1,229 research outputs found
Combining carfilzomib and panobinostat to treat relapsed/refractory multiple myeloma: results of a Multiple Myeloma Research Consortium Phase I Study
Key points CarPan is a highly active, steroid-sparing regimen, effective in both bortezomib-sensitive and refractory patients.The safety profile of CarPan, particularly thrombocytopenia and gastrointestinal adverse events, compares favorably with that of panobinostat and bortezomib
Alginate inhibits iron absorption from ferrous gluconate in a randomized controlled trial and reduces iron uptake into Caco-2 cells
Previous in vitro results indicated that alginate beads might be a useful vehicle for food iron fortification. A human study was undertaken to test the hypothesis that alginate enhances iron absorption. A randomised, single blinded, cross-over trial was carried out in which iron absorption was measured from serum iron appearance after a test meal. Overnight-fasted volunteers (n=15) were given a test meal of 200g cola-flavoured jelly plus 21 mg iron as ferrous gluconate, either in alginate beads mixed into the jelly or in a capsule. Iron absorption was lower from the alginate beads than from ferrous gluconate (8.5% and 12.6% respectively, p=0.003). Sub-group B (n=9) consumed the test meals together with 600 mg calcium to determine whether alginate modified the inhibitory effect of calcium. Calcium reduced iron absorption from ferrous gluconate by 51%, from 11.5% to 5.6% (p=0.014), and from alginate beads by 37%, from 8.3% to 5.2% (p=0.009). In vitro studies using Caco-2 cells were designed to explore the reasons for the difference between the previous in vitro findings and the human study; confirmed the inhibitory effect of alginate. Beads similar to those used in the human study were subjected to simulated gastrointestinal digestion, with and without cola jelly, and the digestate applied to Caco-2 cells. Both alginate and cola jelly significantly reduced iron uptake into the cells, by 34% (p=0.009) and 35% (p=0.003) respectively. The combination of cola jelly and calcium produced a very low ferritin response, 16.5% (p<0.001) of that observed with ferrous gluconate alone. The results of these studies demonstrate that alginate beads are not a useful delivery system for soluble salts of iron for the purpose of food fortification
The Primordial Inflation Polarization Explorer (PIPER)
The Primordial Inflation Polarization Explorer (PIPER) is a balloon-borne
cosmic microwave background (CMB) polarimeter designed to search for evidence
of inflation by measuring the large-angular scale CMB polarization signal.
BICEP2 recently reported a detection of B-mode power corresponding to the
tensor-to-scalar ratio r = 0.2 on ~2 degree scales. If the BICEP2 signal is
caused by inflationary gravitational waves (IGWs), then there should be a
corresponding increase in B-mode power on angular scales larger than 18
degrees. PIPER is currently the only suborbital instrument capable of fully
testing and extending the BICEP2 results by measuring the B-mode power spectrum
on angular scales = ~0.6 deg to 90 deg, covering both the reionization
bump and recombination peak, with sensitivity to measure the tensor-to-scalar
ratio down to r = 0.007, and four frequency bands to distinguish foregrounds.
PIPER will accomplish this by mapping 85% of the sky in four frequency bands
(200, 270, 350, 600 GHz) over a series of 8 conventional balloon flights from
the northern and southern hemispheres. The instrument has background-limited
sensitivity provided by fully cryogenic (1.5 K) optics focusing the sky signal
onto four 32x40-pixel arrays of time-domain multiplexed Transition-Edge Sensor
(TES) bolometers held at 140 mK. Polarization sensitivity and systematic
control are provided by front-end Variable-delay Polarization Modulators
(VPMs), which rapidly modulate only the polarized sky signal at 3 Hz and allow
PIPER to instantaneously measure the full Stokes vector (I, Q, U, V) for each
pointing. We describe the PIPER instrument and progress towards its first
flight.Comment: 11 pages, 7 figures. To be published in Proceedings of SPIE Volume
9153. Presented at SPIE Astronomical Telescopes + Instrumentation 2014,
conference 915
Rape, inequality and the criminal justice response in England: The importance of age and gender
© The Author(s) 2019. This article draws upon quantitative and content analysis of 585 reports of rape recorded within two police force areas in England in 2010 and in 2014 tracking individual incidents to eventual outcome to examine the impact, if any, of intersecting inequalities on trajectories of rape cases reported to police. The data were collected as part of the wider Economic and Social Research Council funded Justice, Inequality and Gender-Based Violence research project which examined victim-survivor experiences and perspectives on justice. Building on existing distinctions between types of rape case based on the relationship between victim-survivor and accused, the results suggest age and gender are significant factors in how sexual violence, and the criminal justice system, is experienced. While younger women and girls were disproportionately affected by certain types of sexual violence case and more likely to come into contact with the criminal justice system compared to men and older women, they were not necessarily more likely to achieve a conviction. The findings also confirm that some of the most vulnerable victims-survivors of sexual violence, especially those with poor mental health, are still not achieving criminal justice. Victims-survivors from Black and minority ethnic group or lesbian, gay, bisexual, transgender, transsexual, queer groups are underrepresented within the criminal justice system, implying these groups are not seeking a criminal justice response in the same way as ‘white’ heterosexual victims-survivors
Dissociable effects of 5-HT2C receptor antagonism and genetic inactivation on perseverance and learned non-reward in an egocentric spatial reversal task
Cognitive flexibility can be assessed in reversal learning tests, which are sensitive to modulation of 5-HT2C receptor (5-HT2CR) function. Successful performance in these tests depends on at least two dissociable cognitive mechanisms which may separately dissipate associations of previous positive and negative valence. The first is opposed by perseverance and the second by learned non-reward. The current experiments explored the effect of reducing function of the 5-HT2CR on the cognitive mechanisms underlying egocentric reversal learning in the mouse. Experiment 1 used the 5-HT2CR antagonist SB242084 (0.5 mg/kg) in a between-groups serial design and Experiment 2 used 5-HT2CR KO mice in a repeated measures design. Animals initially learned to discriminate between two egocentric turning directions, only one of which was food rewarded (denoted CS+, CS−), in a T- or Y-maze configuration. This was followed by three conditions; (1) Full reversal, where contingencies reversed; (2) Perseverance, where the previous CS+ became CS− and the previous CS− was replaced by a novel CS+; (3) Learned non-reward, where the previous CS− became CS+ and the previous CS+ was replaced by a novel CS-. SB242084 reduced perseverance, observed as a decrease in trials and incorrect responses to criterion, but increased learned non-reward, observed as an increase in trials to criterion. In contrast, 5-HT2CR KO mice showed increased perseverance. 5-HT2CR KO mice also showed retarded egocentric discrimination learning. Neither manipulation of 5-HT2CR function affected performance in the full reversal test. These results are unlikely to be accounted for by increased novelty attraction, as SB242084 failed to affect performance in an unrewarded novelty task. In conclusion, acute 5-HT2CR antagonism and constitutive loss of the 5-HT2CR have opposing effects on perseverance in egocentric reversal learning in mice. It is likely that this difference reflects the broader impact of 5HT2CR loss on the development and maintenance of cognitive function
Ancient Adaptive Evolution of the Primate Antiviral DNA-Editing Enzyme APOBEC3G
Host genomes have adopted several strategies to curb the proliferation of transposable elements and viruses. A recently discovered novel primate defense against retroviral infection involves a single-stranded DNA-editing enzyme, APOBEC3G, that causes hypermutation of HIV. The HIV-encoded virion infectivity factor (Vif) protein targets APOBEC3G for destruction, setting up a genetic conflict between the APOBEC3G and Vif genes. This kind of conflict leads to rapid fixation of mutations that alter amino acids at the protein–protein interface, referred to as positive selection. We show that the APOBEC3G gene has been subject to strong positive selection throughout the history of primate evolution. Unexpectedly, this selection appears more ancient than, and is likely only partially caused by, modern lentiviruses. Furthermore, five additional APOBEC genes in the human genome appear to be engaged in similar genetic conflicts, displaying some of the highest signals for positive selection in the human genome. Despite being only recently discovered, editing of RNA and DNA may thus represent an ancient form of host defense in primate genomes
The Atacama Cosmology Telescope: A Measurement of the Cosmic Microwave Background Power Spectrum at 148 and 218 GHz from the 2008 Southern Survey
We present measurements of the cosmic microwave background (CMB) power
spectrum made by the Atacama Cosmology Telescope at 148 GHz and 218 GHz, as
well as the cross-frequency spectrum between the two channels. Our results
clearly show the second through the seventh acoustic peaks in the CMB power
spectrum. The measurements of these higher-order peaks provide an additional
test of the {\Lambda}CDM cosmological model. At l > 3000, we detect power in
excess of the primary anisotropy spectrum of the CMB. At lower multipoles 500 <
l < 3000, we find evidence for gravitational lensing of the CMB in the power
spectrum at the 2.8{\sigma} level. We also detect a low level of Galactic dust
in our maps, which demonstrates that we can recover known faint, diffuse
signals.Comment: 19 pages, 13 figures. Submitted to ApJ. This paper is a companion to
Hajian et al. (2010) and Dunkley et al. (2010
The Atacama Cosmology Telescope: Data Characterization and Map Making
We present a description of the data reduction and mapmaking pipeline used
for the 2008 observing season of the Atacama Cosmology Telescope (ACT). The
data presented here at 148 GHz represent 12% of the 90 TB collected by ACT from
2007 to 2010. In 2008 we observed for 136 days, producing a total of 1423 hours
of data (11 TB for the 148 GHz band only), with a daily average of 10.5 hours
of observation. From these, 1085 hours were devoted to a 850 deg^2 stripe (11.2
hours by 9.1 deg) centered on a declination of -52.7 deg, while 175 hours were
devoted to a 280 deg^2 stripe (4.5 hours by 4.8 deg) centered at the celestial
equator. We discuss sources of statistical and systematic noise, calibration,
telescope pointing, and data selection. Out of 1260 survey hours and 1024
detectors per array, 816 hours and 593 effective detectors remain after data
selection for this frequency band, yielding a 38% survey efficiency. The total
sensitivity in 2008, determined from the noise level between 5 Hz and 20 Hz in
the time-ordered data stream (TOD), is 32 micro-Kelvin sqrt{s} in CMB units.
Atmospheric brightness fluctuations constitute the main contaminant in the data
and dominate the detector noise covariance at low frequencies in the TOD. The
maps were made by solving the least-squares problem using the Preconditioned
Conjugate Gradient method, incorporating the details of the detector and noise
correlations. Cross-correlation with WMAP sky maps, as well as analysis from
simulations, reveal that our maps are unbiased at multipoles ell > 300. This
paper accompanies the public release of the 148 GHz southern stripe maps from
2008. The techniques described here will be applied to future maps and data
releases.Comment: 20 pages, 18 figures, 6 tables, an ACT Collaboration pape
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