Three-dose versus four-dose primary schedules for tick-borne encephalitis (TBE) vaccine FSME-immun for those aged 50 years or older : A single-centre, open-label, randomized controlled trial

Background: TBE vaccination failures among those past middle age have raised concern about immune response declining with age. We investigated immunogenicity of the TBE-vaccine FSME-Immun among those aged 50+ years using the standard three-dose primary series and alternative four-dose schedules. Methods: In this single-centre, open-label, randomized controlled trial, 200 TBE-naive Swedish adults were given primary TBE vaccination with FSME-Immun. Those aged 50+ years (n = 150) were randomized to receive the standard three-dose (days 0-30-360) or one of two four-dose series (0-7-21-360; 0-30- 90-360). For participants < 50 years (n = 50) the standard three-dose schedule was used. Titres of neu-tralizing antibodies were determined on days 0, 60, 120, 360, and 400. The main outcome was the log titre of TBE virus-specific neutralizing antibodies on day 400. Results: The three-dose schedule yielded lower antibody titres among those aged 50+ years than the younger participants on day 400 (geometric mean titre 41 versus 74, p < 0.05). The older group showed higher titres for the four-dose 0-7-21-360 than the standard three-dose schedule both on day 400 (103 versus 41, p < 0.01; primary end point) and at the other testing points (days 60,120, 360). Using the other four-dose schedule (0-30-90-360), no such difference was observed on day 400 (63 versus 41, NS). Conclusion: Immune response to the TBE vaccine declined with age. A four-dose schedule (0-7-21-360) may benefit those aged 50 years or older. This study is registered at ClinicalTrials.gov, NCT01361776. (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).Peer reviewe

Age truncation and portfolio effects in Puget Sound Pacific herring

Forage fish undergo dramatic changes in abundance through time. Long-term fluctuations, which have historically been attributed to changes in recruitment, may also be due to changes in adult mortality. Pacific herring, a lightly exploited forage fish in Puget Sound, WA, have exhibited shifts in age structure and decreases in spawning biomass during the past 30 years. Here, we investigate changes in adult mortality as a potential explanation for these shifts. Using a hierarchical, age-structured population model, we indicate that adult natural mortality for Puget Sound Pacific herring has increased since 1973. We find that natural mortality has increased for every age class of adult (age 3+), especially age 4 fish, whose estimated mortality has doubled over the survey time period (from M=0.84 to M=1.76). We demonstrate that long-term shifts in mortality explain changes in age structure, and may explain biomass declines and failure to reach management thresholds for some spawning sites in Puget Sound. Temporal shifts in natural adult mortality could have negative implications for herring and herring predators. For predators, these implications include a reduction in the stability of the herring resource

Understanding initial data for black hole collisions

Numerical relativity, applied to collisions of black holes, starts with initial data for black holes already in each other's strong field. The initial hypersurface data typically used for computation is based on mathematical simplifying prescriptions, such as conformal flatness of the 3-geometry and longitudinality of the extrinsic curvature. In the case of head on collisions of equal mass holes, there is evidence that such prescriptions work reasonably well, but it is not clear why, or whether this success is more generally valid. Here we study these questions by considering the ``particle limit'' for head on collisions of nonspinning holes. Einstein's equations are linearized in the mass of the small hole, and described by a single gauge invariant spacetime function psi, for each multipole. The resulting equations have been solved by numerical evolution for collisions starting from various initial separations, and the evolution is studied on a sequence of hypersurfaces. In particular, we extract hypersurface data, that is psi and its time derivative, on surfaces of constant background Schwarzschild time. These evolved data can then be compared with ``prescribed'' data, evolved data can be replaced by prescribed data on any hypersurface, and evolved further forward in time, a gauge invariant measure of deviation from conformal flatness can be evaluated, etc. The main findings of this study are: (i) For holes of unequal mass the use of prescribed data on late hypersurfaces is not successful. (ii) The failure is likely due to the inability of the prescribed data to represent the near field of the smaller hole. (iii) The discrepancy in the extrinsic curvature is more important than in the 3-geometry. (iv) The use of the more general conformally flat longitudinal data does not notably improve this picture.Comment: 20 pages, REVTEX, 26 PS figures include

Inference with interference between units in an fMRI experiment of motor inhibition

An experimental unit is an opportunity to randomly apply or withhold a treatment. There is interference between units if the application of the treatment to one unit may also affect other units. In cognitive neuroscience, a common form of experiment presents a sequence of stimuli or requests for cognitive activity at random to each experimental subject and measures biological aspects of brain activity that follow these requests. Each subject is then many experimental units, and interference between units within an experimental subject is likely, in part because the stimuli follow one another quickly and in part because human subjects learn or become experienced or primed or bored as the experiment proceeds. We use a recent fMRI experiment concerned with the inhibition of motor activity to illustrate and further develop recently proposed methodology for inference in the presence of interference. A simulation evaluates the power of competing procedures.Comment: Published by Journal of the American Statistical Association at http://www.tandfonline.com/doi/full/10.1080/01621459.2012.655954 . R package cin (Causal Inference for Neuroscience) implementing the proposed method is freely available on CRAN at https://CRAN.R-project.org/package=ci

Dissipative fluids out of hydrostatic equilibrium

In the context of the M\"{u}ller-Israel-Stewart second order phenomenological theory for dissipative fluids, we analyze the effects of thermal conduction and viscosity in a relativistic fluid, just after its departure from hydrostatic equilibrium, on a time scale of the order of relaxation times. Stability and causality conditions are contrasted with conditions for which the ''effective inertial mass'' vanishes.Comment: 21 pages, 1 postscript figure (LaTex 2.09 and epsfig.sty required) Submitted to Classical and Quantum Gravit

Head-on collision of unequal mass black holes: close-limit predictions

The close-limit method has given approximations in excellent agreement with those of numerical relativity for collisions of equal mass black holes. We consider here colliding holes with unequal mass, for which numerical relativity results are not available. We try to ask two questions: (i) Can we get approximate answers to astrophysical questions (ideal mass ratio for energy production, maximum recoil velocity, etc.), and (ii) can we better understand the limitations of approximation methods. There is some success in answering the first type of question, but more with the second, especially in connection with the issue of measures of the intrinsic mass of the colliding holes, and of the range of validity of the method.Comment: 19 pages, RevTeX + 9 postscript figure

The imposition of Cauchy data to the Teukolsky equation I: The nonrotating case

Gravitational perturbations about a Kerr black hole in the Newman-Penrose formalism are concisely described by the Teukolsky equation. New numerical methods for studying the evolution of such perturbations require not only the construction of appropriate initial data to describe the collision of two orbiting black holes, but also to know how such new data must be imposed into the Teukolsky equation. In this paper we show how Cauchy data can be incorporated explicitly into the Teukolsky equation for non-rotating black holes. The Teukolsky function $$ and its first time derivative $\partial_t \Psi$ can be written in terms of only the 3-geometry and the extrinsic curvature in a gauge invariant way. Taking a Laplace transform of the Teukolsky equation incorporates initial data as a source term. We show that for astrophysical data the straightforward Green function method leads to divergent integrals that can be regularized like for the case of a source generated by a particle coming from infinity.Comment: 9 pages, REVTEX. Misprints corrected in formulas (2.4)-(2.7). Final version to appear in PR