To provide a summary of evidence for the diagnostic accuracies of three multiplex PCR systems (mPCRs)—BioFire FilmArray RP (FilmArray), Nanosphere Verigene RV+ test (Verigene RV+) and Hologic ...Gen-Probe Prodesse assays—on the detection of viral respiratory infections.
A comprehensive search up to 1 July 2017 was conducted on Medline and Embase for studies that utilized FilmArray, Verigene RV+ and Prodesse for diagnosis of viral respiratory infections. A summary of diagnostic accuracies for the following five viruses were calculated: influenza A virus (FluA), influenza B virus, respiratory syncytial virus, human metapneumovirus and adenovirus. Hierarchical summary receiver operating curves were used for estimating the viral detection performance per assay.
Twenty studies of 5510 patient samples were eligible for analysis. Multiplex PCRs demonstrated high diagnostic accuracy, with area under the receiver operating characteristic curve (AUROC) equal to or more than 0.98 for all the above viruses except for adenovirus (AUROC 0.89). FilmArray, Verigene RV+ and ProFlu+ (the only Prodesse assay with enough data) demonstrated a summary sensitivity for FluA of 0.911 (95% confidence interval, 0.848–0.949), 0.949 (95% confidence interval, 0.882–0.979) and 0.954 (95% confidence interval, 0.871–0.985), respectively. The three mPCRs were comparable in terms of detection of FluA.
Point estimates calculated from eligible studies showed that the three mPCRs (FilmArray, Verigene RV+ and ProFlu+) are highly accurate and may provide important diagnostic information for early identification of respiratory virus infections. In patients with low pretest probability for FluA, these three mPCRs can predict a low possibility of infection and may justify withholding empirical antiviral treatments.
Previous mass screening studies have shown that IgA antibodies against Epstein–Barr Virus (EBV) can facilitate early detection of nasopharyngeal carcinoma (NPC), but the impact of EBV-antibody ...screening for NPC-specific mortality remains unknown.
A prospective, cluster randomized, controlled trial for NPC screening (PRO-NPC-001) was conducted in 3 selected towns of Zhongshan City and 13 selected towns of Sihui City in southern China beginning in 2008. Serum samples of the screening group were tested for two previously selected anti-EBV antibodies. Subjects with serological medium risk were subsequently retested annually for 3 years, and those with serological high risk were referred to otorhinolaryngologists for diagnostic check-up. An interim analysis was carried out to evaluate the primary end points of the NPC-specific mortality and the early diagnostic rate, and the secondary end point of the NPC incidence, through linkage with the database of Zhongshan City.
Among 70 296 total subjects, 29 413 screened participants (41.8% of the total subjects) in the screening group and 50 636 in the control group, 153 (43.3 per 100 000 person-year), 62 (55.3 per 100 000 person-year) and 99 (33.1 per 100 000 person-year) NPC cases were identified. The early diagnostic rates of NPC were significantly higher in the participants (79.0%, P < 0.0001) and the screening group (45.9%, P < 0.0001) compared with the control group (20.6%). Although no differences were found between NPC-specific mortality of the screening group and the control group relative risk (RR)= 0.82, 95% confidence interval (CI) 0.37–1.79, lower NPC-specific mortality was noticed among participants from the screening group versus the control group (RR = 0.22, 95% CI 0.09–0.49).
IgA antibodies against EBV can identify high-risk population and was effective in screening for early asymptomatic NPC. Although the mortality reduction was not significant in the primary end point, we noted encouraging evidence of a mortality reduction in screening participants in this interim analysis.
NCT00941538.
More than 400 membrane transporters in two major superfamilies—ATP‐binding cassette (ABC) and solute carrier (SLC)—are annotated in the human genome. Preclinical and clinical studies indicate that ...transport is an important determinant of drug disposition, as well as therapeutic and adverse drug effects. Importantly, transporters may represent the rate‐determining step of drug absorption, distribution, and elimination in the intestine, liver, kidney, and blood–brain barrier (BBB), and they are often the sites of drug–drug interactions.
Clinical Pharmacology & Therapeutics (2013); 94 1, 3–9. doi:10.1038/clpt.2013.86
We present new observational determinations of the evolution of the 2–10 keV X-ray luminosity function (XLF) of active galactic nuclei (AGN). We utilize data from a number of surveys including both ...the 2 Ms Chandra Deep Fields and the AEGIS-X 200 ks survey, enabling accurate measurements of the evolution of the faint end of the XLF. We combine direct, hard X-ray selection and spectroscopic follow-up or photometric redshift estimates at z < 1.2 with a rest-frame UV colour pre-selection approach at higher redshifts to avoid biases associated with catastrophic failure of the photometric redshifts. Only robust optical counterparts to X-ray sources are considered using a likelihood ratio matching technique. A Bayesian methodology is developed that considers redshift probability distributions, incorporates selection functions for our high-redshift samples and allows robust comparison of different evolutionary models. We statistically account for X-ray sources without optical counterparts to correct for incompleteness in our samples. We also account for Poissonian effects on the X-ray flux estimates and sensitivities and thus correct for the Eddington bias. We find that the XLF retains the same shape at all redshifts, but undergoes strong luminosity evolution out to z∼ 1, and an overall negative density evolution with increasing redshift, which thus dominates the evolution at earlier times. We do not find evidence that a luminosity-dependent density evolution, and the associated flattening of the faint-end slope, is required to describe the evolution of the XLF. We find significantly higher space densities of low-luminosity, high-redshift AGN than in prior studies, and a smaller shift in the peak of the number density to lower redshifts with decreasing luminosity. The total luminosity density of AGN peaks at z= 1.2 ± 0.1, but there is a mild decline to higher redshifts. We find that >50 per cent of black hole growth takes place at z > 1, with around half in LX < 1044 erg s−1 AGN.
We describe generation of stable mode-locked pulse trains from on-chip normal dispersion microresonators. The excitation of hyperparametric oscillation is facilitated by the local dispersion ...disruptions induced by mode interactions. The system is then driven from hyperparametric oscillation to the mode-locked state with over 200 nm spectral width by controlled pump power and detuning. With the continuous-wave-driven nonlinearity, the pulses sit on a pedestal, akin to a cavity soliton. We identify the importance of pump detuning and wavelength-dependent quality factors in stabilizing and shaping the pulse structure, to achieve a single pulse inside the cavity. We examine the mode-locking dynamics by numerically solving the master equation and provide analytic solutions under appropriate approximations.
Physiologically based pharmacokinetic (PBPK) models are increasingly used by drug developers to evaluate the effect of patient factors on drug exposure. Between June 2008 and December 2011, the ...Office of Clinical Pharmacology at the US Food and Drug Administration (FDA) received 25 submissions containing PBPK analyses. This report summarizes the essential content of a PBPK analysis needed in a regulatory submission for the purpose of addressing clinical pharmacology questions.
Clinical Pharmacology & Therapeutics (2012); 92 1, 17–20. doi:10.1038/clpt.2012.68
Primary liver cancer, predominantly consisting of hepatocellular carcinoma (HCC), is one of the most common and aggressive human malignancies worldwide. MicroRNAs (miRNAs) are a class of small ...non-coding RNAs that regulate gene expression post-transcriptionally. Emerging evidence indicates that miRNAs are often deregulated in HCC, and that some specific miRNAs are associated with the clinicopathological features of HCC. Recent work demonstrates that miRNAs have essential roles in HCC progression and directly contribute to cell proliferation, avoidance of apoptotic cell death, and metastasis of HCC by targeting a large number of critical protein-coding genes. The discovery of the aberrantly expressed miRNAs and their corresponding targets has opened a novel avenue to investigate the molecular mechanism of HCC progression and to develop potential therapeutics against HCC. In this review, we summarise current knowledge about the roles and validated targets of miRNAs in liver cancer progression.
In single-spacecraft observations the Taylor frozen-in-flow hypothesis is usually used to infer wavenumber spectra of turbulence from the frequency ones. While this hypothesis can be valid at MHD ...scales in the solar wind because of the small phase speeds of the fluctuations in comparison with the solar wind flow speed, its validity at electron scales is questionable. In this paper, we use Cluster data to verify the validity of the Taylor hypothesis in solar wind turbulence using the test proposed in Sahraoui et al. based on the assumption that the spectral breaks occur at i and e. Using a model based on the dispersion relation of the linear whistler mode and the estimated ratios of the spectral breaks of the magnetic energy observed in the free-streaming solar wind, we find that 32% of the events would violate the Taylor hypothesis because of their high frequency (in the plasma rest frame) compared to the Doppler shift ( plas/k V > 0.5). Furthermore, the model shows that those events would correspond to whistler modes with propagation angles θkB ≤ 68°. The limitations of the method used and the implications of the results on future spacecraft measurements of electron-scale turbulence are discussed.
ABSTRACT
The deep, wide-area (∼800–900 arcmin
2
) near-infrared/WFC3/IR +
Spitzer
/IRAC observations over the CANDELS fields have been a remarkable resource for constraining the bright end of ...high-redshift UV luminosity functions. However, the lack of
Hubble Space Telescope
(
HST
) 1.05
μ
m observations over the CANDELS fields has made it difficult to identify
z
∼ 9–10 sources robustly, since such data are needed to confirm the presence of an abrupt Lyman break at 1.2
μ
m. Here, we report on the successful identification of many such
z
∼ 9–10 sources from a new
HST
program (z9-CANDELS) that targets the highest-probability
z
∼ 9–10 galaxy candidates with observations at 1.05
μ
m, to search for a robust Lyman-break at 1.2
μ
m. The potential
z
∼ 9–10 candidates were preselected from the full
HST
,
Spitzer
/IRAC S-CANDELS observations, and the deepest-available ground-based optical+near-infrared observations (CFHTLS-DEEP+HUGS+UltraVISTA+ZFOURGE). We identified 15 credible
z
∼ 9–10 galaxies over the CANDELS fields. Nine of these galaxies lie at
z
∼ 9 and five are new identifications. Our targeted follow-up strategy has proven to be very efficient in making use of scarce
HST
time to secure a reliable sample of
z
∼ 9–10 galaxies. Through extensive simulations, we replicate the selection process for our sample (both the preselection and follow-up) and use it to improve current estimates for the volume density of bright
z
∼ 9 and
z
∼ 10 galaxies. The volume densities we find are 5
and
lower, respectively, than those found at
z
∼ 8. When compared with the best-fit evolution (i.e.,
) in the UV luminosity densities from
z
∼ 8 to
z
∼ 4 integrated to
(−20 mag), these luminosity densities are
and
lower, respectively, than the extrapolated trends. Our new results are broadly consistent with the “accelerated evolution” scenario at
z
> 8, consistent with that seen in many models.
Abstract
Photon upconversion is an anti-Stokes process in which an absorption of a photon leads to a reemission of a photon at an energy higher than the excitation energy. The upconversion ...photoemission has been already demonstrated in rare earth atoms in glasses, semiconductor quantum wells, nanobelts, carbon nanotubes and atomically thin semiconductors. Here, we demonstrate a room temperature upconversion photoluminescence process in a monolayer semiconductor WS
2
, with energy gain up to 150 meV. We attribute this process to transitions involving trions and many phonons and free exciton complexes. These results are very promising for energy harvesting, laser refrigeration and optoelectronics at the nanoscale.
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