Pneumococcal conjugate vaccine failure in children: A systematic review of the literature.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) are highly effective in preventing pneumococcal invasive disease (IPD) due to serotypes included in the vaccines. The risk of vaccine-type IPD in immunised children (i.e. vaccine failure) has not been systematically assessed in countries with established PCV programmes. METHODS: We undertook a systematic review of the English literature published from January 2000 to April 2016 to evaluate the vaccine schedule, risk factors, serotype distribution, clinical presentation and outcomes of vaccine failure in children vaccinated with the 7-valent (PCV7), 10-valent (PCV10), and 13-valent (PCV13) vaccines. Data sources included MEDLINE, EMBASE, Cochrane library, and references within identified articles. RESULTS: We identified 1742 potential studies and included 20 publications involving 7584 participants in children aged ⩽5year-olds: 5202 received 2 doses followed by a booster in 10 studies, (68.6%), 64 (0.8%) received 3 doses without a booster in 2 studies, and 2318 received a 3+1 schedule (30.6%) in 8 studies. A total of 159 vaccine failure cases were identified, representing 2.1% [95% CI: 1.8-2.4%] of the reported IPD cases. Most studies did not report clinical characteristics or outcomes. Among eight studies reporting comorbidities, 33/77 patients (42.9%) had an underlying condition. The main serotypes associated with vaccine failure were 19F (51/128 cases with known serotype; 39.8%), 6B (33/128; 25.8%), and 4 (10/128; 7.8%). Only five studies reported patient outcomes, with a crude case fatality rate of 2.4% (2/85; 95%CI: 0.3-8.5%). CONCLUSION: Pneumococcal conjugate vaccines have been implemented in national immunisation programmes for more than a decade, yet there are only a few studies reporting vaccine failure. PCV failure is rare, irrespective of vaccine or schedule. Co-morbidity prevalence was high amongst vaccine failure cases but case fatality rate was relatively low. There is a need for more systematic reporting vaccine failure cases in countries with established pneumococcal vaccination programmes

Timbral and spatial fidelity improvement in ambisonics

© 2015 Elsevier Ltd. All rights reserved. Ambisonics renders a sound field through different kinds of loudspeaker layouts, which leads to different listening perceptions. While some loudspeaker arrays reinforce timbral fidelity, some improve localization accuracy. A split-band decoding is proposed that aims to select and then mix the better reconstructed frequency components from different loudspeaker arrays, thereby achieving the improved quality. The spectral reconstruction errors caused by truncation, comb filtering, and low-pass filtering are illustrated. The proposed solution is described, along with the experimental results from the listening tests. The split-band decoding method is especially suitable for binaural rendering and can also be applied to conventional loudspeaker arrays

Characteristics and serotype distribution of childhood cases of invasive pneumococcal disease following pneumococcal conjugate vaccination in England and Wales, 2006-14

Background The 7-valent (PCV7) and 13-valent (PCV13) pneumococcal conjugate vaccines are highly effective in preventing invasive pneumococcal disease (IPD) caused by vaccine serotypes. Vaccine failure (vaccine-type IPD after age-appropriate immunisation) is rare. Little is known about the risk, clinical characteristics or outcomes of PCV13 compared to PCV7 vaccine failure. Methods Public Health England conducts IPD surveillance and provides a national reference service for serotyping pneumococcal isolates in England and Wales. We compared the epidemiology, rates, risk factors, serotype distribution, clinical characteristics, and outcomes of IPD in children with PCV13 and PCV7 vaccine failure. Results A total of 163 episodes of PCV failure were confirmed in 161 children over eight years (04 September 2006 to 03 September 2014) in ten birth cohorts. After three vaccine doses, PCV7 and PCV13 failure rates were 0.19/100,000 (95% CI, 0.10-0.33; 57 cases) and 0.66/100,000 (95% CI, 0.44-0.99; 104 cases) vaccinated person-years, respectively. Children with PCV13 failure were more likely to be healthy (87/105 [82.9%] vs. 37/56 [66.1%]; P=0.02), present with bacteremic lower respiratory tract infection (61/105 [58.1%] vs. 11/56 [19.6%]; P<0.001) and develop empyema (41/61 [67.2%] vs. 1/11 [9.1%]; P<0.001) compared to PCV7 failures. Serotypes 3 (n=38, 36.2%) and 19A (n=30, 28.6%) were responsible for most PCV13 failures. Five children died (3.1%; 95% CI, 1.0-7.1%), including four with co-morbidities. Conclusions PCV failure is rare and, compared to PCV7 serotypes, the additional PCV13 serotypes are more likely to cause bacteremic lower respiratory tract infection and empyema in healthy vaccinated children

Invasive Pneumococcal Disease in UK Children <1 Year of Age in the Post–13-Valent Pneumococcal Conjugate Vaccine Era: What Are the Risks Now?

Background Invasive pneumococcal disease (IPD) has declined significantly since the introduction of pneumococcal conjugate vaccines (PCVs). It is not known whether certain infant populations remain at higher risk of IPD in countries with established 13-valent PCV (PCV13) programs. We aimed to describe the epidemiology, clinical characteristics, serotype distribution, and outcomes of IPD in infants, and to estimate the relative risk of PCV13-type, non-PCV13-type, and overall IPD in premature infants compared to term infants during a 4-year period after the PCV13 program was established. Methods This was a prospective, enhanced national surveillance of laboratory-confirmed IPD in England in infants aged <1 year diagnosed during 2013–2016. Results There were 517 cases of IPD (incidence: 19/100000 infants). Incidence was significantly higher in premature infants compared with those born at term (49/100000 vs 17/100000; incidence rate ratio [IRR], 2.87; P < .001), with infants born before 28 weeks’ gestation having the highest incidence (150/100000; IRR, 8.8; P < .001). Of the 454 IPD cases with serotyped isolates, most were caused by non-PCV13 serotypes (369 cases, 71.4%), with 85 cases (16.4%) due to PCV13 serotypes. There were 31 deaths (case fatality rate [CFR], 6.2% [95% confidence interval, 4.3%–8.6%]). Premature infants did not have a higher CFR than term infants (P = .62). Conclusions IPD incidence in infants remains lower than rates reported prior to PCV7 introduction in England. The risk of IPD remains significantly higher in premature infants compared to infants born at term, for both PCV13 and non-PCV13 serotypes. Any changes to the infant PCV13 immunization schedule may disproportionally affect premature infants

Measuring optical activity in the far-field from a racemic nanomaterial: Diffraction spectroscopy from plasmonic nanogratings

Recent progress in nanofabrication has redrawn the boundaries of the applicability of chiroptical (chiral optical) effects. Chirality, often expressed as a twist in biomolecules, is crucial for pharmaceuticals, where it can result in extremely different chemical properties. Because chiroptical effects are typically very weak in molecules, plasmonic nanomaterials are often proposed as a promising platform to significantly enhance these effects. Unfortunately, the ideal plasmonic nanomaterial has conflicting requirements: Its chirality should enhance that of the chiral molecules and yet it should have no chiroptical response on its own. Here, we propose a unique reconciliation to satisfy the requirements: A racemic plasmonic nanomaterial, consisting of equal amounts of opposite chiral unit cells. We show how diffraction spectroscopy can be used to unveil the presence of chirality in such racemic nanogratings in the far-field. Our experiments are supported by numerical simulations and yield a circular intensity difference of up to 15%. The physical origin is demonstrated by full wave simulations in combination with a Green's function-group-theory-based analysis. Contributions from Circular Dichroism in the Angular Distribution of Photoelectrons (CDAD) and pseudo/extrinsic chirality are ruled out. Our findings enable the far-field measurement and tuning of racemic nanomaterials, which is crucial for hyper-sensitive chiral molecular characterization.V. K. V. acknowledges support from the Royal Society through the University Research Fellowships. We acknowledge Royal Society grants CHG\R1\170067, PEF1\170015 and RGF\EA\180228, as well as STFC grant ST/R005842/1 and EPSRC grant EP/L015544/1. C. W. acknowledges financial support from Cancer Research UK (CRUK) Pioneer Award (C55962/A24669) and Wolfson College, Cambridge, UK. C. W. further acknowledges research support from S. Bohndiek, T. Wilkinson and G. Gordon. X. Z. and G. A. E. V. are grateful for the financial support from the FWO (G090017N) and KU Leuven internal research funds (C24/15/015)

Reproducible kk-means clustering in galaxy feature data from the GAMA survey

A fundamental bimodality of galaxies in the local Universe is apparent in many of the features used to describe them. Multiple sub-populations exist within this framework, each representing galaxies following distinct evolutionary pathways. Accurately identifying and characterising these sub-populations requires that a large number of galaxy features be analysed simultaneously. Future galaxy surveys such as LSST and Euclid will yield data volumes for which traditional approaches to galaxy classification will become unfeasible. To address this, we apply a robust $k$-means unsupervised clustering method to feature data derived from a sample of 7338 local-Universe galaxies selected from the Galaxy And Mass Assembly (GAMA) survey. This allows us to partition our sample into $k$ clusters without the need for training on pre-labelled data, facilitating a full census of our high dimensionality feature space and guarding against stochastic effects. We find that the local galaxy population natively splits into $2$, $3$, $5$ and a maximum of $6$ sub-populations, with each corresponding to a distinct ongoing evolutionary mechanism. Notably, the impact of the local environment appears strongly linked with the evolution of low-mass ($M_{*} < 10^{10}$ M$_{\odot}$) galaxies, with more massive systems appearing to evolve more passively from the blue cloud onto the red sequence. With a typical run time of $\sim3$ minutes per value of $k$ for our galaxy sample, we show how $k$-means unsupervised clustering is an ideal tool for future analysis of large extragalactic datasets, being scalable, adaptable, and providing crucial insight into the fundamental properties of the local galaxy population

Characteristics of Invasive Pneumococcal Disease Caused by Emerging Serotypes After the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in England: A Prospective Observational Cohort Study, 2014-2018.

BACKGROUND: England is experiencing a rapid increase in invasive pneumococcal disease (IPD) caused by serotypes 8, 12F, and 9N; their clinical characteristics and outcomes have not been described. METHODS: Public Health England conducts national IPD surveillance. Cases due to emerging serotypes were compared with those included in the 13-valent pneumococcal conjugate vaccine (PCV13) and the remaining non-PCV13 serotypes. RESULTS: There were 21 592 IPD cases during 2014-15 to 2017-18, including 20 108 (93.1%) with serotyped isolates and 17 450 (86.8%) with completed questionnaires. PCV13 serotypes were responsible for 20.1% (n = 4033), while serotype 8 (3881/20 108 [19.3%]), 12F (2365/20 108 [11.8%]), and 9N (1 296/20 108 [6.4%]) were together responsible for 37.5% of cases. Invasive pneumonia was the most common presentation (11 424/16 346 [69.9%]) and, overall, 67.0% (n = 11 033) had an underlying comorbidity. The median age (interquartile range) at IPD due to serotypes 8 (59 [45-72] years) and 12F (56 [41-70] years) was lower than serotype 9N (67 [53-80] years), PCV13 serotypes (68 [52-81] years), and remaining non-PCV13 serotypes (70 [53-82] years). Serotype 9N IPD cases also had higher comorbidity prevalence (748/1087 [68.8%]) compared to serotype 8 (1901/3228 [58.9%]) or 12F (1042/1994 [52.3%]), and higher case fatality (212/1128 [18.8%]) compared to 8.6% (291/3365) or 10.0% (209/2086), respectively. CONCLUSIONS: Serotypes 8 and 12F were more likely to cause IPD in younger, healthier individuals and less likely to be fatal, while serotype 9N affected older adults with comorbidities and had higher case fatality

TiO2 -coated CoCrMo: Improving the osteogenic differentiation and adhesion of mesenchymal stem cells in vitro.

The current gold standard material for orthopedic applications is titanium (Ti), however, other materials such as cobalt-chromium-molybdenum (CoCrMo) are often preferred due to their wear resistance and mechanical strength. This study investigates if the bioactivity of CoCrMo can be enhanced by coating the surface with titanium oxide (TiO2 ) by atmospheric pressure chemical vapor deposition (CVD), thereby replicating the surface oxide layer found on Ti. CoCrMo, TiO2 -coated CoCrMo (CCMT) and Ti substrates were used for this study. Cellular f-actin distribution was shown to be noticeably different between cells on CCMT and CoCrMo after 24 h in osteogenic culture, with cells on CCMT exhibiting greater spread with developed protrusions. Osteogenic differentiation was shown to be enhanced on CCMT compared to CoCrMo, with increased calcium ion content per cell (p < 0.05), greater hydroxyapatite nodule formation (p < 0.05) and reduced type I collagen deposition per cell (p < 0.05). The expression of the focal adhesion protein vinculin was shown to be marginally greater on CCMT compared to CoCrMo, whereas AFM results indicated that CCMT required more force to remove a single cell from the substrate surface compared to CoCrMo (p < 0.0001). These data suggest that CVD TiO2 coatings may have the potential to increase the biocompatibility of CoCrMo implantable devices. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1208-1217, 2015

Quantum Gravity in Everyday Life: General Relativity as an Effective Field Theory

This article is meant as a summary and introduction to the ideas of effective field theory as applied to gravitational systems. Contents: 1. Introduction 2. Effective Field Theories 3. Low-Energy Quantum Gravity 4. Explicit Quantum Calculations 5. ConclusionsComment: 56 pages, 2 figures, JHEP style, Invited review to appear in Living Reviews of Relativit