Real-time dynamic modelling for the design of a cluster-randomized phase 3 Ebola vaccine trial in Sierra Leone.

BACKGROUND: Declining incidence and spatial heterogeneity complicated the design of phase 3 Ebola vaccine trials during the tail of the 2013-16 Ebola virus disease (EVD) epidemic in West Africa. Mathematical models can provide forecasts of expected incidence through time and can account for both vaccine efficacy in participants and effectiveness in populations. Determining expected disease incidence was critical to calculating power and determining trial sample size. METHODS: In real-time, we fitted, forecasted, and simulated a proposed phase 3 cluster-randomized vaccine trial for a prime-boost EVD vaccine in three candidate regions in Sierra Leone. The aim was to forecast trial feasibility in these areas through time and guide study design planning. RESULTS: EVD incidence was highly variable during the epidemic, especially in the declining phase. Delays in trial start date were expected to greatly reduce the ability to discern an effect, particularly as a trial with an effective vaccine would cause the epidemic to go extinct more quickly in the vaccine arm. Real-time updates of the model allowed decision-makers to determine how trial feasibility changed with time. CONCLUSIONS: This analysis was useful for vaccine trial planning because we simulated effectiveness as well as efficacy, which is possible with a dynamic transmission model. It contributed to decisions on choice of trial location and feasibility of the trial. Transmission models should be utilised as early as possible in the design process to provide mechanistic estimates of expected incidence, with which decisions about sample size, location, timing, and feasibility can be determined

New occurrence of B chromosomes in Partamonahelleri (Friese, 1900) (Hymenoptera, Meliponini)

Cytogenetic analyses of the stingless bee Partamona helleri collected in the state of Bahia, Northeast Brazil revealed the chromosome numbers n = 18 in the haploid males and 2n = 35 in the diploid females. All karyotypes displayed one large acrocentric B chromosome, which differs from the minute B chromosomes previously described in the populations from southeastern Brazil. Giemsa staining, C-banding and DAPI/CMA3 fluorochrome staining also revealed a remarkable interpopulational divergence regarding both the regular karyotype and the B chromosomes. The B chromosomes found in the samples from Jequié, Bahia, were entirely heterochromatic, while those found in Cravolândia, Bahia, displayed a euchromatic portion at the telomeric end of the long arm. CMA 3 labeling sites varied from seven to eight between the two localities in Bahia, due to the presence of an extra GC-rich block in the karyotype of the samples from Jequié. This is the first report of a large B chromosome in P. helleri and reveals the occurrence of a geographic differentiation within this species

Changes in intracellular ion activities induced by adrenaline in human and rat skeletal muscle

To study the stimulating effect of adrenaline (ADR) on active Na+/K+ transport we used double-barrelled ion-sensitive micro-electrodes to measure the activities of extracellular K+ (aKe) and intracellular Na+ (aNai) in isolated preparations of rat soleus muscle, normal human intercostal muscle and one case of hyperkalemic periodic paralysis (h.p.p.). In these preparations bath-application of ADR (10−6 M) resulted in a membrane hyperpolarization and transient decreasesaKe andaNai which could be blocked by ouabain (3×10−4 M). In the h.p.p. muslce a continuous rise ofaNai induced by elevation ofaKe to 5.2 mM could be stopped by ADR. In addition, the intracellular K+ activity (aKi), the free intracellular Ca2+ concentration (pCai) and intracellular pH (pHi) were monitored in rat soleus muscle. During ADRaKi increased, pHi remained constant and intracellular Ca2+ apparently decreased. In conclusion, our data show that ADR primarily stimulates the Na+/K+ pump in mammalian skeletal muscle. This stimulating action is not impaired in the h.p.p. muscle

A microchip optomechanical accelerometer

The monitoring of accelerations is essential for a variety of applications ranging from inertial navigation to consumer electronics. The basic operation principle of an accelerometer is to measure the displacement of a flexibly mounted test mass; sensitive displacement measurement can be realized using capacitive, piezo-electric, tunnel-current, or optical methods. While optical readout provides superior displacement resolution and resilience to electromagnetic interference, current optical accelerometers either do not allow for chip-scale integration or require bulky test masses. Here we demonstrate an optomechanical accelerometer that employs ultra-sensitive all-optical displacement read-out using a planar photonic crystal cavity monolithically integrated with a nano-tethered test mass of high mechanical Q-factor. This device architecture allows for full on-chip integration and achieves a broadband acceleration resolution of 10 \mu g/rt-Hz, a bandwidth greater than 20 kHz, and a dynamic range of 50 dB with sub-milliwatt optical power requirements. Moreover, the nano-gram test masses used here allow for optomechanical back-action in the form of cooling or the optical spring effect, setting the stage for a new class of motional sensors.Comment: 16 pages, 9 figure

Towards high-speed optical quantum memories

Quantum memories, capable of controllably storing and releasing a photon, are a crucial component for quantum computers and quantum communications. So far, quantum memories have operated with bandwidths that limit data rates to MHz. Here we report the coherent storage and retrieval of sub-nanosecond low intensity light pulses with spectral bandwidths exceeding 1 GHz in cesium vapor. The novel memory interaction takes place via a far off-resonant two-photon transition in which the memory bandwidth is dynamically generated by a strong control field. This allows for an increase in data rates by a factor of almost 1000 compared to existing quantum memories. The memory works with a total efficiency of 15% and its coherence is demonstrated by directly interfering the stored and retrieved pulses. Coherence times in hot atomic vapors are on the order of microsecond - the expected storage time limit for this memory.Comment: 13 pages, 5 figure

Cytogenetic characterization of Partamona cupira (Hymenoptera, Apidae) by fluorochromes

Four colonies of the stingless bee Partamona cupira (Hymenoptera: Apidae) were cytogenetically analyzed using conventional staining and the fluorochromes CMA3 e DAPI. The females have 2n = 34 chromosomes (2K = 32 M¯+2 A¯). Some females, however, presented an additional large B acrocentric chromosome, to a total of 2n = 35. Chromosome B and the chromosomal pairs 2, 9 and 10 showed CMA 3+ bands, indicating an excess of CG base-pairs. A clear association was verified between the P. helleri B chromosome SCAR marker and the presence of a B chromosome in P. cupira. The data obtained suggests that B chromosomes in P. helleri and P. cupira share a common origin

Structural and Thermodynamic Approach to Peptide Immunogenicity

In the conventional paradigm of humoral immunity, B cells recognize their cognate antigen target in its native form. However, it is well known that relatively unstable peptides bearing only partial structural resemblance to the native protein can trigger antibodies recognizing higher-order structures found in the native protein. On the basis of sound thermodynamic principles, this work reveals that stability of immunogenic proteinlike motifs is a critical parameter rationalizing the diverse humoral immune responses induced by different linear peptide epitopes. In this paradigm, peptides with a minimal amount of stability (ΔGX<0 kcal/mol) around a proteinlike motif (X) are capable of inducing antibodies with similar affinity for both peptide and native protein, more weakly stable peptides (ΔGX>0 kcal/mol) trigger antibodies recognizing full protein but not peptide, and unstable peptides (ΔGX>8 kcal/mol) fail to generate antibodies against either peptide or protein. Immunization experiments involving peptides derived from the autoantigen histidyl-tRNA synthetase verify that selected peptides with varying relative stabilities predicted by molecular dynamics simulations induce antibody responses consistent with this theory. Collectively, these studies provide insight pertinent to the structural basis of immunogenicity and, at the same time, validate this form of thermodynamic and molecular modeling as an approach to probe the development/evolution of humoral immune responses

Control of Ebola virus disease outbreaks: Comparison of health care worker-targeted and community vaccination strategies

Background Health care workers (HCW) are at risk of infection during Ebola virus disease outbreaks and therefore may be targeted for vaccination before or during outbreaks. The effect of these strategies depends on the role of HCW in transmission which is understudied. Methods To evaluate the effect of HCW-targeted or community vaccination strategies, we used a transmission model to explore the relative contribution of HCW and the community to transmission. We calibrated the model to data from multiple Ebola outbreaks. We quantified the impact of ahead-of-time HCW-targeted strategies, and reactive HCW and community vaccination. Results We found that for some outbreaks (we call “type 1″) HCW amplified transmission both to other HCW and the community, and in these outbreaks prophylactic vaccination of HCW decreased outbreak size. Reactive vaccination strategies had little effect because type 1 outbreaks ended quickly. However, in outbreaks with longer time courses (“type 2 outbreaks”), reactive community vaccination decreased the number of cases, with or without prophylactic HCW-targeted vaccination. For both outbreak types, we found that ahead-of-time HCW-targeted strategies had an impact at coverage of 30%. Conclusions The vaccine strategies tested had a different impact depending on the transmission dynamics and previous control measures. Although we will not know the characteristics of a new outbreak, ahead-of-time HCW-targeted vaccination can decrease the total outbreak size, even at low vaccine coverage