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Kumar, S K,Dimopoulos, M A,Kastritis, E,Terpos, E,Nahi, H,Goldschmidt, H,Hillengass, J,Leleu, X,Beksac, M,Alsina, M,Oriol, A,Cavo, M,Ocio, E M,Mateos, M V,O'Donnell, E K,Vij, R,Lokhorst, H M,van de Do Macmillan Publishers Limited, part of Springer Nat 2017 Leukemia Vol.31 No.11
<P>Introduction of new myeloma therapies offers new options for patients refractory to immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). In this multicenter study, patients with relapsed multiple myeloma, who have received at least three prior lines of therapy, are refractory to both an IMiD (lenalidomide or pomalidomide) and a PI (bortezomib or carfilzomib), and have been exposed to an alkylating agent were identified. The time patients met the above criteria was defined as time zero (T-0). Five hundred and forty-three patients diagnosed between 2006 and 2014 were enrolled in this study. Median age at T-0 was 62 years (range 31-87); 61% were males. The median duration between diagnosis and T-0 was 3.1 years. The median number of lines of therapy before T-0 was 4 (range 3-13). The median overall survival (OS) from T-0 for the entire cohort was 13 (95% confidence interval (CI) 11, 15) months. At least one regimen recorded after T-0 in 462 (85%) patients, with a median (95% CI) progression-free survival and OS from T-0 of 5 (4, 6), and 15.2 (13, 17) months, respectively. The study provides the expected outcome of relapsed multiple myeloma that is refractory to a PI and an IMiD, a benchmark for comparison of new therapies being evaluated.</P>
Mateo, Joaquin,Ganji, Gopinath,Lemech, Charlotte,Burris, Howard A.,Han, Sae-Won,Swales, Karen,Decordova, Shaun,DeYoung, M. Phillip,Smith, Deborah A.,Kalyana-Sundaram, Shanker,Wu, Jiuhua,Motwani, Monic American Association for Cancer Research 2017 Clinical Cancer Research Vol.23 No.19
<P><B>Background:</B> The PI3K/protein kinase B (AKT) pathway is commonly activated in several tumor types. Selective targeting of p110β could result in successful pathway inhibition while avoiding the on- and off-target effects of pan-PI3K inhibitors. GSK2636771 is a potent, orally bioavailable, adenosine triphosphate-competitive, selective inhibitor of PI3Kβ.</P><P><B>Methods:</B> We evaluated the safety, pharmacokinetics, pharmacodynamics and antitumor activity of GSK2636771 to define the recommended phase II dose (RP2D). During the dose-selection and dose-escalation stages (parts 1 and 2), patients with <I>PTEN</I>-deficient advanced solid tumors received escalating doses of GSK2636771 (25–500 mg once daily) using a modified 3+3 design to determine the RP2D; tumor type-specific expansion cohorts (part 3) were implemented to further assess tumor responses at the RP2D.</P><P><B>Results:</B> A total of 65 patients were enrolled; dose-limiting toxicities were hypophosphatemia and hypocalcemia. Adverse events included diarrhea (48%), nausea (40%), and vomiting (31%). Single- and repeat-dose exposure increased generally dose proportionally. GSK2636771 400 mg once daily was the RP2D. Phospho/total AKT ratio decreased with GSK2636771 in tumor and surrogate tissue. A castrate-resistant prostate cancer (CRPC) patient harboring <I>PIK3CB</I> amplification had a partial response for over a year; an additional 10 patients derived durable (≥24 weeks) clinical benefit, including two other patients with CRPC with <I>PIK3CB</I> alterations (≥34 weeks). GSK2636771 400 mg once daily orally induced sufficient exposure and target inhibition with a manageable safety profile.</P><P><B>Conclusions:</B> Genomic aberrations of <I>PIK3CB</I> may be associated with clinical benefit from GSK2636771. <I>Clin Cancer Res; 23(19); 5981–92. ©2017 AACR</I>.</P>
Passive Q-switching of microchip lasers based on Ho:YAG ceramics
Lan, R.,Loiko, P.,Mateos, X.,Wang, Y.,Li, J.,Pan, Y.,Choi, S. Y.,Kim, M. H.,Rotermund, F.,Yasukevich, A.,Yumashev, K.,Griebner, U.,Petrov, V. Optical Society of America 2016 Applied Optics Vol.55 No.18
<P>A Ho:YAG ceramic microchip laser pumped by a Tm fiber laser at 1910 nm is passively Q-switched by single-and multi-layer graphene, single-walled carbon nanotubes (SWCNTs), and Cr2+:ZnSe saturable absorbers (SAs). Employing SWCNTs, this laser generated an average power of 810 mW at 2090 nm with a slope efficiency of 68% and continuous wave to Q-switching conversion efficiency of 70%. The shortest pulse duration was 85 ns at a repetition rate of 165 kHz, and the pulse energy reached 4.9 mu J. The laser performance and pulse stability were superior compared to graphene SAs even for a different number of graphene layers (n = 1 to 4). A model for the description of the Ho:YAG laser Q-switched by carbon nanostructures is presented. This modeling allowed us to estimate the saturation intensity for multi-layered graphene and SWCNT SAs to be 1.2 +/- 0.2 and 7 +/- 1 MW/cm(2), respectively. When using Cr2+:ZnSe, the Ho:YAG microchip laser generated 11 ns/25 mu J pulses at a repetition rate of 14.8 kHz. (C) 2016 Optical Society of America</P>
Bashar Zaidat,Nancy Shrestha,Ashley M. Rosenberg,Wasil Ahmed,Rami Rajjoub,Timothy Hoang,Mateo Restrepo Mejia,Akiro H. Duey,Justin E. Tang,Jun S. Kim,Samuel K. Cho 대한척추신경외과학회 2024 Neurospine Vol.21 No.1
Objective: Large language models, such as chat generative pre-trained transformer (ChatGPT), have great potential for streamlining medical processes and assisting physicians in clinical decision-making. This study aimed to assess the potential of ChatGPT’s 2 models (GPT-3.5 and GPT-4.0) to support clinical decision-making by comparing its responses for antibiotic prophylaxis in spine surgery to accepted clinical guidelines. Methods: ChatGPT models were prompted with questions from the North American Spine Society (NASS) Evidence-based Clinical Guidelines for Multidisciplinary Spine Care for Antibiotic Prophylaxis in Spine Surgery (2013). Its responses were then compared and assessed for accuracy. Results: Of the 16 NASS guideline questions concerning antibiotic prophylaxis, 10 responses (62.5%) were accurate in ChatGPT’s GPT-3.5 model and 13 (81%) were accurate in GPT4.0. Twenty-five percent of GPT-3.5 answers were deemed as overly confident while 62.5% of GPT-4.0 answers directly used the NASS guideline as evidence for its response. Conclusion: ChatGPT demonstrated an impressive ability to accurately answer clinical questions. GPT-3.5 model’s performance was limited by its tendency to give overly confident responses and its inability to identify the most significant elements in its responses. GPT-4.0 model’s responses had higher accuracy and cited the NASS guideline as direct evidence many times. While GPT-4.0 is still far from perfect, it has shown an exceptional ability to extract the most relevant research available compared to GPT-3.5. Thus, while ChatGPT has shown far-reaching potential, scrutiny should still be exercised regarding its clinical use at this time.
ARRAKIS: atlas of resonance rings as known in the S<sup>4</sup>G
Comeró,n, S.,Salo, H.,Laurikainen, E.,Knapen, J. H.,Buta, R. J.,Herrera-Endoqui, M.,Laine, J.,Holwerda, B. W.,Sheth, K.,Regan, M. W.,Hinz, J. L.,Muñ,oz-Mateos, J. C.,Gil de Paz, A.,Men&eac Springer-Verlag 2014 Astronomy and astrophysics Vol.562 No.-
<P>Context. Resonance rings and pseudorings (here collectively called rings) are thought to be related to the gathering of material near dynamical resonances caused by non-axisymmetries in galaxy discs. This means that they are the result of secular evolution processes that redistribute material and angular momentum in discs. Studying them may give clues on the formation and growth of bars and other disc non-axisymmetries. Aims. Our aims are to produce a catalogue and an atlas of the rings detected in the Spitzer Survey of Stellar Structure in Galaxies (S<SUP>4</SUP>G) and to conduct a statistical study of the data in the catalogue. Methods. We traced the contours of rings previously identified and fitted them with ellipses. We found the orientation of bars by studying the galaxy ellipse fits from the S<SUP>4</SUP>G pipeline 4. We used the galaxy orientation data obtained by the S<SUP>4</SUP>G pipeline 4 to obtain intrinsic ellipticities and orientations of rings and the bars. Results. ARRAKIS contains data on 724 ringed galaxies in the S<SUP>4</SUP>G. The frequency of resonance rings in the S<SUP>4</SUP>G is of 16 ±1% and 35 ±1% for outer and inner features, respectively. Outer rings are mostly found in Hubble stages −1 ≤T≤ 4. Inner rings are found in a broad distribution that covers the range −1 ≤T≤7. We confirm that outer rings have two preferred orientations, namely parallel and perpendicular to the bar. We confirm a tendency for inner rings to be oriented parallel to the bar, but we report the existence of a significant fraction (maybe as large as 50%) of inner features that have random orientations with respect to the bar. These misaligned inner rings are mostly found in late-type galaxies (T ≥4). We find that the fraction of barred galaxies hosting outer (inner) rings is ~1.7 times (~1.3 times) that in unbarred galaxies. Conclusions. We confirm several results from previous surveys as well as predictions from simulations of resonant rings and/or from manifold flux tube theory. We report that a significant fraction of inner rings in late-type galaxies have a random orientation with respect to the bar. This may be caused by spiral modes that are decoupled from the bar and dominate the Fourier amplitude spectrum at the radius of the inner ring. The fact that rings are only mildly favoured by bars suggests that those in unbarred galaxies either formed because of weak departures from the axisymmetry of the galactic potential or that they are born because of bars that were destroyed after the ring formation.</P>