3,545 research outputs found
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
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Invasive Pneumococcal Disease in UK Children <1 Year of Age in the Postâ13-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 2013â2016.
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 weeksâ 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%â8.6%]). 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
Access Anglesey 2018: Lessons from an inclusive field course
Abstract. Traditional methods of fieldwork delivery can present learners with a range of physical, cognitive and social challenges which may subsequently hinder their ability to engage effectively with learning. We developed a residential geoscience field course designed to be physically accessible to, and socially inclusive of, a diverse range of learners including those with limited physical mobility and neurodiverse conditions. This paper presents the logistical and pedagogical challenges involved in delivering such a field course. In terms of pedagogic design scheduling, pace and timing, and the ability to access content in multiple ways were critical to ensuring that all students were included in the learning. The most effective mitigations were the simplest and benefitted the whole group. Practical interventions found to support access and inclusion for the benefit of all participants included using an audio tour-guide system to communicate with students at field locations, using a four-wheel drive vehicle to improve access to specific locations, providing alternative exercises such as prepared photomicrographs and rock specimens, providing electronic tablets with suitable apps, and selecting accommodation with accessible common-room spaces, and a dedicated quiet room. </jats:p
A multi-phenotypic imaging screen to identify bacterial effectors by exogenous expression in a HeLa cell line
We present a high-content screen (HCS) for the simultaneous analysis of multiple phenotypes in HeLa cells expressing an autophagy reporter (mcherry-LC3) and one of 209 GFP-fused proteins from the Crohnâs Disease (CD)-associated bacterium, Adherent Invasive E. coli (AIEC) strain LF82. Using automated confocal microscopy and image analysis (CellProfiler), we localised GFP fusions within cells, and monitored their effects upon autophagy (an important innate cellular defence mechanism), cellular and nuclear morphology, and the actin cytoskeleton. This data will provide an atlas for the localisation of 209 AIEC proteins within human cells, as well as a dataset to analyse their effects upon many aspects of host cell morphology. We also describe an open-source, automated, image-analysis workflow to identify bacterial effectors and their roles via the perturbations induced in reporter cell lines when candidate effectors are exogenously expressed
Semi-analytical approach to magnetized temperature autocorrelations
The cosmic microwave background (CMB) temperature autocorrelations, induced
by a magnetized adiabatic mode of curvature inhomogeneities, are computed with
semi-analytical methods. As suggested by the latest CMB data, a nearly
scale-invariant spectrum for the adiabatic mode is consistently assumed. In
this situation, the effects of a fully inhomogeneous magnetic field are
scrutinized and constrained with particular attention to harmonics which are
relevant for the region of Doppler oscillations. Depending on the parameters of
the stochastic magnetic field a hump may replace the second peak of the angular
power spectrum. Detectable effects on the Doppler region are then expected only
if the magnetic power spectra have quasi-flat slopes and typical amplitude
(smoothed over a comoving scale of Mpc size and redshifted to the epoch of
gravitational collapse of the protogalaxy) exceeding 0.1 nG. If the magnetic
energy spectra are bluer (i.e. steeper in frequency) the allowed value of the
smoothed amplitude becomes, comparatively, larger (in the range of 20 nG). The
implications of this investigation for the origin of large-scale magnetic
fields in the Universe are discussed. Connections with forthcoming experimental
observations of CMB temperature fluctuations are also suggested and partially
explored.Comment: 40 pages, 13 figure
Grand Challenges: Improving HIV Treatment Outcomes by Integrating Interventions for Co-Morbid Mental Illness.
In the fourth article of a five-part series providing a global perspective on integrating mental health, Sylvia Kaaya and colleagues discuss the importance of integrating mental health interventions into HIV prevention and treatment platforms. Please see later in the article for the Editors' Summary
WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics
Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Î-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Î-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe
The epidemiology of patellar luxation in dogs attending primary-care veterinary practices in England
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