No systemic reactions to influenza vaccination in egg-sensitized tertiary-care pediatric patients

<p>Abstract</p> <p>Background</p> <p>There are numerous, disparate guidelines for influenza vaccination in egg-allergic patients. We aimed to describe the outcome of selectively applied guidelines, based on risk-stratification, to our high risk, egg-allergic, tertiary-care pediatric population.</p> <p>Methods</p> <p>Egg allergy was confirmed with skin testing. The vaccine administered was an adjuvunated 2009 H1N1 influenza A vaccine with < 0.165 mcg/ml ovalbumin. Patients with mild egg allergy were to receive the vaccination in 1 dose, those with severe egg allergy were to receive 2 split doses, and patients with exquisite egg allergy or significant co-morbidities were to be skin tested with the vaccine (prick full strength, intradermal 1:100 of final concentration without adjuvant) and had 5 step desensitization if the testing was positive, or 1-2 step administration if negative. Patients were observed for 60 minutes after the final dose and anaphylaxis treatment was available. We report the frequency of allergic reactions.</p> <p>Results</p> <p>Ninety-nine patients were referred and 79 had positive egg testing. Asthma was present in 67% and 30% had prior anaphylaxis to egg. We vaccinated 77 of 79 patients: 71 without performing vaccine skin testing. Two refused vaccination. No patient had a systemic reaction or required treatment. Two patients experienced positive testing to the adjuvanated intradermal vaccine, but were negative without adjuvant.</p> <p>Conclusions</p> <p>Our results suggest that most egg-allergic tertiary care pediatric patients can be vaccinated with a low ovalbumin content influenza vaccine without prior vaccine testing. Vaccine skin testing, if used at all, can be reserved for special circumstances. The squalene adjuvant may cause an irritant reaction with intradermal testing.</p

The Visual Orbit of the 1.1-day Spectroscopic Binary \sigma^2 Coronae Borealis from Interferometry at the CHARA Array

We present an updated spectroscopic orbit and a new visual orbit for the double-lined spectroscopic binary \sigma^2 Coronae Borealis based on radial velocity measurements at the Oak Ridge Observatory in Harvard, Massachusetts and interferometric visibility measurements at the CHARA Array on Mount Wilson. \sigma^2 CrB is composed of two Sun-like stars of roughly equal mass in a circularized orbit with a period of 1.14 days. The long baselines of the CHARA Array have allowed us to resolve the visual orbit for this pair, the shortest period binary yet resolved interferometrically, enabling us to determine component masses of 1.137 \pm 0.037 M_sun and 1.090 \pm 0.036 M_sun. We have also estimated absolute V-band magnitudes of MV (primary) = 4.35 \pm 0.02 and MV(secondary) = 4.74 \pm 0.02. A comparison with stellar evolution models indicates a relatively young age of 1-3 Gyr, consistent with the high Li abundance measured previously. This pair is the central component of a quintuple system, along with another similar-mass star, \sigma^1 CrB, in a ~ 730-year visual orbit, and a distant M-dwarf binary, \sigma CrB C, at a projected separation of ~ 10 arcmin. We also present differential proper motion evidence to show that components C & D (ADS 9979C & D) listed for this system in the Washington Double Star Catalog are optical alignments that are not gravitationally bound to the \sigma CrB system.Comment: 40 pages, 14 figures. Accepted by Ap

Measuring the predictability of life outcomes with a scientific mass collaboration.

How predictable are life trajectories? We investigated this question with a scientific mass collaboration using the common task method; 160 teams built predictive models for six life outcomes using data from the Fragile Families and Child Wellbeing Study, a high-quality birth cohort study. Despite using a rich dataset and applying machine-learning methods optimized for prediction, the best predictions were not very accurate and were only slightly better than those from a simple benchmark model. Within each outcome, prediction error was strongly associated with the family being predicted and weakly associated with the technique used to generate the prediction. Overall, these results suggest practical limits to the predictability of life outcomes in some settings and illustrate the value of mass collaborations in the social sciences

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Phenotyping heart failure using model‐based analysis and physiology‐informed machine learning

To phenotype mechanistic differences between heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fraction, a closed‐loop model of the cardiovascular system coupled with patient‐specific transthoracic echocardiography (TTE) and right heart catheterization (RHC) data was used to identify key parameters representing haemodynamics. Thirty‐one patient records (10 HFrEF, 21 HFpEF) were obtained from the Cardiovascular Health Improvement Project database at the University of Michigan. Model simulations were tuned to match RHC and TTE pressure, volume, and cardiac output measurements in each patient. The underlying physiological model parameters were plotted against model‐based norms and compared between HFrEF and HFpEF. Our results confirm the main mechanistic parameter driving HFrEF is reduced left ventricular (LV) contractility, whereas HFpEF exhibits a heterogeneous phenotype. Conducting principal component analysis, k‐means clustering, and hierarchical clustering on the optimized parameters reveal (i) a group of HFrEF‐like HFpEF patients (HFpEF1), (ii) a classic HFpEF group (HFpEF2), and (iii) a group of HFpEF patients that do not consistently cluster (NCC). These subgroups cannot be distinguished from the clinical data alone. Increased LV active contractility (p<0.001) and LV passive stiffness (p<0.001) at rest are observed when comparing HFpEF2 to HFpEF1. Analysing the clinical data of each subgroup reveals that elevated systolic and diastolic LV volumes seen in both HFrEF and HFpEF1 may be used as a biomarker to identify HFrEF‐like HFpEF patients. These results suggest that modelling of the cardiovascular system and optimizing to standard clinical data can designate subgroups of HFpEF as separate phenotypes, possibly elucidating patient‐specific treatment strategies.Key pointsAnalysis of data from right heart catheterization (RHC) and transthoracic echocardiography (TTE) of heart failure (HF) patients using a closed‐loop model of the cardiovascular system identifies key parameters representing haemodynamic cardiovascular function in patients with heart failure with reduced and preserved ejection fraction (HFrEF and HFpEF).Analysing optimized parameters representing cardiovascular function using machine learning shows mechanistic differences between HFpEF groups that are not seen analysing clinical data alone.HFpEF groups presented here can be subdivided into three subgroups: HFpEF1 described as ‘HFrEF‐like HFpEF’, HFpEF2 as ‘classic HFpEF’, and a third group of HFpEF patients that do not consistently cluster.Focusing purely on cardiac function consistently captures the underlying dysfunction in HFrEF, whereas HFpEF is better characterized by dysfunction in the entire cardiovascular system.Our methodology reveals that elevated left ventricular systolic and diastolic volumes are potential biomarkers for identifying HFrEF‐like HFpEF patients.Abstract figure legend Patient specific modeling and heart failure classification workflow.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171042/1/tjp14830_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171042/2/tjp14830-sup-0003-PeerReview.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171042/3/tjp14830.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171042/4/tjp14830-sup-0002-SuppMat.pd

Development and applications of oncolytic Maraba virus vaccines

International audienceOncolytic activity of the MG1 strain of the Maraba vesiculovirus has proven efficacy in numerous preclinical cancer models, and relied not only on a direct cytotoxicity but also on the induction of both innate and adaptive antitumor immunity. To further expand tumor-specific T-cell effector and long-lasting memory compartments, we introduced the MG1 virus in a prime-boost cancer vaccine strategy. To this aim, a replication-incompetent adenoviral [Ad] vector together with the oncolytic MG1 have each been armed with a transgene expressing a same tumor antigen. Immune priming with the Ad vaccine subsequently boosted with the MG1 vaccine mounted tumor-specific responses of remarkable magnitude, which significantly prolonged survival in various murine cancer models. Based on these promising results, we validated the safety profile of the Ad:MG1 oncolytic vaccination strategy in nonhuman primates and initiated clinical investigations in cancer patients. Two clinical trials are currently under way (NCT02285816; NCT02879760). The present review will recapitulate the discoveries that led to the development of MG1 oncolytic vaccines from bench to bedside