Objective
Novel autoantibody specificities including anti‐CCAR1 were recently discovered in adult patients with anti‐transcriptional intermediary factor (TIF1)–positive dermatomyositis (DM) and were ...associated with attenuated cancer emergence. The aims of the present study were to examine whether these autoantibodies occur in patients with juvenile‐onset DM (JDM) and to determine their associated features.
Methods
Sera from 150 patients with anti‐TIF1γ autoantibody‐positive JDM in a cross‐sectional cohort and 90 juvenile healthy controls were assayed for anti‐CCAR1, anti‐C1Z1, anti‐IMMT, anti‐TBL1XR1, and anti‐Sp4 autoantibodies. Demographics, myositis autoantibodies, clinical features, medications, outcomes, and HLA‐DRB1 and HLA‐DQA1 alleles were compared between those with and without these autoantibodies.
Results
Any one of the anti‐TIF1γ‐associated autoantibodies was present in 44 patients (29%) overall, including 25 (17%) with anti‐Sp4, 22 (15%) with anti‐TBL1XR1, 14 (9%) with anti‐CCAR1, 2 (1%) with anti‐C1Z1, and 2 (1%) with anti‐IMMT autoantibodies. These anti‐TIF1γ‐associated autoantibodies frequently co‐occurred. Patients with any of the anti‐TIF1γ‐associated autoantibodies had less frequent falling (34% 15 vs. 53% 56, P = 0.032) and lower peak muscle enzymes. None of the patients had cancer. Among White patients, HLA‐DRB1*03 was protective against an anti‐TIF1γ‐associated autoantibody (odds ratio 0.20, 95% confidence interval 0.07–0.52).
Conclusion
Autoantibodies associated with anti‐TIF1γ were found in isolation and in combination among a subset of patients with JDM. Patients with these autoantibodies had less severe muscle disease and were not enriched for HLA‐DRB1*03. Additional autoantibodies among patients with positive anti‐TIF1γ with JDM likely contribute to the heterogeneity of the anti‐TIF1γ serologic subgroup.
Surgery alone is currently still accepted “standard of care” for patients with operable NSCLC, this includes stages IA and IIB, as well as selected early subsets of IIIA disease. In more advanced and ...inoperable stage III disease, combinations of chemotherapy and radiotherapy remain the standard treatment approach for patients with good performance status. The role of surgery following induction therapy in these advanced stage III patients is at the moment not conclusively defined. More evidence from randomized trials is clearly needed to tailor treatment for the large number of patients that present in these locally advanced stages. Enrollment of patients into ongoing prospective clinical trials should be encouraged, whenever possible, to further define prognostic factors and improve multimodality strategies in this clinical setting.
IceCube is a neutrino observatory deployed in the glacial ice at the geographic South Pole. The
ν
μ
energy unfolding described in this paper is based on data taken with IceCube in its 79-string ...configuration. A sample of muon neutrino charged-current interactions with a purity of 99.5% was selected by means of a multivariate classification process based on machine learning. The subsequent unfolding was performed using the software
Truee
. The resulting spectrum covers an E
ν
-range of more than four orders of magnitude from 125 GeV to 3.2 PeV. Compared to the Honda atmospheric neutrino flux model, the energy spectrum shows an excess of more than
1.9
σ
in four adjacent bins for neutrino energies
E
ν
≥
177.8
TeV
. The obtained spectrum is fully compatible with previous measurements of the atmospheric neutrino flux and recent IceCube measurements of a flux of high-energy astrophysical neutrinos.
We present the results of the first IceCube search for dark matter annihilation in the center of the Earth. Weakly interacting massive particles (WIMPs), candidates for dark matter, can scatter off ...nuclei inside the Earth and fall below its escape velocity. Over time the captured WIMPs will be accumulated and may eventually self-annihilate. Among the annihilation products only neutrinos can escape from the center of the Earth. Large-scale neutrino telescopes, such as the cubic kilometer IceCube Neutrino Observatory located at the South Pole, can be used to search for such neutrino fluxes. Data from 327 days of detector livetime during 2011/2012 were analyzed. No excess beyond the expected background from atmospheric neutrinos was detected. The derived upper limits on the annihilation rate of WIMPs in the Earth and the resulting muon flux are an order of magnitude stronger than the limits of the last analysis performed with data from IceCube’s predecessor AMANDA. The limits can be translated in terms of a spin-independent WIMP–nucleon cross section. For a WIMP mass of 50 GeV this analysis results in the most restrictive limits achieved with IceCube data.
We report on the confirmation and follow-up characterization of two long-period transiting substellar companions on low-eccentricity orbits around TIC 4672985 and TOI-2529, whose transit events were ...detected by the TESS space mission. Ground-based photometric and spectroscopic follow-up from different facilities, confirmed the substellar nature of TIC 4672985 b , a massive gas giant in the transition between the super-Jupiters and brown dwarfs mass regime. From the joint analysis we derived the following orbital parameters: P = 69.0480 −0.0005 +0.0004 d, M p = 12.74 −1.01 +1.01 M j , R p = 1.026 −0.067 +0.065 R j and e = 0.018 −0.004 +0.004 . In addition, the RV time series revealed a significant trend at the ~350 m s −1 yr −1 level, which is indicative of the presence of a massive outer companion in the system. TIC 4672985 b is a unique example of a transiting substellar companion with a mass above the deuterium-burning limit, located beyond 0.1 AU and in a nearly circular orbit. These planetary properties are difficult to reproduce from canonical planet formation and evolution models. For TOI-2529 b , we obtained the following orbital parameters: P = 64.5949 −0.0003 +0.0003 d, M p = 2.340 −0.195 +0.197 M j , R p = 1.030 −0.050 +0.050 R j and e = 0.021 −0.015 +0.024 , making this object a new example of a growing population of transiting warm giant planets.
CD4+CD25(high) forkhead box P3+ regulatory T cells (Treg) are critical mediators of peripheral self-tolerance and immune homeostasis. Treg suppress proliferation and cytokine production of ...conventional T cells (Tcon). The exact mechanism of suppression, however, is still unknown. To gain a better understanding of Treg function, we investigated the kinetics of cytokine suppression in Tcon reisolated from cocultures with preactivated human Treg. Treg inhibited induction of Th1 cytokine mRNA as early as 1 h after stimulation, whereas induction/suppression of Th2 cytokines was delayed to 10-15 h. We show that immediate cytokine mRNA suppression in Tcon was neither dependent on TGF-beta/IL-10 or IL-2 consumption, nor on induction of the transcriptional-repressor forkhead box P3 or other anergy-related genes (e.g., gene related to anergy, transducer of ErbB-2, forkhead homolog-4, repressor of GATA, inducible cAMP early repressor). In contrast, lymphocyte activation gene 3, suppressor of cytokine signaling 1, and suppressor of cytokine signaling 3 mRNA were strongly up-regulated in Tcon in the presence of Treg. However, protein analysis did not confirm a role for these proteins in early suppression. Thus, the identification of a fast inhibitory mechanism in Tcon induced by Treg constitutes an important step for future efforts to unravel the entire elusive suppressive mechanism.
Endoscopic valve implantation is an effective treatment for patients with advanced emphysema. Despite the minimally invasive procedure, valve placement is associated with risks, the most common of ...which is pneumothorax. This study was designed to identify predictors of pneumothorax following endoscopic valve implantation.
Preinterventional clinical measures (vital capacity, forced expiratory volume in 1 second, residual volume, total lung capacity, 6-minute walk test), qualitative computed tomography (CT) parameters (fissure integrity, blebs/bulla, subpleural nodules, pleural adhesions, partial atelectasis, fibrotic bands, emphysema type) and quantitative CT parameters (volume and low attenuation volume of the target lobe and the ipsilateral untreated lobe, target air trapping, ipsilateral lobe volume/hemithorax volume, collapsibility of the target lobe and the ipsilateral untreated lobe) were retrospectively evaluated in patients who underwent endoscopic valve placement (n=129). Regression analysis was performed to compare those who developed pneumothorax following valve therapy (n=46) with those who developed target lobe volume reduction without pneumothorax (n=83).
Low attenuation volume% of ipsilateral untreated lobe (odds ratio OR =1.08, P=0.001), ipsilateral untreated lobe volume/hemithorax volume (OR =0.93, P=0.017), emphysema type (OR =0.26, P=0.018), pleural adhesions (OR =0.33, P=0.012) and residual volume (OR =1.58, P=0.012) were found to be significant predictors of pneumothorax. Fissure integrity (OR =1.16, P=0.075) and 6-minute walk test (OR =1.05, P=0.077) were also indicative of pneumothorax. The model including the aforementioned parameters predicted whether a patient would experience a pneumothorax 84% of the time (area under the curve =0.84).
Clinical and CT parameters provide a promising tool to effectively identify patients at high risk of pneumothorax following endoscopic valve therapy.
Thin-film solar modules based on Cu(In,Ga)Se
2 (CIGS) promise to become a lower-cost alternative to polycrystalline silicon. The ZSW and Wuerth Solar are developing and running industrial processes ...suitable for the mass production of CIGS modules. Yield and output in the Wuerth Solar pilot line are steadily improving, with average module efficiencies exceeding 10%. New developments at the ZSW include doubling the length of the linear evaporation source to increase the throughput and adjusting the processes to enable production of flexible modules. New calculations regarding module design for optimized performance are presented as well as results from outdoor testing of Wuerth Solar modules.
Coercivity Determines Magnetic Particle Heating Starsich, Fabian H. L.; Eberhardt, Christian; Boss, Andreas ...
Advanced healthcare materials,
10/2018, Letnik:
7, Številka:
19
Journal Article
Recenzirano
Odprti dostop
Diseased cell treatment by heating with magnetic nanoparticles is hindered by their required high concentrations. A clear relationship between heating efficiency and magnetic properties of ...nanoparticles has not been attained experimentally yet due to limited availability of magnetic nanoparticles with varying size and composition. Here, versatile flame aerosol technology is used for the synthesis of 21 types of ferro‐/ferrimagnetic nanocrystals with varying composition, size, and morphology for hyperthermia and thermoablation therapy. Heating efficiency, magnetic hysteresis, and first‐order reversal curves of these materials are compared. The maximum heating performance occurs near the transition from superparamagnetic to single domain state, regardless of particle composition. Most importantly, the ratio between saturation magnetization and coercivity can be linked to the heating properties of magnetic nanoparticles. Magnetic interaction is controlled by changes in the architecture of the nanoparticles and closely analyzed by first‐order reversal curves. Silica‐coated nonstoichiometric Gd‐Zn ferrite exhibits the most promising therapeutic capability at relatively low particle concentrations, as shown in vitro with cancerous prostate cells.
Widespread therapeutic applications of magnetic particle heating are still limited by the required high nanoparticle concentrations for a sufficient temperature increase. Here, efficiencies of 21 different nanocrystals are systematically investigated. Novel relationships between efficiency and magnetism are established revealing the significance of coercivity in magnetic particle heating. This reduces the required dose of heating agents for a successful therapy.
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