Summary of the NACI Statement on Public Health Level Recommendations on the Use of Pneumococcal Vaccines in Adults, Including the Use of 15-valent and 20-valent Conjugate Vaccines.

Background: Age and certain medical/social conditions are risk factors for invasive pneumococcal disease (IPD). For prevention of IPD, the National Advisory Committee on Immunization (NACI) has recommended the 23-valent polysaccharide pneumococcal vaccine, PNEU-P-23, for adults 65 years of age and older and adults over 18 years of age living with certain underlying conditions. NACI has also recommended 13-valent conjugate pneumococcal vaccine, PNEU-C-13, for adults; however, in publicly funded programs, this recommendation is limited to individuals with risk factors for IPD. Two new conjugate vaccines, PNEU-C-15 and PNEU-C-20, have been authorized by Health Canada for prevention of IPD in adults. This article summarizes NACI public health recommendations for pneumococcal vaccines in adults given these new conjugate vaccines that provide additional serotype coverage over PNEU-C-13. Methods: Key studies evaluating the immunogenicity and safety of PNEU-C-15 and PNEU-C-20 were reviewed. The Grading of Recommendations, Assessment, Development and Evaluations framework methodology was used to assess the certainty of evidence. Results: The PNEU-C-15 and PNEU-C-20 vaccines showed comparable immune responses, and safety profiles for all mild, moderate, and severe adverse events, to the currently used vaccines. No data were available on the efficacy or effectiveness of PNEU-C-15 or PNEU-C-20. Economic evidence and feasibility assessments supported the use of the PNEU-C-20 vaccine. Conclusion: NACI recommends PNEU-C-20 for adults 65 years of age and older, 50-64 years of age and living with factors placing them at higher risk of pneumococcal disease, and 18-49 years of age with immunocompromising conditions, with PNEU-C-15+PNEU-P-23 an alternative.

Comparing Deep Learning Approaches for Understanding Genotype × Phenotype Interactions in Biomass Sorghum.

We explore the use of deep convolutional neural networks (CNNs) trained on overhead imagery of biomass sorghum to ascertain the relationship between single nucleotide polymorphisms (SNPs), or groups of related SNPs, and the phenotypes they control. We consider both CNNs trained explicitly on the classification task of predicting whether an image shows a plant with a reference or alternate version of various SNPs as well as CNNs trained to create data-driven features based on learning features so that images from the same plot are more similar than images from different plots, and then using the features this network learns for genetic marker classification. We characterize how efficient both approaches are at predicting the presence or absence of a genetic markers, and visualize what parts of the images are most important for those predictions. We find that the data-driven approaches give somewhat higher prediction performance, but have visualizations that are harder to interpret; and we give suggestions of potential future machine learning research and discuss the possibilities of using this approach to uncover unknown genotype × phenotype relationships.

Immunization stress-related response - Redefining immunization anxiety-related reaction as an adverse event following immunization.

The Council for the International Organizations of Medical Sciences (CIOMS) and WHO working group on pharmacovigilance defines five cause specific AEFI which includes an immunization anxiety-related reaction. Historically this term has been used to describe a range of symptoms and signs that may arise after immunization that are related to "anxiety" about the immunization. However, the term "anxiety" does not adequately capture all the elements of this cause specific AEFI. In 2015, the Global Advisory Committee for Vaccine Safety convened an expert working group with the purpose of redefining, preventing and managing this particular AEFI. The term "Immunization Stress-Related Response" is proposed to replace the former terminology. We present a manual that redefines this AEFI and present a framework for prevention, diagnosis and management in both an individual and also when such events occur as clusters and affect multiple individuals. Since such mass events can result in cessation of immunization programmes and/or a loss of public confidence, a communication response is essential.

Direct Estimation of Surface Strain Fields From a Stereo Vision System.

Estimating strain on surfaces of deforming three-dimensional (3D) structures is a critical need in experimental mechanics. Although single-camera techniques excel at estimating deformation on a surface parallel to the imaging plane, they are prone to artifact for 3D motion because they cannot distinguish between out-of-plane motion and in-plane dilatation. Multiview (e.g., stereo) camera systems overcome this via a three-step process consisting of: (1) independent surface registration, (2) triangulation to estimate surface displacements, and (3) deformation estimation. However, existing methods are prone to errors associated with numerical differentiation when computing estimating strain fields from displacement fields unless regularization schemes are used. Such regularization schemes can introduce inaccuracy into strain estimation. Inspired by previous work which combined registration and deformation estimation into a single step for 2D images and 3D imaging stacks, we developed a theory for simultaneous image registration, 3D triangulation, and deformation estimation in a multiview system. The deformation estimation does not require numerical differentiation of displacement fields to estimate strain fields. We present here the theoretical foundations and derivation of two related implementations of this approach, and discuss their strengths and weaknesses.

High-throughput phenotyping with deep learning gives insight into the genetic architecture of flowering time in wheat.

BACKGROUND: Measurement of plant traits with precision and speed on large populations has emerged as a critical bottleneck in connecting genotype to phenotype in genetics and breeding. This bottleneck limits advancements in understanding plant genomes and the development of improved, high-yielding crop varieties. RESULTS: Here we demonstrate the application of deep learning on proximal imaging from a mobile field vehicle to directly estimate plant morphology and developmental stages in wheat under field conditions. We developed and trained a convolutional neural network with image datasets labeled from expert visual scores and used this "breeder-trained" network to classify wheat morphology and developmental stages. For both morphological (awned) and phenological (flowering time) traits, we demonstrate high heritability and very high accuracy against the "ground-truth" values from visual scoring. Using the traits predicted by the network, we tested genotype-to-phenotype association using the deep learning phenotypes and uncovered novel epistatic interactions for flowering time. Enabled by the time-series high-throughput phenotyping, we describe a new phenotype as the rate of flowering and show heritable genetic control for this trait. CONCLUSIONS: We demonstrated a field-based high-throughput phenotyping approach using deep learning that can directly measure morphological and developmental phenotypes in genetic populations from field-based imaging. The deep learning approach presented here gives a conceptual advancement in high-throughput plant phenotyping because it can potentially estimate any trait in any plant species for which the combination of breeder scores and high-resolution images can be obtained, capturing the expert knowledge from breeders, geneticists, pathologists, and physiologists to train the networks.

Regularization-Free Strain Mapping in Three Dimensions, With Application to Cardiac Ultrasound.

Quantifying dynamic strain fields from time-resolved volumetric medical imaging and microscopy stacks is a pressing need for radiology and mechanobiology. A critical limitation of all existing techniques is regularization: because these volumetric images are inherently noisy, the current strain mapping techniques must impose either displacement regularization and smoothing that sacrifices spatial resolution, or material property assumptions that presuppose a material model, as in hyperelastic warping. Here, we present, validate, and apply the first three-dimensional (3D) method for estimating mechanical strain directly from raw 3D image stacks without either regularization or assumptions about material behavior. We apply the method to high-frequency ultrasound images of mouse hearts to diagnose myocardial infarction. We also apply the method to present the first ever in vivo quantification of elevated strain fields in the heart wall associated with the insertion of the chordae tendinae. The method shows promise for broad application to dynamic medical imaging modalities, including high-frequency ultrasound, tagged magnetic resonance imaging, and confocal fluorescence microscopy.

Safety Surveillance of Dietary Supplements: Importance, Challenges, and New Horizons.

Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other possible drug-related problems.1 While current models of pharmacovigilance, with their tools and methodologies, were developed for prescription drugs, safety surveillance is just as important for over-the-counter health products such as dietary supplements. The practice of pharmacovigilance is challenging in itself; however, there are unique challenges associated with dietary supplements.2.

Longitudinal Outcomes in the 2014 Acute Flaccid Paralysis Cluster in Canada.

We describe the presenting features and long-term outcome of an unusual cluster of pediatric acute flaccid paralysis cases that occurred in Canada during the 2014 enterovirus D68 outbreak. Children (n = 25; median age 7.8 years) presenting to Canadian centers between July 1 and October 31, 2014, and who met diagnostic criteria for acute flaccid paralysis were evaluated retrospectively. The predominant presenting features included prodromal respiratory illness (n = 22), cerebrospinal fluid lymphocytic pleocytosis (n = 18), pain in neck/back (n = 14) and extremities (n = 10), bowel/bladder dysfunction (n = 9), focal central gray matter lesions found in all regions of the spinal cord within the cohort (n = 16), brain stem lesions (n = 8), and bulbar symptoms (n = 5). Enterovirus D68 was detectable in nasopharyngeal specimens (n = 7) but not in cerebrospinal fluid. Acute therapies (corticosteroids, intravenous immunoglobulins, plasmapheresis) were well tolerated with few side effects. Fourteen of 16 patients who were followed beyond 12 months post onset had neurologic deficits but showed ongoing clinical improvement and motor recovery.

Global alignment of immunization safety assessment in pregnancy - The GAIA project.

Immunization in pregnancy provides a promising contribution to globally reducing neonatal and under-five childhood mortality and morbidity. Thorough assessment of benefits and risks for the primarily healthy pregnant women and their unborn babies is required. The GAIA project was formed in response to the call of the World Health Organization for a globally concerted approach to actively monitor the safety of vaccines and immunization in pregnancy programs. GAIA aims to improve the quality of outcome data from clinical vaccine trials in pregnant women with a specific focus on the needs and requirements for safety monitoring in LMIC. In the first year of the project, a large and functional network of experts was created. The first outputs include a guidance document for clinical trials of immunization in pregnancy, a basic data collection guide, ten case definitions of key obstetric and neonatal health outcomes, an ontology of key terms and a map of pertinent disease codes. The GAIA Network is designed as an open and growing forum for professionals sharing the GAIA vision and aim. Based on the initial achievements, tools and services are developed to support investigators and strengthen immunization in pregnancy programs with specific focus on LMIC.

Webcams, Crowdsourcing, and Enhanced Crosswalks: Developing a Novel Method to Analyze Active Transportation.

INTRODUCTION: Active transportation opportunities and infrastructure are an important component of a community's design, livability, and health. Features of the built environment influence active transportation, but objective study of the natural experiment effects of built environment improvements on active transportation is challenging. The purpose of this study was to develop and present a novel method of active transportation research using webcams and crowdsourcing, and to determine if crosswalk enhancement was associated with changes in active transportation rates, including across a variety of weather conditions. METHODS: The 20,529 publicly available webcam images from two street intersections in Washington, DC, USA were used to examine the impact of an improved crosswalk on active transportation. A crowdsource, Amazon Mechanical Turk, annotated image data. Temperature data were collected from the National Oceanic and Atmospheric Administration, and precipitation data were annotated from images by trained research assistants. RESULTS: Summary analyses demonstrated slight, bi-directional differences in the percent of images with pedestrians and bicyclists captured before and after the enhancement of the crosswalks. Chi-square analyses revealed these changes were not significant. In general, pedestrian presence increased in images captured during moderate temperatures compared to images captured during hot or cold temperatures. Chi-square analyses indicated the crosswalk improvement may have encouraged walking and biking in uncomfortable outdoor conditions (P < 0.5). CONCLUSION: The methods employed provide an objective, cost-effective alternative to traditional means of examining the effects of built environment changes on active transportation. The use of webcams to collect active transportation data has applications for community policymakers, planners, and health professionals. Future research will work to validate this method in a variety of settings as well as across different built environment and community policy initiatives.

Contributions and challenges for worldwide vaccine safety: The Global Advisory Committee on Vaccine Safety at 15 years.

In 1999, the Global Advisory Committee on Vaccine Safety (GACVS) was established by the World Health Organization (WHO) to provide independent scientific advice on issues relating to the safety of vaccines and immunization. Fifteen years onward, we conducted a multi-faceted review to evaluate the impact, reach and challenges facing GACVS, including the role GACVS plays in informing global, regional and WHO member state vaccine policy. The methods included measures of organizational structure, citation impact, themes approached, and a discussion by previous and current members to evaluate past, present and future challenges. Given the increasing range of data sources and the deployment of many new vaccines, the Committee is facing the complex task of identifying the best available evidence for recommendations on vaccine safety. To help meet the increased demand for public transparency in decision making, GACVS-structured methodology for evidence-based decisions is evolving. GACVS also promotes best practices and capacity building for timely and accurate risk assessment; risk communications; outreach to help countries maintain and, if needed, rebuild public trust in vaccines; and advocacy for bridging the major gaps in vaccine safety capacity globally.

Fasting protects mice from lethal DNA damage by promoting small intestinal epithelial stem cell survival.

Short-term fasting protects mice from lethal doses of chemotherapy through undetermined mechanisms. Herein, we demonstrate that fasting preserves small intestinal (SI) architecture by maintaining SI stem cell viability and SI barrier function following exposure to high-dose etoposide. Nearly all SI stem cells were lost in fed mice, whereas fasting promoted sufficient SI stem cell survival to preserve SI integrity after etoposide treatment. Lineage tracing demonstrated that multiple SI stem cell populations, marked by Lgr5, Bmi1, or HopX expression, contributed to fasting-induced survival. DNA repair and DNA damage response genes were elevated in SI stem/progenitor cells of fasted etoposide-treated mice, which importantly correlated with faster resolution of DNA double-strand breaks and less apoptosis. Thus, fasting preserved SI stem cell viability as well as SI architecture and barrier function suggesting that fasting may reduce host toxicity in patients undergoing dose intensive chemotherapy.

Safety of immunization during pregnancy: a review of the evidence of selected inactivated and live attenuated vaccines.

Vaccine-preventable infectious diseases are responsible for significant maternal, neonatal, and young infant morbidity and mortality. While there is emerging scientific evidence, as well as theoretical considerations, indicating that certain vaccines are safe for pregnant women and fetuses, policy formulation is challenging because of perceived potential risks to the fetus. This report presents an overview of available evidence on pregnant women vaccination safety monitoring in pregnant women, from both published literature and ongoing surveillance programs. Safety data were reviewed for vaccines against diseases which increase morbidity in pregnant women, their fetus or infant as well as vaccines which are used in mass vaccination campaigns against diseases. They include inactivated seasonal and pandemic influenza, mono- and combined meningococcal polysaccharide and conjugated vaccines, tetanus toxoid and acellular pertussis combination vaccines, as well as monovalent or combined rubella, oral poliomyelitis virus and yellow fever vaccines. No evidence of adverse pregnancy outcomes has been identified from immunization of pregnant women with these vaccines.

Simple and accurate methods for quantifying deformation, disruption, and development in biological tissues.

When mechanical factors underlie growth, development, disease or healing, they often function through local regions of tissue where deformation is highly concentrated. Current optical techniques to estimate deformation can lack precision and accuracy in such regions due to challenges in distinguishing a region of concentrated deformation from an error in displacement tracking. Here, we present a simple and general technique for improving the accuracy and precision of strain estimation and an associated technique for distinguishing a concentrated deformation from a tracking error. The strain estimation technique improves accuracy relative to other state-of-the-art algorithms by directly estimating strain fields without first estimating displacements, resulting in a very simple method and low computational cost. The technique for identifying local elevation of strain enables for the first time the successful identification of the onset and consequences of local strain concentrating features such as cracks and tears in a highly strained tissue. We apply these new techniques to demonstrate a novel hypothesis in prenatal wound healing. More generally, the analytical methods we have developed provide a simple tool for quantifying the appearance and magnitude of localized deformation from a series of digital images across a broad range of disciplines.

Fast-scale network dynamics in human cortex have specific spectral covariance patterns.

Whether measured by MRI or direct cortical physiology, infraslow rhythms have defined state invariant cortical networks. The time scales of this functional architecture, however, are unlikely to be able to accommodate the more rapid cortical dynamics necessary for an active cognitive task. Using invasively monitored epileptic patients as a research model, we tested the hypothesis that faster frequencies would spectrally bind regions of cortex as a transient mechanism to enable fast network interactions during the performance of a simple hear-and-repeat speech task. We term these short-lived spectrally covariant networks functional spectral networks (FSNs). We evaluated whether spectrally covariant regions of cortex, which were unique in their spectral signatures, provided a higher degree of task-related information than any single site showing more classic physiologic responses (i.e., single-site amplitude modulation). Taken together, our results showing that FSNs are a more sensitive measure of task-related brain activation and are better able to discern phonemic content strongly support the concept of spectrally encoded interactions in cortex. Moreover, these findings that specific linguistic information is represented in FSNs that have broad anatomic topographies support a more distributed model of cortical processing.

Two cloud-based cues for estimating scene structure and camera calibration.

We describe algorithms that use cloud shadows as a form of stochastically structured light to support 3D scene geometry estimation. Taking video captured from a static outdoor camera as input, we use the relationship of the time series of intensity values between pairs of pixels as the primary input to our algorithms. We describe two cues that relate the 3D distance between a pair of points to the pair of intensity time series. The first cue results from the fact that two pixels that are nearby in the world are more likely to be under a cloud at the same time than two distant points. We describe methods for using this cue to estimate focal length and scene structure. The second cue is based on the motion of cloud shadows across the scene; this cue results in a set of linear constraints on scene structure. These constraints have an inherent ambiguity, which we show how to overcome by combining the cloud motion cue with the spatial cue. We evaluate our method on several time lapses of real outdoor scenes.

Capillary and arteriolar pericytes attract innate leukocytes exiting through venules and 'instruct' them with pattern-recognition and motility programs.

Coordinated navigation within tissues is essential for cells of the innate immune system to reach the sites of inflammatory processes, but the signals involved are incompletely understood. Here we demonstrate that NG2(+) pericytes controlled the pattern and efficacy of the interstitial migration of leukocytes in vivo. In response to inflammatory mediators, pericytes upregulated expression of the adhesion molecule ICAM-1 and released the chemoattractant MIF. Arteriolar and capillary pericytes attracted and interacted with myeloid leukocytes after extravasating from postcapillary venules, 'instructing' them with pattern-recognition and motility programs. Inhibition of MIF neutralized the migratory cues provided to myeloid leukocytes by NG2(+) pericytes. Hence, our results identify a previously unknown role for NG2(+) pericytes as an active component of innate immune responses, which supports the immunosurveillance and effector function of extravasated neutrophils and macrophages.

Physically-induced cytoskeleton remodeling of cells in three-dimensional culture.

Characterizing how cells in three-dimensional (3D) environments or natural tissues respond to biophysical stimuli is a longstanding challenge in biology and tissue engineering. We demonstrate a strategy to monitor morphological and mechanical responses of contractile fibroblasts in a 3D environment. Cells responded to stretch through specific, cell-wide mechanisms involving staged retraction and reinforcement. Retraction responses occurred for all orientations of stress fibers and cellular protrusions relative to the stretch direction, while reinforcement responses, including extension of cellular processes and stress fiber formation, occurred predominantly in the stretch direction. A previously unreported role of F-actin clumps was observed, with clumps possibly acting as F-actin reservoirs for retraction and reinforcement responses during stretch. Responses were consistent with a model of cellular sensitivity to local physical cues. These findings suggest mechanisms for global actin cytoskeleton remodeling in non-muscle cells and provide insight into cellular responses important in pathologies such as fibrosis and hypertension.