Low cancer awareness contributes to delay in presentation for cancer symptoms and may lead to delay in cancer diagnosis. The aim of this study was to review the evidence for the effectiveness of ...interventions to raise cancer awareness and promote early presentation in cancer to inform policy and future research.
We searched bibliographic databases and reference lists for randomised controlled trials of interventions delivered to individuals, and controlled or uncontrolled studies of interventions delivered to communities.
We found some evidence that interventions delivered to individuals modestly increase cancer awareness in the short term and insufficient evidence that they promote early presentation. We found limited evidence that public education campaigns reduce stage at presentation of breast cancer, malignant melanoma and retinoblastoma.
Interventions delivered to individuals may increase cancer awareness. Interventions delivered to communities may promote cancer awareness and early presentation, although the evidence is limited.
Planck 2018 results Aghanim, N.; Akrami, Y.; Aumont, J. ...
Astronomy and astrophysics (Berlin),
09/2020, Letnik:
641
Journal Article
Recenzirano
Odprti dostop
We present cosmological parameter results from the final full-mission
Planck
measurements of the cosmic microwave background (CMB) anisotropies, combining information from the temperature and ...polarization maps and the lensing reconstruction. Compared to the 2015 results, improved measurements of large-scale polarization allow the reionization optical depth to be measured with higher precision, leading to significant gains in the precision of other correlated parameters. Improved modelling of the small-scale polarization leads to more robust constraints on many parameters, with residual modelling uncertainties estimated to affect them only at the 0.5
σ
level. We find good consistency with the standard spatially-flat 6-parameter ΛCDM cosmology having a power-law spectrum of adiabatic scalar perturbations (denoted “base ΛCDM” in this paper), from polarization, temperature, and lensing, separately and in combination. A combined analysis gives dark matter density Ω
c
h
2
= 0.120 ± 0.001, baryon density Ω
b
h
2
= 0.0224 ± 0.0001, scalar spectral index
n
s
= 0.965 ± 0.004, and optical depth
τ
= 0.054 ± 0.007 (in this abstract we quote 68% confidence regions on measured parameters and 95% on upper limits). The angular acoustic scale is measured to 0.03% precision, with 100
θ
*
= 1.0411 ± 0.0003. These results are only weakly dependent on the cosmological model and remain stable, with somewhat increased errors, in many commonly considered extensions. Assuming the base-ΛCDM cosmology, the inferred (model-dependent) late-Universe parameters are: Hubble constant
H
0
= (67.4 ± 0.5) km s
−1
Mpc
−1
; matter density parameter Ω
m
= 0.315 ± 0.007; and matter fluctuation amplitude
σ
8
= 0.811 ± 0.006. We find no compelling evidence for extensions to the base-ΛCDM model. Combining with baryon acoustic oscillation (BAO) measurements (and considering single-parameter extensions) we constrain the effective extra relativistic degrees of freedom to be
N
eff
= 2.99 ± 0.17, in agreement with the Standard Model prediction
N
eff
= 3.046, and find that the neutrino mass is tightly constrained to ∑
m
ν
< 0.12 eV. The CMB spectra continue to prefer higher lensing amplitudes than predicted in base ΛCDM at over 2
σ
, which pulls some parameters that affect the lensing amplitude away from the ΛCDM model; however, this is not supported by the lensing reconstruction or (in models that also change the background geometry) BAO data. The joint constraint with BAO measurements on spatial curvature is consistent with a flat universe, Ω
K
= 0.001 ± 0.002. Also combining with Type Ia supernovae (SNe), the dark-energy equation of state parameter is measured to be
w
0
= −1.03 ± 0.03, consistent with a cosmological constant. We find no evidence for deviations from a purely power-law primordial spectrum, and combining with data from BAO, BICEP2, and Keck Array data, we place a limit on the tensor-to-scalar ratio
r
0.002
< 0.06. Standard big-bang nucleosynthesis predictions for the helium and deuterium abundances for the base-ΛCDM cosmology are in excellent agreement with observations. The
Planck
base-ΛCDM results are in good agreement with BAO, SNe, and some galaxy lensing observations, but in slight tension with the Dark Energy Survey’s combined-probe results including galaxy clustering (which prefers lower fluctuation amplitudes or matter density parameters), and in significant, 3.6
σ
, tension with local measurements of the Hubble constant (which prefer a higher value). Simple model extensions that can partially resolve these tensions are not favoured by the
Planck
data.
Abstract
The Hobby–Eberly Telescope (HET) Dark Energy Experiment (HETDEX) is undertaking a blind wide-field low-resolution spectroscopic survey of 540 deg
2
of sky to identify and derive redshifts ...for a million Ly
α
-emitting galaxies in the redshift range 1.9 <
z
< 3.5. The ultimate goal is to measure the expansion rate of the universe at this epoch, to sharply constrain cosmological parameters and thus the nature of dark energy. A major multiyear Wide-Field Upgrade (WFU) of the HET was completed in 2016 that substantially increased the field of view to 22′ diameter and the pupil to 10 m, by replacing the optical corrector, tracker, and Prime Focus Instrument Package and by developing a new telescope control system. The new, wide-field HET now feeds the Visible Integral-field Replicable Unit Spectrograph (VIRUS), a new low-resolution integral-field spectrograph (LRS2), and the Habitable Zone Planet Finder, a precision near-infrared radial velocity spectrograph. VIRUS consists of 156 identical spectrographs fed by almost 35,000 fibers in 78 integral-field units arrayed at the focus of the upgraded HET. VIRUS operates in a bandpass of 3500−5500 Å with resolving power
R
≃ 800. VIRUS is the first example of large-scale replication applied to instrumentation in optical astronomy to achieve spectroscopic surveys of very large areas of sky. This paper presents technical details of the HET WFU and VIRUS, as flowed down from the HETDEX science requirements, along with experience from commissioning this major telescope upgrade and the innovative instrumentation suite for HETDEX.
We report the INTernational Gamma-ray Astrophysics Laboratory (INTEGRAL) detection of the short gamma-ray burst GRB 170817A (discovered by Fermi-GBM) with a signal-to-noise ratio of 4.6, and, for the ...first time, its association with the gravitational waves (GWs) from binary neutron star (BNS) merging event GW170817 detected by the LIGO and Virgo observatories. The significance of association between the gamma-ray burst observed by INTEGRAL and GW170817 is 3.2 , while the association between the Fermi-GBM and INTEGRAL detections is 4.2 . GRB 170817A was detected by the SPI-ACS instrument about 2 s after the end of the GW event. We measure a fluence of (1.4 0.4 0.6) × 10−7 erg cm−2 (75-2000 keV), where, respectively, the statistical error is given at the 1 confidence level, and the systematic error corresponds to the uncertainty in the spectral model and instrument response. We also report on the pointed follow-up observations carried out by INTEGRAL, starting 19.5 hr after the event, and lasting for 5.4 days. We provide a stringent upper limit on any electromagnetic signal in a very broad energy range, from 3 keV to 8 MeV, constraining the soft gamma-ray afterglow flux to <7.1 × 10−11 erg cm−2 s−1 (80-300 keV). Exploiting the unique capabilities of INTEGRAL, we constrained the gamma-ray line emission from radioactive decays that are expected to be the principal source of the energy behind a kilonova event following a BNS coalescence. Finally, we put a stringent upper limit on any delayed bursting activity, for example, from a newly formed magnetar.
Clinical and biological studies on nodal marginal zone lymphoma (NMZL) are hampered by the lack of specific diagnostic markers and the low reproducibility of this diagnosis. A comparative ...expression-profiling study has shown a set of markers to be differentially expressed in NMZL compared with follicular lymphoma (FL), including myeloid cell nuclear differentiation antigen (MNDA), a nuclear protein expressed by myeloid cells and a subset of B-cells. The aim of this study was to characterize the expression of MNDA in normal and reactive human tissue, and in a large series of non-Hodgkin's B-cell lymphomas, with particular emphasis on NMZL and FL. Our results showed that MNDA is expressed in normal tissue by a subset of the marginal zone B cells. They also showed MNDA expression in subgroups of chronic lymphocytic leukemia, mantle-cell lymphoma, and diffuse large B-cell lymphoma, but MNDA was especially expressed by lymphomas derived from the marginal zone, such as mucosa-associated lymphoid-tissue lymphoma, splenic marginal-zone lymphoma and NMZL. MNDA expression was rarely observed in FL, a characteristic that is of potential value in distinguishing between NMZL and FL. MNDA expression is thus a useful tool for the recognition of NMZL.
Summary
Background
Chilblains (‘COVID toes’) are being seen with increasing frequency in children and young adults during the COVID‐19 pandemic. Detailed histopathological descriptions of COVID‐19 ...chilblains have not been reported, and causality of SARS‐CoV‐2 has not yet been established.
Objectives
To describe the histopathological features of COVID‐19 chilblains and to explore the presence of SARS‐CoV‐2 in the tissue.
Methods
We examined skin biopsies from seven paediatric patients presenting with chilblains during the COVID‐19 pandemic. Immunohistochemistry for SARS‐CoV‐2 was performed in all cases and electron microscopy in one.
Results
Histopathology showed variable degrees of lymphocytic vasculitis ranging from endothelial swelling and endotheliitis to fibrinoid necrosis and thrombosis. Purpura, superficial and deep perivascular lymphocytic inflammation with perieccrine accentuation, oedema, and mild vacuolar interface damage were also seen. SARS‐CoV‐2 immunohistochemistry was positive in endothelial cells and epithelial cells of eccrine glands. Coronavirus particles were found in the cytoplasm of endothelial cells on electron microscopy.
Conclusions
Although the clinical and histopathological features were similar to other forms of chilblains, the presence of viral particles in the endothelium and the histological evidence of vascular damage support a causal relation of the lesions with SARS‐CoV‐2. Endothelial damage induced by the virus could be the key mechanism in the pathogenesis of COVID‐19 chilblains and perhaps also in a group of patients severely affected by COVID‐19 presenting with features of microangiopathic damage.
What is already known about this topic?
Despite the high number of cases of chilblains seen during the COVID‐19 pandemic, a definite causative role for SARS‐CoV‐2 has not yet been proven.
Different pathogenetic hypotheses have been proposed, including coagulation anomalies, interferon release and external factors.
What does this study add?
The demonstration of SARS‐CoV‐2 in endothelial cells of skin biopsies by immunohistochemistry and electron microscopy confirms that these lesions are part of the spectrum of COVID‐19.
Virus‐induced vascular damage and secondary ischaemia could explain the pathophysiology of COVID‐19 chilblains.
Our findings support the hypothesis that widespread endothelial infection by SARS‐CoV‐2 could have a pathogenetic role in the severe forms of COVID‐19.
Linked Comment: Wetter. Br J Dermatol 2020; 183:611.
Linked Comment: Wetter. Br J Dermatol 2020; 183:611.
Plain language summary available online
Summary Background The 2014 Zaire Ebola virus outbreak highlighted the need for a safe, effective vaccine with a rapid onset of protection. We report the safety and immunogenicity of the recombinant ...vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSV∆G-ZEBOV-GP) across a 6 log10 dose range in two sequential cohorts. Methods In this phase 1b double-blind, placebo-controlled, dose-response study we enrolled and randomly assigned healthy adults (aged 18–61 years) at eight study sites in the USA to receive a single injection of vaccine or placebo, administered by intramuscular injection. In cohort 1, participants were assigned to receive 3 × 103 , 3 × 104 , 3 × 105 , or 3 × 106 PFU doses of rVSV∆G-ZEBOV-GP or placebo. In cohort 2, participants were assigned to receive 3 × 106 , 9 × 106 , 2 × 107 , or 1 × 108 PFU doses of rVSV∆G-ZEBOV-GP or placebo. Participants were centrally allocated by the study statistician to vaccine groups or placebo through computer-generated randomisation lists. The primary safety outcome was incidence of adverse events within 14 days in the modified intention-to-treat population (all randomly assigned participants who received vaccine or placebo), and the primary outcome for immunogenicity was IgG ELISA antibody titres at day 28 in the per-protocol population. Surveillance was enhanced for arthritis and dermatitis through to day 56. This study is registered with ClinicalTrials.gov , number NCT02314923. Findings Between Dec 26, 2014, and June 8, 2015, 513 participants were enrolled and randomly assigned; one was not immunised because of unsuccessful phlebotomy. In cohort 1, 256 participants received vaccine (3 × 103 n=64, 3 × 104 n=64, 3 × 105 n=64, or 3 × 106 PFU n=64) and 74 received placebo. In cohort 2, 162 participants received vaccine (3 × 106 n=20, 9 × 106 n=47, 2 × 107 n=47, or 1 × 108 PFU n=48) and 20 received placebo. Most adverse events occurred in the first day after vaccination, and were mild to moderate in intensity, of a short duration, and more frequent at high vaccine doses (9 × 106 PFU and greater). At the 2 × 107 PFU dose (used in phase 3 trials), the most common local adverse events versus placebo within the first 14 days were arm pain (57·4% 27 of 47 vs 7·4% seven of 94) and local tenderness (59·6% 28 of 47 vs 8·5% eight of 94). The most common systemic adverse events at the 2 × 107 PFU dose versus placebo, occurring in the first 14 days, were headache (46·8% 22 of 47 vs 27·7% 26 of 94), fatigue (38·3% 18 of 47 vs 19·1% 18 of 94), myalgia (34·0% 16 of 47 vs 10·6% 10 of 94), subjective fever (29·8% 14 of 47 vs 2·1% two of 94), shivering or chills (27·7% 13 of 47 vs 7·4% seven of 94), sweats (23·4% 11 of 47 vs 3·2% three of 94), joint aches and pain (19·1% nine of 47 vs 7·4% seven of 94), objective fever (14·9% seven of 47 vs 1·1% one of 94), and joint tenderness or swelling (14·9% seven of 47 vs 2·1% two of 94). Self-limited, post-vaccination arthritis occurred in 4·5% (19 of 418) of vaccinees (median onset 12·0 days IQR 10–14; median duration 8·0 days 6–15) versus 3·2% (three of 94) of controls (median onset 15·0 days 6–20; median duration 47·0 days 37–339), with no apparent dose relationship. Post-vaccination dermatitis occurred in 5·7% (24 of 418) of vaccinees (median onset 9·0 days IQR 2–12; median duration 7·0 days 4–9) versus 3·2% (three of 94) of controls (median onset 5·0 days 3–53; median duration 33·0 days 5–370). A low-level, transient, dose-dependent viraemia occurred in concert with early reactogenicity. Antibody responses were observed in most participants by day 14. IgG and neutralising antibody titres were dose-related (p=0·0003 for IgG ELISA and p<0·0001 for the 60% plaque-reduction neutralisation test PRNT60 by linear trend). On day 28 at the 2 × 107 PFU dose, the geometric mean IgG ELISA endpoint titre was 1624 (95% CI 1146–2302) and seroconversion was 95·7% (95% CI 85·5–98·8); the geometric mean neutralising antibody titre by PRNT60 was 250 (176–355) and seroconversion was 95·7% (85·5–98·8). These robust immunological responses were sustained for 1 year. Interpretation rVSV∆G-ZEBOV-GP was well tolerated and stimulated a rapid onset of binding and neutralising antibodies, which were maintained through to day 360. The immunogenicity results support selection of the 2 × 107 PFU dose. Funding Biomedical Advanced Research and Development Authority, US Department of Health and Human Services.