TDCOSMO Birrer, S.; Shajib, A. J.; Galan, A. ...
Astronomy and astrophysics (Berlin),
11/2020, Letnik:
643
Journal Article, Web Resource
Recenzirano
Odprti dostop
The H0LiCOW collaboration inferred via strong gravitational lensing time delays a Hubble constant value of
H
0
= 73.3
−1.8
+1.7
km s
−1
Mpc
−1
, describing deflector mass density profiles by either a ...power-law or stars (constant mass-to-light ratio) plus standard dark matter halos. The mass-sheet transform (MST) that leaves the lensing observables unchanged is considered the dominant source of residual uncertainty in
H
0
. We quantify any potential effect of the MST with a flexible family of mass models, which directly encodes it, and they are hence maximally degenerate with
H
0
. Our calculation is based on a new hierarchical Bayesian approach in which the MST is only constrained by stellar kinematics. The approach is validated on mock lenses, which are generated from hydrodynamic simulations. We first applied the inference to the TDCOSMO sample of seven lenses, six of which are from H0LiCOW, and measured
H
0
= 74.5
−6.1
+5.6
km s
−1
Mpc
−1
. Secondly, in order to further constrain the deflector mass density profiles, we added imaging and spectroscopy for a set of 33 strong gravitational lenses from the Sloan Lens ACS (SLACS) sample. For nine of the 33 SLAC lenses, we used resolved kinematics to constrain the stellar anisotropy. From the joint hierarchical analysis of the TDCOSMO+SLACS sample, we measured
H
0
= 67.4
−3.2
+4.1
km s
−1
Mpc
−1
. This measurement assumes that the TDCOSMO and SLACS galaxies are drawn from the same parent population. The blind H0LiCOW, TDCOSMO-only and TDCOSMO+SLACS analyses are in mutual statistical agreement. The TDCOSMO+SLACS analysis prefers marginally shallower mass profiles than H0LiCOW or TDCOSMO-only. Without relying on the form of the mass density profile used by H0LiCOW, we achieve a ∼5% measurement of
H
0
. While our new hierarchical analysis does not statistically invalidate the mass profile assumptions by H0LiCOW – and thus the
H
0
measurement relying on them – it demonstrates the importance of understanding the mass density profile of elliptical galaxies. The uncertainties on
H
0
derived in this paper can be reduced by physical or observational priors on the form of the mass profile, or by additional data.
Background and purpose
The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion‐weighted magnetic ...resonance imaging (DWI‐MRI) and whether ischaemic core size affects this rate remain to be investigated.
Methods
This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI‐MRI that was categorized into three groups: small Diffusion‐Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI‐ASPECTS) (8–10), moderate (5–7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0–2). The interaction between onset‐to‐groin puncture time (OTP) and DWI‐ASPECTS categories regarding functional outcomes was investigated.
Results
Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI‐ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction = 0.06). Every 60‐min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity = 0.15).
Conclusions
Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI‐ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.
This study is an epidemiologic investigation of nosocomial severe fever with thrombocytopenia syndrome virus (SFTSV) transmission among healthcare workers (HCWs) after contact with an index patient. ...The aim of this study was to determine whether exposure to blood or bloody respiratory secretion is associated with human-to-human transmission of SFTSV.
Eleven days after the index patient died, two HCWs who had close exposure to the patient presented with typical symptoms of SFTS. An epidemiological investigation was conducted on all 25 HCWs who had been in close contact with the index patient. Clinical and laboratory data were collected, and transmission rate before and after the index patient had haemorrhagic manifestations was analysed.
Among 25 HCWs who had direct contact with the index patient, five HCWs were confirmed to have SFTS. All five HCWs had contact to blood or bloody respiratory secretions of the index patient without adequate use of personal protective equipment (PPE). No HCW with contact before haemorrhagic manifestations of the index patient contracted SFTS. Overall, the transmission rate was higher for HCWs who had contact after the index patient had haemorrhagic manifestations (33.3%, five of 15 HCWs, vs. 0%, zero of ten HCWs, p 0.041).
In HCWs who are inadequately protected, person-to-person transmission of SFTSV may be associated with contact with blood or bloody respiratory secretions. Therefore, universal precaution and full PPE is highly recommended for protection against SFTSV when there are signs of bleeding.
The discovery of a two-dimensional electron gas (2DEG) at the LaAlO
/SrTiO
interface
has resulted in the observation of many properties
not present in conventional semiconductor heterostructures, and ...so become a focal point for device applications
. Its counterpart, the two-dimensional hole gas (2DHG), is expected to complement the 2DEG. However, although the 2DEG has been widely observed
, the 2DHG has proved elusive. Herein we demonstrate a highly mobile 2DHG in epitaxially grown SrTiO
/LaAlO
/SrTiO
heterostructures. Using electrical transport measurements and in-line electron holography, we provide direct evidence of a 2DHG that coexists with a 2DEG at complementary heterointerfaces in the same structure. First-principles calculations, coherent Bragg rod analysis and depth-resolved cathodoluminescence spectroscopy consistently support our finding that to eliminate ionic point defects is key to realizing a 2DHG. The coexistence of a 2DEG and a 2DHG in a single oxide heterostructure provides a platform for the exciting physics of confined electron-hole systems and for developing applications.
Mammalian sirtuin 1 (SIRT1) has connected to an ever widening circle of activities that encompass cellular stress resistance, energy metabolism and tumorigenesis. However, underlying mechanisms ...leading to oncogenic SIRT1 overexpression are less understood. In this study, we identified SIRT1 regulatory microRNA (miRNA) and its function in hepatocellular carcinoma (HCC). Aberrant SIRT1 overexpression was demonstrated in a subset of human HCCs. SIRT1 knockdown suppressed HCC cell growth by transcriptional deregulation of cell cycle proteins. This led to hypophosphorylation of pRb, which inactivated E2F/DP1 target gene transcription, and thereby caused significant increase of HCC cells to remain in the G1/S phase. A comprehensive miRNA profiling analysis indentified five putative endogenous miRNAs that are significantly downregulated in HCC. Ectopic expression of miRNA mimics evidenced miR-29c to suppress SIRT1 in HCC cells. Notably, ectopic miR-29c expression repressed cancer cell growth and proliferation, and it recapitulated SIRT1 knockdown effects in HCC cells. In addition, miR-29c expression was downregulated in a large cohort of HCC patients, and low expression of miR-29c was significantly associated with poor prognosis of HCC patients. Taken together, we demonstrated that miR-29c suppresses oncogenic SIRT1 by way of binding to 3'-untranslated region of SIRT1 mRNA causing translational inhibition in liver cancer cells. The loss or suppression of miR-29c may cause aberrant SIRT1 overexpression and promotes liver tumorigenesis. Overall, we suggest that miR-29c functions as a tumor suppressor by regulating abnormal SIRT1 activity in liver.
Lysophosphatidic acid (LPA), produced extracellularly by autotaxin (ATX), has diverse biological activities implicated in tumor initiation and progression, including increasing cell survival, ...angiogenesis, invasion and metastasis. ATX, LPA and the matrix metalloproteinase (MMP)-9 have all been implicated in hepatocellular carcinoma (HCC) invasion and metastasis. We, thus sought to determine whether ATX with subsequent LPA production and action, including induction of MMP-9 could provide a unifying mechanism. ATX transcripts and LPA receptor type 1 (LPA1) protein are elevated in HCC compared with normal tissues. Silencing or pharmacological inhibition of LPA1 significantly attenuated LPA-induced MMP-9 expression and HCC cell invasion. Further, reducing MMP-9 activity or expression significantly inhibits LPA-induced HCC cell invasion, demonstrating that MMP-9 is downstream of LPA1. Inhibition of phosphoinositide-3 kinase (PI3K) signaling or dominant-negative mutants of protein kinase Cδ and p38 mitogen-activated protein kinase (MAPK) abrogated LPA-induced MMP-9 expression and subsequent invasion. We thus demonstrate a mechanistic cascade of ATX-producing LPA with LPA activating LPA1 and inducing MMP-9 through coordinate activation of the PI3K and the p38 MPAK signaling cascades, providing novel biomarkers and potential therapeutic targets for HCC.
KSTAR has demonstrated divertor heat flux broadening during edge-localized mode (ELM) crash suppression using ITER-like three-row resonant magnetic perturbation (RMP) for the first time. To address a ...couple of critical issues in ITER RMP, robust ELM-crash-suppression methodology has been explored at low q95 and established in KSTAR using low-n RMPs. Taking full advantage of the ITER-like three-row in-vessel control coils (IVCC) in KSTAR, a set of intentionally misaligned RMP configurations (IMC) was tested to investigate whether or not IMC could be compatible with ELM crash suppression, while minimizing electromagnetic loads on RMP coils. As a result, the ITER-like three-row IMCs were found not only to have been compatible with the ELM crash suppression, but also to have broadened the divertor heat fluxes in the vicinity of the outer strike point. In comparison, the two-row RMPs have rarely affected the near scrape-off layer (SOL) heat flux despite slightly broadened profile change in the far-SOL. Since the divertor heat flux broadening reflects the dispersal of the peaked near-SOL heat flux, the experimental outcome is quite favorable to the ITER choice of three rows, instead of two rows. Nonetheless, since the IMC-driven broadening observed in the attached plasmas in KSTAR might appear substantially different in the partially detached plasmas in ITER, additional investigation has been conducted to see if RMP-driven, ELM crash suppression could be compatible with detached plasmas. Although no detached plasmas have been identified with ELM crash suppression yet, significantly reduced divertor heat flux was confirmed in high density, ELM-crash-suppressed plasmas at q95 = 3.4 using n = 2 RMPs. These new findings elevate the confidence level about the ITER RMP system, while the remaining uncertainties need to be further clarified using the three-row IVCCs in KSTAR.
Background
Sentinel node navigation surgery reduces the extent of gastric and lymph node dissection, and may improve quality of life. The benefit and harm of laparoscopic sentinel node navigation ...surgery (LSNNS) for early gastric cancer is unknown. The SENORITA (SEntinel Node ORIented Tailored Approach) trial investigated the pathological and surgical outcomes of LSNNS compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection.
Methods
The SENORITA trial was an investigator‐initiated, open‐label, parallel‐assigned, non‐inferiority, multicentre RCT conducted in Korea. The primary endpoint was 3‐year disease‐free survival. The secondary endpoints, morbidity and mortality within 30 days of surgery, are reported in the present study.
Results
A total of 580 patients were randomized to LSG (292) or LSNNS (288). Surgery was undertaken in 527 patients (LSG 269, LSNNS 258). LSNNS could be performed according to the protocol in 245 of 258 patients, and a sentinel node basin was detected in 237 (96·7 per cent) Stomach‐preserving surgery was carried out in 210 of 258 patients (81·4 per cent). Postoperative complications occurred in 51 patients in the LSG group (19·0 per cent) and 40 (15·5 per cent) in the LSNNS group (P = 0·294). Complications with a Clavien–Dindo grade of III or higher occurred in 16 (5·9 per cent) and 13 (5·0 per cent) patients in the LSG and LSNNS groups respectively (P = 0·647).
Conclusion
The rate and severity of complications following LSNNS for early gastric cancer are comparable to those after LSG with lymph node dissection. Registration number: NCT01804998 (
http://www.clinicaltrials.gov).
Antecedentes
La cirugía de navegación del ganglio centinela (sentinel node navigation surgery, SNNS) reduce la extensión de la resección gástrica y ganglionar, y puede mejorar la calidad de vida. Se desconoce el beneficio y el daño de la cirugía de navegación del ganglio centinela por vía laparoscópica (laparoscopic sentinel node navigation surgery, LSNNS) para el cáncer gástrico precoz. El ensayo clínico SENORITA investigó los resultados patológicos y quirúrgicos de LSNNS en comparación con la gastrectomía laparoscópica estándar (laparoscopic gastrectomy, LSG) con disección ganglionar (lymph node dissection, LND).
Métodos
El ensayo SENORITA fue un ensayo multicéntrico aleatorizado y controlado, iniciado por investigadores, abierto, con asignación a grupos paralelos y de no inferioridad llevado a cabo en Corea. El resultado primario fue la supervivencia libre de enfermedad a los 3 años. En el presente estudio, se describen los resultados secundarios correspondientes a morbilidad y mortalidad a los 30 días del postoperatorio.
Resultados
Un total de 580 pacientes fueron aleatorizados a LG (n = 292) o LSNNS (n = 288). La cirugía se realizó en 527 pacientes (LG 269, LSNNS 258). LSNNS pudo ser realizada de acuerdo con el protocolo en 245 de 258 pacientes y en 237 de 245 pacientes (96,7%) se detectó un ganglio centinela. La cirugía con preservación del estómago se realizó en 210 de 258 pacientes (81,4%). Las complicaciones postoperatorias se presentaron en 51 pacientes del grupo LSG (19,0%) y en 40 pacientes (15,5%) del grupo LSNNS (P = 0,294). Las complicaciones grado III o mayor de Clavien‐Dindo se detectaron en 16 (5,9%) y 13 pacientes (5,0%) de los grupos LSG y LSNNS, respectivamente (P = 0,647).
Conclusión
El porcentaje y la gravedad de las complicaciones tras LSNNS para cancer gástrico precoz son comparables a la LSG con LND.
The prospective, multicentre, randomized controlled phase III SENORITA trial evaluated the surgical and oncological outcomes of laparoscopic sentinel node navigation surgery (LSNNS) compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection (LND) for early gastric cancer (EGC). LSNNS for EGC is a safe procedure in terms of postoperative morbidity and mortality compared with LSG and LND. ESD, endoscopic submucosal dissection; mITT, modified intention to treat; FAS, full analysis set; OGJ, oesophagogastric junction; LDG, laparoscopic distal gastrectomy; LTG, laparoscopic total gastrectomy; LPPG, laparoscopic pylorus‐preserving gastrectomy; LPG, laparoscopic proximal gastrectomy; ODG, open distal gastrectomy; OTG, open total gastrectomy; PP, per protocol; SBD, sentinel basin dissection; EFTR, endoscopic full‐thickness resection; LWR, laparoscopic wedge resection; LSR, laparoscopic segmental resection.
Similar morbidity
Summary Objective The present study was performed to elucidate the possible role of SIRT1 signaling in joint inflammation in human articular chondrocytes. Design Real-time quantitative reverse ...transcription polymerase chain reaction (qRT-PCR) and Western blotting were performed to detect gene products and proteins involved in tumor necrosis factor α (TNF-α)-induced inflammation and cartilage degradation in human primary chondrocytes. Matrix metalloproteinase (MMP)-2 and MMP-9 activity was evaluated by gelatin zymography. Overexpression and knockdown of SIRT1 were also performed to investigate whether SIRT1 is associated with the anti-inflammatory activity of resveratrol in chondrocytes. Results Resveratrol dose-dependently inhibited TNF-α-induced cyclooxygenase-2 (COX-2), MMP-1, MMP-3, MMP-13 and PGE2 production in human chondrocytes. Moreover, MMP-2 and MMP-9 activity was increased by treatment with TNF-α; however, SIRT1 activation decreased the proinflammatory effects induced by TNF-α. In addition, treatment of SIRT1 activator and overexpression of SIRT1 inhibited the expression and activation of the main proinflammatory regulator NF-κB, which was increased by TNF-α. When SIRT1 was overexpressed in chondrocytes, the anti-inflammatory action of SIRT1 was similar to that exerted by resveratrol. Conclusions SIRT1 activation deacetylates and inactivates NF-κB, and thereby, exerts an anti-inflammatory effect on chondrocytes, suggesting that SIRT1 activators could be explored as potential treatments for arthritis.
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