Experiments that pursue detection of signals from the Epoch of Reionization (EoR) are relying on spectral smoothness of source spectra at low frequencies. This article empirically explores the effect ...of foreground spectra on EoR experiments by measuring high-resolution full-polarization spectra for the 586 brightest unresolved sources in one of the Murchison Widefield Array (MWA) EoR fields using 45 h of observation. A novel peeling scheme is used to subtract 2500 sources from the visibilities with ionospheric and beam corrections, resulting in the deepest, confusion-limited MWA image so far. The resulting spectra are found to be affected by instrumental effects, which limit the constraints that can be set on source-intrinsic spectral structure. The sensitivity and power-spectrum of the spectra are analysed, and it is found that the spectra of residuals are dominated by point spread function sidelobes from nearby undeconvolved sources. We release a catalogue describing the spectral parameters for each measured source.
We report two microlensing events, KMT-2017-BLG-1038 and KMT-2017-BLG-1146, that are caused by planetary systems. These events were discovered by Korea Microlensing Telescope Network survey ...observations from the 2017 bulge season. The discovered systems consist of a planet and host star with mass ratios of and , respectively. Based on a Bayesian analysis assuming a Galactic model without stellar remnant hosts, we find that the planet KMT-2017-BLG-1038Lb is a super-Jupiter-mass planet ( ) orbiting a mid-M dwarf host ( ) that is located at kpc toward the Galactic bulge. The other planet, KMT-2017-BLG-1146Lb, is a sub-Jupiter-mass planet ( ) orbiting a mid-M dwarf host ( ) at a distance of kpc toward the Galactic bulge. Both are potentially gaseous planets that are beyond their hosts' snow lines. These typical microlensing planets will be routinely discovered by second-generation microlensing surveys, rapidly increasing the number of detections.
Genexol-PM is a novel Cremophor EL (CrEL)-free polymeric micelle formulation of paclitaxel (Taxol). This multicenter phase II study was designed to evaluate the efficacy and safety of the combination ...of Genexol-PM and cisplatin for the treatment of advanced non-small-cell lung cancer (NSCLC).
Patients with advanced NSCLC received Genexol-PM 230 mg/m2 and cisplatin 60 mg/m2 on day 1 of a 3-week cycle as first-line therapy. Intrapatient dose escalation of Genexol-PM to 300 mg/m2 was carried out from the second cycle if the prespecified toxic effects were not observed after the first cycle.
Sixty-nine patients were enrolled in this study. Overall response rate was 37.7%. The median time to progression was 5.8 months and the median survival period was 21.7 months. The major non-hematologic toxic effects included grade 3 peripheral sensory neuropathy (13.0%) and grade 3/4 arthralgia (7.3%). Four patients (5.8%) experienced grade 3/4 hypersensitivity reactions. The major hematological toxic effects were grade 3/4 neutropenia (29.0% and 17.4%, respectively).
Genexol-PM plus cisplatin combination chemotherapy showed significant antitumor activity. The use of CrEL-free, polymeric micelle formulation of paclitaxel allowed administration of higher doses of paclitaxel compared with the CrEL-based formulation without significant increased toxicity.
Background
In gallbladder cancer, stage T2 is subdivided by tumour location into lesions on the peritoneal side (T2a) or hepatic side (T2b). For tumours on the peritoneal side (T2a), it has been ...suggested that liver resection may be omitted without compromising the prognosis. However, data to validate this argument are lacking. This study aimed to investigate the prognostic value of tumour location in T2 gallbladder cancer, and to clarify the adequate extent of surgical resection.
Methods
Clinical data from patients who underwent surgery for gallbladder cancer were collected from 14 hospitals in Korea, Japan, Chile and the USA. Survival and risk factor analyses were conducted.
Results
Data from 937 patients were available for evaluation. The overall 5‐year disease‐free survival rate was 70·6 per cent, 74·5 per cent for those with T2a and 65·5 per cent among those with T2b tumours (P = 0·028). Regarding liver resection, extended cholecystectomy was associated with a better 5‐year disease‐free survival rate than simple cholecystectomy (73·0 versus 61·5 per cent; P = 0·012). The 5‐year disease‐free survival rate was marginally better for extended than simple cholecystectomy in both T2a (76·5 versus 66·1 per cent; P = 0·094) and T2b (68·2 versus 56·2 per cent; P = 0·084) disease. Five‐year disease‐free survival rates were similar for extended cholecystectomies including liver wedge resection versus segment IVb/V segmentectomy (74·1 versus 71·5 per cent; P = 0·720). In multivariable analysis, independent risk factors for recurrence were presence of symptoms (hazard ratio (HR) 1·52; P = 0·002), R1 resection (HR 1·96; P = 0·004) and N1/N2 status (N1: HR 3·40, P < 0·001; N2: HR 9·56, P < 0·001). Among recurrences, 70·8 per cent were metastatic.
Conclusion
Tumour location was not an independent prognostic factor in T2 gallbladder cancer. Extended cholecystectomy was marginally superior to simple cholecystectomy. A radical operation should include liver resection and adequate node dissection.
Antecedentes
En el cáncer de vesícula biliar, la ubicación del tumor subdivide el estadio T2 en tumores con invasión del lado peritoneal y del lado del hígado (T2a y T2b). Para los tumores que invaden el lado peritoneal (T2a) se sugiere que se puede obviar la resección hepática sin que ello comprometa el pronóstico. Sin embargo, este argumento no ha sido validado. El estudio tuvo como objetivo investigar el valor pronóstico de la localización del tumor en el cáncer de vesícula biliar T2 y establecer la extensión adecuada de la resección quirúrgica.
Métodos
Se recogieron los datos clínicos de pacientes que se sometieron a cirugía por cáncer de vesícula biliar en 14 hospitales de Corea, Japón, Chile y Estados Unidos. Se realizaron análisis de la supervivencia y de los factores de riesgo.
Resultados
Se dispuso de datos de 937 pacientes para ser evaluados. La tasa de supervivencia global libre de enfermedad a los 5 años fue del 70,6%, y las de T2a y T2b del 74,5% y 65,5% (P = 0,028). Con respecto a la resección hepática, la colecistectomía extendida presentó una tasa mejor de supervivencia libre de enfermedad a los 5 años que la colecistectomía simple (73,0% versus 61,5%, P = 0,012). La tasa de supervivencia libre de enfermedad a los 5 años fue marginalmente mejor para la colecistectomía extendida que para la colecistectomía simple tanto en T2a (76,5% versus 66,1%, P = 0,094) como en T2b (68,2% versus 56,2%, P = 0,084). Las tasas de supervivencia libre de enfermedad a los 5 años no fueron diferentes entre la resección hepática en cuña y la segmentectomía S4b+S5 (74,1% versus 71,5%, P = 0,720). En el análisis multivariable, los factores de riesgo independientes para la recidiva fueron la presencia de síntomas (cociente de riesgos instantáneos, hazard ratio, HR 1,52, P = 0,002), la resección R1 (HR 1,96, P = 0,004) y el estadio N1/N2 (N1 HR 3,40, P < 0,001; N2 HR 9,56, P < 0,001). El 70,8% de las recidivas eran metastásicas.
Conclusión
La localización del tumor no fue un factor pronóstico independiente en el cáncer de vesícula biliar T2. La colecistectomía extendida fue marginalmente superior que la colecistectomía simple. La cirugía radical debe incluir una resección hepática y una linfadenectomía adecuada.
This multinational multicentre cohort study was undertaken to investigate the prognostic value of tumour location in T2 gallbladder cancer and to clarify the adequate extent of surgical resection. Although tumour location influenced prognosis, it was not an independent prognostic factor in T2 gallbladder cancer. T2 gallbladder cancer requires extended cholecystectomy including hepatic resection and lymph node dissection, regardless of the location.
challenges current TNM system
The autocrine and paracrine activation of the renin–angiotensin system (RAS) within cells of the kidney plays a role in the overall pathophysiology of the renal disease due to diabetes. In this ...study, we focus on components of the RAS in the podocyte as these cells are important in the pathogenesis of glomerulosclerosis and proteinuria. Immortalized mouse podocytes were exposed to media containing normal glucose (NG) or high glucose (HG) for in vitro studies. In vivo studies utilized kidney tissue obtained from rats treated for 3 months with streptozotocin to induce diabetes. Angiotensinogen (AGT) and the angiotensin II (AII) type 1 receptor mRNA and protein were significantly increased in the podocytes cultured under the high glucose conditions. Both angiotensins I and II levels were significantly higher in cell lysates and the conditioned media of cells grown in high glucose. There were no differences in renin activity, angiotensin-converting enzyme level, or AII type 2 receptor level. Glomerular AGT and AII type 1 receptor assessed by means of immunohistochemistry were increased in diabetic rats compared with the control rats. Other measured components of the RAS within the glomeruli were not different. We suggest that increased AGT, an attendant increase in AII and increased AII type 1 receptor in podocytes experiencing diabetic conditions play an important role in the pathogenesis of diabetic nephropathy.
Peripheral inflammation produces pain hypersensitivity by sensitizing nociceptors. Potentiation of P2X3 receptor activity in nociceptors may play an important role in this peripheral sensitization. ...However, we do not fully understand how P2X3 activity is elevated in inflammation. Thus, we investigated whether P2X3 activity in trigeminal nociceptive neurons is regulated by the neurokinin-1 (NK-1) receptor that is activated by an inflammatory mediator, substance P. Single-cell RT-PCR and immunohistochemistry revealed that NK-1 in nociceptive neurons was mainly co-expressed with P2X3. Ca2+ imaging and whole-cell patch-clamp recordings indicated that both substance P and Sar-substance P, a selective NK-1 agonist, significantly potentiated α,β-meATP-induced currents and Ca2+i responses in nociceptive neurons. These potentiating effects were completely blocked by GR82334, a specific NK-1 antagonist. Our results demonstrate that substance P sensitizes P2X3 receptor through the activation of NK-1, thus warranting these receptors as possible targets for pain therapy in the orofacial region. Abbreviations: α,β-methylene adenosine 5′-triphosphate (ATP), α,β-meATP; neurokinin-1, NK-1; single-cell reverse-transcription polymerase chain-reaction, single-cell RT-PCR; Sar9,Met(O2)11-substance P, Sar-substance P.
Despite ionizing radiation (IR) is being widely used as a standard treatment for lung cancer, many evidences suggest that IR paradoxically promotes cancer malignancy. However, its molecular ...mechanisms underlying radiation-induced cancer progression remain obscure. Here, we report that exposure to fractionated radiation (2 Gy per day for 3 days) induces the secretion of granulocyte-colony-stimulating factor (G-CSF) that has been commonly used in cancer therapies to ameliorate neutropenia. Intriguingly, radiation-induced G-CSF promoted the migratory and invasive properties by triggering the epithelial-mesenchymal cell transition (EMT) in non-small-cell lung cancer cells (NSCLCs). By irradiation, G-CSF was upregulated transcriptionally by β-catenin/TCF4 complex that binds to the promoter region of G-CSF as a transcription factor. Importantly, irradiation increased the stability of β-catenin through the activation of PI3K/AKT (phosphatidylinositol 3-kinase/AKT), thereby upregulating the expression of G-CSF. Radiation-induced G-CSF is recognized by G-CSFR and transduced its intracellular signaling JAK/STAT3 (Janus kinase/signal transducers and activators of transcription), thereby triggering EMT program in NSCLCs. Taken together, our findings suggest that the application of G-CSF in cancer therapies to ameliorate neutropenia should be reconsidered owing to its effect on cancer progression, and G-CSF could be a novel therapeutic target to mitigate the harmful effect of radiotherapy for the treatment of NSCLC.
Objectives: To examine the prevalence of sarcopenia and sarcopenic obesity (SO) as defined by different indices, including appendicular skeletal muscle mass (ASM)/height2, skeletal muscle mass index ...(SMI) and residuals for Korean adults, and to explore the association between SO and metabolic syndrome. Methods: Our study sample included 526 participants (328 women, 198 men) for whom complete data on body composition were collected using available dual X-ray absorptiometry. Modified National Cholesterol Education Program Adult Treatment Panel III criteria were used to identify the individuals with metabolic syndrome. Results: The prevalence of sarcopenia and SO is higher in older adults. Using two s.d. of ASM/height2 below reference values from young, healthy adults as a definition of sarcopenia, the prevalence of sarcopenia and SO was 6.3% and 1.3% in older (60 years) men and 4.1% and 0.8% in older women, respectively. The prevalence of sarcopenia using the residuals method was 15.4% in older men and 22.3% in older women. In addition, using two s.d. of SMI, the prevalence of sarcopenia and SO was 5.1% and 5.1%, respectively, in older men and 14.2% and 12.5%, respectively, in older women. Among women, SO subjects defined by the SMI had three times the risk of metabolic syndrome (odds ratios (OR)=3.24, 95% confidence interval (CI)=1.21-8.66) and non-sarcopenic obese subjects had approximately twice the risk of metabolic syndrome (OR=2.17, 95% CI=1.22-3.88) compared with normal subjects. Similar trends were observed in men. Conclusion: The prevalence and cutoff values of sarcopenia and SO in the Korean population were evaluated using different methods. Among the different indices of sarcopenia and SO, SO only defined using the SMI was associated with the risk of metabolic syndrome. As the Korean population gets older and more obese, the problematics of SO need to be elucidate.
In order to overcome the issues of rework and height difference in the manufacturing of smart devices, UV/UV stepwise curing was conducted on acrylate-based optically clear adhesives. Photo ...differential scanning calorimetry was used to confirm the results of curing of samples that were processed both with and without acrylic acid, over a range of UV light exposure times for a primary curing process. The samples processed at 0.6 J/cm2 of UV energy with and without acrylic acid showed the highest amount of residual monomers after primary curing. The amount of residual monomers observed in primary-cured samples decreased as the amount of UV light energy increased, from 0.9 to 1.5 J/cm2. After secondary curing, only the samples cured at 0.6 J/cm2 showed small amounts of residual monomers, while the samples exposed to other UV energies showed very few residual monomers, implying that these samples were completely cured during the secondary curing step. Adhesion properties were evaluated using peel and tack tests, while the viscoelastic properties of the samples were confirmed by dynamic mechanical analysis. Our results indicate that uniform physical properties were achieved after secondary curing. The effects of stepwise curing are demonstrated by the difference in gel fractions determined after primary and secondary curing.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We evaluated whether ELISPOT assay can predict tuberculosis (TB) development in kidney‐transplantation (KT) recipients with a negative tuberculin skin test (TST). All adult patients admitted to a KT ...institute between June 2008 and December 2009 were enrolled; TB development after KT was observed between June 2008 and December 2010. Isoniazid (INH) was given to those patients with positive TST or clinical risk factors for latent TB infection (LTBI). ELISPOT assay was performed on all patients, and TB development after KT was observed by a researcher blinded to the results of ELISPOT. A total of 312 KT recipients including 242 (78%) living‐donor KT were enrolled. Of the 312 patients, 40 (13%) had positive TST or clinical risk factors for LTBI and received INH; none developed TB after KT. Of the remaining 272 patients, 4 (6%) of 71 with positive ELISPOT assay developed TB after KT, whereas none of the 201 patients with negative (n = 171) or indeterminate ELISPOTs (n = 30) developed TB after KT (rate difference between positive and negative/indeterminate ELISPOT, 3.3 per 100 person‐years 95% CI 1.4–5.1, p<0.001). Positive ELISPOT results predict subsequent development of TB in KT recipients in whom LTBI cannot be detected by TST or who lack clinical risk factors for LTBI.
Positive results of an interferon‐gamma releasing assay anticipate the subsequent development of tuberculosis in kidney transplant recipients in whom latent tuberculosis infection cannot be detected by tuberculin skin test or who lack clinical risk factors for latent tuberculosis infection. See editorial by Torre‐Cisneros and Doblas on page 1769.