In a randomized trial of bortezomib, cyclophosphamide, and dexamethasone as compared with the same therapy plus daratumumab, patients with light-chain amyloidosis who received daratumumab had a ...higher frequency of hematologic complete response than those who did not (53.3% vs. 18.1%). Deaths were most commonly due to cardiac failure.
Practical components for three-dimensional molecular nanofabrication must be simple to produce, stereopure, rigid, and adaptable. We report a family of DNA tetrahedra, less than 10 nanometers on a ...side, that can self-assemble in seconds with near-quantitative yield of one diastereomer. They can be connected by programmable DNA linkers. Their triangulated architecture confers structural stability; by compressing a DNA tetrahedron with an atomic force microscope, we have measured the axial compressibility of DNA and observed the buckling of the double helix under high loads.
We report on the measurement of the all-particle cosmic ray energy spectrum with the High Altitude Water Cherenkov (HAWC) Observatory in the energy range 10 to 500 TeV. HAWC is a ground-based ...air-shower array deployed on the slopes of Volcan Sierra Negra in the state of Puebla, Mexico, and is sensitive to gamma rays and cosmic rays at TeV energies. The data used in this work were taken over 234 days between June 2016 and February 2017. The primary cosmic-ray energy is determined with a maximum likelihood approach using the particle density as a function of distance to the shower core. Introducing quality cuts to isolate events with shower cores landing on the array, the reconstructed energy distribution is unfolded iteratively. The measured all-particle spectrum is consistent with a broken power law with an index of −2.49±0.01 prior to a break at (45.7±0.1) TeV, followed by an index of −2.71±0.01. The spectrum also represents a single measurement that spans the energy range between direct detection and ground-based experiments. As a verification of the detector response, the energy scale and angular resolution are validated by observation of the cosmic ray Moon shadow’s dependence on energy.
Release 6, the latest reference genome assembly of the fruit fly Drosophila melanogaster, was released by the Berkeley Drosophila Genome Project in 2014; it replaces their previous Release 5 genome ...assembly, which had been the reference genome assembly for over 7 years. With the enormous amount of information now attached to the D. melanogaster genome in public repositories and individual laboratories, the replacement of the previous assembly by the new one is a major event requiring careful migration of annotations and genome-anchored data to the new, improved assembly. In this report, we describe the attributes of the new Release 6 reference genome assembly, the migration of FlyBase genome annotations to this new assembly, how genome features on this new assembly can be viewed in FlyBase (http://flybase.org) and how users can convert coordinates for their own data to the corresponding Release 6 coordinates.
We analyze the Sun as a source for the indirect detection of dark matter through a search for gamma rays from the solar disk. Capture of dark matter by elastic interactions with the solar nuclei ...followed by annihilation to long-lived mediators can produce a detectable gamma-ray flux. We search 3 years of data from the High Altitude Water Cherenkov (HAWC) observatory and find no statistically significant detection of TeV gamma-ray emission from the Sun. Using this, we constrain the spin-dependent elastic scattering cross section of dark matter with protons for dark matter masses above 1 TeV, assuming a sufficiently long-lived mediator. The results complement constraints obtained from Fermi-LAT observations of the Sun and together cover WIMP masses between 4 and 106 GeV . In the optimal scenario, the cross-section constraints for mediator decays to gamma rays can be as strong as ∼ 10−45 cm2 , which is more than 4 orders of magnitude stronger than current direct-detection experiments for a 1 TeV dark matter mass. The cross-section constraints at higher masses are even better, nearly 7 orders of magnitude better than the current direct-detection constraints for a 100 TeV dark matter mass. This demonstration of sensitivity encourages detailed development of theoretical models in light of these powerful new constraints.
Local dwarf spheroidal galaxies (dSphs) are nearby dark-matter dominated systems, making them excellent targets for searching for gamma rays from particle dark matter interactions. If dark matter ...annihilates or decays directly into two gamma rays (or a gamma ray and a neutral particle), a monochromatic spectral line is created. At TeV energies, no other process is predicted to produce spectral lines, making this a very clean indirect dark matter search channel. With the development of event-by-event energy reconstruction, we can now search for spectral lines with the High Altitude Water Cherenkov (HAWC) Observatory. HAWC is a wide field of view survey instrument located in central Mexico that observes gamma rays from ∼ 200 GeV to ∼ 200 TeV . In this work we present results from a recent search for spectral lines from local, dark matter dominated, dwarf galaxies using 1038 days of HAWC data. We also present updated limits on several continuum channels that were reported in a previous publication. Our gamma-ray spectral line limits are the most constraining obtained so far from 20 TeV to 100 TeV.
We present the result of a search of the Milagro sky map for spatial correlations with sources from a subset of the recent Fermi Bright Source List (BSL). The BSL consists of the 205 most significant ...sources detected above 100 MeV by the Fermi Large Area Telescope. We select sources based on their categorization in the BSL, taking all confirmed or possible Galactic sources in the field of view of Milagro. Of the 34 Fermi sources selected, 14 are observed by Milagro at a significance of 3 standard deviations or more. We conduct this search with a new analysis which employs newly optimized gamma-hadron separation and utilizes the full eight-year Milagro data set. Milagro is sensitive to gamma rays with energy from 1 to 100 TeV with a peak sensitivity from 10 to 50 TeV depending on the source spectrum and declination. These results extend the observation of these sources far above the Fermi energy band. With the new analysis and additional data, multi-TeV emission is definitively observed associated with the Fermi pulsar, J2229.0+6114, in the Boomerang pulsar wind nebula (PWN). Furthermore, an extended region of multi-TeV emission is associated with the Fermi pulsar, J0634.0+1745, the Geminga pulsar.
Background
The pain and autonomic symptoms of cluster headache (CH) result from activation of the trigeminal parasympathetic reflex, mediated through the sphenopalatine ganglion (SPG). We ...investigated the safety and efficacy of on-demand SPG stimulation for chronic CH (CCH).
Methods
A multicenter, multiple CH attack study of an implantable on-demand SPG neurostimulator was conducted in patients suffering from refractory CCH. Each CH attack was randomly treated with full, sub-perception, or sham stimulation. Pain relief at 15 minutes following SPG stimulation and device- or procedure-related serious adverse events (SAEs) were evaluated.
Findings
Thirty-two patients were enrolled and 28 completed the randomized experimental period. Pain relief was achieved in 67.1% of full stimulation-treated attacks compared to 7.4% of sham-treated and 7.3% of sub-perception-treated attacks (p < 0.0001). Nineteen of 28 (68%) patients experienced a clinically significant improvement: seven (25%) achieved pain relief in ≥50% of treated attacks, 10 (36%), a ≥50% reduction in attack frequency, and two (7%), both. Five SAEs occurred and most patients (81%) experienced transient, mild/moderate loss of sensation within distinct maxillary nerve regions; 65% of events resolved within three months.
Interpretation
On-demand SPG stimulation using the ATI Neurostimulation System is an effective novel therapy for CCH sufferers, with dual beneficial effects, acute pain relief and observed attack prevention, and has an acceptable safety profile compared to similar surgical procedures.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present the first catalog of gamma-ray sources emitting above 56 and 100 TeV with data from the High Altitude Water Cherenkov Observatory, a wide field-of-view observatory capable of detecting ...gamma rays up to a few hundred TeV. Nine sources are observed above 56 TeV, all of which are likely galactic in origin. Three sources continue emitting past 100 TeV, making this the highest-energy gamma-ray source catalog to date. We report the integral flux of each of these objects. We also report spectra for three highest-energy sources and discuss the possibility that they are PeVatrons.
Given the importance of flexible use of different COVID-19 vaccines within the same schedule to facilitate rapid deployment, we studied mixed priming schedules incorporating an adenoviral-vectored ...vaccine (ChAdOx1 nCoV-19 ChAd, AstraZeneca), two mRNA vaccines (BNT162b2 BNT, Pfizer–BioNTech, and mRNA-1273 m1273, Moderna) and a nanoparticle vaccine containing SARS-CoV-2 spike glycoprotein and Matrix-M adjuvant (NVX-CoV2373 NVX, Novavax).
Com-COV2 is a single-blind, randomised, non-inferiority trial in which adults aged 50 years and older, previously immunised with a single dose of ChAd or BNT in the community, were randomly assigned (in random blocks of three and six) within these cohorts in a 1:1:1 ratio to receive a second dose intramuscularly (8–12 weeks after the first dose) with the homologous vaccine, m1273, or NVX. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentrations measured by ELISA in heterologous versus homologous schedules at 28 days after the second dose, with a non-inferiority criterion of the GMR above 0·63 for the one-sided 98·75% CI. The primary analysis was on the per-protocol population, who were seronegative at baseline. Safety analyses were done for all participants who received a dose of study vaccine. The trial is registered with ISRCTN, number 27841311.
Between April 19 and May 14, 2021, 1072 participants were enrolled at a median of 9·4 weeks after receipt of a single dose of ChAd (n=540, 47% female) or BNT (n=532, 40% female). In ChAd-primed participants, geometric mean concentration (GMC) 28 days after a boost of SARS-CoV-2 anti-spike IgG in recipients of ChAd/m1273 (20 114 ELISA laboratory units ELU/mL 95% CI 18 160 to 22 279) and ChAd/NVX (5597 ELU/mL 4756 to 6586) was non-inferior to that of ChAd/ChAd recipients (1971 ELU/mL 1718 to 2262) with a GMR of 10·2 (one-sided 98·75% CI 8·4 to ∞) for ChAd/m1273 and 2·8 (2·2 to ∞) for ChAd/NVX, compared with ChAd/ChAd. In BNT-primed participants, non-inferiority was shown for BNT/m1273 (GMC 22 978 ELU/mL 95% CI 20 597 to 25 636) but not for BNT/NVX (8874 ELU/mL 7391 to 10 654), compared with BNT/BNT (16 929 ELU/mL 15 025 to 19 075) with a GMR of 1·3 (one-sided 98·75% CI 1·1 to ∞) for BNT/m1273 and 0·5 (0·4 to ∞) for BNT/NVX, compared with BNT/BNT; however, NVX still induced an 18-fold rise in GMC 28 days after vaccination. There were 15 serious adverse events, none considered related to immunisation.
Heterologous second dosing with m1273, but not NVX, increased transient systemic reactogenicity compared with homologous schedules. Multiple vaccines are appropriate to complete primary immunisation following priming with BNT or ChAd, facilitating rapid vaccine deployment globally and supporting recognition of such schedules for vaccine certification.
UK Vaccine Task Force, Coalition for Epidemic Preparedness Innovations (CEPI), and National Institute for Health Research. NVX vaccine was supplied for use in the trial by Novavax.
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