Primary cosmic-ray elemental spectra have been measured with the balloon-borne Cosmic Ray Energetics And Mass (CREAM) experiment since 2004. The third CREAM payload (CREAM-III) flew for 29 days ...during the 2007-2008 Antarctic season. Energies of incident particles above 1 TeV are measured with a calorimeter. Individual elements are clearly separated with a charge resolution of ∼0.12 e (in charge units) and ∼0.14 e for protons and helium nuclei, respectively, using two layers of silicon charge detectors. The measured proton and helium energy spectra at the top of the atmosphere are harder than other existing measurements at a few tens of GeV. The relative abundance of protons to helium nuclei is 9.53 0.03 for the range of 1 TeV/n to 63 TeV/n. This ratio is considerably smaller than other measurements at a few tens of GeV/n. The spectra become softer above ∼20 TeV. However, our statistical uncertainties are large at these energies and more data are needed.
Hospital admissions for non-coronavirus disease 2019 (COVID-19) pathology have decreased significantly. It is believed that this may be due to public anxiety about acquiring COVID-19 infection in ...hospital and the subsequent risk of mortality.
To identify patients who acquire COVID-19 in hospital (nosocomial COVID-19 infection (NC)) and their risk of mortality compared to those with community-acquired COVID-19 (CAC) infection.
The COPE-Nosocomial Study was an observational cohort study. The primary outcome was the time to all-cause mortality (estimated with an adjusted hazard ratio (aHR)), and secondary outcomes were day 7 mortality and the time-to-discharge. A mixed-effects multivariable Cox's proportional hazards model was used, adjusted for demographics and comorbidities.
The study included 1564 patients from 10 hospital sites throughout the UK, and one in Italy, and collected outcomes on patients admitted up to April 28th, 2020. In all, 12.5% of COVID-19 infections were acquired in hospital; 425 (27.2%) patients with COVID died. The median survival time in NC patients was 14 days compared with 10 days in CAC patients. In the primary analysis, NC infection was associated with lower mortality rate (aHR: 0.71; 95% confidence interval (CI): 0.51–0.98). Secondary outcomes found no difference in day 7 mortality (adjusted odds ratio: 0.79; 95% CI: 0.47–1.31), but NC patients required longer time in hospital during convalescence (aHR: 0.49, 95% CI: 0.37–0.66).
The minority of COVID-19 cases were the result of NC transmission. No COVID-19 infection comes without risk, but patients with NC had a lower risk of mortality compared to CAC infection; however, caution should be taken when interpreting this finding.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Streptococcus pneumoniae is a major pathogen of humans, causing diseases such as pneumonia and meningitis. The organism produces several virulence factors that are involved in the disease process. ...The molecular basis of the action of some of these virulence factors is being elucidated. The advent of whole genome sequencing combined with biological studies has demonstrated that genome variation is important in the ability of pneumococci to interact with the host. This review discusses the biological activity of several pneumococcal virulence factors, and describes how genome variation may impact on the ability of pneumococci to cause disease.
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BFBNIB, DOBA, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UKNU, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ABSTRACT We report abundances of elements from 26Fe to 40Zr in the cosmic radiation measured by the SuperTIGER (Trans-Iron Galactic Element Recorder) instrument during 55 days of exposure on a ...long-duration balloon flight over Antarctica. These observations resolve elemental abundances in this charge range with single-element resolution and good statistics. These results support a model of cosmic ray origin in which the source material consists of a mixture of % material from massive stars and ∼81% normal interstellar medium material with solar system abundances. The results also show a preferential acceleration of refractory elements (found in interstellar dust grains) by a factor of ∼4 over volatile elements (found in interstellar gas) ordered by atomic mass (A). Both the refractory and volatile elements show a mass-dependent enhancement with similar slopes.
Background:
Platelet-rich plasma (PRP) has been used extensively in clinical practice to treat patients with symptomatic knee osteoarthritis (OA). Leukocyte-poor PRP (LP-PRP) has been clinically ...preferred over leukocyte-rich PRP (LR-PRP); however, it is unclear which cytokine mediators of pain and inflammation are present in LR-PRP and LP-PRP from patients with mild to moderate knee OA in order to rationalize a specific formulation.
Hypothesis:
LP-PRP would be predominantly anti-inflammatory and have reduced nociceptive pain mediators compared with LR-PRP from the same individual with mild to moderate knee OA.
Study Design:
Controlled laboratory study.
Methods:
A total of 24 unique samples of PRP were prepared in order to assess 48 samples of LR-PRP and LP-PRP taken from 12 patients (6 male and 6 female) with symptomatic knee OA of Kellgren-Lawrence grade 2 to 3. Patients underwent blood collection for LR-PRP and LP-PRP preparation through a double-spin protocol to obtain baseline whole blood, platelet concentration, and white blood cell subtypes. LR-PRP and LP-PRP from the same patient were produced at the same time and underwent a comprehensive panel through Luminex (multicytokine profiling) to assess key mediators of inflammation: interleukin 1 receptor antagonist (IL-1Ra), interleukin 4, 6, 8, and 10 (IL-4, IL-6, IL-8, and IL-10), IL-1β, tissue necrosis factor α (TNF-α), and matrix metalloproteinase 9 (MMP-9). To assess mediators of nociceptive pain, nerve growth factor (NGF) and tartrate resistant acid phosphatase 5 (TRAP5) were also assessed.
Results:
LR-PRP from patients with mild to moderate knee OA expressed significantly more IL-1Ra, IL-4, IL-8, and MMP-9 compared with LP-PRP formulations from the same patients. No significant differences were found between LR-PRP and LP-PRP in mediators of nociceptive pain—namely, NGF and TRAP5. Other mediators including TNF-α, IL-1β, IL-6, and IL-10 were also found to have no significant expression differences between LR-PRP and LP-PRP.
Conclusion:
LR-PRP expressed significantly more IL-1Ra, IL-4, and IL-8, suggesting that LR-PRP may be more anti-inflammatory than LP-PRP. MMP-9 was expressed in higher concentrations in LR-PRP, suggesting that LR-PRP may be more chondrotoxic than LP-PRP.
Clinical Relevance:
LR-PRP was found to have a robust expression of anti-inflammatory mediators compared with LP-PRP and may be beneficial to patients with long-term knee OA where chronic low-grade inflammation is present. Mechanistic clinical trials are needed to elucidate the key mediators in both LR-PRP and LP-PRP to assess their effect on long-term progression of knee OA.
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FSPLJ, NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
6.
The safety and side effects of monoclonal antibodies Hansel, Trevor T; Kropshofer, Harald; Singer, Thomas ...
Nature reviews. Drug discover/Nature reviews. Drug discovery,
04/2010, Volume:
9, Issue:
4
Journal Article
Peer reviewed
Open access
Monoclonal antibodies (mAbs) are now established as targeted therapies for malignancies, transplant rejection, autoimmune and infectious diseases, as well as a range of new indications. However, ...administration of mAbs carries the risk of immune reactions such as acute anaphylaxis, serum sickness and the generation of antibodies. In addition, there are numerous adverse effects of mAbs that are related to their specific targets, including infections and cancer, autoimmune disease, and organ-specific adverse events such as cardiotoxicity. In March 2006, a life-threatening cytokine release syndrome occurred during a first-in-human study with TGN1412 (a CD28-specific superagonist mAb), resulting in a range of recommendations to improve the safety of initial human clinical studies with mAbs. Here, we review some of the adverse effects encountered with mAb therapies, and discuss advances in preclinical testing and antibody technology aimed at minimizing the risk of these events.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract High-energy neutral solar radiation in the form of γ -rays and neutrons is produced as secondary products in solar flares. The characteristics of this emission can provide key information ...regarding the energization of charged particles, particularly when primary particles remain trapped in the corona. The Integrated Science Investigation of the Sun (IS⊙IS) suite on Parker Solar Probe is composed of instruments primarily intended to measure energetic charged particles. However, the High Energy Telescope (HET) in IS⊙IS was also designed with a supplementary neutral mode intended to measure γ -rays and neutrons. HET observed its first clear solar γ -ray event in connection with a hard X-ray flare, the eruption of a coronal mass ejection, and a solar energetic particle event on 2022 September 5. The X-ray spectral shape was observed to harden over the course of the event, culminating with the observation of γ -rays by HET. A coincident enhancement in the lower-energy Energetic Particle Instrument (EPI-Lo) was also observed, likely produced by incident solar γ -rays despite the EPI-Lo instrument not having any special neutral measurement capabilities. We use Monte Carlo modeling to reconstruct the incident γ -ray spectrum based on the measured spectrum to demonstrate that the combination of IS⊙IS instruments can measure hard X-rays and γ -rays from ∼60 keV–7 MeV. Despite the fact that this is a supplemental science goal of the mission, the capability of the IS⊙IS instruments to measure γ -rays is important for the study of this population due to the very limited instruments currently observing the Sun in γ -rays.
The interaction of the solar wind with Earth's magnetosphere gives rise to the bright polar aurorae and to geomagnetic storms, but the relation between the solar wind and the dynamics of the outer ...planets' magnetospheres is poorly understood. Jupiter's magnetospheric dynamics and aurorae are dominated by processes internal to the jovian system, whereas Saturn's magnetosphere has generally been considered to have both internal and solar-wind-driven processes. This hypothesis, however, is tentative because of limited simultaneous solar wind and magnetospheric measurements. Here we report solar wind measurements, immediately upstream of Saturn, over a one-month period. When combined with simultaneous ultraviolet imaging we find that, unlike Jupiter, Saturn's aurorae respond strongly to solar wind conditions. But in contrast to Earth, the main controlling factor appears to be solar wind dynamic pressure and electric field, with the orientation of the interplanetary magnetic field playing a much more limited role. Saturn's magnetosphere is, therefore, strongly driven by the solar wind, but the solar wind conditions that drive it differ from those that drive the Earth's magnetosphere.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In patients with ischemic stroke and a proximal cerebral arterial occlusion and salvageable tissue on imaging, alteplase followed by thrombectomy with a stent retriever was more effective than ...alteplase alone in improving reperfusion, neurologic recovery, and functional outcome.
The results of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) trial,
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which showed reduced disability among patients with ischemic stroke who were treated with endovascular thrombectomy in addition to standard care, represent an advance in stroke care. The MR CLEAN study followed several trials that had neutral findings with respect to the use of endovascular thrombectomy.
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–
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In the largest of these trials, the Interventional Management of Stroke 3 (IMS-3) study, investigators compared the administration of 0.9 mg of alteplase per kilogram of body weight to a bridging strategy of . . .
Highlights • Novel bioreactor system was used for in vitro cyclic loading of tooth filling samples. • We grew biofilms on simulated tooth restorations with bioactive and control composites. • ...Bacteria penetrated less into marginal gaps for the bioactive glass containing samples. • Bioactive glass fillers may have promise for slowing secondary caries formation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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