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The mammalian target of rapamycin (mTOR) is a critical regulator of cell growth, integrating multiple signalling cues and pathways. Key among the downstream activities of mTOR is the control of the protein synthesis machinery. This is achieved, in part, via the co-ordinated regulation of mRNAs that contain a terminal oligopyrimidine tract (TOP) at their 5'ends, although the mechanisms by which this occurs downstream of mTOR signalling are still unclear. We used RNA-binding protein (RBP) capture to identify changes in the protein-RNA interaction landscape following mTOR inhibition. Upon mTOR inhibition, the binding of LARP1 to a number of mRNAs, including TOP-containing mRNAs, increased. Importantly, non-TOP-containing mRNAs bound by LARP1 are in a translationally-repressed state, even under control conditions. The mRNA interactome of the LARP1-associated protein PABPC1 was found to have a high degree of overlap with that of LARP1 and our data show that PABPC1 is required for the association of LARP1 with its specific mRNA targets. Finally, we demonstrate that mRNAs, including those encoding proteins critical for cell growth and survival, are translationally repressed when bound by both LARP1 and PABPC1., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Purpose: Patients want personalized information before surgery; most do not receive personalized risk estimates. Inadequate information contributes to poor experience and medicolegal complaints. We hypothesized that exposure to the Personalized Risk Evaluation and Decision Making in Preoperative Clinical Assessment (PREDICT) app, a personalized risk communication tool, would improve patient knowledge and satisfaction after anesthesiology consultations compared with standard care., Methods: We conducted a prospective clinical study (before-after design) and used patient-reported data to calculate personalized risks of morbidity, mortality, and expected length of stay using a locally calibrated National Surgical Quality Improvement Program risk calculator embedded in the PREDICT app. In the standard care (before) phase, the application's materials and output were not available to participants; in the PREDICT app (after) phase, personalized risks were communicated. Our primary outcome was knowledge score after the anesthesiology consultation. Secondary outcomes included patient satisfaction, anxiety, feasibility, and acceptability., Results: We included 183 participants (90 before; 93 after). Compared with standard care phase, the PREDICT app phase had higher post-consultation: knowledge of risks (14.3% higher; 95% confidence interval [CI], 6.5 to 22.0; P < 0.001) and satisfaction (0.8 points; 95% CI, 0.1 to 1.4; P = 0.03). Anxiety was unchanged (- 1.9%; 95% CI, - 4.2 to 0.5; P = 0.13). Acceptability was high for patients and anesthesiologists., Conclusion: Exposure to a patient-facing, personalized risk communication app improved knowledge of personalized risk and increased satisfaction for adults before elective inpatient surgery., Trial Registration: www.clinicaltrials.gov (NCT03422133); registered 5 February 2018.

To ensure the effectiveness of increasingly complex immunization programs in upper-middle and high-income settings, comprehensive information systems are needed to track immunization uptake at individual and population levels. The maturity of cloud systems and mobile technologies has created new possibilities for immunization information systems. In this paper, we describe a vision for the next generation of digital immunization information systems for upper-middle and high-income settings based on our experience in Canada. These systems center on the premise that the public is engaged and informed about the immunization process beyond their interaction with primary care, and that they will be a contributor and auditor of immunization data. The digital immunization system of the future will facilitate reporting of adverse events following immunization, issue digital immunization receipts, permit identification of areas of need and allow for delivery of interventions targeting these areas. Through features like immunization reminders and targeted immunization promotion campaigns, the system will reduce many of the known barriers that influence immunization rates. In light of the global COVID-19 pandemic, adaptive digital public health information systems will be required to guide the rollout and post-market surveillance of the SARS-CoV-2 vaccine., Competing Interests: Conflict of interest statement: KA, KW and CB are cofounders and shareholders of CANImmunize Inc, a corporation which provides consumer facing solutions to immunization information systems. TRA is an employee of CANImmunize Inc., (© The Author(s), 2020.)

The maternal cardiovascular system undergoes profound changes to support the increasing demands of fetal growth during pregnancy. An accumulating body of evidence has shown that common pregnancy complications, including gestational diabetes mellitus, preeclampsia, low birth weight, and preterm delivery, can be associated with future cardiovascular adverse events in mothers. Factors such as glucose metabolism, hyperlipidemia, inflammatory markers, and large- and small-vessel stiffness/functionality have been linked with these pregnancy conditions. Critically, there are no established guidelines to account for these maternal factors when considering future cardiovascular disease risk, one of the leading causes of female mortality. This article reviews the study of cardiovascular disease and pregnancy, and proposes possible connections that should spur future investigation in an area of medicine that requires significant research., (Copyright © 2019. Published by Elsevier Inc.)

Mobile health (mHealth) technology is increasingly being used, but academic evaluations supporting its use are not keeping pace. This is partly due to the disconnect between the traditional pharmaceutical approach to product evaluation, with its incremental approach, and the flexible way in which mHealth products are developed. An important step to addressing these problems lies in establishing agile research methods that complement the agile development methodologies used to create modern digital health applications. We describe an mHealth research model that mirrors traditional clinical research methods in its attention to safety and efficacy, while also accommodating the rapid and iterative development and evaluation required to produce effective, evidence-based, and sustainable digital products. This approach consists of a project identification stage followed by four phases of clinical evaluation: Phase 1: User Experience Design, Development, & Alpha Testing; Phase 2: Beta testing; Phase 3: Clinical Trial Evaluation; and Phase 4: Post-Market Surveillance. These phases include sample gating questions and are adapted to accommodate the unique nature of digital product development., Competing Interests: Competing interestsThe authors declare no competing interests.

Daily burn wound care for nonintubated patients involves administration of intravenous analgesic and sedation agents. Vital signs and oxygen saturation monitoring alone can result in late signs of oversedation and ineffective breathing. End-tidal carbon dioxide (EtCo2) monitoring provides immediate feedback of effective breathing during procedural sedation. The purpose of this study was to describe the nurse's sedation and analgesic therapy management of nonintubated patients during burn wound care when EtCo2 was used. This IRB approved study involved observing 22 burn nurses and 4 burn technicians during burn wound care of nonintubated patients. This descriptive, observational study compared adverse breathing/airway events, pain measurements, and sedation effectiveness, before and after introducing EtCo2 monitoring. Patients observed in this study were similar in age, type and size of burn, and use of recreational substances. Nurses and technicians also had similar burn experience. No statistically significant findings were found in this study; however, nurses in practice longer were found to apply oxygen sooner, which prevented decreased oxygen saturation events. When EtCo2 was used, less analgesia and sedation were required to maintain patient comfort. Time required for burn wound care was reduced by 22%, and 30% less overall analgesic and sedation agent dosages were administered after the introduction of EtCo2 monitoring. EtCo2 was found to enhance nurses' assessment of patients' response to intravenous analgesia and sedation effectiveness during burn wound care for nonintubated patients. Nurses with greater experience used oxygen sooner in the procedure, and patients had fewer decreases in SpO2.

Improving injury prediction accuracy and fidelity for mounted Warfighters has become an area of focus for the U.S. military in response to improvised explosive device (IED) use in both Iraq and Afghanistan. Although the Hybrid III anthropomorphic test device (ATD) has historically been used for crew injury analysis, it is only capable of predicting a few select skeletal injuries. The Computational Anthropomorphic Virtual Experiment Man (CAVEMAN) human body model is being developed to expand the injury analysis capability to both skeletal and soft tissues. The CAVEMAN model is built upon the Zygote 50 th percentile male human CAD model and uses a finite element modeling approach developed for high performance computing (HPC). The lower extremity subset of the CAVEMAN human body model presented herein includes: 28 bones, 26 muscles, 40 ligaments, fascia, cartilage and skin. Sensitivity studies have been conducted with the CAVEMAN lower extremity model to determine the structures critical for load transmission through the leg in the underbody blast (UBB) environment. An evaluation of the CAVEMAN lower extremity biofidelity was also carried out using 14 unique data sets derived by the Warrior Injury Assessment Manikin (WIAMan) program cadaveric lower leg testing. Extension of the CAVEMAN lower extremity model into anatomical tissue failure will provide additional injury prediction capabilities, beyond what is currently achievable using ATDs, to improve occupant survivability analyses within military vehicles.

Collection of timely and accurate immunization information is essential for effective immunization programs. Current immunization information systems have important limitations that impact the ability to collect this data. Based on our experience releasing a national immunization app we describe a cloud-based platform that would allow individuals to store their records digitally and exchange these records with public health information systems thus improving the quality of immunization information held by individuals and public health officials.

Medicine is experiencing a paradigm shift, where patients are increasingly involved in the management of their health data. We created a mobile app which permitted parental reporting of immunization status to public health authorities. We describe app use as a proxy for feasibility and acceptability as well as data utility for public health surveillance. The evaluation period ran from April 27, 2015, to April 18, 2017, during which time 2,653 unique children's records were transmitted, containing 36,105 vaccinations. Our findings suggest that mobile immunization reporting is feasible and may be an acceptable complement to existing reporting methods. Measures of data utility suggest that mobile reporting could enable more accurate assessments of vaccine coverage.

The Canadian National Vaccine Safety network (CANVAS) gathers and analyzes safety data on individuals receiving the influenza vaccine during the early stages of annual influenza vaccination campaigns with data collected via participant surveys through the Internet. We sought to examine whether it was feasible to use a mobile application (app) to facilitate AEFI reporting for the CANVAS network. To explore this, we developed a novel smartphone app, recruited participants from a hospital influenza immunization clinic and by word of mouth and instructed them to download and utilize the app. The app reminded participants to complete the CANVAS AEFI surveillance surveys ("AEFI surveys") on day 8 and 30, a survey capturing app usability metrics at day 30 ("usability survey") and provided a mechanism to report AEFI events spontaneously throughout the whole study period. All survey results and spontaneous reports were recorded on a privacy compliant, cloud server. A software plug-in, Lookback, was used to record the on-screen experience of the app sessions. Of the 76 participants who consented to participate, 48(63%) successfully downloaded the app and created a profile. In total, 38 unique participants completed all of the required surveillance surveys; transmitting 1104 data points (survey question responses and spontaneous reports) from 83 completed surveys, including 21 usability surveys and one spontaneous report. In total, we received information on new or worsening health conditions after receiving the influenza vaccine from 11(28%) participants. Of the usability survey responses, 86% agreed or strongly agreed that they would prefer to use a mobile app based reporting system instead of a web-based system. The single spontaneous report received was from a participant who had also reported using the Day 8 survey. Of Lookback observable sessions, an accurate transmission proportion of 100% (n=290) was reported for data points. We demonstrated that a mobile app can be used for AEFI reporting, although download and survey completion proportions suggest potential barriers to adoption. Future studies should examine implementation of mobile reporting in a broader audience and impact on the quality of reporting of adverse events following immunization.

Background: Two-dimensional (2D) barcoding has the potential to enhance documentation of vaccine encounters at the point of care. However, this is currently limited to environments equipped with dedicated barcode scanners and compatible record systems. Mobile devices may present a cost-effective alternative to leverage 2D vaccine vial barcodes and improve vaccine product-specific information residing in digital health records., Objective: Mobile devices have the potential to capture product-specific information from 2D vaccine vial barcodes. We sought to examine the feasibility, performance, and potential limitations of scanning 2D barcodes on vaccine vials using 4 different mobile phones., Methods: A unique barcode scanning app was developed for Android and iOS operating systems. The impact of 4 variables on the scan success rate, data accuracy, and time to scan were examined: barcode size, curvature, fading, and ambient lighting conditions. Two experimenters performed 4 trials 10 times each, amounting to a total of 2160 barcode scan attempts., Results: Of the 1832 successful scans performed in this evaluation, zero produced incorrect data. Five-millimeter barcodes were the slowest to scan, although only by 0.5 seconds on average. Barcodes with up to 50% fading had a 100% success rate, but success rate deteriorated beyond 60% fading. Curved barcodes took longer to scan compared with flat, but success rate deterioration was only observed at a vial diameter of 10 mm. Light conditions did not affect success rate or scan time between 500 lux and 20 lux. Conditions below 20 lux impeded the device's ability to scan successfully. Variability in scan time was observed across devices in all trials performed., Conclusions: 2D vaccine barcoding is possible using mobile devices and is successful under the majority of conditions examined. Manufacturers utilizing 2D barcodes should take into consideration the impact of factors that limit scan success rates. Future studies should evaluate the effect of mobile barcoding on workflow and vaccine administrator acceptance.

At present, proof of immunization against diseases such as yellow fever is required at some international borders in concordance with the International Health Regulations. The current standard, the International Certificate of Vaccination or Prophylaxis (ICVP), has limitations as a paper record including the possibility of being illegible, misplaced, or damaged. We believe that a complementary, digital record would offer advantages to public health and travelers alike. These include enhanced availability and reliability, potential to include lot specific information, and integration with immunization information systems. Challenges exist in implementation, particularly pertaining to verification at border crossings. We describe a potential course for the development and implementation of a digital ICVP record., (© The American Society of Tropical Medicine and Hygiene.)

Butane hash oil (BHO), also known as "amber," "dab," "glass," "honey," "shatter," or "wax," is a potent marijuana concentrate, containing up to 90 % tetrahydrocannabinol (THC). BHO is easily manufactured using highly volatile butane as a solvent. Our objective was to characterize hydrocarbon burns associated with BHO manufacture in Colorado. This was a cross-sectional study utilizing the National Burn Repository to capture all hydrocarbon burns reported to the local burn center from January 1st, 2008, through August 31st, 2014. We abstracted demographic and clinical variables from medical records for patients admitted for hydrocarbon burns associated with butane hash oil extraction. Twenty-nine cases of BHO burns were admitted to the local burn center during the study period. Zero cases presented prior to medical liberalization, 19 (61.3 %) during medical liberalization (Oct 2009-Dec 2013), and 12 (38.7 %) in 2014 since legalization. The majority of cases were Caucasian (72.4 %) males (89.7 %). Median age was 26 (range 15-58). The median total-body-surface-area (TBSA) burn size was 10 % (TBSA range 1-90 %). Median length of hospital admission was 10 days. Six required intubation for airway protection (21 %). Nineteen required skin grafting, eight wound care only, one required surgical fracture repair, and one required surgical debridement. Hydrocarbon burns associated with hash oil production have increased since the liberalization of marijuana policy in Colorado. A combination of public health messaging, standardization of manufacturing processes, and worker safety regulations are needed to decrease the risks associated with BHO production.

Background: Pancreatoduodenectomy offers the only chance of cure for patients with periampullary cancers. This, however, is a major undertaking in most patients and is associated with a significant morbidity and mortality. A multidisciplinary approach to the workup and follow-up of patients undergoing pancreatoduodenectomy was initiated at our institution to improve the diagnosis, resection rate, mortality and morbidity. We undertook the study to assess the effect of this approach on diagnosis, resection rates and short-term outcomes such as morbidity and mortality., Methods: A prospective database of patients presenting with periampullary cancers to a single surgeon between April 2004 and April 2010 was reviewed. All cases were discussed at a multidisciplinary meeting comprising surgeons, gastroenterologists, radiologists, oncologists, radiation oncologists, pathologists and nursing staff. A standardized investigation and management algorithm was followed. Complications were graded according to the Clavien-Dindo classification., Results: A total of 295 patients with a periampullary lesion were discussed and 178 underwent pancreatoduodenectomy (resection rate 60%). Sixty-one patients (34%) required either a vascular or an additional organ resection. Eighty-nine patients experienced complications, of which the commonest was blood transfusion (12%). Thirty-four patients (19%) had major complications, i.e. grade 3 or above. There was no in-hospital, 30-day or 60-day mortality., Conclusions: Pancreatoduodenectomy can safely be performed in high-volume centers with very low mortality. The surgeon's role should be careful patient selection, intensive preoperative investigations, use of a team approach, and an unbiased discussion at a multidisciplinary meeting to optimize the outcome in these patients.

Cement-within-cement (C-C) revision arthroplasty minimizes the complications associated with removal of secure polymethylmethacrylate. Failure at the interfacial region between new and old cement mantles remains a theoretical concern. This article assesses the cyclic fatigue properties of bilaminar cement mantles after C-C revision in vitro with the Exeter stem. Seven Exeter stems were cemented into Sawbone femurs and removed, and new undersized stems were cemented into the preserved mantle. The new constructs were loaded for 1,000,000 cycles at body temperature. Cement mantles were inspected postcycling. In no case was there delamination or failure of the cement mantle. The findings support the hypothesis that use of a thin revision cement mantle in conjunction with a polished double-tapered stem is not detrimental to the overall success of the implant. In the presence of a secure cement-bone interface in suitable patients, we recommend C-C revision techniques using double-tapered polished femoral stems.

Blade design can have a large effect on the surgical wear debris produced during TKA, and has quantified the weight of debris lost from the blades and cutting blocks. In the effort to address this metal debris generation, an oscillating-tip blade such as the Precision blade can significantly reduce the amount of debris produced.

The effect of cyclic loading on the torsional stiffness of a polished double-tapered femoral stem was investigated in vitro. Initial torsional stability was compared with torsional stability after cyclic loading. Stems were removed from the cement mantle and reinserted without the use of additional cement. Torsional stability was measured after reinsertion and after further cyclic loading. Subsidence of the stem was observed. No difference in torsional stiffness was observed during loading. No difference between the stiffness before extraction and after reinsertion was observed. Torsional stiffness of an Exeter stem does not decrease after axial subsidence under cyclic loading. Stability is retained after reinsertion into the original cement mantle. Debonding of the Exeter stem is not associated with rotational instability of the implant.

Although cement-within-cement revision arthroplasty minimizes the complications associated with removal of secure PMMA, failure at the interfacial region between new and old cement mantles remains a theoretical concern. This article assesses the variability in shear properties of bilaminar cement mantles related to duration of postcure and the use of antibiotic cements. Bilaminar cement mantles were 15% to 20% weaker than uniform mantles (P < .001) and demonstrated variability in shear strength related to duration of postcure of the freshly applied cement (P < .001). The use of Antibiotic Simplex did not significantly influence interfacial cement adhesion (P = .52). Interfacial adhesion by mechanisms other than mechanical interlock plays a significant role in the bond formed between new and old PMMA cements, with an important contribution by diffusion-based molecular interdigitation. In the presence of a secure cement-bone interface, we recommend cement-within-cement revision techniques in suitable patients.

This report describes one of the largest egg-associated outbreaks of foodborne illness in Australia for many years. Between June and December 2005, five outbreaks of Salmonella Typhimurium phage type 135 were identified in Tasmania, leading to 125 laboratory-confirmed cases. Public health investigations included case and food handler interviews, cohort studies, environmental health investigations of food businesses, microbiological testing, traceback, and inspections and drag swabbing of an egg farm. These investigations enabled identification of foods containing raw egg or foods contaminated through inadequate food handling and/or storage procedures as possible vehicles for infection. A particular poultry farm was reported as the common source of eggs. Interventions targeting the general public and food handlers to promote better handling of egg products, and advice to egg producers regarding harm minimisation strategies led to the series of outbreaks being brought under control.

Proteomic techniques promise to improve the diagnosis of cholangiocarcinoma (CC) in both tissue and serum as histological diagnosis and existing serum markers exhibit poor sensitivities. We explored the use of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) to identify potential protein biomarkers of CC. Twenty-two resected CC samples were compared with adjacent noninvolved bile duct tissue. Serum from patients with CC (n=20) was compared with patients with benign disease (n=20), and healthy volunteers (n=25). Samples were analyzed on hydrophobic protein chips via SELDI-TOF MS, and classification models were developed using logistic regression and cross-validation analysis. Univariate analysis revealed 14 individual peaks differentially expressed between CC and bile duct tissue, 4 peaks between CC and benign disease, and 12 peaks between CC and sera of healthy volunteers. The 4,462 mass-to-charge serum peak had superior discriminatory ability to carbohydrate antigen 19.9 (CA19.9) and carcinoembryonic antigen (CEA) (P=.004; receiver operating characteristic [ROC] area under the curve [AUC]=0.76, 0.73, and 0.70, respectively). The training models developed panels of peaks that distinguished CC from bile duct tissue (92.5% sensitivity, 92.3% specificity; ROC AUC=0.96), CC from benign serum (65.0% sensitivity, 70.0% specificity; ROC AUC=0.83), and CC from sera of healthy volunteers (75.0% sensitivity, 100% specificity; ROC AUC=0.92). Serum results were further improved with the inclusion of CA19.9 and CEA (ROC AUC=0.86 and 0.99 for CC vs benign and healthy volunteer serum, respectively). In conclusion, biomarker panels are capable of distinguishing CC from nonmalignant tissue; serum markers have important diagnostic implications for unknown bile duct stricture.