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Objective To develop and validate algorithms for predicting 30-day fatal and nonfatal opioid-related overdose using statewide data sources including prescription drug monitoring program data, Hospital Discharge Data System data, and Tennessee (TN) vital records. Current overdose prevention efforts in TN rely on descriptive and retrospective analyses without prognostication. Materials and Methods Study data included 3 041 668 TN patients with 71 479 191 controlled substance prescriptions from 2012 to 2017. Statewide data and socioeconomic indicators were used to train, ensemble, and calibrate 10 nonparametric “weak learner” models. Validation was performed using area under the receiver operating curve (AUROC), area under the precision recall curve, risk concentration, and Spiegelhalter z-test statistic. Results Within 30 days, 2574 fatal overdoses occurred after 4912 prescriptions (0.0069%) and 8455 nonfatal overdoses occurred after 19 460 prescriptions (0.027%). Discrimination and calibration improved after ensembling (AUROC: 0.79–0.83; Spiegelhalter P value: 0–.12). Risk concentration captured 47–52% of cases in the top quantiles of predicted probabilities. Discussion Partitioning and ensembling enabled all study data to be used given computational limits and helped mediate case imbalance. Predicting risk at the prescription level can aggregate risk to the patient, provider, pharmacy, county, and regional levels. Implementing these models into Tennessee Department of Health systems might enable more granular risk quantification. Prospective validation with more recent data is needed. Conclusion Predicting opioid-related overdose risk at statewide scales remains difficult and models like these, which required a partnership between an academic institution and state health agency to develop, may complement traditional epidemiological methods of risk identification and inform public health decisions.

This article overviews the prairie and tree planting tool or PT2 (1.0), an online GIS-based decision support tool for landowners interested in exploring opportunities to plant prairie or trees in and around their farm fields for conservation or production purposes. PT2 1.0 can be found online at: https://pt2.nrem.iastate.edu/. With the PT2 (1.0) users locate farm fields of interest in an online aerial photograph and mapping geographic information system (GIS). Users explore areas they are considering for prairie or tree cover by examining different data layers: soil maps, 2-foot contour topography maps, LiDAR hillshade maps, and a map of current land values based on estimated land rent. Users then utilize scaled dimensional drawing tools to measure and delineate areas of interest for planting trees and or prairie. Once an area is delineated, users select from drop-down menus prairie seed mixes or woody species that are suitable for the soils present, and users can select basic long-term management options. PT2 (1.0) estimates total annualized costs for tree or prairie establishment, long-term management, and opportunity costs (based on area weighted expected soil rent), and factors in the potential benefit of utilizing government cost-share programming, e.g., Environmental Quality Incentive Program or the Conservation Reserve Program. Key data layers are currently functional in Iowa, likewise the financial data underlying the cost analysis are specific to Iowa. PT2 (1.0) is, however, open source and open code and guidance is provided regarding how to access and adapt the data for use in other states. Supplementary Information The online version contains supplementary material available at 10.1007/s10457-021-00686-8.

Objectives To investigate the effect of ACE inhibitors (ACEi) on the incidence of scleroderma renal crisis (SRC) when given prior to SRC in the prospectively collected cohort from the European Scleroderma Trial and Research Group (EUSTAR). Methods SSc patients without prior SRC and at least one follow-up visit were included and analyzed regarding SRC, arterial hypertension, and medication focusing on antihypertensive medication and glucocorticoids (GC). Results Out of 14,524 patients in the database, we identified 7648 patients with at least one follow-up. In 27,450 person-years (py), 102 patients developed SRC representing an incidence of 3.72 (3.06–4.51) per 1000 py. In a multivariable time-to-event analysis adjusted for age, sex, disease severity, and onset, 88 of 6521 patients developed SRC. The use of ACEi displayed an increased risk for the development of SRC with a hazard ratio (HR) of 2.55 (95% confidence interval (CI) 1.65–3.95). Adjusting for arterial hypertension resulted in a HR of 2.04 (95%CI 1.29–3.24). There was no evidence for an interaction of ACEi and arterial hypertension (HR 0.83, 95%CI 0.32–2.13, p = 0.69). Calcium channel blockers (CCB), angiotensin receptor blockers (ARB), endothelin receptor antagonists, and GC—mostly in daily dosages below 15 mg of prednisolone—did not influence the hazard for SRC. Conclusions ACEi in SSc patients with concomitant arterial hypertension display an independent risk factor for the development of SRC but are still first choice in SRC treatment. ARBs might be a safe alternative, yet the overall safety of alternative antihypertensive drugs in SSc patients needs to be further studied.

Background The development of specialized panoramic radiograph machine software has spawned the introduction of an innovative and promising dental radiographic examination type: extraoral bite-wings. But does this unconventional type of imaging belong in the bite-wing family? Is there any relationship at all to the conventional bite-wing radiograph? Objectives The purpose of this article is not to make a case for the diagnostic effectiveness of one system over the other; this is best left to further clinical evaluation. Instead, the authors intend to provide an outline of a few key and distinguishing elements of the intraoral bite-wing radiographic examination followed by those of the extraoral panoramic substitute and draw attention to the importance of reimagining the increasingly universal naming convention of this novel radiographic examination, the paradoxical “extraoral bite-wing radiograph”, based on the fundamental principles of each of these imaging systems. Practical Implications The accuracy of clinical and technical terminology in oral radiography is of paramount importance to both the profession and patients, especially when considering emerging technologies.

BackgroundIn October 2015, discharge data coding in the USA shifted to the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM), necessitating new indicator definitions for drug overdose morbidity. Amid the drug overdose crisis, characterising discharge records that have ICD-10-CM drug overdose codes can inform the development of standardised drug overdose morbidity indicator definitions for epidemiological surveillance.MethodsEight states submitted aggregated data involving hospital and emergency department (ED) discharge records with ICD-10-CM codes starting with T36–T50, for visits occurring from October 2015 to December 2016. Frequencies were calculated for (1) the position within the diagnosis billing fields where the drug overdose code occurred; (2) primary diagnosis code grouped by ICD-10-CM chapter; (3) encounter types; and (4) intents, underdosing and adverse effects.ResultsAmong all records with a drug overdose code, the primary diagnosis field captured 70.6% of hospitalisations (median=69.5%, range=66.2%–76.8%) and 79.9% of ED visits (median=80.7%; range=69.8%–88.0%) on average across participating states. The most frequent primary diagnosis chapters included injury and mental disorder chapters. Among visits with codes for drug overdose initial encounters, subsequent encounters and sequelae, on average 94.6% of hospitalisation records (median=98.3%; range=68.8%–98.8%) and 95.5% of ED records (median=99.5%; range=79.2%–99.8%), represented initial encounters. Among records with drug overdose of any intent, adverse effect and underdosing codes, adverse effects comprised an average of 74.9% of hospitalisation records (median=76.3%; range=57.6%–81.1%) and 50.8% of ED records (median=48.9%; range=42.3%–66.8%), while unintentional intent comprised an average of 11.1% of hospitalisation records (median=11.0%; range=8.3%–14.5%) and 28.2% of ED records (median=25.6%; range=20.8%–40.7%).ConclusionResults highlight considerations for adapting and standardising drug overdose indicator definitions in ICD-10-CM.

Background Armed conflict between the militant Islamist group Boko Haram, other insurgents, and the Nigerian military has principally affected three states of northeastern Nigeria (Borno, Adamawa, Yobe) since 2002. An intensification of the conflict in 2009 brought the situation to increased international visibility. However, full-scale humanitarian intervention did not occur until 2016. Even prior to this period of armed conflict, reproductive, maternal, neonatal, and child health indicators were extremely low in the region. The presence of local and international humanitarian actors, in the form of United Nations agencies and non-governmental organizations, working in concert with concerned federal, state, and local entities of the Government of Nigeria, were able to prioritize and devise strategies for the delivery of health services that resulted in marked improvement of health status in the subset of the population in which this could be measured. Prospects for the future remain uncertain. Methods Interviews were conducted with more than 60 respondents from government, United Nations agencies, and national and international non-governmental organizations. Quantitative data on intervention coverage indicators from publicly available national surveys (Demographic and Health Surveys (DHS), Multiple Indicator Cluster Surveys (MICS)), National Nutrition and Health Surveys (NNHS)) were descriptively analyzed. Results Overall, indicators of low reproductive, maternal, neonatal, and child health (RMNCH) status and intervention coverage were found in the pre-intervention period (prior to 2016) and important improvements were noted following the arrival of international humanitarian assistance, even while armed conflict and adverse conditions persisted. Security issues, workforce limitations, and inadequate financing were frequently cited obstacles. Conclusion It is assumed that armed conflict would have a negative impact on the health status of the affected population, but pre-conflict indicators can be so depressed that this effect is difficult to measure. When this is the case, health sector intervention by the international community can often result in marked improvements in the accessible population. What might happen upon the departure of the humanitarian organizations cannot be predicted with an appreciable degree of certainty.

Background Total shoulder arthroplasty is an accepted treatment for glenohumeral osteoarthritis. The Arthrex Eclipse shoulder prosthesis is a stemless, canal-sparing humeral prosthesis with bone ingrowth capacity on the trunnion, as well as through the fenestrated hollow screw, that provides both diaphyseal and metaphyseal load sharing and fixation. Methods Between 2013 and 2018, 16 sites in the United States enrolled 327 patients (Eclipse in 237 and Arthrex Univers II in 90). All patients had glenohumeral arthritis refractory to nonsurgical care. Strict exclusion criteria were applied to avoid confounding factors such as severe patient comorbidities, arthritis not consistent with osteoarthritis, and medical or prior surgical treatments that may have affected outcomes. Patients were randomized to the Eclipse or Univers II group via block randomization. Results In total, 149 Eclipse and 76 Univers II patients reached 2-year follow-up (139 Eclipse patients [93.3%] and 68 Univers II patients [89.5%] had complete data). The success rate using the Composite Clinical Success score was 95% in the Eclipse group vs. 89.7% in the Univers II group. No patient exhibited radiographic evidence of substantial humeral radiolucency, humeral migration, or subsidence at any point. Reoperations were performed in 7 patients (3.2%) in the Eclipse group and 3 (3.8%) in the Univers II group. Conclusion The Arthrex Eclipse shoulder prosthesis is a safe and effective humeral implant for patients with glenohumeral arthritis at 2-year follow-up, with no differences in outcomes compared with the Univers II shoulder prosthesis.

BACKGROUND The profitability of farming varies based on factors such as a crop's market value, input costs and occurrence of resistant pests, all capable of altering the value of pest management tactics in an integrated pest management program. We provide a framework for calculating expected yield and expected net revenue of pest management scenarios, using the soybean aphid (Aphis glycines) as a case study. Foliar insecticide and host‐plant resistance are effective management tactics for preventing yield loss from soybean aphid outbreaks; however, pyrethroid‐resistant aphid populations pose a management challenge for farmers. We evaluated eight scenarios relevant to soybean aphid management in Iowa with varying probabilities of aphid outbreaks and insecticide‐resistant aphids occurring. RESULTS Our equation suggests that insecticide use is profitable when the probability of an aphid outbreak is ≥29%, and soybean production will become more costly with increasing probability of pyrethroid‐resistant aphids. If farmers continue to use pyrethroids, they will not experience financial consequences from pyrethroid‐resistant aphids until the chance of insecticide resistance is 48%. Aphid‐resistant varieties provided consistent yield and offered the highest net revenue under all conditions. CONCLUSION This framework can be used for other crop–pest systems to evaluate the profitability of management tactics and investigate how resistance impacts revenue for farmers. Including the cost of resistance in crop budgets can help farmers and agronomic consultants comprehend these impacts and enhance decision‐making to increase revenue and curb resistance development., We developed a framework to evaluate the profitability of management scenarios across varying probabilities of a pest outbreak occurring and probabilities that the pest is resistant to the management tactic.

Objective A Phase 3 randomized multicenter, double-blind, placebo-controlled trial (NCT02720692) compared once-daily intravenous (IV) meloxicam 30 mg to placebo, when added to the standard of care pain management regimens, in adults with moderate-to-severe pain following major elective surgery and concluded that meloxicam IV had a safety profile similar to placebo and reduced opioid consumption. Methods In this post hoc subgroup analysis of orthopedic surgery subjects, 379 subjects received meloxicam IV 30 mg or IV-administered placebo every 24 hrs for ≤7 doses. Safety was assessed via AEs, laboratory tests, vital signs, and ECG, with an emphasis on specific AEs, including injection site reactions, bleeding, cardiovascular, hepatic, renal, thrombotic, and wound healing events. Daily opioid consumption was assessed during treatment. Results Among meloxicam IV-treated subjects, 64.7% experienced ≥1 AE versus 68.8% of placebo-treated subjects. Investigators assessed most AEs to be mild or moderate in intensity and unrelated to treatment. Total opioid consumption (36.8 mg versus 50.3 mg IV morphine equivalent dose; P=0.0081) and opioid consumption during time points 0‒24, 24‒48, 0‒48, and 0‒72 hrs were statistically significantly lower in the meloxicam IV group. Conclusion Meloxicam IV demonstrated no significant differences in the number and frequency of AEs versus placebo in subjects following orthopedic surgery. Opioid consumption was reduced in the meloxicam IV group versus placebo. Trial registration ClinicalTrials.gov (Identifier: NCT02720692).

© 2019 Background: Falls may result in significant patient harm. A recommended strategy to prevent falls is the use of a falls risk assessment tool, but these tools are often specific for older people. Evidence suggests context-specific tools are more effective. Although a rare event in the intensive care unit (ICU), patients in the ICU are at high risk of falling. The primary trigger for the current study was an increase in falls in the study ICU. Aim: The objective of this study was to develop and implement a valid and reliable ICU-specific falls risk assessment tool, with the aim of reducing falls. Methods: Retrospective incident-monitoring database audits were performed. Prospective validity and reliability testing of an ICU-specific tool (Tyndall Bailey Falls Risk Assessment Tool [TB FRAT]) and the existing method for assessing falls risk (ONTARIO Modified Stratify [Sydney Scoring] Falls Risk Screen) was conducted. Seven raters (nurse clinicians) independently performed falls risk assessment using both tools on two occasions for six patients. Results: Correlation for risk stratification categories between the two tools was moderate (r = 0.60, P < .001). Intrarater reliability (correlation) for individual rater's scores was strong (r = 0.86, P < .001). Interrater reliability for the TB FRAT was moderate to excellent (interclass correlations = 0.76 [95% confidence interval: 0.54–0.94]), and internal consistency was excellent (Cronbach's alpha, 0.97). Falls resulting in serious injury reduced from 3.35 per 1000 separations 12 months before implementing the specific ICU tool to 0.85 per 1000 in the 12 months after implementation. Conclusions: The TB FRAT provided a more reliable falls risk assessment than the existing method of assessing falls risk in this single-room occupancy ICU. This TB FRAT could be a valuable addition to quality improvement initiatives aimed at improving patient safety related to falls; however, adaptation to the local context should be considered.

INTRODUCTION Traumatic brain injury (TBI) is a major global health issue, resulting in debilitating consequences to families, communities, and health-care systems. Prior research has found that biomarkers aid in the pathophysiological characterization and diagnosis of TBI. Significantly, the FDA has recently cleared both a bench-top assay and a rapid point-of-care assays of tandem biomarker (UCH-L1/GFAP)-based blood test to aid in the diagnosis mTBI patients. With the global necessity of TBI biomarkers research, several major consortium multicenter observational studies with biosample collection and biomarker analysis have been created in the USA, Europe, and Canada. As each geographical region regulates its data and findings, the International Initiative for Traumatic Brain Injury Research (InTBIR) was formed to facilitate data integration and dissemination across these consortia. AREAS COVERED This paper covers heavily investigated TBI biomarkers and emerging non-protein markers. Finally, we analyze the regulatory pathways for converting promising TBI biomarkers into approved in-vitro diagnostic tests in the United States, European Union, and Canada. EXPERT OPINION TBI biomarker research has significantly advanced in the last decade. The recent approval of an iSTAT point of care test to detect mild TBI has paved the way for future biomarker clearance and appropriate clinical use across the globe.

Winter cover crops are plants used to protect soils during the period between the harvest and establishment of cash crops such as corn and soybeans, effectively providing farm fields with perennial cover. The total cost of cover crops varies considerably from site to site and year to year, yet the single costliest aspect of using cover crops is the cost of seed. Seed cost also tends to be the most volatile component of the cost of cover crop use, subject to complex supply dynamics associated with producing viable seed, storage capacity, and unpredictable regional demand. We conducted a survey of seed dealers who sell cover crop seeds using the state of Indiana as a case study. The majority of the respondents believe that sales for cover crop seeds over the next five years in Indiana will increase. In response to this expected increased demand, seed dealers noted they intend to (in no particular order): increase contracted cover crop seed production and invest in seed handling and storage capacity; increase direct interaction with farmers; become more active with workshops and demonstration field days; and/or create marketing materials that specifically promote the soil health benefits of cover crops. The top three factors seed dealers believed would improve the Indiana cover crop seed market the most were: (1) financial incentives for cover crop use; (2) improved customer knowledge of cover crop management; and tied for (3) reduced seed production costs, and broader support of cover crop usage from commodity groups. The top three topics of publicly funded research most useful to the cover crop industry were: (1) understanding factors that influence farmer cover crop adoption; (2) cover crop impact on field profitability; and (3) understanding long-term soil benefits of cover crops. Seed dealers play a unique role in conservation practices such as cover crops, not just because they are often trusted facilitators of information and guidance, but also because their business actions strongly influence available conservation opportunities, management options, and direct cost to farmers. The respondents to the survey offered their opinions regarding a number of issues that would help their business viability in a sustainable way while promoting farmer adoption of cover crops and their long-term commitment to the practice.

Objectives: To assess ultra-early neuroprognostic significance of GFAP, NF-L, UCH-L1, tau, and S100B concentrations, change trajectory, and combination profile after Out-of-Hospital Cardiac Arrest (OHCA). Methods: Prospective enrollment of 22 OHCA and 10 control patients at an academic tertiary care center between May 1, 2017 and January 28, 2020. Blood was collected within one hour of return of spontaneous circulation (ROSC) (H0), at hours 6 (H6), 12, 18, 24, and daily or until discharge or death. Biomarker concentrations, multifactor score, and trajectory change were assessed and compared to final neurologic status (good vs poor Cerebral Performance Category; CPC 1–2 vs CPC 3–5, respectively). Results: 10 patients had good and 12 had poor neurologic outcomes. Poor outcome patients had higher biomarker concentrations and combined biomarker scores at early time points. The earliest significant difference between good and poor outcome patients’ serum biomarkers were at H12 for GFAP (good median: 425 pg/mL [IQR:370−630] vs poor: 5954[1712–65,055] pg/mL; p

The advent of interconnected devices, sensors, and systems requires increasingly large data transmission rates. Optical communications has met these bandwidth needs due to the large information-carrying capacity of light, although new modulation and multiplexing approaches are required to keep up with increasing demand. To this end, mode-division multiplexing (MDM), in which light propagates in on-chip waveguides with distinct and orthogonal spatial mode shapes, may offer a promising solution. To date, however, most chip-scale MDM devices have relied on (de)multiplexing on-chip of fixed optical modes as opposed to tunable mode conversion. In this Letter we demonstrate a new approach to mode conversion and mode-division multiplexing (MDM) that takes advantage of MEMS-tunable optical phase matching. We show via simulations that the approach enables mode conversion with high purity. Measurements on fabricated devices demonstrate the feasibility of this new MEMS index perturbation and phase matching approach for on-demand and dynamic mode conversion for MDM data/communications links. [2020-0107]

Effectiveness of direct-acting antiviral (DAA) therapies could be influenced by patient characteristics such as comorbid conditions, which could lead to premature treatment discontinuation and/or irregular medical follow-ups. Here, we evaluate loss to follow-up and treatment effectiveness of sofosbuvir/ledipasvir ± ribavirin (SOF/LDV ± RBV), ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (OBV/PTV/r + DSV ± RBV) for hepatitis C virus (HCV) genotype 1 (GT1) and sofosbuvir + ribavirin (SOF + RBV) for genotype 3 (GT3) in British Columbia Canada: The British Columbia Hepatitis Testers Cohort includes data on individuals tested for HCV since 1992, integrated with medical visit, hospitalization and prescription drug data. HCV-positive individuals who initiated DAA regimens, irrespective of treatment completion, for GT1 and GT3 until 31 December, 2017 were included. Factors associated with sustained virological response (SVR) and loss to follow-up were assessed by using multivariable logistic regression models. In total 4477 individuals initiated DAAs. The most common prescribed DAA was SOF/LDV ± RBV with SVR of 95%. The highest SVR of 99.5% was observed among OBV/PTV/r + DSV-treated patients. Overall, 453 (10.1%) individuals were lost to follow-up. Higher loss to follow-up was observed among GT1 patients treated with OBV (17.8%) and GT3 patients (15.7%). The loss to follow-up rate was significantly higher among individuals aged

Background The incidence of positional plagiocephaly has increased significantly over the last two decades, which has caused a service delivery challenge for pediatric neurosurgeons. As a potential solution to the long waitlists for abnormal head shape, a plagiocephaly clinic was established at BC Children's Hospital (BCCH) in Vancouver, Canada. This clinic was supervised by an occupational therapist who had been trained by a neurosurgeon to independently assess and manage patients with a referring diagnosis of positional plagiocephaly. Objectives To determine the efficiency of the BCCH Plagiocephaly Clinic in the management of positional plagiocephaly patients and to investigate the clinic's ability to appropriately identify and refer patients with craniosynostosis to pediatric neurosurgeons for further assessment. Methods A retrospective chart review was conducted to identify patients who were assessed and managed at the BCCH Plagiocephaly Clinic between 2008 and 2014. Data on patient demographics, head shape measurements, and treatment recommendations were collected, and the BC Children's neurosurgical database was cross-referenced to identify craniosynostosis cases missed by the Plagiocephaly Clinic. A descriptive analysis of the clinic's average wait times, severity of the patients' plagiocephaly, and recommended interventions was conducted. In addition, the sensitivity and specificity of the clinic's ability to appropriately refer craniosynostosis patients to pediatric neurosurgery were calculated. Results Of 1752 patients seen in the BC Children's Plagiocephaly Clinic between 2008 and 2014, 66% of patients received counseling about repositioning, 34% were referred for head banding, 19% were referred to physiotherapy for torticollis, and 1.4% were referred to the BC Children's Pediatric Neurosurgery Clinic for suspicion of craniosynostosis. The mean time from referral to first assessment by the Plagiocephaly Clinic was 41 days, and time from referral by the plagiocephaly clinic to diagnosis of craniosynostosis by a pediatric neurosurgeon was 8 days. Pediatric neurosurgeons requested imaging for 6 of the referred patients (25% ). The sensitivity and specificity of the plagiocephaly clinic for referral of craniosynostosis patients to the Pediatric Neurosurgery Clinic were 100 and 99%, respectively. Conclusion The BC Children's Plagiocephaly Clinic is efficient and safe for the initial evaluation and treatment of patients with positional plagiocephaly. The clinic's model decreases wait times, appropriately manages patients with positional plagiocephaly, screens for craniosynostosis with high sensitivity and specificity, and takes pressure off outpatient neurosurgical clinics. This model for assessment of plagiocephaly could be considered in other medical centers.

ObjectiveBystander cardiopulmonary resuscitation (CPR) after out-of-hospital cardiac arrest (OHCA) improves survival and neurological outcomes. Nonetheless, many OHCA patients do not receive bystander CPR during a witnessed arrest. Our aim was to identify potential barriers to bystander CPR.MethodsParticipants at CPR training events conducted in the USA between February and May 2018 answered a 14-question survey prior to training. Respondents were asked about their overall comfort level performing CPR, and about potential concerns specific to performing CPR on a middle-aged female, a geriatric male, and male and female adolescent patients. Open-ended responses were analysed qualitatively by categorising responses into themes.ResultsOf the 677 participants, 582 (86.0%) completed the survey, with 509 (88.1%) between 18 and 29 years of age, 341 (58.6%) without prior CPR training and 556 (96.0%) without prior CPR experience. Across all four scenarios of patients in cardiac arrest, less than 65% of respondents reported that they would be ‘Extremely Likely’ (20.6%–29.1%) or ‘Moderately Likely’ (26.9%–34.8%) to initiate CPR. The leading concerns were ‘causing injury to patient’ for geriatric (n=193, 63.1%), female (n=51, 20.5%) and adolescent (n=148, 50.9%) patients. Lack of appropriate skills was the second leading concern when the victim was a geriatric (n=41, 13.4%) or adolescent (n=68, 23.4%) patient, whereas for female patients, 35 (14.1%) were concerned about exposing the patient or the patient’s breasts interfering with performance of CPR and 15 (6.0%) were concerned about being accused of sexual assault. Significant differences were observed in race, ethnicity and age regarding the likelihood of starting to perform CPR on female and adolescent patients.ConclusionsParticipants at CPR training events have multiple concerns and fears related to performing bystander CPR. Causing additional harm and lack of skills were among the leading reservations reported. These findings should be considered for improved CPR training and public education.

OBJECTIVE: Global and national trends of out-of-hospital cardiac arrest (OHCA) have been examined, however geographic variation and socioeconomic disparities of OHCA outcomes in the community setting are less understood. We developed and tested a replicable, community-oriented assessment strategy aimed to identify spatial variations in OHCA outcomes using socioeconomic, prehospital, and in-hospital factors. METHODS: Emergency medical service records of adult, non-traumatic OHCA within Alachua County, FL (2012-2017) were retrospectively reviewed and matched to corresponding medical records at the University of Florida (UF). Incidence of cardiac arrest was geocoded to census tracts and connected to U.S. census socioeconomic attribute data. Primary outcomes include survival to emergency department (ED), hospital admission, discharge, and discharge to home. Multilevel mixed-effects logistic regression models were developed to assess sub-county geographic variance, probabilities of survival, and prehospital risk factors. Getis-Ord Gi statistic and Moran’s I-test was applied to assess spatial clustering in outcome survival rates. RESULTS: Of the 1562 OHCA cases extracted from EMS records, 1335 (85.5%) were included with 372 (27.9%) transported to study site ED. Predicted probability of survival to ED was 57.0% (95CI: 51.3–62.3%). Of transported cases to study site ED, predicted probabilities of survival was to 41.7% (95CI: 36.1–47.6%) for hospital admission, 16.1% (95CI: 10.7–23.5%) for hospital discharge, and 7.1% (95CI: 3.7–13.3%) for home discharge. Census tracts accounted for significant variability in survival to ED (p

Background High costs of direct-acting antivirals (DAAs) have led health-care insurers to limit access worldwide. Using a natural experiment, we evaluated the impact of removing fibrosis stage restrictions on hepatitis C (HCV) treatment initiation rates among people living with human immunodeficiency virus (HIV), and then examined who was left to be treated. Methods Using data from the Canadian HIV-HCV Coinfection Cohort, we applied a difference-in-differences approach. Changes in treatment initiation rates following the removal of fibrosis stage restrictions were assessed using a negative binomial regression with generalized estimating equations. The policy change was then specifically assessed among people who inject drugs (PWID). We then identified the characteristics of participants who remained to be treated using a modified Poisson regression. Results Between 2010–2018, there were a total of 585 HCV initiations among 1130 eligible participants. After removing fibrosis stage restrictions, DAA initiations increased by 1.8-fold (95% confidence interval [CI] 1.3–2.4) controlling for time-invariant differences and secular trends. Among PWID the impact appeared even stronger, with an adjusted incidence rate ratio of 3.6 (95% CI 1.8–7.4). However, this increased treatment uptake was not sustained. At 1 year following universal access, treatment rates declined to 0.8 (95% CI .5–1.1). Marginalized participants (PWID and those of indigenous ethnicity) and those disengaged from care were more likely to remain HCV RNA positive. Conclusions After the removal of fibrosis restrictions, HCV treatment initiations nearly doubled immediately, but this treatment rate was not sustained. To meet the World Health Organization elimination targets, the minimization of structural barriers and adoption of tailored interventions are needed to engage and treat all vulnerable populations., People coinfected with human immunodeficiency virus and hepatitis C virus were 1.8 times more likely to initiate treatments after fibrosis stage restrictions were removed, after controlling for temporal trends. Marginalized populations and those disengaged from care remain to be treated.

The shortage of nurse scientists in the United States complicates nursing's ability to sustain research-intensive environments, build knowledge for translation, and advance nursing science. More emphasis is needed on the preparation of PhD doctoral students to better equip them for a career of scholarship. Four recent PhD graduates participating in a writing group, examined the influence of social capital on their ability to develop capacity for scholarship. They found that a strong social factor supported their efforts to engage as scholars, be accountable for their writing, and make contributions to the research community. Although the writing group provided a space to practice scholarly writing and increased scholarly productivity, the experience was transformative in building capacity for scholarship. This article includes recommendations for academic leaders to both create and support writing groups within doctoral nursing programs using a social capital framework. Strategies are provided using the three dimensions of social capital: structural, relational, and cognitive. Investing in strategies that build social capital within a community can directly impact the advancement of science by elevating capacity for scholarship.

Evidence from both preclinical and clinical studies suggests aerobic exercise may dampen age-related decline in cognitive performance. Alterations in hypothalamic-pituitary-adrenal (HPA) axis function and reactivity may be a mechanism by which aerobic exercise benefits cognitive performance, and reduces perceived stress. This investigation was completed as an ancillary investigation of the Brain in Motion (BIM) study, a 6-month supervised aerobic exercise intervention. Participants were generally healthy and screened for inclusion/exclusion criteria for the parent study. Thirty-eight participants were recruited (Mean age = 65.0 [SD = 5.1]; 60% female) and the final longitudinal sample was 32 participants. Participants provided a passive drool sample at: waking, 15, 30, and 45 min post-waking to assess the cortisol awakening response (CAR) and 3, 6, 9, and 12 h post-waking to assess daily area under the curve for cortisol. Salivary cortisol was quantified by liquid chromatography coupled to tandem mass spectrometry. The exercise intervention increased CAR but no differences were observed in daily AUC. In addition, larger increases in CAR were positively associated with greater decreases in subjective stress. Thus, aerobic exercise improved the CAR in otherwise healthy, but sedentary older adults and greater improvements in CAR were associated with greater reductions in perceived stress.

The importance of substitution patterns between public transit and carsharing has been discussed in prior literature. This study provides empirical evidence of significant interaction between the two modes. On November 24, 2015 the public transit rail system in Vancouver, Canada experienced a significant service disruption due to an unforeseen mechanical failure. This study exploits this event as a natural experiment and investigates to what extent the city's largest carsharing service was utilized as a substitute. Extensive carsharing vehicle location data are used to examine how the carsharing network responded to the transit service disruption. Empirical results show a dramatic increase in the use of carsharing vehicles during the transit outage, particularly in areas close to affected transit stations. Through regression analysis, the quantity of vehicle trips accommodated by the carsharing system in response to the outage is estimated to be approximately 800. There is clear evidence of extemporaneous substitution between public transit and carsharing, suggesting the two modes act as parts of an integrated network.

Infectious syphilis has increased substantially over the past decade. Targeting limited public health resources toward subpopulations with multiple reinfections may have a large impact in reducing onward transmission within a community.A chart review was conducted for individuals with 4 or more infectious syphilis diagnoses between 2005 and 2014 (the top 1% of all syphilis diagnoses in British Columbia, Canada). We characterized the sociodemographics, partner notification outcomes and social network.Between 2005 and 2014, there were 30 individuals with 4 or more syphilis diagnoses, accounting for 139 diagnoses. All were men who have sex with men and 29 (96%) were human immunodeficiency virus-positive. Of the 139 diagnoses, 65% occurred in the early latent stage of infection, 22% in the secondary stage, and 14% in the primary stage. The median number of sexual partners per diagnosis was 5 (range, 1-50). Among the 838 partners reported, 79% were notifiable, 53% were notified, and 23% were reported to be tested or treated. Sexual network mapping showed that almost half of the members of this group could be linked to one another either directly or indirectly via partners over 10 years. Social network mapping demonstrated high connectivity, with 4 venues associated with almost two thirds of the study population.The connectivity and recurrent diagnoses in this study population suggest potential benefits of targeted interventions to individuals with multiple diagnoses and their partners. Our study highlights the need for enhanced care, increased syphilis testing frequency, and exploring alternative preventative methods among individuals with syphilis rediagnoses to reduce syphilis incidence.

Objective This study compares and contrasts new graduate nurse attributes and perceptions using findings from a 2010 study and a recent analysis of new graduate nurses participating in the same residency program. Background As millennials saturate the healthcare work environment, their unique views and needs will influence the evolution of new graduate nurse residencies. Methods This study used previously reported data on new graduate nurses between 1999 and 2009 and compared it with a secondary analysis of data collected on new graduate nurses between 2011 and 2016. Results This study provides evidence that millennial new graduate nurses' levels of commitment and satisfaction do not moderate turnover intentions in the 1st 2 years of practice as they did in the previous group of new graduate nurses. Conclusions Job embeddedness, a construct that measures the likelihood of whether a person is going to stay, may be a better measurement among new graduate nurses than commitment or satisfaction because millennials, a generation that is predominant in current new graduate nurses, are more engaged than loyal.

PURPOSE Exercise intervention studies for brain health can be difficult to interpret due to heterogeneity in exercise intensity, exercise duration, and in adherence to the exercise intervention. This study aimed to characterize heterogeneity in these components in a cohort of healthy middle-age and older adults who participated in a prescribed 6-month supervised aerobic exercise intervention as part of the Brain in Motion study. METHODS AND RESULTS Group-based multitrajectory analysis (GBMTA) was used to characterize variation in the trajectory of exercise intensity and duration for male and female participants in the first 3 months of the exercise program. The GBMTA for males and females revealed two distinct trajectory subgroups, namely, "high-increasing" (HI) and "low-increasing" (LI). Logistic regression was used to assess the association between the identified latent subgroups and (i) demographic characteristics; (ii) physiological characteristics, including cardiovascular and cerebrovascular function; (iii) genetic characteristics; and (iv) adherence with American College of Sports Medicine guidelines on exercise for older adults. Of the 196 participants, 54.1% met the American College of Sports Medicine aerobic exercise targets for intensity and duration during the intervention. Aerobic fitness (maximal oxygen uptake; odds ratio, 1.27; P < 0.01) was significantly different between these trajectory subgroups in males, and cerebrovascular function (cerebrovascular resistance; odds ratio, 0.14; P < 0.01) was significantly different between these trajectory subgroups in females. CONCLUSION This novel approach to tracking a prespecified exercise program highlights that there are individual and group-specific variations within a prescribed exercise intervention. Characterizing exercise adherence in this way holds promise in developing optimized exercise prescriptions tailored to individual baseline characteristics, and additionally highlighting those participants at greatest risk of not meeting minimum dosage requirements for physiological and/or cognitive health.

We evaluated the effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in treating hepatitis C virus (HCV) genotype 1 and SOF/velpatasvir (SOF/VEL) for all genotypes among people who inject drugs (PWID) and those not injecting drugs and who were on or off opioid agonist therapy (OAT). Study participants comprised a population‐based cohort in British Columbia, Canada. The British Columbia Hepatitis Testers Cohort includes data on individuals tested for HCV from 1990 to 2016 that are integrated with medical visits, hospitalization, and prescription drug data. We classified study participants as off OAT/recent injection drug use (off‐OAT/RIDU), off OAT/past IDU (off‐OAT/PIDU), off OAT/no IDU (off‐OAT/NIDU), on OAT/IDU (on‐OAT/IDU), and on OAT/no IDU (on‐OAT/NIDU). We assessed sustained virologic response (SVR) 10 weeks after HCV treatment among study groups treated with LDV/SOF or SOF/VEL until January 13, 2018. Analysis included 5,283 eligible participants: 390 off‐OAT/RIDU, 598 off‐OAT/PIDU, 3,515 off‐OAT/NIDU, 609 on‐OAT/IDU, and 171 on‐OAT/NIDU. The majority were male patients (64%‐74%) and aged ≥50 years (58%‐85%). The SVRs for off‐OAT/RIDU, off‐OAT/PIDU, off‐OAT/NIDU, on‐OAT/IDU, and on‐OAT/NIDU were 91% (355/390), 95% (570/598), 96% (3,360/3,515), 93% (567/609), and 95% (163/171), respectively. Among those with no SVR, 14 individuals died while on treatment or before SVR assessment, including 4 from illicit drug overdose. In the overall multivariable model, off‐OAT/RIDU, on‐OAT/IDU, male sex, cirrhosis, treatment duration

BackgroundCluster of Differentiation 80 and CD 86 can also be called B7-1 and B7-2 respectively. They are proteins fundamentally expressed on antigen-presenting cells (APCs), including induced dendritic cells (IDCs), langerhans cells, germinal center dendritic cells (GCDCs), activated monocytes, macrophages and B-cells. They are considered to be a possible therapeutic target and biomarker of great significance. However, there are still inconsistent pieces of information and their clinical importance is yet to be established. MethodsHere we investigated CD 80 and 86 as biomarkers by utilizing several large genomic data collections. (The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Quantitative proteomics Cancer cell line Encyclopedia Genotype-Tissue Expression,) and analyzed CD 80 and CD 86 expression in thousands of normal and cancer samples and cell lines along with their clinical survival analysis.ResultsThis study presented that CD 86 was expressed more in post-treatment blood cancer in the blood and post-treatment blood cancer in the bone marrow while it was expressed least in normal tissues and cell lines. The Hodgkin lymphoma cell line L428 cell lysate illustrated that there was a high relative protein expression of 6.6 for the CD 86 gene. it indicated that cancer in the esophagus had the highest copy number value and indicated a medium level amplification of the CD 86 gene and prostate cancer had a hemizygous deletion of the CD 86 gene with the least copy number value. Furthermore, on the non-Hodgkin lymphoma cell line REC1, illustrated the highest relative protein expression of the CD 86 gene among the other types of cancer cell line, its protein expression value was 8.19. Also, for cancer type leukemia, the subtype acute myeloid leukemia showed a significant relative protein expression. The acute myeloid leukemia cell line EOL1 indicated that there was a high relative protein expression of 6.5. However, the protein expression for CD 80 is yet to be elucidated.ConclusionsTaken together, CD 80 ad 86 may be potential biomarkers of great clinical significance. The Kaplan Meier plots unveiled that CD 86 and CD 80 were significantly associated with overall survival analysis in the Large B-cell lymphoma, and the different tumor types.

Germanium-on-silicon (GOS) represents the leading platform for foundry-based long-wave infrared photonic integrated circuits (LWIR PICs), due to its CMOS compatibility and absence of oxides. We describe ring resonance (Q-factors between 2×103 and 1×104) and thermo-optic tunability in germanium-on-silicon waveguides throughout the long-wave-infrared. The ring resonances are characterized by Q-factors and couplings that agree with measurements of propagation loss (as low as 6 dB/cm) and simulations and are enabled by broadband edge coupling (12dB/facet over a 3 dB bandwidth of over 4 microns). We demonstrate the furthest into the infrared that ring resonators have been measured and show the potential of this platform for photonic integration and waveguide spectroscopy at wavelengths from 7 microns to beyond 11 microns.

The development of a foundry-scale waveguide-enhanced Raman spectroscopy (WERS) platform is a vital for the widespead implementation of this analytical technique. In this work we analyze the waveguide material and fabrication processes offered by AIM Photonics with regard to their effectiveness for WERS, and other sensing techniques. Optical characterization of these materials via white light spectroscopy and fluorescence spectroscopy points to the designation of an optimal wafer composition comprising a thermal bottom oxide and an LPCVD silicon nitride waveguide. This optimal composition has no measurable fluorescence and a propagation loss of 3.2 dB/m at 1064 nm in the TM00 mode. In the c/l band, the optimal wafer build has as thermal bottom oxide, a PECVD silicon nitride waveguide, and is annealed. This build has a propagation loss of 8.1 dB/m at 1550 nm in the TE00 mode.

Objective: To investigate the differences in imaging characteristics and the diagnostic accuracy of 225 intraosseous jaw lesions on panoramic radiographs (PAN) versus cone beam computed tomography (CBCT). Methods: 225 sets of PAN and CBCT images with biopsy-proven histopathological diagnoses were retrospectively compared in terms of radiographic features and diagnostic accuracy. The imaging characteristics of PAN and CBCT were independently evaluated by two oral and maxillofacial radiologists who were required to answer 12 questions and provided up to three differential diagnoses with their confidence scores. Results: Odds ratios (ORs) were statistically significant for border cortication (OR = 1.521; p = .003) and border continuity (OR = 0.421; p = .001), involvement on neurovascular canals (OR = 2.424; p < .001), expansion (OR = 7.948; p < .001), cortical thinning (OR = 20.480; p < .001) as well as its destruction (OR = 25.022; p < .001) and root resorption (OR = 2.477; p < .001). Furthermore, imaging features in the posterior and mandibular regions showed better agreement than those in the anterior and maxillary regions, respectively. The diagnostic accuracy of the first differential diagnosis was higher on CBCT than on PAN (Observer 1:78.7 vs 64.4%; Observer 2: 78.7 vs 70.2% (p < .001)). The observers’ confidence scores were also higher at CBCT interpretation compared with PAN. Conclusions: CBCT demonstrated a greater number of imaging characteristics of intraosseous jaw lesions compared with PAN, especially in the anterior regions of both jaws and in the maxilla. Diagnostic accuracy is improved with CBCT compared to PAN, especially for lesions in the maxilla. Radiologists have greater confidence when using CBCT.

Traumatic brain injury (TBI) is a major cause of mortality and morbidity affecting all ages. It remains to be a diagnostic and therapeutic challenge, in which, to date, there is no Food and Drug Administration‐approved drug for treating patients suffering from TBI. The heterogeneity of the disease and the associated complex pathophysiology make it difficult to assess the level of the trauma and to predict the clinical outcome. Current injury severity assessment relies primarily on the Glasgow Coma Scale score or through neuroimaging, including magnetic resonance imaging and computed tomography scans. Nevertheless, such approaches have certain limitations when it comes to accuracy and cost efficiency, as well as exposing patients to unnecessary radiation. Consequently, extensive research work has been carried out to improve the diagnostic accuracy of TBI, especially in mild injuries, because they are often difficult to diagnose. The need for accurate and objective diagnostic measures led to the discovery of biomarkers significantly associated with TBI. Among the most well‐characterized biomarkers are ubiquitin C‐terminal hydrolase‐L1 and glial fibrillary acidic protein. The current review presents an overview regarding the structure and function of these distinctive protein biomarkers, along with their clinical significance that led to their approval by the US Food and Drug Administration to evaluate mild TBI in patients., Ubiquitin C‐terminal hydrolase‐L1 (UCH‐L1) and glial fibrillary acidic protein (GFAP) proteins have been proposed as promising biomarkers for traumatic brain injury as approved by the US Food and Drug Administration.

People who use drugs (PWUD) face concurrent public health emergencies from overdoses, HIV, hepatitis C, and COVID-19, leading to an unprecedented syndemic. Responses to PWUD that go beyond treatment--such as decriminalization and providing a safe supply of pharmaceutical-grade drugs--could reduce impacts of this syndemic. Solutions already implemented for COVID-19, such as emergency safe-supply prescribing and providing housing to people experiencing homelessness, must be sustained once COVID-19 is contained. This pandemic is not only a public health crisis but also a chance to develop and maintain equitable and sustainable solutions to the harms associated with the criminalization of drug use.

We propose a 1D optical phased array (OPA) utilizing near-field micro-opto-electro- mechanical interaction to tune a waveguide grating’s diffraction angle. Simulations demonstrate steering angles >20 (material, geometry, wavelength, and polarization-dependent). Measurements validate the proposed OPA concept.

Introduction Housing affects an individual’s physical and mental health, particularly among people who use substances. Understanding the association between individual characteristics and housing status can inform housing policy and help optimize the care of people who use drugs. The objective of this study was to explore the factors associated with unstable housing among people who use drugs in Ottawa. Methods This is a cross-sectional analysis of data from 782 participants in the Participatory Research in Ottawa: Understanding Drugs (PROUD) Study. PROUD is a prospective cohort study of people who use drugs in Ottawa. Between March and December 2013, participants were recruited through peer-based recruitment on the streets and in social services settings and completed a peer-administered questionnaire that explored socio-demographic information, drug use patterns, community integration, experiences with police and incarceration, and access to health care and harm reduction services. Eligibility criteria included age of 16 years or older, self-reported illicit drug use within the past 12 months and having lived in Ottawa for at least 3 months. Housing status was determined by self-report. “Stable housing” was defined as residence in a house or apartment and “unstable housing” was defined as all other residence types. Exploratory multivariable logistic regression analyses of the association between characteristics of people who use drugs and their housing status were conducted. Results Factors that were associated with unstable housing included: recent incarceration; not having a regular doctor; not having received support from a peer worker; low monthly income; income source other than public disability support payments; and younger age. Gender, language, ethnicity, education level, opioid use and injection drug use were not independently associated with housing status. Conclusions People who use drugs face significant barriers to stable housing. These results highlight key areas to address in order to improve housing stability among this community.

We demonstrate foundry-processed optomechanical Mach-Zehnder interferometers using standard process development kit components and a post-process release. Measurements show clear optical phase shifting. Pump-probe experiments demonstrate all-optical excitation and readout of mechanical resonances.

This is the first study that explored the self-reported dietary habits of acute psychiatric inpatients. We found that 75% of the psychiatric inpatients have an unhealthy diet, which correlates with higher body mass index (BMI) and lower education level. We also found an increased sugar consumption in inpatients with schizophrenia. The link between nutrition and mental health has been explored to a limited extent owing to the cumbersome nature of conducting research that involves specific dietary intervention and follow up. Yet, there is existing literature linking poor diet with impaired mental health and poor recovery from depression, amongst other disorders. Good nutrition can be exemplified with diets like the Mediterranean diet with a focus on certain food groups that provide the nutrients linked to neurotransmitters and a fairly new concept of the gut-brain axis. A Mediterranean-style dietary intervention supplemented with fish oil improves diet quality and mental health in people with depression. A randomised controlled trial published in the nutritional neuroscience journal yielded a positive outcome and improvement in the overall well-being of the patients enrolled. We explored the dietary habits of acute inpatients. After gathering a detailed diet history, their food habits were compared to a Mediterranean dietary index to assess their dietary patterns. Additionally, variables such as socio-economic characteristics, physical activity, income, BMI, and educational achievement were taken into consideration, with the intention to understand the effect of these factors on a diet consumed by acute patients and the relationship of the diet with their mental wellbeing. Ultimately, this study aims at an important aspect of preventive mental health, i.e., improved dietary habits (e.g., Mediterranean diet) may contribute to more rapid symptoms resolution and acute stabilization on a short-stay inpatient unit.

Objective: To evaluate the occurrence of cervical vertebrae anomalies (CVA) in patients with unilateral (UCLP) and bilateral cleft lip and palate (BCLP) using cone beam computed tomography (CBCT) examinations. Design: Retrospective assessment of CBCT images. Descriptive statistics were calculated. Fisher exact test or χ2 test was performed to evaluate the differences among each CVA between sex and type of cleft. Setting: School of Dentistry. Participants: One hundred fifty-one patients with cleft lip and palate (103 UCLP/48 BCLP). Interventions: No relevant intervention. Main Outcome Measures: Cone beam computed tomography images were assessed for the presence or absence of 12 most commonly observed CVA: spina bifida, dehiscence, cleft of the posterior arch, cleft of the anterior arch, fusion between cervical vertebrae, block fusion, occipitalization, narrowing of the intervertebral space, posterior ponticle, os odontoideum, ossiculum terminale, and subdental cartilaginous remnants. Results: The presence of subdental cartilaginous remnants was the most frequently observed alteration—found in 81.45% of the sample—and it was the only CVA with statistically significant frequencies in the individuals with BCLP. Considering only the other CVA, 22.51% presented 1 and 5.29% presented 2 or more CVA. Conclusions: Patients with cleft lip and palate may present an overall high incidence of CVAs. However, when comparing the distribution of the CVAs among sex and types of cleft, the only significant difference noted was a higher incidence of subdental cartilaginous remnants among patients with BCLP.

The Baryon Mapping eXperiment (BMX) is an interferometric array designed as a pathfinder for a future post-reionization 21 cm intensity mapping survey. It consists of four 4-meter parabolic reflectors each having offset pyramidal horn feed, quad-ridge orthomode transducer, temperature-stabilized RF amplification and filtering, and pulsed noise injection diode. An undersampling readout scheme uses 8-bit digitizers running at 1.1 Gsamples/ sec to provide access to signals from 1.1 - 1.55 GHz (third Nyquist zone), corresponding to HI emission from sources at redshift 0 < z < 0:3. An FX correlator is implemented in GPU and generates 28 GB/day of time-ordered visibility data. About 7,000 hours of data were collected from Jan. 2019 - May 2020, and we will present results on system performance including sensitivity, beam mapping studies, observations of bright celestial targets, and system electronics upgrades. BMX is a pathfinder for the proposed PUMA intensity mapping survey in the 2030s.

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine implicated in the pathogenesis of inflammation and cancer. It is produced by various cells and circulating MIF has been identified as a biomarker for a range of diseases. Extracellular MIF mainly binds to the cluster of differentiation 74 (CD74)/CD44 to activate downstream signaling pathways. These in turn activate immune responses, enhance inflammation and can promote cancer cell proliferation and invasion. Extracellular MIF also binds to the C-X-C chemokine receptors cooperating with or without CD74 to activate chemokine response. Intracellular MIF is involved in Toll-like receptor and inflammasome-mediated inflammatory response. Pharmacological inhibition of MIF has been shown to hold great promise in treating inflammatory diseases and cancer, including small molecule MIF inhibitors targeting the tautomerase active site of MIF and antibodies that neutralize MIF. In the current review, we discuss the role of MIF signaling pathways in inflammation and cancer and summarize the recent advances of the role of MIF in experimental and clinical exocrine pancreatic diseases. We expect to provide insights into clinical translation of MIF antagonism as a strategy for treating acute pancreatitis and pancreatic cancer.

Aging is associated with subjective memory complaints. Approximately half of those with subjective memory complaints have objective cognitive impairment. Previous studies have provided evidence of an association between genetic risk for Alzheimer’s disease and dementia progression. In addition, aging is a significant risk factor for vascular pathology that may underlie at least some of the cognitive changes. This study investigates the relative contribution of subjective cognitive complaints, vascular function and genetic risk for dementia in predicting objective cognitive performance. Multiple regression and relative importance analysis were used to investigate the relative contribution of vascular function, self-reported subjective cognitive complaints, and dementia genetic risk, in predicting objective cognition in a sample of 238 healthy community dwelling older adults. Age, sex, premorbid cognitive abilities, subjective verbal memory complaints, higher cerebrovascular blood flow during submaximal exercise, and certain dementia risk alleles were significant predictors of worse objective verbal memory performance (p < .001, R2 = 35.2-36.4%). Using relative importance analysis, subjective verbal memory complaints and certain dementia risk alleles contributed more variance than cerebrovascular measures. These results suggest that age-related changes in memory in healthy older adults can be predicted by subjective memory complaints, genetic risk, and to a lesser extent, cerebrovascular function.

Genome sequencing is often pivotal in the diagnosis of rare diseases, but many of these conditions lack specific treatments. We describe how molecular diagnosis of a rare, fatal neurodegenerative condition led to the rational design, testing, and manufacture of milasen, a splice-modulating antisense oligonucleotide drug tailored to a particular patient. Proof-of-concept experiments in cell lines from the patient served as the basis for launching an "N-of-1" study of milasen within 1 year after first contact with the patient. There were no serious adverse events, and treatment was associated with objective reduction in seizures (determined by electroencephalography and parental reporting). This study offers a possible template for the rapid development of patient-customized treatments. (Funded by Mila's Miracle Foundation and others.).

Background There may be less primary health care engagement among people who use drugs (PWUD) than among the general population, even though the former have greater comorbidity and more frequent use of emergency department care. We investigated factors associated with primary care engagement among PWUD. Methods The Participatory Research in Ottawa: Understanding Drugs (PROUD) cohort study meaningfully engaged and trained people with lived experience to recruit and survey marginalized PWUD between March–December 2013. We linked this survey data to provincial-level administrative databases held at ICES. We categorized engagement in primary care over the 2 years prior to survey completion as: not engaged ( Results Characteristics of 663 participants included a median age of 43 years, 76% men, and 67% living in the two lowest income quintile neighborhoods. Despite high comorbidity and a median of 4 (interquartile range 0–10) primary care visits in the year prior to survey completion, only 372 (56.1%) were engaged in primary care. Engagement was most strongly associated with the following factors: receiving provincial benefits, including disability payments (adjusted odds ratio [AOR] 4.14 (95% confidence interval [CI] 2.30 to 7.43)) or income assistance (AOR 3.69 (95% CI 2.00 to 6.81)), having ever taken methadone (AOR 3.82 (95% CI 2.28 to 6.41)), mental health comorbidity (AOR 3.43 (95% CI 2.19 to 5.38)), and having stable housing (AOR 2.09 (95% CI 1.29 to 3.38)). Conclusions Despite high comorbidity, engagement in primary care among PWUD was low. Our findings suggest that social care (housing, disability, and income support) and mental health care are associated with improved primary care continuity; integration of these care systems with primary care and opioid substitution therapy may lessen the significant morbidity and acute care use among PWUD.

COVID-19 has turned the world upside down in a very short period of time. The impact of COVID-19 will disproportionately effect people who are least able to protect themselves and this will include people who use drugs. The arrival of the COVID-19 pandemic comes at time when North America is in the midst of a protracted overdose epidemic caused by a toxic illegal drug supply. Overdose deaths are likely to rise when people are isolated, social support programs are cut back, and the illicit drug supply is further compromised. Safer opioid distribution in response to a toxic street drug supply is a pragmatic and effective way to reduce overdose deaths. COVID-19 makes such an approach even more urgent and compelling.

ObjectiveTo test the hypothesis that aerobic exercise is associated with improvements in cognition and cerebrovascular regulation, we enrolled 206 healthy low-active middle-aged and older adults (mean ± SD age 65.9 ± 6.4 years) in a supervised 6-month aerobic exercise intervention and assessed them before and after the intervention.MethodsThe study is a quasi-experimental single group pre/postintervention study. Neuropsychological tests were used to assess cognition before and after the intervention. Transcranial Doppler ultrasound was used to measure cerebral blood flow velocity. Cerebrovascular regulation was assessed at rest, during euoxic hypercapnia, and in response to submaximal exercise. Multiple linear regression was used to examine the association between changes in cognition and changes in cerebrovascular function.ResultsThe intervention was associated with improvements in some cognitive domains, cardiorespiratory fitness, and cerebrovascular regulation. Changes in executive functions were negatively associated with changes in cerebrovascular resistance index (CVRi) during submaximal exercise (β = −0.205,p= 0.013), while fluency improvements were positively associated with changes in CVRi during hypercapnia (β = 0.106,p =0.03).ConclusionThe 6-month aerobic exercise intervention was associated with improvements in some cognitive domains and cerebrovascular regulation. Secondary analyses showed a novel association between changes in cognition and changes in cerebrovascular regulation during euoxic hypercapnia and in response to submaximal exercise.

BACKGROUND To visualize and assess brain metastases on magnetic resonance imaging, radiologists face an ever-increasing pressure to perform faster and more efficiently. The usage of maximum intensity projections (MIPs) of contrast-enhanced T1-weighed (T1ce) magnetization-prepared rapid acquisition with gradient echo (MP-RAGE) images proposes to increase reading efficiency by increasing lesion conspicuity while reducing in the number of images to be reviewed. AIM To assess if MIPs save reading time and achieve the same level of diagnostic accuracy as standard 1 mm T1ce images for the detection of brain metastases. METHODS Forty-four patients were included in this retrospective study. Axial reformations of T1ce MP-RAGE (TR/TE = 2300/2.25 ms, resolution = 1 mm$^{3}$ ) images were analyzed and post-processed into 5 and 10 mm MIPs. Two readers evaluated the randomly assorted images and recorded reading time. Reading time differences were analyzed using the Wilcoxon test, and inter-reader statistics were performed using Bland-Altman plots. RESULTS About 22.5 61.2 s/study and 43.8 ± 159.9 s/study were saved using 5 and 10 mm MIPs, respectively. Combined average sensitivity was 92.0% for 5 mm MIPs and 86.3% for 10 mm MIPs compared to standard 1 mm axial slices, with an average rate of 0.98 and 0.57 false positives per study, respectively CONCLUSION: While 5 mm and 10 mm T1ce MP-RAGE MIPs showed a clinical benefit in reducing reading times for evaluation of brain metastases, they should be used in conjunction with standard 1 mm images for best sensitivity and specificity, a practice which possibly annuls their benefit.