112 research outputs found
Living for the weekend: youth identities in northeast England
Consumption and consumerism are now accepted as key contexts for the construction of youth identities in de-industrialized Britain. This article uses empirical evidence from interviews with young people to suggest that claims of `new community' are overstated, traditional forms of friendship are receding, and increasingly atomized and instrumental youth identities are now being culturally constituted and reproduced by the pressures and anxieties created by enforced adaptation to consumer capitalism. Analysis of the data opens up the possibility of a critical rather than a celebratory exploration of the wider theoretical implications of this process
High-contrast imaging constraints on gas giant planet formation - The Herbig Ae/Be star opportunity
Planet formation studies are often focused on solar-type stars, implicitly
considering our Sun as reference point. This approach overlooks, however, that
Herbig Ae/Be stars are in some sense much better targets to study planet
formation processes empirically, with their disks generally being larger,
brighter and simply easier to observe across a large wavelength range. In
addition, massive gas giant planets have been found on wide orbits around early
type stars, triggering the question if these objects did indeed form there and,
if so, by what process. In the following I briefly review what we currently
know about the occurrence rate of planets around intermediate mass stars,
before discussing recent results from Herbig Ae/Be stars in the context of
planet formation. The main emphasis is put on spatially resolved polarized
light images of potentially planet forming disks and how these images - in
combination with other data - can be used to empirically constrain (parts of)
the planet formation process. Of particular interest are two objects, HD100546
and HD169142, where, in addition to intriguing morphological structures in the
disks, direct observational evidence for (very) young planets has been
reported. I conclude with an outlook, what further progress we can expect in
the very near future with the next generation of high-contrast imagers at 8-m
class telescopes and their synergies with ALMA.Comment: Accepted by Astrophysics and Space Science as invited short review in
special issue about Herbig Ae/Be stars; 12 pages incl. 5 figures, 2 tables
and reference
Study of the production of and hadrons in collisions and first measurement of the branching fraction
The product of the () differential production
cross-section and the branching fraction of the decay () is
measured as a function of the beauty hadron transverse momentum, ,
and rapidity, . The kinematic region of the measurements is and . The measurements use a data sample
corresponding to an integrated luminosity of collected by the
LHCb detector in collisions at centre-of-mass energies in 2011 and in 2012. Based on previous LHCb
results of the fragmentation fraction ratio, , the
branching fraction of the decay is
measured to be \begin{equation*} \mathcal{B}(\Lambda_b^0\rightarrow J/\psi
pK^-)= (3.17\pm0.04\pm0.07\pm0.34^{+0.45}_{-0.28})\times10^{-4},
\end{equation*} where the first uncertainty is statistical, the second is
systematic, the third is due to the uncertainty on the branching fraction of
the decay , and the
fourth is due to the knowledge of . The sum of the
asymmetries in the production and decay between and
is also measured as a function of and .
The previously published branching fraction of , relative to that of , is updated.
The branching fractions of are determined.Comment: 29 pages, 19figures. All figures and tables, along with any
supplementary material and additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-032.htm
Projected WIMP sensitivity of the LUX-ZEPLIN dark matter experiment
LUX-ZEPLIN (LZ) is a next-generation dark matter direct detection experiment that will operate 4850 feet underground at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, USA. Using a two-phase xenon detector with an active mass of 7 tonnes, LZ will search primarily for low-energy interactions with weakly interacting massive particles (WIMPs), which are hypothesized to make up the dark matter in our galactic halo. In this paper, the projected WIMP sensitivity of LZ is presented based on the latest background estimates and simulations of the detector. For a 1000 live day run using a 5.6-tonne fiducial mass, LZ is projected to exclude at 90% confidence level spin-independent WIMP-nucleon cross sections above 1.4 × 10-48cm2 for a 40 GeV/c2 mass WIMP.
Additionally, a 5σ discovery potential is projected, reaching cross sections below the exclusion limits of recent experiments. For spin-dependent WIMP-neutron(-proton) scattering, a sensitivity of 2.3 × 10−43 cm2 (7.1 × 10−42 cm2) for a 40 GeV/c2
mass WIMP is expected. With underground installation well underway, LZ is on track for commissioning at SURF in 2020
Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Background:
In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation.
Methods:
This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).
Findings:
Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001).
Interpretation:
In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids.
Funding:
UK Research and Innovation (Medical Research Council) and National Institute of Health Research
Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial
Background:
Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19.
Methods:
This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.
Findings:
Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79).
Interpretation:
In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes.
Funding:
UK Research and Innovation (Medical Research Council) and National Institute of Health Research
Tumor-infiltrating dendritic cells exhibit defective cross-presentation of tumor antigens, but is reversed by chemotherapy
Cross-presentation defines the unique capacity of an APC to present exogenous Ag via MHC class I molecules to CD8+ T cells. DCs are specialized cross-presenting cells and as such have a critical role in antitumor immunity. DCs are routinely found within the tumor microenvironment, but their capacity for endogenous or therapeutically enhanced cross-presentation is not well characterized. In this study, we examined the tumor and lymph node DC cross-presentation of a nominal marker tumor Ag, HA, expressed by the murine mesothelioma tumor AB1-HA. We found that tumors were infiltrated by predominantly CD11b+ DCs with a semimature phenotype that could not cross-present tumor Ag, and therefore, were unable to induce tumor-specific T-cell activation or proliferation. Although tumor-infiltrating DCs were able to take, process, and cross-present exogenous cell-bound and soluble Ags, this was significantly impaired relative to lymph node DCs. Importantly, however, systemic chemotherapy using gemcitabine reversed the defect in Ag cross-presentation of tumor DCs. These data demonstrate that DC cross-presentation within the tumor microenvironment is defective, but can be reversed by chemotherapy. These results have important implications for anticancer therapy, particularly regarding the use of immunotherapy in conjunction with cytotoxic chemotherapy
S100A1 increases the gain of excitation-contraction coupling in isolated rabbit ventricular cardiomyocytes
The effect of S100A1 protein on cardiac excitation-contraction (E-C) coupling was studied using recombinant human S100A1 protein (0.01-10 mu M) introduced into single rabbit ventricular cardiomyocytes via a patch pipette. Voltage clamp experiments (20 degrees C) indicated that 0.1 mu M S100A1 increased Ca2+ transient amplitude by similar to 41% but higher or lower S100A1 concentrations had no significant effect. L-type Ca2+ current amplitude or Ca2+ efflux rates via the Na+/Ca2+ exchanger (NCX) were unaffected. The rate of Ca2+ uptake associated with the SR Ca2+-ATPase (SERCA2a) was increased by similar to 22% with 0.1 mu M S100A1, but not at other S100A1 concentrations. Based on the intracellular Ca2+ and I-NXC signals in response to 10 mM caffeine, no significant change in SR Ca2+ content was observed with S100A1 (0.01-10 mu M). Therefore, 0.1 mu M S100A1 appeared to increase the fractional Ca2+ release from the SR. This result was confirmed by measurements of Ca2+ transient amplitude at a range of SR Ca2+ contents. The hyperbolic relationship between these two parameters was shifted to the left by 0.1 mu M S100A1. [H-3]-ryanodine binding studies indicated that S100A1 increased ryanodine receptor (RyR) activity at 0.1 and 0.3 mu M Ca-2. As with the effects on E-C coupling, 0.1 mu M S100A1 produced the largest effect. Co-immunoprecipitation studies on a range of Ca2+- handling proteins support the selective interaction of S100A1 on SERCA2a and RyR. In summary, S100A1 had a stimulatory action on RyR2 and SERCA2a in rabbit cardiomyocytes. Under the conditions of this study, the net effect of this dual action is to enhance the Ca2+ transient amplitude without significantly affecting the SR Ca2+ content
The efficacy of tumor debulking surgery is improved by adjuvant immunotherapy using imiquimod and anti-CD40
BACKGROUND
Tumor debulking surgery followed by adjuvant chemotherapy or radiotherapy is a standard treatment for many solid malignancies. Although this approach can be effective, it often has limited success against recurrent or metastatic cancers and new multimodality approaches are needed. Adjuvant immunotherapy is another potentially effective approach. We therefore tested the efficacy of the TLR7 agonist imiquimod (IMQ) combined with agonistic anti-CD40 in an incomplete debulking model of malignant mesothelioma.
METHODS
Established subcutaneous murine ABA-HA mesothelioma tumors in BALB/c mice were surgically debulked by 75% and treated with either: i) saline; ii) intratumoral IMQ; iii) systemic anti-CD40 antibody, or using a combination of IMQ and anti-CD40. Tumour growth and survival were monitored, and the role of anti-tumor CD4 and CD8 T cells in therapeutic responses was determined.
RESULTS
The combination therapy of partial debulking surgery, IMQ and anti-CD40 significantly delayed tumor growth in a CD8 T cell dependent manner, and promoted tumor regression in 25% of animals with establishment of immunological memory. This response was associated with an increase in ICOS+ CD8 T cells and tumor-specific CTL activity in tumor draining lymph nodes along with an increase in ICOS+ CD8 T cells in responding tumours.
CONCLUSIONS
We show that the post-surgical environment can be significantly altered by the co-administration of adjuvant IMQ and anti-CD40, resulting in strong, systemic anti-tumor activity. Both adjuvants are available for clinical use/trial, hence this treatment regimen has clear translational potential
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