The time–energy information of ultrashort X-ray free-electron laser pulses generated by the Linac Coherent Light Source is measured with attosecond resolution via angular streaking of neon 1s ...photoelectrons. The X-ray pulses promote electrons from the neon core level into an ionization continuum, where they are dressed with the electric field of a circularly polarized infrared laser. This induces characteristic modulations of the resulting photoelectron energy and angular distribution. From these modulations we recover the single-shot attosecond intensity structure and chirp of arbitrary X-ray pulses based on self-amplified spontaneous emission, which have eluded direct measurement so far. We characterize individual attosecond pulses, including their instantaneous frequency, and identify double pulses with well-defined delays and spectral properties, thus paving the way for X-ray pump/X-ray probe attosecond free-electron laser science.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UL, UM, UPUK
Oral immunotherapy (OIT) is an emerging approach to the treatment of patients with IgE-mediated food allergy and is in the process of transitioning to clinical practice.
To develop patient-oriented ...clinical practice guidelines on oral immunotherapy based on evidence and ethical imperatives for the provision of safe and efficient food allergy management.
Recommendations were developed using a reflective patient-centered multicriteria approach including 22 criteria organized in five dimensions (clinical, populational, economic, organizational and sociopolitical). Data was obtained from: (1) a review of scientific and ethic literature; (2) consultations of allergists, other healthcare professionals (pediatricians, family physicians, nurses, registered dieticians, psychologists, peer supporters), patients and caregivers; and patient associations through structured consultative panels, interviews and on-line questionnaire; and (3) organizational and economic data from the milieu of care. All data was synthesized by criteria in a multicriteria deliberative guide that served as a platform for structured discussion and development of recommendations for each dimension, based on evidence, ethical imperatives and other considerations.
The deliberative grid included 162 articles from the literature and media reviews and data from consultations involving 85 individuals. Thirty-eight (38) recommendations were made for the practice of oral immunotherapy for the treatment of IgE mediated food allergy, based on evidence and a diversity of ethical imperatives. All recommendations were aimed at fostering a context conducive to achieving objectives identified by patients and caregivers with food allergy. Notably, specific recommendations were developed to promote a culture of shared responsibility between patients and healthcare system, equity in access, patient empowerment, shared decision making and personalization of OIT protocols to reflect patients' needs. It also provides recommendations to optimize organization of care to generate capacity to meet demand according to patient choice, e.g. OIT or avoidance. These recommendations were made acknowledging the necessity of ensuring sustainability of the clinical offer in light of various economic considerations.
This innovative CPG methodology was guided by patients' perspectives, clinical evidence as well as ethical and other rationales. This allowed for the creation of a broad set of recommendations that chart optimal clinical practice and define the conditions required to bring about changes to food allergy care that will be sustainable, equitable and conducive to the well-being of all patients in need.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
COSINUS is a dark matter (DM) direct search experiment that uses sodium iodide (NaI) crystals as cryogenic calorimeters. Thanks to the low nuclear recoil energy threshold and event-by-event ...discrimination capability, COSINUS will address the long-standing DM claim made by the DAMA/LIBRA collaboration. The experiment is currently under construction at the Laboratori Nazionali del Gran Sasso, Italy, and employs a large cylindrical water tank as a passive shield to meet the required background rate. However, muon-induced neutrons can mimic a DM signal therefore requiring an active veto system, which is achieved by instrumenting the water tank with an array of photomultiplier tubes (PMTs). This study optimizes the number, arrangement, and trigger conditions of the PMTs as well as the size of an optically invisible region. The objective was to maximize the muon veto efficiency while minimizing the accidental trigger rate due to the ambient and instrumental background. The final configuration predicts a veto efficiency of 99.63 ± 0.16% and 44.4 ± 5.6% in the tagging of muon events and showers of secondary particles, respectively. The active veto will reduce the cosmogenic neutron background rate to 0.11 ± 0.02 cts
·
kg
-
1
·
year
-
1
,
corresponding to less than one background event in the region of interest for the whole COSINUS-1
π
exposure of 1000 kg
·
days.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present 5-28 m SOFIA FORECAST spectroscopy complemented by panchromatic X-ray through infrared observations of the CO nova V5668 Sgr documenting the formation and destruction of dust during ∼500 ...days following outburst. Dust condensation commenced by 82 days after outburst at a temperature of ∼1090 K. The condensation temperature indicates that the condensate was amorphous carbon. There was a gradual decrease of the grain size and dust mass during the recovery phase. Absolute parameter values given here are for an assumed distance of 1.2 kpc. We conclude that the maximum mass of dust produced was 1.2 × 10−7 M if the dust was amorphous carbon. The average grain radius grew to a maximum of ∼2.9 m at a temperature of ∼720 K around day 113 when the shell visual optical depth was τv ∼ 5.4. Maximum grain growth was followed by a period of grain destruction. X-rays were detected with Swift from day 95 to beyond day 500. The Swift X-ray count rate due to the hot white dwarf peaked around day 220, when its spectrum was that of a kT = 35 eV blackbody. The temperature, together with the supersoft X-ray turn-on and turn-off times, suggests a white dwarf mass of ∼1.1 M . We show that the X-ray fluence was sufficient to destroy the dust. Our data show that the post-dust event X-ray brightening is not due to dust destruction, which certainly occurred, as the dust is optically thin to X-rays.
Neointimal hyperplasia contributes to arterial restenosis after percutaneous transluminal coronary angioplasty or vascular surgery. Neointimal thickening after arterial injury is determined by ...inflammatory processes. We investigated the role of the innate immune receptor toll-like receptor 2 (TLR2) in neointima formation after arterial injury in mice.
Carotid artery injury was induced by 10% ferric chloride in C57Bl/6J wild type (WT), TLR2 deficient (B6.129-Tlr2tm1Kir/J, TLR2−/−) and WT mice treated with a TLR2 blocking antibody. 21 days after injury, carotid arteries were assessed histomorphometrically and for smooth muscle cell (SMC) content. To identify the contribution of circulating cells in mediating the effects of TLR2-deficiency, arterial injury was induced in WT/TLR2−/−-chimeric mice and the paracrine modulation of bone marrow-derived cells from WT and TLR2−/− on SMC migration compared in vitro.
TLR2−/− mice and WT mice treated with TLR2 blocking antibodies exhibited reduced neointimal thickening (23.7 ± 4.2 and 6.5 ± 3.0 vs. 43.1 ± 5.9 μm, P < 0.05 and P < 0.01), neointimal area (5491 ± 1152 and 315 ± 76.7 vs. 13,756 ± 2627 μm2, P < 0.05 and P < 0.01) and less luminal stenosis compared to WT mice (8.5 ± 1.6 and 5.0 ± 1.3 vs. 22.4 ± 2.2%, both P < 0.001n = 4–8 mice/group). The phenotypes of TLR2−/− vs. WT mice were completely reverted in WT/TLR2−/− bone marrow chimeric mice (5.9 ± 1.5 μm neointimal thickness, 874.2 ± 290.2 μm2 neointima area and 2.7 ± 0.6% luminal stenoses in WT mice transplanted with TLR2−/− bone marrow vs. 23.6 ± 5.1 μm, 3555 ± 511 μm2 and 12.0 ± 1.3% in WT mice receiving WT bone marrow, all P < 0.05, n = 6/group). Neointimal lesions of WT and WT mice transplanted with TLR2−/− bone marrow chimeric mice showed increased numbers of SMC (10.8 ± 1.4 and 12.6 ± 1.4 vs. 3.8 ± 0.9 in TLR2−/− and 3.5 ± 1.1 cells in WT mice transplanted with TLR2−/− bone marrow, all P < 0.05, n = 6). WT bone marrow cells stimulated SMC migration more than TLR2-deficient bone marrow cells (1.7 ± 0.05 vs. 1.3 ± 0.06-fold, P < 0.05, n = 7) and this effect was aggravated by TLR2 stimulation and diminished by TLR2 blockade (1.1 ± 0.03-fold after stimulation with TLR2 agonists and 0.8 ± 0.02-fold after TLR2 blockade vs. control treated cells defined as 1.0, P < 0.05, n = 7).
TLR2-deficiency on hematopoietic but not vessel wall resident cells augments vascular healing after arterial injury. Pharmacological blockade of TLR2 may thus be a promising therapeutic option to improve vessel patency after iatrogenic arterial injury.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Highlights • Five weeks of high-fat diet (HFD) intake increases anxiety in female C57BL/6 mice. • Short-term object recognition memory is intact after 5 weeks of HFD intake. • Six-week HFD intake ...alters prefrontocortical/ventral hippocampal (vHIP) monoamines. • Eleven to twelve weeks of HFD consumption reduces synaptic plasticity in the vHIP. • Overall, HFD intake alters specific behaviors and linked monoamines in female mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background
To our knowledge, an international consensus is lacking regarding the development of an adequate informed consent form for a patch test (PT) and the information that should be included in ...such document.
Objectives
The aim of the study was to reach a consensus on the specific points that need to be addressed in a PT consent form.
Methods
A Delphi survey, comprising 2 rounds and 1 final discussion, was used to gather and analyse data, which was conducted over the Internet. Each statement that reached a consensus with the respondents (9 expert dermatologists from Europe) was defined as a median consensus score (MED) of ≥7 and agreement among panelists as an interquartile range (IQR) of ≤3. All study participants were members of the EADV task force on contact dermatitis.
Results
The expert panel addressed several topics that should be included in an informed consent form for a PT: introduction, preparation for PT, testing procedure, allowed activities, adverse events and additional authorizations.
Conclusions
Our results assess recommendations regarding points to be contained in an informed consent form for a PR. Future actions towards standardization and harmonization of this specific consent form are needed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
9.
V445 Puppis: Dustier than a Thousand Novae Banerjee, D. P. K.; Evans, A.; Woodward, C. E. ...
Astrophysical journal. Letters,
08/2023, Volume:
952, Issue:
2
Journal Article
Peer reviewed
Open access
Abstract
V445 Puppis, the only known Galactic helium nova, is a unique test bed to verify supernova (SN) theories in the single-degenerate channel that involve a white dwarf (WD) accreting matter ...from a helium-rich donor. An estimate of the mass of the helium shell on the WD is crucial to deciding whether or not it will undergo an SN detonation. In this context, this study estimates the dust and ejecta masses in the 2000 November eruption of V445 Pup. Subsequent to its outburst, the star became cocooned in a dust envelope. An analysis of the spectral energy distribution (SED) of the dust using infrared data shows that V445 Pup produced at least 10
−3
M
⊙
of dust, which is unprecedented for a classical or recurrent nova. The SED can be explained by a combination of a cold dust component at 105 ± 10 K, mass (1.9 ± 0.8) × 10
−3
M
⊙
, and a warm dust component at 255 ± 10 K, mass (2.2 ± 1.2) × 10
−5
M
⊙
. For a conservative choice of the gas-to-dust mass ratio in the range 10–100, the mass of the ejecta is 0.01–0.1
M
⊙
. Such a high mass range raises the question: why did V445 Pup not detonate as a Type Ia SN as is predicted in certain double-detonation sub-Chandrasekhar supernovae formalisms? We reexamine the nature of V445 Pup and discuss its role as a potential SN progenitor.
Antiangiogenic therapy of glioblastoma (GBM) with bevacizumab, a VEGFA-blocking antibody, may accelerate tumor cell invasion and induce alternative angiogenic pathways. Here we investigate the roles ...of the proangiogenic apelin receptor APLNR and its cognate ligand apelin in VEGFA/VEGFR2 antiangiogenic therapy against distinct subtypes of GBM. In proneural GBM, apelin levels were downregulated by VEGFA or VEGFR2 blockade. A central role for apelin/APLNR in controlling GBM vascularization was corroborated in a serial implantation model of the angiogenic switch that occurs in human GBM. Apelin and APLNR are broadly expressed in human GBM, and knockdown or knockout of
in orthotopic models of proneural or classical GBM subtypes significantly reduced GBM vascularization compared with controls. However, reduction in apelin expression led to accelerated GBM cell invasion. Analysis of stereotactic GBM biopsies from patients as well as from
and
experiments revealed increased dissemination of APLNR-positive tumor cells when apelin levels were reduced. Application of apelin-F13A, a mutant APLNR ligand, blocked tumor angiogenesis and GBM cell invasion. Furthermore, cotargeting VEGFR2 and APLNR synergistically improved survival of mice bearing proneural GBM. In summary, we show that apelin/APLNR signaling controls GBM angiogenesis and invasion and that both pathologic features are blunted by apelin-F13A. We suggest that apelin-F13A can improve the efficiency and reduce the side effects of established antiangiogenic treatments for distinct GBM subtypes. SIGNIFICANCE: Pharmacologic targeting of the APLNR acts synergistically with established antiangiogenic treatments in glioblastoma and blunts therapy resistance to current strategies for antiangiogenesis.
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