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Background: Emergency Medicine Service (EMS) provider compliance with American Heart Association (AHA) guidelines for acute stroke care is low. While early recognition improves in-hospital quality of care, including door-to-computed tomography (CT) time, the impact of compliance with individual recommendations on in-hospital outcomes is unknown. Methods: We identified 410 acute ischemic stroke patients who presented to a Comprehensive Stroke Center via EMS between January 1, 2018, and December 31, 2019. Guideline concordant care was defined as encounters in which EMS documented: a blood glucose, a 12-lead electrocardiogram, a stroke scale result, and time of the last known well; were enroute within less than 2 minutes from dispatch and spent less than 15 minutes on scene. We used a multivariable linear regression model to determine the effect of individual metrics, race/ethnicity, sex, and age on door-to-CT times. Results: There was low compliance with all quality-of-care metrics (37/410 encounters, 9%), but most encounters met at least 4 metrics (60.3%). Compliance with recommendations to maintain short dispatch-to-enroute times and to obtain a blood glucose were the highest (88.1% and 74.5%, respectively). Only 44.5% of encounters documented a stroke scale, but 95.9% documented a neurological exam. A linear regression model identified documentation of classic symptoms (unilateral weakness, facial droop, or speech changes) (parameter estimate -16.6, 95% CI -21.8 to -11.5) and documentation of the last known well time (parameter estimate -15.9, 95% CI -21.6 to -10.1) as significant predictors of door-to-CT times. However, documentation of a last known well occurred only in 59.9% encounters. Conclusions: Like prior studies, this study finds similarly low compliance with AHA stroke guideline and also identifies two key EMS actions that are associated with shorter door-to-CT times - documentation of last known well and recognition and documentation of classic stroke symptoms. Further education is needed to reinforce the importance of individual recommendations such as documentation of last known well and its impact on in-hospital care. Broader analysis of EMS practices is needed to fully understand the impact on additional patient outcomes.

Medication automatic dispensing systems (ADS) have been implemented in many settings, including fire-based EMS stations. The aim of this study was to evaluate the impact of in-station ADSs on controlled substance administration rates and EMS response intervals.This study was a retrospective review of data from a single fire-based EMS agency. Medication administration rates and EMS response intervals were compared before ADS implementation (P1; 6/1/15 to 5/31/16) and after ADS implementation (P3; 6/1/17-5/31/19). Cases with missing data and during a one-year implementation period were excluded.4045 cases were identified in P1 and 8168 in P3. The odds of morphine or versed administration increased following ADS implementation: OR = 1.77 (95% CI: 1.53, 2.03) and OR = 1.53 (95%CI: 1.18, 2.00) respectively. There were statistically, but likely not operationally significant increases in median response interval and transport interval from P1 to P3 of 14 seconds, (p 0.001) and 39 seconds (p 0.001) respectively. Time at hospital for all calls decreased by more than 11 minutes for all transports, from a median of 34 minutes (IQR; 23.7, 45.5) to 22.7 minutes (IQR:18.5, 27.6) in P3, p 0.001 and by 27.9 minutes for calls in which a controlled substance was given: P1 = 50.6 minutes (IQR: 34.6, 63.2), P3 = 22.7 minutes (IQR: 18.3, 27.4), p 0.001.In this system, medication ADS implementation was associated with an increase in the rates of controlled substance administration and a decrease in the time units were at hospitals.

We develop a new modeling framework for jointly modeling first prescription times and the presence of risk-mitigating behavior for prescription drugs using real-world data. We are interested in active surveillance of clinical quality improvement programs, especially for drugs which enter the market under an FDA-mandated Risk Evaluation and Mitigation Strategy (REMS). Our modeling framework attempts to jointly model two important aspects of prescribing, the time between a drug's initial marketing and a patient's first prescription of that drug, and the presence of risk-mitigating behavior at the first prescription. First prescription times can be flexibly modeled as a mixture of component distributions to accommodate different subpopulations and allow the proportion of prescriptions that exhibit risk-mitigating behavior to change for each component. Risk-mitigating behavior is defined in the context of each drug. We develop a joint model using a mixture of positive unimodal distributions to model first prescription times, and a logistic regression model conditioned on component membership to model the presence of risk-mitigating behavior. We apply our model to two recently approved extended release/long-acting (ER/LA) opioids, which have an FDA-approved blueprint for best prescribing practices to inform our definition of risk-mitigating behavior. We also apply our methods to simulated data to evaluate their performance under various conditions such as clustering.

Sex discrepancies have been reported in chronic rhinosinusitis (CRS), but limited data exist exploring sex-specific biological processes and sinonasal quality of life.Prospective cohort.Academic medical center.Demographics, clinical data, and sinonasal mucus were collected from patients with CRS presenting for surgical consideration over a 5-year period. A random forest model and linear regression were used to assess predictor variables for the 22-item Sino-Nasal Outcome Test (SNOT-22) and subdomains. Enzyme-linked immunosorbent assays were used to measure substance P and tryptase in a subset of mucus samples to explore biological differences by sex.In total, 520 patients were studied (mean age 48.3 years, 50.9% female). Males were older (50.1 vs 46.6 years,Sex differences exist in CRS disease manifestations and presentation for surgical consideration. Detection of mucus (substance P and tryptase) was reliable, but in this exploratory study, we were not able to establish neurogenic or allergic inflammatory processes as a large source of differential disease features between sexes.

OBJECTIVE: Chondrosarcoma is the most common primary malignant chest wall tumor and is historically associated with poor prognosis. Recommendations regarding surgical excision are on the basis of small, single-institution studies. We used a large national database to assess outcomes of surgery for chest wall chondrosarcoma (CWC) hypothesizing that surgical excision remains standard of care. METHODS: The National Cancer Databases for bone and soft tissue were merged to identify patients with chondrosarcoma from 2004 to 2018. Clinical and demographic characteristics of CWC were compared with chondrosarcoma from other sites. The primary outcome was overall survival described using Kaplan–Meier estimate. Univariable and multivariable Cox analysis was used to determine risk factors for poor survival among CWC patients who underwent surgery. Multivariable analysis of predictors of margin status was performed because of worse prognosis associated with positive margins. RESULTS: Among 11,925 patients with chondrosarcoma, 1934 (16.2%) had a CWC. Relative to other sites, CWC was associated with older age, male sex, White race, surgical resection, and care at a nonacademic institution. CWC was associated with 1-, 3-, 5-, and 10-year survival of 91.5%, 82.0%, 75.5%, and 62.7%, respectively. In univariable analysis, survival was associated with surgery (hazard ratio, 0.02; P

BACKGROUND AND OBJECTIVES Acute hematogenous musculoskeletal infections (MSKI) are medical emergencies with the potential for life-altering complications in afflicted children. Leveraging administrative data to study pediatric MSKI is difficult as many infections are chronic, nonhematogenous, or occur in children with significant comorbidities. The objective of this study was to validate a case-finding algorithm to accurately identify children hospitalized with acute hematogenous MSKI using administrative billing codes. METHODS This was a multicenter validation study using the Pediatric Health Information System (PHIS) database. Hospital admissions for MSKI were identified from 6 PHIS hospitals using discharge diagnosis codes. A random subset of admissions underwent manual chart review at each site using predefined criteria to categorize each admission as either “acute hematogenous MSKI” (AH-MSKI) or “not acute hematogenous MSKI.” Ten unique coding algorithms were developed using billing data. The sensitivity and specificity of each algorithm to identify AH-MSKI were calculated using chart review categorizations as the reference standard. RESULTS Of the 492 admissions randomly selected for manual review, 244 (49.6%) were classified as AH-MSKI and 248 (50.4%) as not acute hematogenous MSKI. Individual algorithm performance varied widely (sensitivity 31% to 91%; specificity 52% to 98%). Four algorithms demonstrated potential for future use with receiver operating characteristic area under the curve greater than 80%. CONCLUSIONS Identifying children with acute hematogenous MSKI based on discharge diagnosis alone is challenging as half have chronic or nonhematogenous infections. We validated several case-finding algorithms using administrative billing codes and detail them here for future use in pediatric MSKI outcomes.

Upper gastrointestinal bleeding (UGIB) is associated with substantial morbidity, mortality, and intensive care unit (ICU) utilization. Initial risk stratification and disposition from the Emergency Department (ED) can prove challenging due to limited data points during a short period of observation. An ED-based ICU (ED-ICU) may allow more rapid delivery of ICU-level care, though its impact on patients with UGIB is unknown.A retrospective observational study was conducted at a tertiary U.S. academic medical center. An ED-ICU (the Emergency Critical Care Center [EC3]) opened in February 2015. Patients presenting to the ED with UGIB undergoing esophagogastroduodenoscopy within 72 h were identified and analyzed. The Pre- and Post-EC3 cohorts included patients from 9/2/2012-2/15/2015 and 2/16/2015-6/30/2019.We identified 3788 ED visits; 1033 Pre-EC3 and 2755 Post-EC3. Of Pre-EC3 visits, 200 were critically ill and admitted to ICU [Cohort A]. Of Post-EC3 visits, 682 were critically ill and managed in EC3 [Cohort B], whereas 61 were critically ill and admitted directly to ICU without care in EC3 [Cohort C]. The mean interval from ED presentation to ICU level care was shorter in Cohort B than A or C (3.8 vs 6.3 vs 7.7 h, p0.05). More patients in Cohort B received ICU level care within six hours of ED arrival (85.3 vs 52.0 vs 57.4%, p0.05). Mean hospital length of stay (LOS) was shorter in Cohort B than A or C (6.2 vs 7.3 vs 10.0 days, p0.05). In the Post-EC3 cohort, fewer patients were admitted to an ICU (9.3 vs 19.4%, p0.001). The rate of floor admission with transfer to ICU within 24 h was similar. No differences in absolute or risk-adjusted mortality were observed.For critically ill ED patients with UGIB, implementation of an ED-ICU was associated with reductions in rate of ICU admission and hospital LOS, with no differences in safety outcomes.

Objective To measure the risk of influenza under-vaccination in children of vaccine-hesitant parents, referent to children of nonhesitant parents, in a sample of disadvantaged families in one influenza season. Study Design A prospective observational cohort study of English- and Spanish-speaking parents of 2-year-olds presenting at random for well, sick, or specialty visit care from August 1, 2019 to February 28, 2020. Parents answered demographic questions and the Parent Attitudes about Childhood Vaccines survey. We followed children until season's end, extracting vaccination data on April 30, 2020. We dichotomized vaccination status as unvaccinated or partially/fully vaccinated, analyzing data with multivariable Poisson regression; in secondary analyses, we conducted adjusted time-to-event analyses. Results Overall, 263 parents consented (response rate: 90%); our final sample included 255 dyads. Thirty-three (13%) parents were vaccine hesitant. In adjusted analyses, children of hesitant parents (n = 33) had a 195% increased risk (adjusted Risk Ratio 2.95; 95% confidence interval 1.91, 4.56) of being unvaccinated at season's end, referent to children of nonhesitant parents (n = 222). In time-to-event analyses, children of vaccine-hesitant parents were also more likely to be unvaccinated before influenza activity peaked (P = .02). Conclusions Parental vaccine hesitancy tripled the risk of pediatric influenza nonvaccination in a sample of poor and minority families during the 2019 to 2020 influenza season. As parental vaccine hesitancy appears to exacerbate pediatric influenza vaccination disparities, future work should explore parental hesitancy with poor and minority stakeholders and tailor evidence-based interventions to benefit children from these communities who receive care at all practice sites.

Hypotension has a powerful effect on patient outcome after traumatic brain injury (TBI). The relative impact of hypotension occurring in the field versus during early hospital resuscitation is unknown. We evaluated the association between hypotension and mortality and non-mortality outcomes in four cohorts defined by where the hypotension occurred [neither prehospital nor hospital, prehospital only, hospital only, both prehospital and hospital].Subjects ≥10 years with major TBI were included. Standard statistics were used for unadjusted analyses. We used logistic regression, controlling for significant confounders, to determine the adjusted odds (aOR) for outcomes in each of the three cohorts.Included were 12,582 subjects (69.8% male; median age 44 (IQR 26-61). Mortality by hypotension status: No hypotension: 9.2% (95%CI: 8.7-9.8%); EMS hypotension only: 27.8% (24.6-31.2%); hospital hypotension only: 45.6% (39.1-52.1%); combined EMS/hospital hypotension 57.6% (50.0-65.0%); (p0.0001). The aOR for death reflected the same progression: 1.0 (reference-no hypotension), 1.8 (1.39-2.33), 2.61 (1.73-3.94), and 4.36 (2.78-6.84), respectively. The proportion of subjects having hospital hypotension was 19.0% (16.5-21.7%) in those with EMS hypotension compared to 2.0% (1.8-2.3%) for those without (p0.0001). Additionally, the proportion of patients with TC hypotension was increased even with EMS "near hypotension" up to an SBP of 120 mmHg [(aOR 3.78 (2.97, 4.82)].While patients with hypotension in the field or on arrival at the trauma center had markedly increased risk of death compared to those with no hypotension, those with prehospital hypotension that was not resolved before hospital arrival had, by far, the highest odds of death. Furthermore, TBI patients who had prehospital hypotension were five times more likely to arrive hypotensive at the trauma center than those who did not. Finally, even "near-hypotension" in the field was strongly and independently associated the risk of a hypotensive hospital arrival (90 mmHg). These findings are supportive of the prehospital guidelines that recommend aggressive prevention and treatment of hypotension in major TBI.

Fisheries are highly complex social-ecological systems that often face 'wicked' problems from unsustainable resource management to climate change. Addressing these challenges requires transdisciplinary approaches that integrate perspectives across scientific disciplines and knowledge systems. Despite widespread calls for transdisciplinary fisheries research (TFR), there are still limitations in personal and institutional capacity to conduct and support this work to the highest potential. The viewpoints of early career researchers (ECRs) in this field can illuminate challenges and promote systemic change within fisheries research. This paper presents the perspectives of ECRs from across the globe, gathered through a virtual workshop held during the 2021 World Fisheries Congress, on goals, challenges, and future potential for TFR. Big picture goals for TFR were guided by principles of co-production and included (i) integrating transdisciplinary thinking at all stages of the research process, (ii) ensuring that research is inclusive and equitable, (iii) co-creating knowledge that is credible, relevant, actionable, and impactful, and (iv) consistently communicating with partners. Institutional inertia, lack of recognition of the extra time and labour required for TFR, and lack of skill development opportunities were identified as three key barriers in conducting TFR. Several critical actions were identified to help ECRs, established researchers, and institutions reach these goals. We encourage ECRs to form peer-mentorship networks to guide each other along the way. We suggest that established researchers ensure consistent mentorship while also giving space to ECR voices. Actions for institutions include retooling education programs, developing and implementing new metrics of impact, and critically examining individualism and privilege in academia. We suggest that the opportunities and actions identified here, if widely embraced now, can enable research that addresses complex challenges facing fishery systems contributing to a healthier future for fish and humans alike.

Background: Locoregionally advanced esophageal cancer is typically treated with neoadjuvant chemoradiation followed by surgery 4 to 8 weeks later. Occasionally surgery is delayed >12 weeks; outcomes of this approach are not well studied. We hypothesized that delayed esophagectomy after chemoradiation would have inferior long-term overall survival relative to planned trimodality esophagectomy. Methods: Adult patients with locally advanced esophageal cancer (T2−4aN0M0, T0−4aN+M0) who received multi-agent chemotherapy, radiation, and esophagectomy were identified in the 2018 National Cancer Database. Esophagectomy performed within 90 days from end of chemoradiation were categorized as “trimodality” and those ≥90 days were categorized as “delayed.” Primary outcome was overall survival measured using Kaplan-Meier estimates and Cox proportional hazard models. Secondary outcomes included surgical margin status, hospital length of stay, and readmission. Results: Included were 19 698 patients, 3905 (19.8%) “delayed.” Median time to surgery for trimodality patients was 51 days (IQR 41-63) versus 110 days (IQR 98-131) for delayed patients. Delayed patients tended to be older, non-white, have non-private insurance, and have more comorbidities. Overall survival was shorter for delayed patients (34.8 months) versus trimodality patients (43.1 months, P ≤ .001). In multivariable analysis, delay was associated with inferior overall survival (HR 1.15, 95% CI 1.08-1.23). Length of stay and readmission rate were similar between cohorts, but delay was associated with a higher rate of positive surgical margins (6.7% vs 4.6%, P ≤ .001). Conclusions: In the National Cancer Database, delayed esophagectomy is associated with inferior long-term survival. Nonetheless, delayed esophagectomy may be appropriate for select patients; further research is needed to identify the optimal approach.

Rheumatic heart disease (RHD) in young people presents a complex management problem. In Australia a significant proportion of those affected are Aboriginal and Torres Strait Islanders. Transcatheter mitral valve-in-valve (TMViV) replacement has emerged as an alternative to redo surgery in high-risk patients with degenerated mitral bioprostheses. The aim of this study is to review outcomes of TMViV replacement in young patients with RHD.A single-centre, retrospective review of prospectively collected data on patients undergoing TMViV from December 2017 to June 2021. Primary outcome was major adverse cardiovascular events. Secondary outcome was post-operative trans-thoracic echocardiogram (TTE) results.There were seven patients with a mean age of 33 years and predominantly female (n = 5). Pre-operative comorbidities included diabetes (29%), chronic obstructive pulmonary disease (43%), left ventricular dysfunction (43%) and current smoking status (80%). Post-operative median length of hospital stay was 4 days with no post-operative renal failure, stroke, return to theatre, valve embolization or in hospital mortality. Post-operative TTE showed either nil or trivial central mitral regurgitation, no paravalvular leak and a median gradient of 5 mmHg (IQR 4.5, 7) across the new bioprosthesis; sustained at median follow-up of 22 months.Current literature of TMViV replacement is focused on an older population with concurrent comorbidities. This study provides a unique insight into TMViV replacement in a young cohort of patients with complex social and geographical factors which sometimes prohibits the use of a mechanical valve. The prevalence of RHD remains high for Aboriginal and Torres Strait Islanders, planning for future repeat valve operations should be considered from the outset. We consider TMViV as a part of a staged procedural journey for young patients with RHD.

The southern branch of the Elizabeth River near Portsmouth, Virginia, USA, is one of the most creosote-polluted subestuaries in North America and the former location of the Atlantic Wood US Environmental Protection Agency Superfund site. We previously demonstrated that adult Atlantic Wood killifish collected in situ had severe hepatic lesions, including hepatoblastoma and hepatocellular carcinoma, as well as suppressed circulating antibody responses compared to a historical reference site. Moreover, several innate immune functions were higher in Atlantic Wood fish, including elevated expression of hepatic cyclooxygenase-2 (COX-2), suggesting a proinflammatory environment. To further examine the potential of Atlantic Wood contaminants to modulate innate immune function(s), the present study used RAW264.7 mouse macrophages as an in vitro model to develop new approach methodologies for rapid screening. Lipopolysaccharide (LPS)-stimulated nitric oxide secretion by macrophages is a rapid, sensitive, and predictive in vitro system for screening potentially immunotoxic contaminants as single compounds or as complex mixtures. Compared to the reference site, filter-sterilized Atlantic Wood sediment extracts (water accommodated fractions) induced nitric oxide and IL-6 secretion as well as inducible nitric oxide synthase and COX-2 proteins at levels comparable to or higher than those induced by LPS treatments alone. Extracts also increased phagocytic activity by macrophages. Using a limulus lysate assay, we show that bacterial endotoxin levels in Atlantic Wood extracts are higher than in reference extracts and that polymyxin-B chelation ameliorates proinflammatory effects. These findings illuminate the reality of sediment constituents other than toxic compounds previously associated with developmental abnormalities and carcinogenesis in killifish from the Atlantic Wood site. Perhaps these data also suggest the presence of contaminant-adapted consortia of sediment microbes at many heavily polluted sites worldwide compared to less contaminated sites. Environ Toxicol Chem 2021;40:1576-1585. © 2021 SETAC.

BackgroundSurgical stabilization of rib fractures (SSRF) is performed on only a small subset of patients who meet guideline-recommended indications for surgery. Although previous studies show that provider specialization was associated with SSRF procedural competency, little is known about the impact of provider specialization on SSRF performance frequency. We hypothesize that provider specialization would impact performance of SSRF.MethodsThe Premier Hospital Database was used to identify adult patients with rib fractures from 2015 and 2019. The outcome of interest was performance of SSRF, defined using International Classification of Diseases—10th Revision Procedure Coding System coding. Patients were categorized as receiving their procedures from a thoracic, general surgeon, or orthopedic surgeon. Patients with missing or other provider types were excluded. Multivariate modeling was performed to evaluate the effect of surgical specialization on outcomes of SSRF. Given a priori assumptions that trauma centers may have different practice patterns, a subgroup analysis was performed excluding patients with ‘trauma center’ admissions.ResultsAmong 39 733 patients admitted with rib fractures, 2865 (7.2%) received SSRF. Trauma center admission represented a minority (1034, 36%) of SSRF procedures relative to other admission types (1831, 64%, p=0.15). In a multivariable analysis, thoracic (OR 6.94, 95% CI 5.94–8.11) and orthopedic provider (OR 2.60, 95% CI 2.16–3.14) types were significantly more likely to perform SSRF. In further analyses of trauma center admissions versus non-trauma center admissions, this pattern of SSRF performance was found at non-trauma centers.ConclusionThe majority of SSRF procedures in the USA are being performed by general surgeons and at non-trauma centers. ‘Subspecialty’ providers in orthopedics and thoracic surgery are performing fewer total SSRF interventions, but are more likely to perform SSRF, especially at non-trauma centers. Provider specialization as a barrier to SSRF may be related to competence in the SSRF procedures and requires further study.TypeTherapeutic/care management.Level of evidenceIV

Cd3As2 provides an excellent platform for studying the physics of three-dimensional Dirac semimetals due to its stability as well as its compatibility with thin film growth. Crystals made using both bulk and thin film synthesis are unintentionally doped n-type, and other than introducing Zn to reduce the carrier concentration, no efforts have been reported to alter this intrinsic doping without major changes to the band structure. Here, group VI elements Te and Se are introduced during epitaxy to increase the electron concentration of the films. Starting from an unintentionally doped electron concentration of 1–2 × 1017 cm−3, concentrations of up to 3 × 1018 cm−3 are achieved. Analysis of Shubnikov–de Haas oscillations reveals good agreement in calculated effective mass and Fermi velocity of highly doped films with unintentionally doped single crystals with similar electron concentrations. The density functional theory is also performed to study the effects of group VI substitutions and confirms no strong perturbations in the electronic structure. This work ultimately demonstrates tunability in the carrier concentration using extrinsic dopants without substantial changes in the band structure, allowing for intentional design of Fermi-level position for device applications.

Introduction We sought to (i) adapt a Spanish-language vaccine hesitancy (VH) tool to rural Guatemala, (ii) pilot the tool with 150 parents of children ≤ 5 years, and (iii) measure if parent scores associated with child under-vaccination. Methods We used implementation science to develop the adapted Guatemalan Vaccine Attitudes (GuaVA) tool, piloting it with 150 parents of children ≤ 5 years, and performing descriptive and adjusted regression analyses. Results Of 150 parents (response rate 99%), 55% (n = 83) of parents expressed a degree of VH. Children of parents with highly hesitant scores (n = 22) had 2.5 times the odds (OR 2.5; 95% CI: 1.2, 5.4) of being undervaccinated at 19 months, referent children of non-hesitant parents (n = 67). Conclusions Vaccine hesitancy may be more prevalent in rural Guatemala than suspected. Implementation science facilitated the adaptation of a VH tool to rural Guatemala and may assist investigators in other settings.

Background Video capsule endoscopy (VCE), approved by the U.S. Food and Drug Administration (FDA) in 2001, represented a disruptive technology that transformed evaluation of the small intestine. Adoption of this technology over time and current use within the U.S. clinical population has not been well described. Methods To assess the growth of capsule endoscopy within the U.S. Medicare provider population (absolute growth and on a population-adjusted basis), characterize the providers performing VCE, and describe potential regional differences in use. Medicare summary data from 2003 to 2019 were used to retrospectively analyze capsule endoscopy use in a multiple cross-sectional design. In addition, detailed provider summary files were used from 2012 to 2018 to characterize provider demographics. Results VCE use grew rapidly from 2003 to 2008 followed by a plateau from 2008 to 2019. There was significant variation in use of VCE between states, with up to 10-fold variation between states (14.6 to 156.1 per 100,000 enrollees in 2018). During this time, the adjusted VCE use on a population-adjusted basis declined, reflecting saturation of growth. Conclusions Growth of VCE use over time follows an S-shaped diffusion of innovation curve demonstrating a successful diffusion of innovation within gastroenterology. The lack of additional growth since 2008 suggests that current levels of use are well matched to overall population need within the constraints of reimbursement. Future studies should examine whether this lack of growth has implications for access and healthcare inequities.

Microrubber (MR) encompasses all tire-related particles in the micro-scale and has recently drawn increased attention as a subclass of the broader group of microplastics. While tire particles entered the environment since the introduction of rubber tires for vehicles, the concern regarding tire wear particles (TWP) as an environmental contaminant is relatively new. Recent studies have examined physical and chemical toxicity of MR particles and leachates to a variety of organisms. However, there is a lack of information on the long-term effects of tire particle exposure under environmentally realistic conditions. The current study examined the chronic toxicity of crumb rubber (CR) particles to the estuarine fish species, mummichog (Fundulus heteroclitus) under episodic exposures at environmentally relevant concentrations. Immunohistochemistry (IHC) of fish gill, intestine, and liver was performed to assess CYP1A induction in these organs. Bile fluorescence was measured as an indicator of exposure to polycyclic aromatic hydrocarbons (PAHs) from CR. DNA damage was measured through the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) together with other oxidative stress measures as lipid peroxidation (TBARS assay), free glutathione (GSH), and oxidized glutathione (GSSG) concentrations. Upregulation of CYP1A in gill, intestine, and liver was observed especially in gill filaments and general vasculature. Increased bile fluorescence demonstrated exposure to aromatic compounds, especially pyrene-like PAHs. Data for DNA damage indicated greater plasma 8-OHdG concentrations as a result of increased DNA repair. There was a decrease in malondialdehyde (MDA) production and an increase in total GSH at higher concentrations of CR. It appeared that under long-term repeated dosing, antioxidant systems in mummichog were upregulated to deal with exogenous stressors released by the CR particles. Combined, these data demonstrate that fish exposed to tire crumb rubber particles illicit significant biomarker responses under environmentally relevant CR concentrations, but induced antioxidant and detoxification pathways may prevent mortality and serious physiological effects in F. heteroclitus when exposed to environmentally relevant concentrations of CR.

Physical activity (PA) counseling is under-utilized in primary care for patients with type 2 diabetes mellitus (T2D), despite improving important health outcomes, including physical function. We adapted evidence-based PA counseling programs to primary care patients, staff, and leader's needs, resulting in "Be ACTIVE" comprised of shared PA tracker data (FitBit©), six theory-informed PA coaching calls, and three in-person clinician visits. In a pilot randomized pragmatic trial, we evaluated the feasibility, acceptability, and effectiveness of Be ACTIVE. Sedentary patients with T2D were randomized to Be ACTIVE versus an enhanced control condition. Mixed methods assessments of feasibility and acceptability included costs. Objective pilot effectiveness outcomes included PA (primary outcome, accelerometer steps/week), the Short Physical Performance Battery (SPPB) physical function measure, and behavioral PA predictors. Fifty patients were randomized to Be ACTIVE or control condition. Acceptability was90% for patients and clinic staff. Coaching and PA tracking costs of ~$90/patient met Medicare reimbursement criteria. Pre-post PA increased by ~11% (Be ACTIVE) and ~6% in controls (group difference: 1574 ± 4391 steps/week, p = .72). As compared to controls, Be ACTIVE participants significantly improved SPPB (0.9 ± 0.3 vs. -0.1 ± 0.3, p = .01, changes0.5 points prevent falls clinically), and PA predictors of self-efficacy (p = .02) and social-environmental support (p.01). In this pilot trial, Be ACTIVE was feasible and highly acceptable to stakeholders and yielded significant improvements in objective physical function consistent with lower fall risk, whereas PA changes were less than anticipated. Be ACTIVE may need additional adaptation or a longer duration to improve PA outcomes.We report results from a pragmatic and behavioral theory-based physical activity (PA) coaching program, termed “Be ACTIVE,” for patients with type 2 diabetes that was designed to improve PA and function for patients and to be reimbursable and feasible for primary care teams. As compared to those who did not receive coaching, patients who received Be ACTIVE had physical function improvements that lowered their risk of falls. Be ACTIVE was delivered with fidelity and was highly acceptable to the key primary care stakeholders of patients, clinic staff coaches, and clinicians. Patients particularly liked the focus on setting goals to do enjoyable activities, the accountability of wearing a PA monitor, and the support of their coach. Clinical care professionals felt that their role of encouraging behavior change (coach) and safety monitoring (clinician) aligned well with their clinical expertise, and was professionally rewarding. Coaches felt the program helped them guide many patients to overcome preexisting negative perceptions of PA and develop intrinsic motivations to be active. The costs of clinic coach time and PA tracker rental needed to deliver the 12-week program could be reimbursed by the Medicare Chronic Disease Management programs, albeit with a patient co-payment required.

An inverse analysis procedure has been developed to interpret collected pore pressure data and observations during backward erosion piping (BEP) initiation and progression in sandy soils. The procedure has been applied to laboratory models designed to mimic the initiation and progression of BEP through a constricted vertical outlet. The inverse analysis uses three-dimensional (3D) finite element method (FEM) to successively produce models of the hydraulic head regime surrounding progressive stages of BEP based on observations at the sample surface and pore pressure measurements obtained from the laboratory models. The inverse analysis results in a series of 3D contour plots that represent the hydraulic-head regime at each stage of the BEP development, allowing for assessing the development of BEP mechanism as well as calculating the critical hydraulic conditions required for various BEP stages to initiate and progress. Interpretation of the results identified four significant stages of the piping process: (1) loosened zone initiation, (2) channel initiation and progression, (3) riser sand fluidization, and (4) loosened zone progression. Interpretation of the hydraulic head contour plots allows assessment of the critical hydraulic gradients needed to initiate and progress various components of the BEP development.

Traumatic brain injury (TBI) can induce acute lung injury (ALI). The exact pathomechanism of TBI-induced ALI is poorly understood, limiting treatment options. Remote ischemic conditioning (RIC) can mitigate detrimental outcomes following transplants, cardiac arrests, and neurological injuries. In this study, we hypothesized that RIC would reduce TBI-induced ALI by regulating the sphingosine-1-phosphate (S1P)-dependent pathway, a central regulator of endothelial barrier integrity, lymphocyte, and myokine trafficking. Male mice were subjected to either diffuse TBI by midline fluid percussion or control sham injury and randomly assigned among four groups: sham, TBI, sham RIC, or TBI RIC; RIC was performed 1 h prior to TBI. Mice were euthanized at 1-h postinjury or 7 days post-injury (DPI) and lung tissue, bronchoalveolar lavage (BAL) fluid, and blood were collected. Lung tissue was analyzed for histopathology, irisin myokine levels, and S1P receptor levels. BAL fluid and blood were analyzed for cellularity and myokine/S1P levels, respectively. One-hour postinjury, TBI damaged lung alveoli and increased neutrophil infiltration; RIC preserved alveoli. BAL from TBI mice had more neutrophils and higher neutrophil/monocyte ratios compared with sham, where TBI RIC mice showed no injury-induced change. Further, S1P receptor 3 and irisin-associated protein levels were significantly increased in the lungs of TBI mice compared with sham, which was prevented by RIC. However, there was no RIC-associated change in plasma irisin or S1P. At 7 DPI, ALI in TBI mice was largely resolved, with evidence for residual lung pathology. Thus, RIC may be a viable intervention for TBI-induced ALI to preserve lung function and facilitate clinical management.

Background While many clinicians encounter parents or adolescents who refuse HPV vaccine, little is known about the prevalence of hesitancy for HPV vaccine nationally or its association with vaccination. Methods In April 2019, we surveyed families with adolescents 11–17 years using a national online panel (Knowledge Panel®) as the sampling frame. We assessed the prevalence of HPV vaccine hesitancy with the validated 9-item Vaccine Hesitancy Scale (VHS). We used multivariate analyses to assess demographic factors associated with HPV vaccine hesitancy. We also assessed practical barriers to receipt of HPV vaccine and the relationship between barriers and hesitancy. Finally, we evaluated the association between both HPV vaccine hesitancy and practical barriers on HPV vaccine receipt or refusal. Results 2,177 parents out of 4,185 sampled (52%) completed the survey, 2,020 qualified (lived with adolescent). Using a VHS cut-off score > 3 out of 5 points, 23% of US parents were hesitant about HPV vaccine. Hesitancy was lower among those with Hispanic ethnicity. At least one out of five parents disagreed that the HPV vaccine is beneficial for their adolescent, that the vaccine is effective, protects against HPV-related cancers, or that they followed their adolescent’s health-care provider’s recommendation about the vaccine. Many were concerned about vaccine side effects and the novelty of the vaccine. Adolescents living with vaccine-hesitant parents were less than one-third as likely to have received the vaccine (RR = 0.29, 95% CI 0.24, 0.35) or completed the vaccine series (RR = 0.29, 95% CI 0.23, 0.36), and were 6-fold more likely to have refused the vaccine because of parental vaccine-related concerns (RR = 6.09, 95% CI = 5.26, 7.04). Most practical barriers were independently associated with vaccine receipt but not with vaccine refusal. Conclusions HPV vaccine hesitancy is common nationally and strongly related to both under-vaccination and vaccine refusal.