Accelerating vaccine development and deployment: report of a Royal Society satellite meeting.

The Royal Society convened a meeting on the 17th and 18th November 2010 to review the current ways in which vaccines are developed and deployed, and to make recommendations as to how each of these processes might be accelerated. The meeting brought together academics, industry representatives, research sponsors, regulators, government advisors and representatives of international public health agencies from a broad geographical background. Discussions were held under Chatham House rules. High-throughput screening of new vaccine antigens and candidates was seen as a driving force for vaccine discovery. Multi-stakeholder, small-scale manufacturing facilities capable of rapid production of clinical grade vaccines are currently too few and need to be expanded. In both the human and veterinary areas, there is a need for tiered regulatory standards, differentially tailored for experimental and commercial vaccines, to allow accelerated vaccine efficacy testing. Improved cross-fertilization of knowledge between industry and academia, and between human and veterinary vaccine developers, could lead to more rapid application of promising approaches and technologies to new product development. Identification of best-practices and development of checklists for product development plans and implementation programmes were seen as low-cost opportunities to shorten the timeline for vaccine progression from the laboratory bench to the people who need it

Potential research participants’ use of information during the consent process : a qualitative pilot study of patients enrolled in a clinical trial

There is increasing evidence that clinical trial participants are uninformed about the trials in which they participate, raising ethical concerns regarding informed consent. The aim of this pilot study was to explore clinical trial participants’ use of consent discussions and information sheets when considering participating in clinical trials research. A qualitative, interview-based pilot study was designed in order to elicit, through dialogue, details of the reasons for participants’ use of, and preferences regarding, different modes of information provision. Semi-structured interviews were undertaken with two different groups of patients who were participants in the Reinforcement of Closure of Stoma Site trial. The first group comprised newly-consented trial participants, who had been recruited up to 72 hours before our interview; the second group comprised patients attending a follow-up clinic 12 months after joining the trial. Thirteen participants were recruited in total: three newly-consented patients, and ten follow-up patients. The study found that participants’ use of consent discussions to gain information about clinical trials was varied, and that they only minimally used information sheets after providing initial consent for the trial. Participants demonstrated varying degrees of knowledge about the trial, with some having forgotten that they were still involved in the trial. Participants reported a high level of trust in medical staff as a reason for not seeking more information about the trial. Some participants reported dissatisfaction with the timing of information provision. Some were amenable to novel ways of receiving trial information, such as web-based methods. The pilot study demonstrated the feasibility of a larger study into the provision of information to prospective clinical trial participants. The results suggest that considering alternative ways of providing information and the appropriateness of existing information provision may be acceptable to and useful for potential trial participants

Change Point Problem for Censored Data

Department of Probability and Mathematical StatisticsKatedra pravděpodobnosti a matematické statistikyMatematicko-fyzikální fakultaFaculty of Mathematics and Physic

Oxygen Recovery Kinetics in the Forearm Flexors of Multiple Ability Groups of Rock Climbers

Fryer, SM, Stoner, L, Dickson, TG, Draper, SB, McCluskey, MJ, Hughes, JD, How, SC, and Draper, N. Oxygen recovery kinetics in the forearm flexors of multiple ability groups of rock climbers. J Strength Cond Res 29(6): 1633-1639, 2015-The purpose of this study was to determine muscle tissue oxidative capacity and recovery in intermediate, advanced, and elite rock climbers. Forty-four male participants performed (a) sustained and (b) intermittent contractions at 40% of maximal volitional contraction (MVC) on a sport-specific fingerboard until volitional fatigue. Near-infrared spectroscopy was used to assess muscle tissue oxygenation during both the exercise and the 5-minutes passive recovery period, in the flexor digitorum profundus (FDP) and flexor carpi radialis (FCR). During the sustained contraction only, muscle tissue deoxygenation (O2 debt) in the FDP and FCR was significantly greater in elite climbers compared with the control, intermediate, and advanced groups (FDP: 32 vs. 15, 19, 22%; FCR: 19 vs. 11, 8, 15%, respectively). However, elite climbers had a significantly quicker time to half recovery (T1/2) than the control and intermediate groups in the FDP (8 vs. 95 and 47 seconds, respectively) and the FCR (7 vs. 30 and 97 seconds, respectively) because the O2% recovered per second being significantly greater (FDP: 4.2 vs. 0.7 and 0.3; FCR: 4.8 vs. 0.1 and 0.2, respectively). Furthermore, during the intermittent contraction, T1/2 in elite climbers was significantly quicker compared with the control and intermediate groups in the FDP (8 vs. 93 and 83 seconds, respectively) and FCR (16 vs. 76 and 50 seconds, respectively). Consequently, lower-level climbers should focus training on specific intermittent fatigue protocols. Competition or elite climbers should make use of appropriate rests on route to aid recovery and increase the chances of reaching the next hold

Mapping gene-by-gene single-nucleotide variation in 8,535 <i>Mycobacterium tuberculosis</i> genomes:a resource to support potential vaccine and drug development

Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosisMycobacterium bovi

Nucleon Axial Form Factor from Lattice QCD

Results for the isovector axial form factors of the proton from a lattice QCD calculation are presented for both point-split and local currents. They are obtained on a quenched $16^{3} \times 24$ lattice at $\beta= 6.0$ with Wilson fermions for a range of quark masses from strange to charm. We determine the finite lattice renormalization for both the local and point-split currents of heavy quarks. Results extrapolated to the chiral limit show that the $q^2$ dependence of the axial form factor agrees reasonably well with experiment. The axial coupling constant $g_A$ calculated for the local and the point-split currents is about 6\% and 12\% smaller than the experimental value respectively.Comment: 8 pages, 5 figures (included in part 2), UK/93-0

Multiplication and Growth Inhibition Activity Assays for the Zoonotic Malaria Parasite, Plasmodium knowlesi.

Malaria remains a major cause of morbidity and mortality globally. Clinical symptoms of the disease arise from the growth and multiplication of Plasmodium parasites within the blood of the host. Thus in vitro assays to determine how drug, antibody and genetic perturbations affect the growth rate of Plasmodium parasites are essential for the development of new therapeutics and improving our understanding of parasite biology. As both P. falciparum and P. knowlesi can be maintained in culture with human red blood cells, the effect of antimalarial drugs and inhibitory antibodies that target the invasion capacity of Plasmodium parasites are routinely investigated by using multiplication assays or growth inhibition assays against these two species. This protocol gives detailed step-by-step procedures to carry out flow cytometry-based multiplication assays and growth inhibition activity assays to test neutralizing antibodies based on the activity of the parasite enzyme lactate dehydrogenase of Plasmodium knowlesi adapted to human red blood cell culture. Whilst similar assays are well established for P. falciparum, P. knowlesi is more closely related to all other human infective species ( Pacheco et al., 2018 ) and so can be used as a surrogate for testing drugs and vaccines for other malaria species such as P. vivax, which is the most widespread cause of malaria outside of Africa, but cannot yet be cultured under laboratory conditions

Malaria Vaccines: Recent Advances and New Horizons.

The development of highly effective and durable vaccines against the human malaria parasites Plasmodium falciparum and P. vivax remains a key priority. Decades of endeavor have taught that achieving this goal will be challenging; however, recent innovation in malaria vaccine research and a diverse pipeline of novel vaccine candidates for clinical assessment provides optimism. With first-generation pre-erythrocytic vaccines aiming for licensure in the coming years, it is important to reflect on how next-generation approaches can improve on their success. Here we review the latest vaccine approaches that seek to prevent malaria infection, disease, and transmission and highlight some of the major underlying immunological and molecular mechanisms of protection. The synthesis of rational antigen selection, immunogen design, and immunization strategies to induce quantitatively and qualitatively improved immune effector mechanisms offers promise for achieving sustained high-level protection

Re-examining the consumption-wealth relationship : the role of model uncertainty

This paper discusses the consumption-wealth relationship. Following the recent influential workof Lettau and Ludvigson [e.g. Lettau and Ludvigson (2001), (2004)], we use data on consumption, assets andlabor income and a vector error correction framework. Key …ndings of their work are that consumption doesrespond to permanent changes in wealth in the expected manner, but that most changes in wealth are transitoryand have no e¤ect on consumption. We investigate the robustness of these results to model uncertainty andargue for the use of Bayesian model averaging. We …nd that there is model uncertainty with regards to thenumber of cointegrating vectors, the form of deterministic components, lag length and whether the cointegratingresiduals a¤ect consumption and income directly. Whether this uncertainty has important empirical implicationsdepends on the researcher's attitude towards the economic theory used by Lettau and Ludvigson. If we workwith their model, our findings are very similar to theirs. However, if we work with a broader set of models andlet the data speak, we obtain somewhat di¤erent results. In the latter case, we …nd that the exact magnitudeof the role of permanent shocks is hard to estimate precisely. Thus, although some support exists for the viewthat their role is small, we cannot rule out the possibility that they have a substantive role to play