization of peritoneal explants. Host components of the ovarian tumor microenvironment, notably peritoneal mesothelial cells and visceral adipose, secreted Wnt5a. Conditional knockout of host WNT5A significantly reduced peritoneal metastatic tumor burden. Tumors formed in WNT5A knockout mice had elevated cytotoxic T cells, increased M1 macrophages, and decreased M2 macrophages, indicating that host Wnt5a promotes an immunosuppressive microenvironment. The Src family kinase Fgr was identified as a downstream effector of Wnt5a. These results highlight a previously unreported role for host-expressed Wnt5a in ovarian cancer metastasis and suggest Fgr as a novel target for inhibition of ovarian cancer metastatic progression. Significance: This study establishes host-derived Wnt5a, expressed by peritoneal mesothelial cells and adipocytes, as a primary regulator of ovarian cancer intraperitoneal metastatic dissemination and identifies Fgr kinase as novel target for inhibition of metastasis., (©2020 American Association for Cancer Research.)

Research indicates that executive functioning may predict health behavior. This systematic review provides an overview of the relationship between domains of executive functioning and health behaviors associated with the leading causes of death in the United States. A total of 114 articles met the inclusion criteria (adult sample, published in English between 1990 and November 2016) and were reviewed and synthesized. Results indicated that although many studies had mixed findings, at least one executive function component was associated with every health behavior. Based on these results, health professionals should consider the role of executive functions in behavior change interventions.

Background People who inject drugs (PWID) in rural areas of the United States have had limited access to syringe service programs (SSP). Rural SSP have recently surged, but accompanying research is lacking about PWID utilization, barriers, and preferences for SSP design and how those preferences vary by gender. Methods: Interviewer-administered surveys elicited information about utilization, barriers, and preferences for SSP design from 234 PWID recruited using respondent-driven sampling in Appalachian, Kentucky. Gender differences among reported barriers to utilizing SSP and preferences for program design were explored using Mantel-Haenszel chi-square tests. Results: Overall, 49% of PWID had ever utilized an SSP. The most common reasons for not utilizing an SSP were lack of awareness (23%), fear of being seen or disclosing drug use (19%), and lack of need (19%). The most preferred SSP design was located within a health department (74%) and operating during afternoon hours (66%). Men were more likely than women to prefer SSP in health departments (80% vs. 65%, p  = 0.01), while more women than men preferred staffing by health department personnel (62% vs. 46%, p  = 0.02). Women were less likely to favor evening hours (55% vs. 70%, p  = 0.02). Fewer women wanted SSP nurses (78% vs. 90%, p  = 0.01), social workers (11% vs. 24%, p  = 0.01), or people who use drugs (20% vs 34%, p  = 0.02) to staff SSP. Conclusions: Despite recent scale-up, SSP in Appalachia remain under-utilized. PWID were open to a range of options for SSP design and staffing, though there were variations by gender. Implementation research that identifies best strategies for tailored SSP scale-up in rural settings should be considered.

Background: Effects of prolonged nevirapine prophylaxis exposure on growth among HIV-exposed uninfected (HEU) infants are unknown. This study examines the impact of extended nevirapine prophylaxis from 6 weeks to 6 months on the growth of HEU infants followed for 18 months and also identifies correlates of incident wasting, stunting, underweight, and low head circumference in the HPTN 046 trial., Methods: Intention-to-treat analysis examined the effect of extended nevirapine exposure on: weight-for-age Z-score, length-for-age Z-score, weight-for-length Z-score, and head circumference-for-age Z-score. Multivariable linear mixed-effects and Cox proportional hazard models were used to compare growth outcomes between the study arms and identify correlates of incident adverse growth outcomes, respectively., Results: Compared to placebo, extended prophylactic nevirapine given daily from 6 weeks to 6 months did not affect growth in HEU breastfeeding (BF) infants over time (treatment × time: P > 0.05). However, overall growth declined over time (time effect: P < 0.01) when compared with WHO general population norms. Male sex was associated with higher risk of all adverse growth outcomes (P < 0.05), whereas short BF duration was associated with wasting (P = 0.03). Maternal antiretroviral therapy exposure was protective against underweight (P = 0.02). Zimbabwe tended to have worse growth outcomes especially stunting, compared to South Africa, Uganda and Tanzania (P < 0.05)., Conclusions: It is reassuring that prolonged exposure to nevirapine for prevention-of-mother-to-child HIV transmission does not restrict growth. However, targeted interventions are needed to improve growth outcomes among at-risk HEU infants (i.e., male sex, short BF duration, lack of maternal antiretroviral therapy exposure, and resident in Zimbabwe).

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Monitoring vegetation phenology is critical for quantifying climate change impacts on ecosystems. We present an extensive dataset of 1783 site-years of phenological data derived from PhenoCam network imagery from 393 digital cameras, situated from tropics to tundra across a wide range of plant functional types, biomes, and climates. Most cameras are located in North America. Every half hour, cameras upload images to the PhenoCam server. Images are displayed in near-real time and provisional data products, including timeseries of the Green Chromatic Coordinate (Gcc), are made publicly available through the project web page ( https://phenocam.sr.unh.edu/webcam/gallery/ ). Processing is conducted separately for each plant functional type in the camera field of view. The PhenoCam Dataset v2.0, described here, has been fully processed and curated, including outlier detection and expert inspection, to ensure high quality data. This dataset can be used to validate satellite data products, to evaluate predictions of land surface models, to interpret the seasonality of ecosystem-scale CO 2 and H 2 O flux data, and to study climate change impacts on the terrestrial biosphere.

Background: Epicenters of harmful drug use are expanding to US rural areas, with rural young adults bearing a disproportionate burden. A large body of work suggests that place characteristics (eg, spatial access to health services) shape vulnerability to drug-related harms among urban residents. Research on the role of place characteristics in shaping these harms among rural residents is nascent, as are methods of gathering place-based data., Objective: We (1) analyzed whether young rural adults who used drugs answered self-administered Web-based mapping items about locations where they engaged in risk behaviors and (2) determined the precision of mapped locations., Methods: Eligible individuals had to report recently using opioids to get high; be aged between 18 and 35 years; and live in the 5-county rural Appalachian Kentucky study area. We used targeted outreach and peer-referral methods to recruit participants. The survey asked participants to drop a pin in interactive maps to mark where they completed the survey, and where they had slept most; used drugs most; and had sex most in the past 6 months. Precision was assessed by (1) determining whether mapped locations were within 100 m of a structure and (2) calculating the Euclidean distance between the pin-drop home location and the street address where participants reported sleeping most often. Measures of central tendency and dispersion were calculated for all variables; distributions of missingness for mapping items and for the Euclidean distance variable were explored across participant characteristics., Results: Of the 151 participants, 88.7% (134/151) completed all mapping items, and ≥92.1% (>139/151) dropped a pin at each of the 4 locations queried. Missingness did not vary across most participant characteristics, except that lower percentages of full-time workers and peer-recruited participants mapped some locations. Two-thirds of the pin-drop sex and drug use locations were less than 100 m from a structure, as were 92.1% (139/151) of pin-drop home locations. The median distance between the pin-drop and street-address home locations was 2.0 miles (25th percentile=0.8 miles; 75th percentile=5.5 miles); distances were shorter for high-school graduates, staff-recruited participants, and participants reporting no technical difficulties completing the survey., Conclusions: Missingness for mapping items was low and unlikely to introduce bias, given that it varied across few participant characteristics. Precision results were mixed. In a rural study area of 1378 square miles, most pin-drop home addresses were near a structure; it is unsurprising that fewer drug and sex locations were near structures because most participants reported engaging in these activities outside at times. The error in pin-drop home locations, however, might be too large for some purposes. We offer several recommendations to strengthen future research, including gathering metadata on the extent to which participants zoom in on each map and recruiting participants via trusted staff., (©Hannah Luke Fenimore Cooper, Natalie D Crawford, Regine Haardöerfer, Nadya Prood, Carla Jones-Harrell, Umedjon Ibragimov, April M Ballard, April M Young. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 18.10.2019.)

Background: Timely data is key to effective public health responses to epidemics. Drug overdose deaths are identified in surveillance systems through ICD-10 codes present on death certificates. ICD-10 coding takes time, but free-text information is available on death certificates prior to ICD-10 coding. The objective of this study was to develop a machine learning method to classify free-text death certificates as drug overdoses to provide faster drug overdose mortality surveillance., Methods: Using 2017-2018 Kentucky death certificate data, free-text fields were tokenized and features were created from these tokens using natural language processing (NLP). Word, bigram, and trigram features were created as well as features indicating the part-of-speech of each word. These features were then used to train machine learning classifiers on 2017 data. The resulting models were tested on 2018 Kentucky data and compared to a simple rule-based classification approach. Documented code for this method is available for reuse and extensions: https://github.com/pjward5656/dcnlp., Results: The top scoring machine learning model achieved 0.96 positive predictive value (PPV) and 0.98 sensitivity for an F-score of 0.97 in identification of fatal drug overdoses on test data. This machine learning model achieved significantly higher performance for sensitivity (p<0.001) than the rule-based approach. Additional feature engineering may improve the model's prediction. This model can be deployed on death certificates as soon as the free-text is available, eliminating the time needed to code the death certificates., Conclusion: Machine learning using natural language processing is a relatively new approach in the context of surveillance of health conditions. This method presents an accessible application of machine learning that improves the timeliness of drug overdose mortality surveillance. As such, it can be employed to inform public health responses to the drug overdose epidemic in near-real time as opposed to several weeks following events., Competing Interests: The authors have declared that no competing interests exist.

Background: Rural Kentucky is an epicenter of hepatitis C(HCV), especially among young adults who inject drugs. While the Risk Environment Framework (REF) has been used widely to study and address socio-ecological determinants of infectious disease among people who inject drugs (PWID), it has been almost exclusively applied to urban environments. Applying REF to rural environments can enhance our understanding of the drivers of HCV epidemics in these hard-hit areas, and inform the creation and implementation of harm reduction interventions in this local context., Methods: Participants were recruited between March and August 2017 via community-based outreach methods (e.g., cookouts, flyers) and peer referral. Individuals who met eligibility criteria (aged 18-35, recently used prescription opioids and/or heroin to get high, lived in one of the 5 target counties) participated indepth, semi-structured interviews. The interview guide was informed by the REF, and covered HCV-related risk behaviors and environmental features that shaped vulnerability to engaging in these behaviors. Interviews were transcribed and analyzed using constructivist grounded-theory methods., Results: Participants (N=19) described multiple intersecting risk environment features that shaped vulnerability to HCV transmission. Economic decline generated intergenerational poverty, dwindling employment prospects, and diminished social enrichment opportunities that collectively contributed to substance misuse and risky injection practices. Geographic isolation, lack of collective knowledge about HCV transmission risks, scarce harm reduction services, familial poverty, and fear of law enforcement interacted to increase the odds of people injecting in "trap houses" (akin to shooting galleries) or secluded areas, spaces in which they rushed to inject and shared injection equipment. Pervasive stigma was a structural barrier to adopting, expanding, and using harm reduction services., Conclusion: This exploratory study identified features of rural risk environments that may contribute to significant HCV burdens in Appalachian Kentucky. Findings signal the importance of expanding proven harm reduction strategies and anti-stigma interventions tailored to rural contexts., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: To determine the effect of heat on flexural strength (FS), maximum strain (MS), storage modulus (SM), tan delta (TD) and chemical changes through micro-Raman spectroscopy of dentine exposed to 2.5% NaOCl or saline., Method: ology: Dentine bars were randomly allocated to 8 test groups. Half (groups 2,4,6,8) were treated with NaOCl for 20 min; the rest (groups 1,3,5,7) remained in saline. FS/MS were measured in groups 1-4 (n = 15) (3/4 were also heated to 200 °C & re-hydrated in saline). Micro-Raman spectroscopy was performed on bars from groups 1-4. SM/TD were measured in 5-8: in 5/6 (n = 10), repeated after heating (200 °C), then following re-hydration; in 7/8 (n = 3) after heating to 25-185 °C., Results: Increase in MS on heat and FS/MS on heat + NaOCl was not significant (P > 0.05). SM increased (P = 0.06) after heat treatment but reduced to initial state after rehydration (P = 0.03). TD did not change (P = 0.4) after heat (200 °C) treatment but rehydration increased it compared with pre-treatment state (P = 0.001). For dentine bars pre-treated with NaOCl, SM did not change (P = 0.6) after heat (200 °C) treatment or rehydration but TD significantly increased (P = 0.02) upon re-hydration compared with pre- (P=0.007), or post- (P = 0.03) heat-treatment states. SM and TD varied between 25-185 °C with no consistent trend amongst the NaOCl pre-treated bars. Micro-Raman only detected chemical changes following NaOCl treatment in the mineral phase., Conclusions: Exposure of dentine bars to heat and NaOCl produced only moderate changes to quasi-static but marked changes to viscoelastic properties, which may be explained by chemical alterations., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

In the United States, hepatitis C virus (HCV) transmission is rising among people who inject drugs (PWID). Many regions have insufficient prevention intervention coverage. Using modeling, we investigated the impact of scaling up prevention and treatment interventions on HCV transmission among PWID in Perry County, Kentucky, and San Francisco, California, where HCV seroprevalence among PWID is >50%. A greater proportion of PWID access medication-assisted treatment (MAT) or syringe service programs (SSP) in urban San Francisco (established community) than in rural Perry County (young, expanding community). We modeled the proportion of HCV-infected PWID needing HCV treatment annually to reduce HCV incidence by 90% by 2030, with and without MAT scale-up (50% coverage, both settings) and SSP scale-up (Perry County only) from 2017. With current MAT and SSP coverage during 2017-2030, HCV incidence would increase in Perry County (from 21.3 to 22.6 per 100 person-years) and decrease in San Francisco (from 12.9 to 11.9 per 100 person-years). With concurrent MAT and SSP scale-up, 5% per year of HCV-infected PWID would need HCV treatment in Perry County to achieve incidence targets-13% per year without MAT and SSP scale-up. In San Francisco, a similar proportion would need HCV treatment (10% per year) irrespective of MAT scale-up. Reaching the same impact by 2025 would require increases in treatment rates of 45%-82%. Achievable provision of HCV treatment, alongside MAT and SSP scale-up (Perry County) and MAT scale-up (San Francisco), could reduce HCV incidence., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Web-based methods can be used to collect data from hidden populations, including people who use drugs (PWUD). These methods might be especially advantageous among PWUD in rural areas, where transportation barriers are prevalent, stigma may heighten concerns about confidentiality, and internet access is improving. However, Web-based research with PWUD can be challenging, especially in verifying eligibility. Administering quizzes to verify residential and substance use eligibility could prove valuable in online research among PWUD, yet the utility of this approach is currently unknown., Objective: This study describes the implementation of online eligibility quizzes about the local community to verify residence in the target study area along with drug dose, appearance, and price to verify opioid misuse., Methods: To be eligible, individuals had to live in 1 of 5 eastern Kentucky counties, report using opioids to get high in the past 30 days, and be 18 to 35 years old. Participants recruited from August 2017 to July 2018 were asked questions about their opioid use followed by a quiz about drug dose, appearance, and price to verify substance use eligibility. Residential eligibility was verified with 5-question quizzes assessing knowledge of the county where they reported living. Questions tested knowledge about towns, festivals, and landmarks; local school mascots and colors; and presence of certain retail stores, restaurants, and facilities (eg, jails). A subsample that reported using opioids in the past 24 hours was randomly selected to complete urine drug testing (UDT). Nonparametric tests were performed to explore differences across demographic subgroups., Results: Of the 410 entries assessed for eligibility, 39.3% (161/410) were ineligible as they reported no substance use, being outside the age range, or living outside the study area. Of the remaining 249 who met the eligibility criteria based on age, residency, and opioid misuse, 94.0% (234/249) passed the eligibility quizzes. Among those who passed the heroin quiz, 99.4% (167/168) recognized the image of powdered heroin, 94.6% (159/168) answered the cap size (ie, the purchase unit) question correctly, and 97.0% (163/168) answered the street price question correctly. Among those who passed the drug quiz for prescription opioids, 95% (36/38) answered the dose question correctly, and 82% (31/38) selected the correct image. In a random sample of participants who completed UDT within 3 days of their online screening, 74% (25/34) tested positive for an opioid., Conclusions: This study demonstrated the utility of using online eligibility screening quizzes to verify opioid misuse and residence. Participants accurately recognized heroin and prescription opioid doses, prices, and images and correctly answered questions about features of their county. Online quizzes to screen and enroll PWUD hold promise for future research as an alternative to more time- and resource-intensive approaches that could offset the advantages of Web-based methods., (©April M Ballard, Hannah LF Cooper, April M Young. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 18.06.2019.)

Purpose: The aim was to determine effects of diluent monomer and monocalcium phosphate monohydrate (MCPM) on polymerization kinetics and volumetric stability, apatite precipitation, strontium release and fatigue of novel dual-paste composites for vertebroplasty., Materials and Methods: Polypropylene (PPGDMA) or triethylene (TEGDMA) glycol dimethacrylates (25 wt%) diluents were combined with urethane dimethacrylate (70 wt%) and hydroxyethyl methacrylate (5 wt%). 70 wt% filler containing glass particles, glass fibers (20 wt%) and polylysine (5 wt%) was added. Benzoyl peroxide and MCPM (10 or 20 wt%) or N-tolyglycine glycidyl methacrylate and tristrontium phosphate (15 wt%) were included to give initiator or activator pastes. Commercial PMMA (Simplex) and bone composite (Cortoss) were used for comparison. ATR-FTIR was used to determine thermal activated polymerization kinetics of initiator pastes at 50-80°C. Paste stability, following storage at 4-37°C, was assessed visually or through mixed paste polymerization kinetics at 25°C. Polymerization shrinkage and heat generation were calculated from final monomer conversions. Subsequent expansion and surface apatite precipitation in simulated body fluid (SBF) were assessed gravimetrically and via SEM. Strontium release into water was assessed using ICP-MS. Biaxial flexural strength (BFS) and fatigue properties were determined at 37°C after 4 weeks in SBF., Results: Polymerization profiles all exhibited an inhibition time before polymerization as predicted by free radical polymerization mechanisms. Initiator paste inhibition times and maximum reaction rates were described well by Arrhenius plots. Plot extrapolation, however, underestimated lower temperature paste stability. Replacement of TEGDMA by PPGDMA, enhanced paste stability, final monomer conversion, water-sorption induced expansion and strontium release but reduced polymerization shrinkage and heat generation. Increasing MCPM level enhanced volume expansion, surface apatite precipitation and strontium release. Although the experimental composite flexural strengths were lower compared to those of commercially available Simplex, the extrapolated low load fatigue lives of all materials were comparable., Conclusions: Increased inhibition times at high temperature give longer predicted shelf-life whilst stability of mixed paste inhibition times is important for consistent clinical application. Increased volumetric stability, strontium release and apatite formation should encourage bone integration. Replacing TEGDMA by PPGDMA and increasing MCPM could therefore increase suitability of the above novel bone composites for vertebroplasty. Long fatigue lives of the composites may also ensure long-term durability of the materials., Competing Interests: The work is covered by 2 licensed patents of Anne Young which may be considered a conflict of interest as in the future she may receive royalties when a commercial product is produced. This does not alter our adherence to PLoS ONE policies on sharing data and materials. 1. Formulations and materials with cationic polymers (PCT/GB2014/052349, EP3027164A1, US20160184190); 2. Formulations and composites with reactive fillers (PCT/GB2007/003662, EP2066703A1, EP2066703B1, US20100069469, WO2008037991A1).

Purpose: The purpose of this paper is to advance understanding about the facilitation process used in complex implementation projects, by describing the function of novice clinician facilitators, and the barriers and enablers they experience, while implementing a new model of care for managing hospital malnutrition., Design/methodology/approach: Semi-structured interviews were undertaken with local facilitators ( n=7) involved in implementing The SIMPLE Approach (Systematised Interdisciplinary Malnutrition Pathway Implementation and Evaluation) in six hospitals in Queensland, Australia. Facilitator networks and training supported the clinicians acting as novice facilitators., Findings: Key functions of the facilitator role were building relationships and trust; understanding the problem and stimulating change through data; negotiating and implementing the change; and measuring, sharing and reflecting on success. "Dedicated role, time and support" was identified as a theme encompassing the key barriers and enablers to successful facilitation., Practical Implications: When implementing complex interventions within short project timelines, it is critical that novice clinician facilitators are given adequate and protected time within their role, and have access to regular support from peers and experienced facilitators. With these structures in place, facilitators can support iterative improvements through building trust and relationships, co-designing strategies with champions and teams and developing internal capacity for change., Originality/value: This case study extends the knowledge about how facilitation works in action, the barriers faced by clinicians new to working in facilitator roles, and highlights the need for an adapt-to-fit approach for the facilitation process, as well as the innovation itself.

Background: Internet is becoming an increasingly common tool for survey research, particularly among "hidden" or vulnerable populations, such as men who have sex with men (MSM). Web-based research has many advantages for participants and researchers, but fraud can present a significant threat to data integrity., Objective: The purpose of this analysis was to evaluate fraud detection strategies in a Web-based survey of young MSM and describe new protocols to improve fraud detection in Web-based survey research., Methods: This study involved a cross-sectional Web-based survey that examined individual- and network-level risk factors for HIV transmission and substance use among young MSM residing in 15 counties in Central Kentucky. Each survey entry, which was at least 50% complete, was evaluated by the study staff for fraud using an algorithm involving 8 criteria based on a combination of geolocation data, survey data, and personal information. Entries were classified as fraudulent, potentially fraudulent, or valid. Descriptive analyses were performed to describe each fraud detection criterion among entries., Results: Of the 414 survey entries, the final categorization resulted in 119 (28.7%) entries identified as fraud, 42 (10.1%) as potential fraud, and 253 (61.1%) as valid. Geolocation outside of the study area (164/414, 39.6%) was the most frequently violated criterion. However, 33.3% (82/246) of the entries that had ineligible geolocations belonged to participants who were in eligible locations (as verified by their request to mail payment to an address within the study area or participation at a local event). The second most frequently violated criterion was an invalid phone number (94/414, 22.7%), followed by mismatching names within an entry (43/414, 10.4%) and unusual email addresses (37/414, 8.9%). Less than 5% (18/414) of the entries had some combination of personal information items matching that of a previous entry., Conclusions: This study suggests that researchers conducting Web-based surveys of MSM should be vigilant about the potential for fraud. Researchers should have a fraud detection algorithm in place prior to data collection and should not rely on the Internet Protocol (IP) address or geolocation alone, but should rather use a combination of indicators., (©April M Ballard, Trey Cardwell, April M Young. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 04.02.2019.)