The 2014 Ebola virus disease outbreak in Pujehun, Sierra Leone: epidemiology and impact of interventions

BACKGROUND: In July 2014, an outbreak of Ebola virus disease (EVD) started in Pujehun district, Sierra Leone. On January 10th, 2015, the district was the first to be declared Ebola-free by local authorities after 49 cases and a case fatality rate of 85.7 %. The Pujehun outbreak represents a precious opportunity for improving the body of work on the transmission characteristics and effects of control interventions during the 2014–2015 EVD epidemic in West Africa. METHODS: By integrating hospital registers and contact tracing form data with healthcare worker and local population interviews, we reconstructed the transmission chain and investigated the key time periods of EVD transmission. The impact of intervention measures has been assessed using a microsimulation transmission model calibrated with the collected data. RESULTS: The mean incubation period was 9.7 days (range, 6–15). Hospitalization rate was 89 %. The mean time from the onset of symptoms to hospitalization was 4.5 days (range, 1–9). The mean serial interval was 13.7 days (range, 2–18). The distribution of the number of secondary cases (R(0) = 1.63) was well fitted by a negative binomial distribution with dispersion parameter k = 0.45 (95 % CI, 0.19–1.32). Overall, 74.3 % of transmission events occurred between members of the same family or extended family, 17.9 % in the community, mainly between friends, and 7.7 % in hospital. The mean number of contacts investigated per EVD case raised from 11.5 in July to 25 in September 2014. In total, 43.0 % of cases were detected through contact investigation. Model simulations suggest that the most important factors determining the probability of disease elimination are the number of EVD beds, the mean time from symptom onset to isolation, and the mean number of contacts traced per case. By assuming levels and timing of interventions performed in Pujehun, the estimated probability of eliminating an otherwise large EVD outbreak is close to 100 %. CONCLUSIONS: Containment of EVD in Pujehun district is ascribable to both the natural history of the disease (mainly transmitted through physical contacts, long generation time, overdispersed distribution of secondary cases per single primary case) and intervention measures (isolation of cases and contact tracing), which in turn strongly depend on preparedness, population awareness, and compliance. Our findings are also essential to determine a successful ring vaccination strategy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-015-0524-z) contains supplementary material, which is available to authorized users

Alterations in homologous recombination repair genes in prostate cancer brain metastases

Improved survival rates for prostate cancer through more effective therapies have also led to an increase in the diagnosis of metastases to infrequent locations such as the brain. Here we investigate the repertoire of somatic genetic alterations present in brain metastases from 51 patients with prostate cancer brain metastases (PCBM). We highlight the clonal evolution occurring in PCBM and demonstrate an increased mutational burden, concomitant with an enrichment of the homologous recombination deficiency mutational signature in PCBM compared to non-brain metastases. Focusing on known pathogenic alterations within homologous recombination repair genes, we find 10 patients (19.6%) fulfilling the inclusion criteria used in the PROfound clinical trial, which assessed the efficacy of PARP inhibitors (PARPi) in homologous recombination deficient prostate cancer. Eight (15.7%) patients show biallelic loss of one of the 15 genes included in the trial, while 5 patients (9.8%) harbor pathogenic alterations in BRCA1/2 specifically. Uncovering these molecular features of PCBM may have therapeutic implications, suggesting the need of clinical trial enrollment of PCBM patients when evaluating potential benefit from PARPi

Alterations in homologous recombination repair genes in prostate cancer brain metastases.

Improved survival rates for prostate cancer through more effective therapies have also led to an increase in the diagnosis of metastases to infrequent locations such as the brain. Here we investigate the repertoire of somatic genetic alterations present in brain metastases from 51 patients with prostate cancer brain metastases (PCBM). We highlight the clonal evolution occurring in PCBM and demonstrate an increased mutational burden, concomitant with an enrichment of the homologous recombination deficiency mutational signature in PCBM compared to non-brain metastases. Focusing on known pathogenic alterations within homologous recombination repair genes, we find 10 patients (19.6%) fulfilling the inclusion criteria used in the PROfound clinical trial, which assessed the efficacy of PARP inhibitors (PARPi) in homologous recombination deficient prostate cancer. Eight (15.7%) patients show biallelic loss of one of the 15 genes included in the trial, while 5 patients (9.8%) harbor pathogenic alterations in BRCA1/2 specifically. Uncovering these molecular features of PCBM may have therapeutic implications, suggesting the need of clinical trial enrollment of PCBM patients when evaluating potential benefit from PARPi

The Low-Redshift Lyman Continuum Survey. Unveiling the ISM properties of low-zz Lyman continuum emitters

Combining 66 ultraviolet (UV) spectra and ancillary data from the Low-Redshift Lyman Continuum Survey (LzLCS) and 23 LyC observations by earlier studies, we form a statistical sample of star-forming galaxies at $z \sim 0.3$ to study the role of the cold interstellar medium (ISM) gas in the leakage of ionizing radiation. We first constrain the massive star content (ages and metallicities) and UV attenuation, by fitting the stellar continuum with a combination of simple stellar population models. The models, together with accurate LyC flux measurements, allow to determine the absolute LyC photon escape fraction for each galaxy ($f_{\rm esc}^{\rm abs}$). We measure the equivalent widths and residual fluxes of multiple HI and low-ionization state (LIS) lines, and the geometrical covering fraction adopting the picket-fence model. The $f_{\rm esc}^{\rm abs}$ spans a wide range, with a median (0.16, 0.84 quantiles) of 0.04 (0.02, 0.20), and 50 out of the 89 galaxies detected in the LyC. The HI and LIS line equivalent widths scale with the UV luminosity and attenuation, and inversely with the residual flux of the lines. The HI and LIS residual fluxes are correlated, indicating that the neutral gas is spatially traced by the LIS transitions. We find the observed trends of the absorption lines and the UV attenuation are primarily driven by the covering fraction. The non-uniform gas coverage demonstrates that LyC photons escape through low-column density channels in the ISM. The equivalent widths and residual fluxes of the UV lines strongly correlate with $f_{\rm esc}^{\rm abs}$: strong LyC leakers show weak absorption lines, low UV attenuation, and large Ly$\alpha$ equivalent widths. We finally show that simultaneous UV absorption line and dust attenuation measurements can predict, on average, the escape fraction of galaxies and the method can be applied to galaxies across a wide redshift range.Comment: 30 pages, 16 figures, 3 tables; accepted for publication in Astronomy and Astrophysics on December 16, 2021. Tables A1 to A4 are part of the LzLCS science products and will be publicly available in a dedicated websit

The Rise of Adaptive Platform Trials in Critical Care

As durable learning research systems, adaptive platform trials represent a transformative new approach to accelerating clinical evaluation and discovery in critical care. This Perspective provides a brief introduction to the concept of adaptive platform trials, describes several established and emerging platforms in critical care, and surveys some opportunities and challenges for their implementation and impact.<br/

Search for CP Violation in the Decay Z -> b (b bar) g

About three million hadronic decays of the Z collected by ALEPH in the years 1991-1994 are used to search for anomalous CP violation beyond the Standard Model in the decay Z -> b \bar{b} g. The study is performed by analyzing angular correlations between the two quarks and the gluon in three-jet events and by measuring the differential two-jet rate. No signal of CP violation is found. For the combinations of anomalous CP violating couplings, ${\hat{h}}_b = {\hat{h}}_{Ab}g_{Vb}-{\hat{h}}_{Vb}g_{Ab}$ and $h^{\ast}_b = \sqrt{\hat{h}_{Vb}^{2}+\hat{h}_{Ab}^{2}}$, limits of \hat{h}_b < 0.59$and$h^{\ast}_{b} < 3.02$ are given at 95\% CL.Comment: 8 pages, 1 postscript figure, uses here.sty, epsfig.st

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum