The reflectance spectra of the most abundant meteorites, ordinary chondrites, are different from those of the abundant S-type (mnemonic for siliceous) asteroids. This discrepancy has been thought to ...be due to space weathering, which is an alteration of the surfaces of airless bodies exposed to the space environment. Here we report evidence of space weathering on particles returned from the S-type asteroid 25143 Itokawa by the Hayabusa spacecraft. Surface modification was found in 5 out of 10 particles, which varies depending on mineral species. Sulfur-bearing Fe-rich nanoparticles exist in a thin (5 to 15 nanometers) surface layer on olivine, low-Ca pyroxene, and plagioclase, which is suggestive of vapor deposition. Sulfur-free Fe-rich nanoparticles exist deeper inside (<60 nanometers) ferromagnesian silicates. Their texture suggests formation by metamictization and in situ reduction of Fe2+.
Gemcitabine plus cisplatin (GC) is the standard treatment of advanced biliary tract cancer (BTC); however, it causes nausea, vomiting, and anorexia, and requires hydration. Gemcitabine plus S-1 (GS) ...reportedly has equal to, or better, efficacy and an acceptable toxicity profile. We aimed to confirm the non-inferiority of GS to GC for patients with advanced/recurrent BTC in terms of overall survival (OS).
We undertook a phase III randomized trial in 33 institutions in Japan. Eligibility criteria included chemotherapy-naïve patients with recurrent or unresectable BTC, an Eastern Cooperative Oncology Group Performance Status of 0−1, and adequate organ function. The calculated sample size was 350 with a one-sided α of 5%, a power of 80%, and non-inferiority margin hazard ratio (HR) of 1.155. The primary end point was OS, while the secondary end points included progression-free survival (PFS), response rate (RR), adverse events (AEs), and clinically significant AEs defined as grade ≥2 fatigue, anorexia, nausea, vomiting, oral mucositis, or diarrhea.
Between May 2013 and March 2016, 354 patients were enrolled. GS was found to be non-inferior to GC median OS: 13.4months with GC and 15.1months with GS, HR, 0.945; 90% confidence interval (CI), 0.78–1.15; P=0.046 for non-inferiority. The median PFS was 5.8months with GC and 6.8months with GS (HR 0.86; 95% CI 0.70–1.07). The RR was 32.4% with GC and 29.8% with GS. Both treatments were generally well-tolerated. Clinically significant AEs were observed in 35.1% of patients in the GC arm and 29.9% in the GS arm.
GS, which does not require hydration, should be considered a new, convenient standard of care option for patients with advanced/recurrent BTC.
This trial has been registered with the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/index.htm), number UMIN000010667.
The existence of large stationary gravity waves was discovered during Akatsuki's first observation sequence in 2015. In this study, the further detection of large stationary gravity waves in ...brightness temperature images over a 1.5 year period is reported. The waves periodically appeared mostly above four specific highland regions in the low latitudes when these regions were in the local afternoon. The wave amplitudes attenuated after the wave locations passed beyond the evening terminator, and the locations of the waves tended to slowly drift eastward over their lifetimes. The appearances of stationary waves depend not only on surface topography but also on latitude and local time, suggesting that solar heating during the daytime and atmospheric structure affected by solar heating may control the excitation and propagation of stationary waves.
Plain Language Summary
The Japanese Venus satellite “Akatsuki” has repeatedly found large atmospheric waves with north‐south lengths, which sometimes reach more than 10,000 km at the cloud top level on Venus (altitude ~70 km). These waves have repeatedly appeared above the Venusian highlands in low latitudes, such as Aphrodite Terra. Interestingly, the waves appeared and became clearer each time the highlands passed from noon to evening; therefore, they can be regarded as “daily” Venusian phenomena. Despite westward wind speeds reaching 100 m s−1 at the cloud top level (known as atmospheric superrotation), the east‐west propagation speeds of the large waves were nearly zero, and the waves stayed above their initial locations (stationary). This means that the origin of the waves could be the highland terrains below. Because waves can transport energy via propagation, stationary waves may transport atmospheric energy from the lower atmosphere to the cloud top level and may affect the speed of the superrotation. The existence and regular appearance of the large stationary waves indicate a continuous interaction between the lower and upper atmospheres on Venus via wave propagation, which provides a novel perspective of the Venusian atmosphere.
Key Points
Stationary gravity waves with large horizontal extent at the cloud top level of Venus have been repeatedly identified
The locations of these waves show a clear connection to Venusian highlands, and wave amplitude depends on the local time at the highlands
Monitoring of the stationary waves would bring information of the Venusian atmosphere along the wave propagation paths
Background
The use of oral prophylactic antibiotics for the prevention of surgical‐site infection (SSI) in patients undergoing laparoscopic surgery for colorectal cancer is controversial. The aim of ...this RCT was to evaluate whether intravenous perioperative antibiotics are inferior to combined preoperative oral and perioperative intravenous antibiotics in this setting.
Methods
Patients undergoing elective laparoscopic colorectal resection in a single cancer centre were assigned randomly to combined preoperative oral antibiotics (metronidazole and kanamycin) and perioperative intravenous antibiotics (cefmetazole) (oral/IV group) or to perioperative intravenous antibiotics (cefmetazole) alone (IV‐only group). Patients were stratified for the analyses based on type of operation (colonic surgery, anterior resection or abdominoperineal resection), preoperative use of mechanical bowel preparation, preoperative chemoradiotherapy and the presence of diabetes mellitus. The primary endpoint was the overall rate of SSI. Secondary endpoints were the rates of incisional site infection, organ/space infection, anastomotic leakage, intra‐abdominal abscess, adverse events and postoperative complications.
Results
Of 540 patients offered participation in the trial in 2013–2014, 515 agreed to take part and were randomized. Some 256 patients in the IV‐only group and 255 in the oral/IV group completed the treatment per protocol. The overall rate of SSI was 7·8 per cent (20 of 256) in the IV‐only group and 7·8 per cent (20 of 255) in the oral/IV group, confirming that perioperative administration of intravenous antibiotics alone was not inferior to the combined regimen (P = 0·017). There were no differences in rates of incisional site infection (5·5 versus 5·9 per cent respectively), organ/space infection (2·3 versus 2·0 per cent) or other secondary endpoints between the two groups.
Conclusion
Intravenous perioperative antimicrobial prophylaxis alone is not inferior to combined preoperative oral and intravenous perioperative prophylaxis with regard to SSI in patients with colorectal cancer undergoing elective laparoscopic resection. Registration number: UMIN000019339 (
http://www.umin.ac.jp/ctr/).
Non‐inferiority confirmed
Summary
Self‐reported measures of oral health are often used to assess oral health in populations or groups, but their validity or reliability needs repeated confirmation. The objective of this ...cross‐sectional study was to evaluate the validity of self‐reported tooth counts and masticatory status, using data obtained from a sample of Japanese adults. A total of 2356 adults aged 40 to 75 years participated in a questionnaire survey and a clinical oral examination from 2013 through 2016. Self‐reported measures were compared with clinically measured values. For tooth counts, mean clinical and self‐reported tooth counts in all participants were 23.68 and 23.78 teeth, and no significant difference was detected. Spearman's, Pearson's and intra‐class correlation coefficients between clinical and self‐reported tooth counts were 0.771, 0.845 and 0.843, respectively. According to the Bland‐Altman analysis, the mean difference between clinical and self‐reported tooth counts was −0.098 (95% CI: −0.242, 0.047). The upper limit of agreement was 6.919 (95% CI: 6.669, 7.169), and the lower limit of agreement was −7.115 (95% CI: −7.365, −6.865). No significant fixed or proportional bias was observed. For masticatory status, the crude or age‐ and gender‐adjusted mean numbers of total teeth, posterior teeth and 3 kinds of functional tooth units significantly decreased with the deterioration of masticatory status. This study indicated that self‐reports were within an acceptable range of clinical measures. Therefore, self‐reports were considered valid alternatives to clinical measures to estimate tooth counts and masticatory status in a current Japanese adult population.
Human milk is abundant in carbohydrates and includes human milk oligosaccharides (HMOs) and
/
-glycans conjugated to proteins. HMO compositions and concentrations vary in individuals according to the ...maternal secretor status based on the fucosyltransferase 2 genotype; however, the profile of
/
-glycans remains uninvestigated because of the analytical complexity. Herein, we applied a label-free chromatography-mass spectrometry (LC-MS) technique to elucidate the variation in the composition and concentration of
/
-glycans in human milk. We used label-free LC-MS to relatively quantify 16
-glycans and 12
-glycans in 200 samples of Japanese human milk (1-2 months postpartum) and applied high performance anion exchange chromatography with pulsed amperometric detection to absolutely quantify the concentrations of 11 representative HMOs. Cluster analysis of the quantitative data revealed that
-glycans and several HMOs were classified according to the presence or absence of fucose linked to galactose while
-glycans were classified into a different group from
-glycans and HMOs.
-glycans and HMOs with fucose linked to galactose were more abundant in human milk from secretor mothers than from nonsecretor mothers. Thus, secretor status influenced the composition and concentration of HMOs and
-glycans but not those of
-glycans in human milk.
Background
Accumulating evidence suggests that radiotherapy success has an immune‐associated component. The immunogenomic profiles associated with responses to chemoradiotherapy (CRT) were assessed ...in patients with locally advanced rectal cancer in this study.
Methods
CD8+ tumour‐infiltrating lymphocyte (TIL) and stromal lymphocyte densities were assessed by immunohistochemistry using pretreatment biopsies from patients with advanced rectal cancer who had preoperative CRT. Whole‐exome sequencing and gene expression microarray analysis were conducted to investigate the genomic properties associated with the response to CRT and CD8+ TIL density. Response to CRT was determined based on Dworak tumour regression grade (TRG); tumours with complete (TRG 4) or near‐complete (TRG 3) regression were grouped as good responders, and those with TRG 1 as non‐responders.
Results
Immunohistochemical examinations (275 patients) showed that pre‐CRT CD8+ TIL density was associated with better response to CRT and improved recurrence‐free survival, whereas pre‐CRT stromal CD8+ cell density was not associated with either response to CRT or recurrence‐free survival. Whole‐exome sequencing (74 patients) showed that the numbers of single‐nucleotide variations (SNVs) and neoantigens predicted from SNVs were higher in good responders than in non‐responders, and these correlated positively with CD8+ TIL density (rS = 0·315 and rS = 0·334 respectively). Gene expression microarray (90 patients) showed that CD8A expression correlated positively with the expression of programmed cell death 1 (PDCD1) (rS = 0·264) and lymphocyte‐activation gene 3 (LAG3) (rS = 0·507).
Conclusion
Pre‐CRT neoantigen‐specific CD8+ T cell priming may be a key event in CRT responses where immune checkpoint molecules could be useful targets to enhance tumour regression.
Antecedentes
Las evidencias existentes sugieren que el éxito de la radioterapia tiene un componente asociado con el sistema inmunitario. En este estudio se evaluaron los perfiles inmunogenómicos asociados con la respuesta a la quimiorradioterapia (chemoradiotherapy, CRT) en pacientes con cáncer de recto localmente avanzado.
Métodos
Las densidades de los linfocitos infiltrantes de tumor CD8+ (tumour‐infiltrating lymphocyte, TIL) y de los linfocitos del estroma se evaluaron por inmunohistoquímicas en las biopsias antes del tratamiento de pacientes con cáncer de recto localmente avanzado que recibieron CRT preoperatoria. Se realizó secuenciación de todo el exoma, así como microarrays de expresión génica, para investigar las propiedades genómicas asociadas con la respuesta a la CRT y a la densidad de los TIL CD8+. La respuesta a la CRT se determinó según el grado de regresión del tumor de Dworak (tumour regression grade, TRG), agrupándose como buenos respondedores los casos de regresión tumoral completa (TRG4) o casi completa (TRG3) y como no respondedores, los casos de grado TRG1.
Resultados
Los exámenes inmunohistoquímicos (n = 275) mostraron que la densidad pre‐CRT de TIL CD8+ se asoció con una mejor respuesta a la CRT y una mejor supervivencia libre de recidiva, aunque la densidad de células CD8+ del estroma previa a la CRT no se asoció con la respuesta a la CRT ni con la supervivencia libre de recidiva. La secuenciación de todo el exoma (n = 74) mostró que el número de variaciones de nucleótidos únicos (single nucleotide variations, SNVs) y los neoantígenos predichos a partir de los SNVs fueron mayores en los que respondieron bien que en los que no respondieron, y éstos se correlacionaron positivamente con la densidad de los TIL CD8+ (Spearman r = 0,315 y r = 0,334 respectivamente). Los microarrays de expresión génica (n = 90) mostraron que la expresión CD8A se correlacionó positivamente con la expresión del ligando de muerte programada‐1 (r = 0,264) y con el antígeno linfocitario del gen 3 (r = 0,507).
Conclusión
La activación de células T CD8+ específicas para neoantígenos previa a la CRT puede ser un evento clave en la respuesta a la misma donde las moléculas del punto de control inmunitario podrían ser dianas útiles para intensificar la regresión del tumor.
The immunogenomic profiles associated with responses to chemoradiotherapy (CRT) were assessed in patients with locally advanced rectal cancer using immunohistochemistry, whole‐exome sequencing and gene expression microarray. Pre‐CRT neoantigen‐specific CD8+ T cell priming may be a key event in CRT responses where immune checkpoint molecules could be useful targets to enhance tumour regression. SNV, single nucleotide variant; indels, insertions and deletions; TRG, tumour regression grade; MSI‐H, high‐level microsatellite instability; MSS, microsatellite stable.
Lymphocytes are key
Translational diffusion coefficients of diphenylcyclopropenone (DPCP), diphenylacetylene (DPA), and carbon monoxide (CO) in 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ...(BMImNTf2) and 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (EMImNTf2) were determined by the transient grating (TG) spectroscopy under pressure from 0.1 to 200 MPa at 298 K and from 298 to 373 K under 0.1 MPa. Diffusion coefficients of these molecules at high temperatures in tributylmethylphosphonium bis(trifluoromethanesulfonyl)imide (P4441NTf2), and tetraoctylphosphonium bis(trifluoromethanesulfonyl)imide (P8888NTf2), and also in the mixtures of BMImNTf2, N-methyl-N-propylpiperidinium bis(trifluoromethanesulfonyl)imide (Pp13NTf2), and trihexyltetradecylphosphonium bis(trifluoromethanesulfonyl)imide (P66614NTf2) with ethanol or chloroform have been determined. Diffusion coefficients except in ILs of phosphonium cations were well scaled by the power law of T/η, i.e., (T/η) P , where T and η are the absolute temperature and the viscosity, irrespective of the solvent species, pressure and temperature, and the compositions of mixtures. The values of the exponent P were smaller for the smaller size of the molecules. On the other hand, the diffusion coefficients in ILs of phosphonium cations with longer alkyl chains were larger than the values expected from the correlation obtained by other ILs and conventional liquids. The deviation becomes larger with increasing the number of carbon atoms of alkyl-chain of cation, and with decreasing the molecular size of diffusing molecules. The molecular size dependence of the diffusion coefficient was correlated by the ratio of the volume of the solute to that of the solvent as demonstrated by the preceding work (Kaintz et al., J. Phys. Chem. B 2013, 117, 11697 ). Diffusion coefficients have been well correlated with the power laws of both T/η and the relative volume of the solute to the solvent.
The differential cross sections for inclusive neutral pions as a function of transverse and longitudinal momentum in the very forward-rapidity region have been measured at the LHC with the LHC ...forward detector in proton-proton collisions at sradical=2.76 and 7 TeV and in proton-lead collisions at nucleon-nucleon center-of-mass energies of super()sNNradical=5.02TeV. Such differential cross sections in proton-proton collisions are compatible with the hypotheses of limiting fragmentation and Feynman scaling. Comparing proton-proton with proton-lead collisions, we find a sizable suppression of the production of neutral pions in the differential cross sections after subtraction of ultraperipheral proton-lead collisions. This suppression corresponds to the nuclear modification factor value of about 0.1-0.3. The experimental measurements presented in this paper provide a benchmark for the hadronic interaction Monte Carlo simulation codes that are used for the simulation of cosmic ray air showers.
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