Assessing recording delays in general practice records to inform near real-time vaccine safety surveillance using the Clinical Practice Research Datalink (CPRD).

PURPOSE: Near real-time vaccine safety surveillance (NRTVSS) is an option for post-licensure vaccine safety assessment. NRTVSS requires timely recording of outcomes in the database used. Our main objective was to examine recording delays in the Clinical Practice Research Datalink (CPRD) for outcomes of interest for vaccine safety to inform the feasibility of NRTVSS using these data. We also evaluated completeness of recording and further assessed reporting delays for hospitalized events in CPRD. METHODS: We selected Guillain-Barré syndrome (GBS), Bell's palsy (BP), optic neuritis (ON) and febrile seizures (FS), from January 2005 to June 2014. We assessed recording delays (e.g. due to feedback from specialist referral) in stand-alone CPRD by comparing the event and system dates and excluding delays >1 year. We used linked CPRD-hospitalization data to further evaluate delays and completeness of recording in CPRD. RESULTS: Among 51 220 patients for the stand-alone CPRD analysis (GBS: n = 830; BP: n = 12 602; ON: n = 1720; and FS: n = 36 236), most had a record entered within 1 month of the event date (GBS: 73.6%; BP: 93.4%; ON: 76.2%; and FS: 85.6%). A total of 13 482 patients, with a first record in hospital, were included for the analysis of linked data (GBS: n = 678; BP: n = 4060; ON: n = 485; and FS: n = 8321). Of these, <50% had a record in CPRD after 1 year (GBS: 41.3%; BP: 22.1%; ON: 22.4%; and FS: 41.8%). CONCLUSION: This work shows that most diagnoses in CPRD for the conditions examined were recorded with delays of ≤30 days, making NRTVSS possible. The pattern of delays was condition-specific and could be used to adjust for delays in the NRTVSS analysis. Despite low sensitivity of recording, implementing NRTVSS in CPRD is worthwhile and could be carried out, at least on a trial basis, for events of interest. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd

Implementing near real-time vaccine safety surveillance using the Clinical Practice Research Datalink (CPRD).

INTRODUCTION: Near real-time vaccine safety surveillance (NRTVSS) using electronic health records is increasingly used to rapidly detect vaccine safety signals. NRTVSS has not been fully implemented in the UK. We assessed the feasibility of implementing this surveillance using the UK Clinical Practice Research Datalink (CPRD). METHODS: We selected seasonal influenza vaccine/Guillain-Barré Syndrome (GBS) as an example of a rare outcome and measles-mumps-rubella (MMR) vaccine/febrile seizures as a positive control. For influenza/GBS we implemented a system for the 2013/2014 and 2014/2015 influenza seasons; for MMR/seizures the surveillance period was July 2014-June 2015. We used the continuous Poisson-based maximized sequential probability ratio test (PMaxSPRT), comparing observed-to-expected events, for both pairs. We calculated an age-sex-adjusted rate using 5years of historic data and used this rate to calculate the expected number of events in pre-specified post-vaccination risk-window (GBS: 0-42days, seizures: 6-21days). For MMR/seizures we also implemented the system using the Binominal-based maximized sequential probability ratio test (BMaxSPRT). For this, we compared seizures in the risk-window (6-21days) to a control window (0-5 and 22-32days). Delays in recording outcomes influence the data available, so we adjusted the expected number of events using a historical distribution of delays in recording GBS/febrile seizures. Analyses were run using data up to each CPRD monthly release. We also performed power calculations for detecting increases in relative risk (RR) from 1.5 to 10. RESULTS: For influenza/GBS we implemented a system in both seasons with no signal. Power to detect a signal was >80% for RR≥4. For MMR/seizures we were able to identify a signal with PMaxSPRT but not with BMaxSPRT. Power≥80% for RR≥2.5 for both tests. CONCLUSION: CPRD is a potential data source to implement NRTVSS to exclude large increases in the risk of rare outcomes after seasonal influenza and lower increases in risk for more frequent outcomes

CONDOR: Long endurance high altitude vehicle, volume 5

The results of a design study resulting in the proposed CONDOR aircraft are presented. The basic requirements are for the aircraft to maintain continuous altitude at or above 45,000 feet for at least a 3-day mission, be able to comfortably support a two-man crew during this period with their field of vision not obstructed to a significant degree, carry a payload of 200 pounds, and provide a power supply to the payload of 2000 watts. The take-off and landing distances must be below 5000. feet, and time to reach cruise altitude must not exceed 3 hours. The subjects discussed are configuration selection, structural analysis, stability and control, crew and payload accomodations, and economic estimates

SDSS-IV MaNGA: Identification of active galactic nuclei in optical integral field unit surveys

In this paper, we investigate 2727 galaxies observed by MaNGA as of June 2016 to develop spatially resolved techniques for identifying signatures of active galactic nuclei (AGN). We identify 303 AGN candidates. The additional spatial dimension imposes challenges in identifying AGN due to contamination from diffuse ionized gas, extra-planar gas and photoionization by hot stars. We show that the combination of spatially-resolved line diagnostic diagrams and additional cuts on H$\alpha$ surface brighness and H$\alpha$ equivalent width can distinguish between AGN-like signatures and high-metallicity galaxies with LINER-like spectra. Low mass galaxies with high specific star formation rates are particularly difficult to diagnose and routinely show diagnostic line ratios outside of the standard star-formation locus. We develop a new diagnostic -- the distance from the standard diagnostic line in the line-ratios space -- to evaluate the significance of the deviation from the star-formation locus. We find 173 galaxies that would not have been selected as AGN candidates based on single-fibre spectral measurements but exhibit photoionization signatures suggestive of AGN activity in the MaNGA resolved observations, underscoring the power of large integral field unit (IFU) surveys. A complete census of these new AGN candidates is necessary to understand their nature and probe the complex co-evolution of supermassive black holes and their hosts.Comment: 18 pages, 11 figures, accepted to MNRA

Trends in the burden of varicella in UK general practice.

Childhood varicella vaccination has not yet been introduced in the UK. To inform decision-making about future vaccine programmes, data on the burden of varicella in general practice over a 10-year period (01/01/2005-31/12/2014) was calculated by age and ethnicity, using anonymised data from >8 million individuals in the Clinical Practice Research Datalink. Varicella consultations peaked at 20 603 in 2007, then decreased annually in all age groups to 11 243 in 2014. Each year, consultation rates were common among infants, were highest among 1-3 year olds (61·2 consultations/1000 person-years in 2007, 39·7/1000 person-years in 2014) and then fell with increasing age to <1·0/1000 person-years at ages ⩾20 years. Varicella acquisition appeared to be delayed in some ethnic groups, with lower consultation rates for children aged <3 years but increased rates for older children and adults aged ⩽40 years among those of black African, Afro-Caribbean, South Asian or other Asian ethnicity. Decreasing general practice consultation rates over time could reflect changes in healthcare utilisation, with patients seeking care in alternative settings such as Accident and Emergency Departments, although current data prevent full assessment of this. Availability of data on varicella diagnoses across all health settings would enable estimation of the total healthcare burden due to varicella and the cost-effectiveness of introducing varicella vaccination

A mouse polyomavirus-encoded microRNA targets the cellular apoptosis pathway through Smad2 inhibition

AbstractSome viruses and most eukaryotic cells have microRNAs that regulate the expression of many genes. Although many viral miRNAs have been identified, only a few have been included in in vivo functional studies. Here we show that a Py-encoded miRNA downregulates the expression of the pro-apoptotic factor Smad2, resulting in the suppression of the apoptosis pathway. To study the Py miRNA in an in vivo context, a miRNA-deficient mutant virus was created on the background of the LID virus strain which establishes a rapid and lethal infection in newborn mice. Apoptosis analysis on kidney tissues indicates that the pro-apoptotic pathway is targeted in the infected host as well. Suppression of apoptosis through targeting of Smad2 by the Py miRNA is expected to synergize with anti-apoptotic effects previously attributed to the polyoma tumor antigens in support of virus replication in the natural host

Thermal Protection System with Staggered Joints

The thermal protection system disclosed herein is suitable for use with a spacecraft such as a reentry module or vehicle, where the spacecraft has a convex surface to be protected. An embodiment of the thermal protection system includes a plurality of heat resistant panels, each having an outer surface configured for exposure to atmosphere, an inner surface opposite the outer surface and configured for attachment to the convex surface of the spacecraft, and a joint edge defined between the outer surface and the inner surface. The joint edges of adjacent ones of the heat resistant panels are configured to mate with each other to form staggered joints that run between the peak of the convex surface and the base section of the convex surface

Effectiveness of herpes zoster vaccination in an older United Kingdom population.

BACKGROUND: Vaccination against herpes zoster was introduced in the United Kingdom in 2013 for individuals aged 70 years, with a phased catch-up campaign for 71-79 year olds. Vaccine introduction has resulted in a marked fall in incident herpes zoster and in post-herpetic neuralgia (PHN), but formal evaluation of vaccine effectiveness is needed. METHODS: In a population-based cohort study of older individuals born between 1933 and 1946, we used linked UK anonymised primary care health records for the first three years of the vaccination programme (01/09/2013-31/08/2016) and multivariable Poisson regression to obtain incidence rates and vaccine effectiveness (VE) against zoster and PHN. RESULTS: Among 516,547 individuals, 21% were vaccinated. Incidence of zoster was 3.15/1000 person-years in vaccinees and 8.80/1000 person-years in unvaccinated individuals. After adjustment, VE was 64% (95%CI = 60-68%) against incident zoster and 81% (95%CI = 61-91%) against PHN, with very similar VE estimates in the routine and catch-up cohorts. VE against zoster was lower in those with a previous history of zoster: 47% (95%CI = 31-58%) versus 64% (95%CI = 60-68%) in those without previous zoster. There was evidence of waning VE over time, from 69% (95%CI = 65-74%) in the first year after vaccination to 45% (95%CI = 29-57%) by the third year. CONCLUSION: This first formal assessment of VE in the UK zoster vaccination programme demonstrates good effectiveness of zoster vaccine, and very good protection against PHN. The findings provide evidence that VE is similar across the age groups targeted for vaccination in the UK, and on duration of protection of the vaccine in public health use. The study provides key information for decision-makers about the future direction of UK zoster vaccination programme, indicating that the live zoster vaccine may be more cost-effective than estimated previously. It also supports efforts to communicate the benefits of zoster vaccination to address the declining coverage observed across the UK