The mTOR regulated RNA-binding protein LARP1 requires PABPC1 for guided mRNA interaction.

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.

Trainable segmentation for transmission electron microscope images of inorganic nanoparticles.

We present a trainable segmentation method implemented within the python package ParticleSpy. The method takes user labelled pixels, which are used to train a classifier and segment images of inorganic nanoparticles from transmission electron microscope images. This implementation is based on the trainable Waikato Environment for Knowledge Analysis (WEKA) segmentation, but is written in python, allowing a large degree of flexibility and meaning it can be easily expanded using other python packages. We find that trainable segmentation offers better accuracy than global or local thresholding methods and requires as few as 100 user-labelled pixels to produce an accurate segmentation. Trainable segmentation presents a balance of accuracy and training time between global/local thresholding and neural networks, when used on transmission electron microscope images of nanoparticles. We also quantitatively investigate the effectiveness of the components of trainable segmentation, its filter kernels and classifiers, in order to demonstrate the use cases for the different filter kernels in ParticleSpy and the most accurate classifiers for different data types. A set of filter kernels is identified that are effective in distinguishing particles from background but that retain dissimilar features. In terms of classifiers, we find that different classifiers perform optimally for different image contrast; specifically, a random forest classifier performs best for high-contrast ADF images, but that QDA and Gaussian Naïve Bayes classifiers perform better for low-contrast TEM images.

Measurement of the size, shape and composition of nanoparticles is routinely performed using transmission electron microscopy and related techniques. Typically, distinguishing particles from the background in an image is performed using the intensity of each pixel, creating two sets of pixels to separate particles from background. However, this separation of intensity can be difficult if the contrast in an image is low, or if the intensity of the background varies significantly. In this study, an approach that takes into account additional image features (such as boundaries and texture) was investigated to study electron microscope images of metallic nanoparticles. In this 'trainable segmentation' approach, the user labels examples of particle and background pixels in order to train a machine learning algorithm to distinguish between particles and background. The performance of different machine learning algorithms was investigated, in addition to the effect of using different features to aid the segmentation. Overall, a trainable segmentation approach was found to perform better than use of an intensity threshold to distinguish between particles and background in electron microscope images.

Evaluation of a preoperative personalized risk communication tool: a prospective before-and-after study.

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.

RéSUMé: OBJECTIF: Les patients veulent disposer d'informations personnalisées avant leur chirurgie, mais la plupart d'entre eux ne reçoivent pas d'estimations de leur risque personnalisées. Des informations inadéquates contribuent à une mauvaise expérience et à des plaintes médicolégales. Nous avons émis l'hypothèse qu'une exposition à l'application PREDICT (Personalized Risk Evaluation and Decision Making in Preoperative Clinical Assessment), un outil de communication du risque personnalisé, améliorerait les connaissances et la satisfaction des patients après leurs consultations en anesthésiologie comparativement à des soins standard. MéTHODE: Nous avons réalisé une étude clinique prospective (de type avant-après) et utilisé les données rapportées par les patients afin de calculer leur risque personnalisé de morbidité et de mortalité, ainsi que la durée de séjour anticipée à l'aide d'un calculateur de risque tiré du Programme national d'amélioration de la qualité chirurgicale que nous avons calibré localement et intégré à l'application PREDICT. Dans la phase de soins standard (avant), le contenu et les résultats de l'application n'étaient pas divulgués aux participants; dans la phase comportant l'application PREDICT (après), les risques personnalisés étaient communiqués. Notre critère d'évaluation principal était le score des connaissances des patients après la consultation en anesthésiologie. Les critères d'évaluation secondaires comprenaient la satisfaction des patients et leur niveau d'anxiété ainsi que la faisabilité et l'acceptabilité d'une telle approche. RéSULTATS: Nous avons inclus 183 participants (90 avant; 93 après). Comparativement à la phase de soins standard, la phase avec l'application PREDICT a démontré un niveau plus élevé de connaissances des risques post consultation (14,3 % plus élevé; intervalle de confiance [IC] 95 %, 6,5 à 22,0; P < 0,001) et de satisfaction (0,8 point; IC 95 %, 0,1 à 1,4; P = 0,03). L'anxiété est demeurée inchangée (− 1,9 %; IC 95 %, − 4,2 à 0,5; P = 0,13). L'acceptabilité était élevée, tant chez les patients que chez les anesthésiologistes. CONCLUSION: L'exposition des patients à une application de communication du risque personnalisé a amélioré leurs connaissances de leur risque personnalisé et augmenté la satisfaction des adultes avant une chirurgie non urgente et non ambulatoire. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT03422133); enregistrée le 5 février 2018.

Modernizing Immunization Practice Through the Use of Cloud Based Platforms.

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.

Using Mobile Apps to Communicate Vaccination Records: A City-wide Evaluation with a National Immunization App, Maternal Child Registry and Public Health Authorities.

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.

Feasibility and Limitations of Vaccine Two-Dimensional Barcoding Using Mobile Devices.

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.

Using Computed Tomography-Based Three-dimensional Modeling and Computer Navigation for Minimally Invasive Core Decompression and Adjuvant Orthobiologic Therapy of Femoral Head Avascular Necrosis.

Avascular necrosis of the femoral head is a debilitating condition that can lead to femoral head collapse. Core decompression with adjuvant cellular therapies, such as bone marrow aspirate concentrate, delays disease progression and improves outcomes. However, inconsistent results in the literature may be due to limitations in surgical technique and difficulty in targeting the necrotic lesions. Here, we present a surgical technique utilizing computed tomography-based three-dimensional modeling and instrument tracking to guide the therapy to the center of the lesion. This method minimizes the number of attempts to reach the lesion and confirms the three-dimensional positioning of the instrumentation within the lesion. Our technique may improve the outcomes of core decompression and adjuvant therapy and prevent or delay hip collapse in patients with femoral head avascular necrosis.

Fabricating patient-specific 3D printed drill guides to treat femoral head avascular necrosis.

BACKGROUND: Femoral head avascular necrosis (AVN), or death of femoral head tissue due to a lack of blood supply, is a leading cause of total hip replacement for non-geriatric patients. Core decompression (CD) is an effective treatment to re-establish blood flow for patients with AVN. Techniques aimed at improving its efficacy are an area of active research. We propose the use of 3D printed drill guides to accurately guide therapeutic devices for CD. METHODS: Using femur sawbones, image processing software, and 3D modeling software, we created a custom-built device with pre-determined drill trajectories and tested the feasibility of the 3D printed drill guides for CD. A fellowship trained orthopedic surgeon used the drill guide to position an 8 ga, 230 mm long decompression device in the three synthetic femurs. CT scans were taken of the sawbones with the drill guide and decompression device. CT scans were processed in the 3D modeling software. Descriptive statistics measuring the angular and needle-tip deviation were compared to the original virtually planned model. RESULTS: Compared to the original 3D model, the trials had a mean displacement of 1.440 ± 1.03 mm and a mean angle deviation of 1.093 ± 0.749º. CONCLUSIONS: The drill guides were demonstrated to accurately guide the decompression device along its predetermined drill trajectory. Accuracy was assessed by comparing values to literature-reported values and considered AVN lesion size. This study demonstrates the potential use of 3D printing technology to improve the efficacy of CD techniques.

Fabricating Patient-Specific 3D Printed Drill Guides to Treat Femoral Head Avascular Necrosis.

Background: Femoral head avascular necrosis (AVN), or death of femoral head tissue due to a lack of blood supply, is a leading cause of total hip replacement for non-geriatric patients. Core decompression (CD) is an effective treatment to re-establish blood flow for patients with AVN. Techniques aimed at improving its efficacy are an area of active research. We propose the use of 3D printed drill guides to accurately guide therapeutic devices for CD. Methods: Using femur sawbones, image processing software, and 3D modeling software, we created a custom-built device with pre-determined drill trajectories and tested the feasibility of the 3D printed drill guides for CD. A fellowship trained orthopedic surgeon used the drill guide to position an 8 ga, 230 mm long decompression device in the three synthetic femurs. CT scans were taken of the sawbones with the drill guide and decompression device. CT scans were processed in the 3D modeling software. Descriptive statistics measuring the angular and needle-tip deviation were compared to the original virtually planned model. Results: Compared to the original 3D model, the trials had a mean displacement of 1.440±1.03 mm and a mean angle deviation of 1.093±0.749°. Conclusions: The drill guides were demonstrated to accurately guide the decompression device along its predetermined drill trajectory. Accuracy was assessed by comparing values to literature-reported values and considered AVN lesion size. This study demonstrates the potential use of 3D printing technology to improve the efficacy of CD techniques.

Comparing the Use of a Mobile App and a Web-Based Notification Platform for Surveillance of Adverse Events Following Influenza Immunization: Randomized Controlled Trial.

BACKGROUND: Vaccine safety surveillance is a core component of vaccine pharmacovigilance. In Canada, active, participant-centered vaccine surveillance is available for influenza vaccines and has been used for COVID-19 vaccines. OBJECTIVE: The objective of this study is to evaluate the effectiveness and feasibility of using a mobile app for reporting participant-centered seasonal influenza adverse events following immunization (AEFIs) compared to a web-based notification system. METHODS: Participants were randomized to influenza vaccine safety reporting via a mobile app or a web-based notification platform. All participants were invited to complete a user experience survey. RESULTS: Among the 2408 randomized participants, 1319 (54%) completed their safety survey 1 week after vaccination, with a higher completion rate among the web-based notification platform users (767/1196, 64%) than among mobile app users (552/1212, 45%; P<.001). Ease-of-use ratings were high for the web-based notification platform users (99% strongly agree or agree) and 88.8% of them strongly agreed or agreed that the system made reporting AEFIs easier. Web-based notification platform users supported the statement that a web-based notification-only approach would make it easier for public health professionals to detect vaccine safety signals (91.4%, agreed or strongly agreed). CONCLUSIONS: Participants in this study were significantly more likely to respond to a web-based safety survey rather than within a mobile app. These results suggest that mobile apps present an additional barrier for use compared to the web-based notification-only approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT05794113; https://clinicaltrials.gov/show/NCT05794113.

A Smartphone App to Increase Immunizations in the Pediatric Solid Organ Transplant Population: Development and Initial Usability Study.

BACKGROUND: Vaccine-preventable infections result in significant morbidity, mortality, and costs in pediatric transplant recipients. However, at the time of transplant, less than 20% of children are up-to-date for age-appropriate immunizations that could prevent these diseases. Smartphone apps have the potential to increase immunization rates through their ability to provide vaccine education, send vaccine reminders, and facilitate communication between parents and a multidisciplinary medical group. OBJECTIVE: The aim of this study was to describe the development of a smartphone app, Immunize PediatricTransplant, to promote pretransplant immunization and to report on app functionality and usability when applied to the target population. METHODS: We used a mixed methods study design guided by the Mobile Health Agile Development and Evaluation Lifecycle. We first completed a formative research including semistructured interviews with transplant stakeholders (12 primary care physicians, 40 parents or guardians of transplant recipients, 11 transplant nurse coordinators, and 19 transplant subspecialists) to explore the acceptability of an immunization app to be used in the pretransplant period. Based on these findings, CANImmunize Inc developed the Immunize PediatricTransplant app. We next held 2 focus group discussions with 5-6 transplant stakeholders/group (n=11; 5 parents of transplant recipients, 2 primary care physicians, 2 transplant nurse coordinators, and 2 transplant subspecialists) to receive feedback on the app. After the app modifications were made, alpha testing was conducted on the functional prototype. We then implemented beta testing with 12 stakeholders (6 parents of transplant recipients, 2 primary care doctors, 2 transplant nurse coordinators, and 2 transplant subspecialists) to refine the app through an iterative process. Finally, the stakeholders completed the user version of the Mobile Application Rating Scale (uMARS) to assess the functionality and quality of the app. RESULTS: A new Android- and Apple-compatible app, Immunize PediatricTransplant, was developed to improve immunization delivery in the pretransplant period. The app contains information about vaccine use in the pretransplant period, houses a complete immunization record for each child, includes a communication tool for parents and care providers, and sends automated reminders to parents and care providers when immunizations are due. During usability testing, the stakeholders were able to enter a mock vaccine record containing 16 vaccines in an average of 8.1 minutes (SD 1.8) with 87% accuracy. The stakeholders rated engagement, functionality, aesthetics, and information quality of the app as 4.2/5, 4.5/5, 4.6/5, and 4.8/5, respectively. All participants reported that they would recommend this app to families and care teams with a child awaiting solid organ transplant. CONCLUSIONS: Through a systematic, user-centered, agile, iterative approach, the Immunize PediatricTransplant app was developed to improve immunization delivery in the pretransplant period. The app tested well with end users. Further testing and agile development among patients awaiting transplant are needed to understand real-world acceptability and effectiveness in improving immunization rates in children awaiting transplant.

Early warning systems in the UK: variation in content and implementation strategy has implications for a NHS early warning system.

The Royal College of Physicians report Acute medical care: the right person, in the right setting--first time advocates the introduction of a standardised NHS Early Warning Score (NEWS). Recommendations for the optimum scoring system have been released by NHS Quality Improvement Scotland (NHS QIS) and the National Institute for Health and Clinical Excellence (NICE). This study reviewed clinical practice in London and Scotland against national guidelines. All hospitals responsible for acute medical admissions completed a telephone survey (n = 25 London; n = 23 Scotland). All used an early warning system at point of entry to care. Eleven different systems were used in London and five in Scotland. Forty per cent of London hospitals and 70% of Scottish hospitals incorporated the minimum data set recommended by NICE. Overall, Scotland was closer to achieving standardisation. If NEWS is implemented, consideration of the NHS QIS approach may support a more consistent response.

One hundred and seventy-eight consecutive pancreatoduodenectomies without mortality: role of the multidisciplinary approach.

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.

Per- and polyfluoroalkyl substances (PFAS) in livestock and game species: A review.

Per- and polyfluoroalkyl substances (PFAS) are synthetic, organic chemicals that resist environmental breakdown. The properties that made PFAS into an industrial success also led to their persistence and bioaccumulation. As PFAS were widely used for many decades their presence is evident globally, and their persistence and potential for toxicity create concern for human, animal and environmental health. Following the precautionary principle, a reduction in human exposure is generally recommended. The most significant source of human exposure to PFAS is dietary intake (food and water) with additional exposure via dust. As PFAS concentrations have been more frequently studied in aquatic food sources, there is less understanding of exposure via terrestrial animals. To further define human exposure via animal products, it is necessary to determine PFAS concentrations and persistence in terrestrial livestock and game species. Studies assessing ambient concentrations of PFAS have noted that, aside from point sources of contamination, there is generally low input of PFAS into terrestrial agricultural food chains. However, livestock and game species may be exposed to PFAS via contaminated water, soil, substrate, air or food, and the contribution of these exposures to PFAS concentrations in food products is less well studied. This review focuses on perfluoroalkyl substances (PFAAs) and compiles information from terrestrial livestock and game species as a source of dietary exposure in humans, and discusses toxicokinetics and health effects in animals, while identifying future focus areas. Publications describing the transfer of PFAAs to farmed and hunted animals are scarce, and demonstrate large variability in distribution and elimination. We outline several relatively small, short-term studies in cattle, sheep, pigs and poultry. While negative effects have not been noted, the poultry investigations were the only studies to explicitly assess health effects. Comparative information is presented on PFAA concentrations in livestock products and edible tissues of game animals.

YAP Translocation Precedes Cytoskeletal Rearrangement in Podocyte Stress Response: A Podometric Investigation of Diabetic Nephropathy.

Podocyte loss plays a pivotal role in the pathogenesis of glomerular disease. However, the mechanisms underlying podocyte damage and loss remain poorly understood. Although detachment of viable cells has been documented in experimental Diabetic Nephropathy, correlations between reduced podocyte density and disease severity have not yet been established. YAP, a mechanosensing protein, has recently been shown to correlate with glomerular disease progression, however, the underlying mechanism has yet to be fully elucidated. In this study, we sought to document podocyte density in Diabetic Nephropathy using an amended podometric methodology, and to investigate the interplay between YAP and cytoskeletal integrity during podocyte injury. Podocyte density was quantified using TLE4 and GLEPP1 multiplexed immunofluorescence. Fourteen Diabetic Nephropathy cases were analyzed for both podocyte density and cytoplasmic translocation of YAP via automated image analysis. We demonstrate a significant decrease in podocyte density in Grade III/IV cases (124.5 per 106 µm3) relative to Grade I/II cases (226 per 106 µm3) (Student's t-test, p < 0.001), and further show that YAP translocation precedes cytoskeletal rearrangement following injury. Based on these findings we hypothesize that a significant decrease in podocyte density in late grade Diabetic Nephropathy may be explained by early cytoplasmic translocation of YAP.

Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance.

To identify approaches to target DNA repair vulnerabilities in cancer, we discovered nanomolar potent, selective, low molecular weight (MW), allosteric inhibitors of the polymerase function of DNA polymerase Polθ, including ART558. ART558 inhibits the major Polθ-mediated DNA repair process, Theta-Mediated End Joining, without targeting Non-Homologous End Joining. In addition, ART558 elicits DNA damage and synthetic lethality in BRCA1- or BRCA2-mutant tumour cells and enhances the effects of a PARP inhibitor. Genetic perturbation screening revealed that defects in the 53BP1/Shieldin complex, which cause PARP inhibitor resistance, result in in vitro and in vivo sensitivity to small molecule Polθ polymerase inhibitors. Mechanistically, ART558 increases biomarkers of single-stranded DNA and synthetic lethality in 53BP1-defective cells whilst the inhibition of DNA nucleases that promote end-resection reversed these effects, implicating these in the synthetic lethal mechanism-of-action. Taken together, these observations describe a drug class that elicits BRCA-gene synthetic lethality and PARP inhibitor synergy, as well as targeting a biomarker-defined mechanism of PARPi-resistance.

The digital immunization system of the future: imagining a patient-centric, interoperable immunization information system.

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.

In vitro cyclic testing of the Exeter stem after cement within cement revision.

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.

Significance of Obstetrical History with Future Cardiovascular Disease Risk.

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.

Agile research to complement agile development: a proposal for an mHealth research lifecycle.

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.