Characterization of antigen-presenting properties of tumour cells using virus-specific cytotoxic T lymphocytes

Immunotherapy of tumours by induction of tumour-specific cytotoxic T-lymphocytes (CTLs) will only be effective for tumours with a functional antigen processing and presentation machinery. However, many tumours are known to down-regulate expression of major histocompatibility complex (MHC) class I molecules and/or to impair antigen processing. It is therefore desirable to evaluate the ability of a given tumour to present antigenic epitopes before developing an immunotherapy protocol. In this study we have used influenza virus as a tool to determine the antigen-presenting capacities of the murine neuroblastoma C1300 cell line NB41A3, a frequently used model for human neuroblastoma. Immunofluorescence analyses revealed low and moderate expression of MHC class I molecules Ddand Kkrespectively. Nevertheless, infected NB41A3 cells were lysed efficiently by influenza-specific CTLs. These results demonstrate that all steps of the antigen-processing pathway function properly in the NB tumour cells, and that the limited MHC class I expression suffices for efficient recognition by CTLs. In addition, lysis of the NB tumour cells shows that the cells are susceptible to CTL-induced apoptosis, a pathway that is often impaired in tumour cells. These characteristics make neuroblastoma a suitable target for immunotherapy. The presented assay allows evaluation of various immunological properties of tumour cells and, thus, represents a valuable tool to assess whether a given tumour will be susceptible to immunotherapy or not. Copyright 2000 Cancer Research Campaign. © 2000 Cancer Research Campaig

Search for the lepton flavour violating decay tau(-) -> mu(-)mu(+)mu(-)

A search for the lepton flavour violating decay tau(-) -&gt; mu(-)mu(+)mu(-) is performed with the LHCb experiment. The data sample corresponds to an integrated luminosity of 1.0 fb(-1) of proton-proton collisions at a centre-of-mass energy of 7 TeV and 2.0 fb(-1) at 8 TeV. No evidence is found for a signal, and a limit is set at 90% confidence level on the branching fraction, B(tau(-) -&gt; mu(-)mu(+)mu(-)) &lt;4.6 x 10(-8).</p

Angular analysis of the B-0 -&gt; K*(0) e(+) e(-) decay in the low-q(2) region

An angular analysis of the B-0 -&gt; K(*0)e(+) e(-) decay is performed using a data sample, corresponding to an integrated luminosity of 3.0 fb(-1), collected by the LHCb experiment in pp collisions at centre-of-mass energies of 7 and 8TeV during 2011 and 2012. For the first time several observables are measured in the dielectron mass squared (q(2)) interval between 0.002 and 1.120 GeV2/c(4). The angular observables F-L and A(T)(Re) which are related to the K-*0 polarisation and to the lepton forward-backward asymmetry, are measured to be F-L = 0.16 +/- 0.06 +/- 0.03 and A(T)(Re) = 0.10 +/- 0.18 +/- 0.05, where the first uncertainty is statistical and the second systematic. The angular observables A(T)((2)) and A(T)(Im) which are sensitive to the photon polarisation in this q(2) range, are found to be A(T)((2)) = - 0.23 +/- 0.23 +/- 0.05 and A(T)(Im) = 0.14 +/- 0.22 +/- 0.05. The results are consistent with Standard Model predictions.</p

Factors associated with the uptake of newly introduced childhood vaccinations in Ethiopia:the cases of rotavirus and pneumococcal conjugate vaccines

Background: Childhood immunization programmes have made substantial contributions to lowering the burden of disease among children in developing countries, however a large proportion of children still remain unimmunized. This study aimed to explore the determinants of rotavirus vaccine (RVV) and pneumococcal conjugate vaccine (PCV) uptake in Ethiopia. Methods: The 2016 Ethiopian demographic and health survey dataset was used in this analysis. A total of 2004 children aged 12-23 months were included in the analysis. A multivariable logistic regression model was employed to identify the determinants of uptake of the complete schedules of RVV (two doses) and PCV (three doses). Crude and adjusted odds ratios with 95% confidence intervals (CIs) were calculated. Results: The uptakes of the complete schedules of RVV and PCV among children aged 12-23 months were 56 and 49.1%, respectively. The likelihood of immunization with the complete schedule of RVV was significantly lower among children from the relatively poor Afar region in Ethiopia (AOR 0.16; 95%-CI 0.04-0.61). Similarly, children living in not only the Afar region (AOR 0.10; 95%-CI 0.03-0.38), but also the Gambela region (AOR 0.25; 95%-CI 0.08-0.83), were less likely to be vaccinated with PCV. On the other hand, children from more wealthy households had higher odds of vaccination with RVV (AOR 1.69; 95%-CI 1.04-2.75). Also attending antenatal care (ANC) was found to be significantly associated with uptake of the complete schedule of RVV and PCV. Conclusions: The uptake of RVV and PCV is suboptimal in Ethiopia. The uptake of the vaccines were found to be associated with region, ANC use and wealth status

Influenza vaccination of hospital healthcare staff from the perspective of the employer:a positive balance

OBJECTIVE: To assess the annual productivity loss among hospital healthcare workers attributable to influenza and to estimate the costs and economic benefits of a vaccination programme from the perspective of the the employer.DESIGN: Cost-benefit analysis.METHODS: The percentage of work loss due to influenza was determined using monthly age and gender specific figures for productivity loss among healthcare workers of the University Medical Center Groningen (UMCG), the Netherlands over the period January 2006-June 2008. Influenza periods were determined on the basis of national surveillance data. The average increase in productivity loss in these periods was estimated by comparison with the periods outside influenza seasons. The direct costs of productivity loss from the perspective of the employer were estimated using the friction cost method. In the sensitivity analyses various modelling parameters were varied, such as the vaccination coverage.RESULTS: In the UMCG, with approximately 9,400 employees, the estimated annual costs associated with productivity loss due to influenza before the introduction of the yearly influenza vaccination program were € 675,242 or on average, € 72 per employee. The economic benefits of the current vaccination program with a vaccination coverage of 24% with a vaccine effectiveness of 71% were estimated at € 89,858 or € 10 per employee. The nett economic benefits of a vaccination program with a target vaccination coverage of 70% with a vaccine effectiveness of 71% were estimated at € 244,325 or € 26 per employee.CONCLUSION: This modelling study performed from the perspective of the employer showed that an annual influenza vaccination programme for hospital personnel can save costs.</p

Rotavirus Vaccination of Infants Delayed and Limited within the National Immunization Programme in the Netherlands:An Opportunity Lost

In this study, we estimated the benefits of rotavirus vaccination for infants had the rotavirus vaccine been introduced in the Netherlands as of its market authorization in 2006. An age-structured, deterministic cohort model was developed to simulate different birth cohorts over a period of 15 years from 2006 until 2021, comparing both universal and targeted high-risk group vaccination to no vaccination. Different scenarios for the duration of protection (5 or 7 years) and herd immunity (only for universal vaccination) were analyzed. All birth cohorts together included 2.6 million infants, of which 7.9% were high-risk individuals, and an additional 13.2 million children between 1-15 years born prior to the first cohort in 2006. The costs and health outcomes associated with rotavirus vaccination were calculated per model scenario and discounted at 4% and 1.5%, respectively. Our analysis reveals that, had rotavirus vaccination been implemented in 2006, it would have prevented 356,800 (51% decrease) and 32,200 (5% decrease) cases of rotavirus gastroenteritis after universal and targeted vaccination, respectively. Over the last 15 years, this would have led to significant avoided costs and quality-adjusted life year losses for either vaccination strategy with the most favorable outcomes for universal vaccination. Clearly, an opportunity has been lost

Cost-Effectiveness of Pediatric Influenza Vaccination in The Netherlands

Objective: This study evaluates the cost-effectiveness of extending the Dutch influenza vaccination program for elderly and medical high-risk groups to include pediatric influenza vaccination, taking indirect protection into account. Methods: An age-structured dynamic transmission model was used that was calibrated to influenza-associated GP visits over 4 seasons (2010-2011 to 2013-2014). The clinical and economic impact of different pediatric vaccination strategies were compared over 20 years, varying the targeted age range, the vaccine type for children or elderly and high-risk groups. Outcome measures include averted symptomatic infections and deaths, societal costs and quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Costs and QALYs were discounted at 4% and 1.5% annually. Results: At an assumed coverage of 50%, adding pediatric vaccination for 2to 17-year-olds with quadrivalent live-attenuated vaccine to the current vaccination program for elderly and medical high-groups with quadrivalent inactivated vaccine was estimated to avert, on average, 401 820 symptomatic cases and 72 deaths per year. Approximately half of averted symptomatic cases and 99% of averted deaths were prevented in other age groups than 2to 17-year-olds due to herd immunity. The cumulative discounted 20-year economic impact was 35 068 QALYs gained and V1687 million saved, that is, the intervention was cost-saving. This vaccination strategy had the highest probability of being the most cost-effective strategy considered, dominating pediatric strategies targeting 2to 6-year-olds or 2to 12-year-olds or strategies with trivalent inactivated vaccine. Conclusion: Modeling indicates that introducing pediatric influenza vaccination in The Netherlands is cost-saving, reducing the influenza-related disease burden substantially

On-line Excited-State Laser Spectroscopy of Trapped Short-Lived Ra+^+ Ions

As an important step towards an atomic parity violation experiment in one single trapped Ra$^+$ ion, laser spectroscopy experiments were performed with on-line produced short-lived $^{212,213,214}$Ra$^+$ ions. The isotope shift of the 6\,^2D$_{3/2}$\,-\,7\,^2P$_{1/2}$ and 6\,^2D$_{3/2}$\,-\,7\,^2P$_{3/2}$ transitions and the hyperfine structure constant of the 7\,^2S$_{1/2}$ and 6\,^2D$_{3/2}$ states in $^{213}$Ra$^+$ were measured. These values provide a benchmark for the required atomic theory. A lower limit of $232(4)$ ms for the lifetime of the metastable 6\,^2D$_{5/2}$ state was measured by optical shelving.Comment: 4.2 pages, 6 figures, 2 tables

First Test of Lorentz Invariance in the Weak Decay of Polarized Nuclei

A new test of Lorentz invariance in the weak interactions has been made by searching for variations in the decay rate of spin-polarized 20Na nuclei. This test is unique to Gamow-Teller transitions, as was shown in the framework of a recently developed theory that assumes a Lorentz symmetry breaking background field of tensor nature. The nuclear spins were polarized in the up and down direction, putting a limit on the amplitude of sidereal variations of the form |(\Gamma_{up} - \Gamma_{down})| / (\Gamma_{up} + \Gamma_{down}) < 3 * 10^{-3}. This measurement shows a possible route toward a more detailed testing of Lorentz symmetry in weak interactions.Comment: 11 pages, 6 figure