IMPORTANCE: Colorectal cancer is the second leading cause of cancer death in the United States. In 2016, an estimated 134 000 persons will be diagnosed with the disease, and about 49 000 will die ...from it. Colorectal cancer is most frequently diagnosed among adults aged 65 to 74 years; the median age at death from colorectal cancer is 73 years. OBJECTIVE: To update the 2008 US Preventive Services Task Force (USPSTF) recommendation on screening for colorectal cancer. EVIDENCE REVIEW: The USPSTF reviewed the evidence on the effectiveness of screening with colonoscopy, flexible sigmoidoscopy, computed tomography colonography, the guaiac-based fecal occult blood test, the fecal immunochemical test, the multitargeted stool DNA test, and the methylated SEPT9 DNA test in reducing the incidence of and mortality from colorectal cancer or all-cause mortality; the harms of these screening tests; and the test performance characteristics of these tests for detecting adenomatous polyps, advanced adenomas based on size, or both, as well as colorectal cancer. The USPSTF also commissioned a comparative modeling study to provide information on optimal starting and stopping ages and screening intervals across the different available screening methods. FINDINGS: The USPSTF concludes with high certainty that screening for colorectal cancer in average-risk, asymptomatic adults aged 50 to 75 years is of substantial net benefit. Multiple screening strategies are available to choose from, with different levels of evidence to support their effectiveness, as well as unique advantages and limitations, although there are no empirical data to demonstrate that any of the reviewed strategies provide a greater net benefit. Screening for colorectal cancer is a substantially underused preventive health strategy in the United States. CONCLUSIONS AND RECOMMENDATIONS: The USPSTF recommends screening for colorectal cancer starting at age 50 years and continuing until age 75 years (A recommendation). The decision to screen for colorectal cancer in adults aged 76 to 85 years should be an individual one, taking into account the patient’s overall health and prior screening history (C recommendation).
We demonstrate that the pulsed-time structure and high-peak ion intensity provided by the laser-ablation process can be directly combined with the high resolution, high efficiency, and low background ...offered by collinear resonance ionization spectroscopy. This simple, versatile, and powerful method offers new and unique opportunities for high-precision studies of atomic and molecular structures, impacting fundamental and applied physics research. We show that even for ion beams possessing a relatively large energy spread, high-resolution hyperfine-structure measurements can be achieved by correcting the observed line shapes with the time-of-flight information of the resonantly ionized ions. This approach offers exceptional advantages for performing precision measurements on beams with large energy spreads and allows measurements of atomic parameters of previously inaccessible electronic states. The potential of this experimental method in multidisciplinary research is illustrated by performing, for the first time, hyperfine-structure measurements of selected states in the naturally occurring isotopes of indium,In113,115. Ab initio atomic-physics calculations have been performed to highlight the importance of our findings in the development of state-of-the-art atomic many-body methods, nuclear structure, and fundamental-physics studies.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM, UPUK
Molecular spectroscopy offers opportunities for the exploration of the fundamental laws of nature and the search for new particle physics beyond the standard model
. Radioactive molecules-in which ...one or more of the atoms possesses a radioactive nucleus-can contain heavy and deformed nuclei, offering high sensitivity for investigating parity- and time-reversal-violation effects
. Radium monofluoride, RaF, is of particular interest because it is predicted to have an electronic structure appropriate for laser cooling
, thus paving the way for its use in high-precision spectroscopic studies. Furthermore, the effects of symmetry-violating nuclear moments are strongly enhanced
in molecules containing octupole-deformed radium isotopes
. However, the study of RaF has been impeded by the lack of stable isotopes of radium. Here we present an experimental approach to studying short-lived radioactive molecules, which allows us to measure molecules with lifetimes of just tens of milliseconds. Energetically low-lying electronic states were measured for different isotopically pure RaF molecules using collinear resonance ionisation at the ISOLDE ion-beam facility at CERN. Our results provide evidence of the existence of a suitable laser-cooling scheme for these molecules and represent a key step towards high-precision studies in these systems. Our findings will enable further studies of short-lived radioactive molecules for fundamental physics research.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Zitterbewegung, a force-free trembling motion first predicted for relativistic fermions like electrons, was an unexpected consequence of the Dirac equation's unification of quantum mechanics and ...special relativity. Though the oscillatory motion's large frequency and small amplitude have precluded its measurement with electrons, zitterbewegung is observable via quantum simulation. We engineered an environment for 87Rb Bose-Einstein condensates where the constituent atoms behaved like relativistic particles subject to the one-dimensional Dirac equation. With direct imaging, we observed the sub-micrometre trembling motion of these clouds, demonstrating the utility of neutral ultracold quantum gases for simulating Dirac particles.
The wide application of silver nanoparticles (AgNPs) has pointed out the need to evaluate their potential risk and toxic effects on human health. Herein, the cytotoxic effects of Argovit™ AgNPs were ...evaluated on eight cancer cell lines. Further cytotoxic studies were performed in gynecological cancer cell lines from cervical (HeLa) and breast (MDA-MB-231 and MCF7) cancer. In both cases, the half maximal inhibitory concentration (IC50) of AgNPs produced the formation of reactive oxygen species (ROS) after 24 h of incubation, but it was not statistically significant compared with untreated cells. However, HeLa, MDA-MB-231, and MCF7 cells treated with the maximal IC of AgNPs induced the formation of ROS either at 12 or 24 h of incubation. Genotoxicity achieved by comet assay in HeLa, MDA-MB-231, and MCF7 cells revealed that exposure to IC50 of AgNPs does not induced noticeable DNA damage in the cells. However, the IC of AgNPs provoked severe DNA damage after 12 and 24 h of exposure. We conclude that, Argovit (polyvinylpyrrolidone-coated AgNPs) induce a cytotoxic effect in a time and dose-dependent manner in all the eight cancer cell lines tested. Nevertheless, the genotoxic effect is mainly restricted by the concentration effect. The results contribute to explore new therapeutic applications of AgNPs for malignances in murine models and to study in deep the cytotoxic and genotoxic effects of AgNPs in healthy cells at the surrounding tissue of the neoplasia.
We report on the synthesis of undoped ∼5 μm YSZ-Ni porous thin films prepared by reactive pulsed DC magnetron sputtering at an oblique angle of incidence. Pre-calcination of the amorphous unmodified ...precursor layers followed by reduction produces a film consisting of uniformly distributed tilted columnar aggregates having extensive three-phase boundaries and favorable gas diffusion characteristics. Similarly prepared films doped with 1.2 at.% Au are also porous and contain highly dispersed gold present as Ni-Au alloy particles whose surfaces are strongly enriched with Au. With hydrogen as fuel, the performance of the undoped thin film anodes is comparable to that of 10–20 times thicker typical commercial anodes. With a 1:1 steam/carbon feed, the un-doped anode cell current rapidly falls to zero after 60 h. In striking contrast, the initial performance of the Au-doped anode is much higher and remains unaffected after 170 h. Under deliberately harsh conditions the performance of the Au-doped anodes decreases progressively, almost certainly due to carbon deposition. Even so, the cell maintains some activity after 3 days operation in dramatic contrast with the un-doped anode, which stops working after only three hours of use. The implications and possible practical application of these findings are discussed.
•Magnetron sputtering is very effective for fabrication of Ni-YSZ thin film anodes.•Films deposited at oblique angles have enhanced porosity compared to typical cermets.•They possess an extensive three phase boundary and thus high electrical conductivity.•Addition of Au greatly increases resistance to poisoning by carbon deposition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
IMPORTANCE: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States, accounting for 1 of every 3 deaths among adults. OBJECTIVE: To update the 2008 US ...Preventive Services Task Force (USPSTF) recommendation on screening for lipid disorders in adults. EVIDENCE REVIEW: The USPSTF reviewed the evidence on the benefits and harms of screening for and treatment of dyslipidemia in adults 21 years and older; the benefits and harms of statin use in reducing CVD events and mortality in adults without a history of CVD events; whether the benefits of statin use vary by subgroup, clinical characteristics, or dosage; and the benefits of various treatment strategies in adults 40 years and older without a history of CVD events. CONCLUSIONS AND RECOMMENDATIONS: The USPSTF recommends initiating use of low- to moderate-dose statins in adults aged 40 to 75 years without a history of CVD who have 1 or more CVD risk factors (dyslipidemia, diabetes, hypertension, or smoking) and a calculated 10-year CVD event risk of 10% or greater (B recommendation). The USPSTF recommends that clinicians selectively offer low- to moderate-dose statins to adults aged 40 to 75 years without a history of CVD who have 1 or more CVD risk factors and a calculated 10-year CVD event risk of 7.5% to 10% (C recommendation). The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of initiating statin use in adults 76 years and older (I statement).
Brightness variations due to dark spots on the stellar surface encode information about stellar surface rotation and magnetic activity. In this work, we analyze the Kepler long-cadence data of 26,521 ...main-sequence stars of spectral types M and K in order to measure their surface rotation and photometric activity level. Rotation-period estimates are obtained by the combination of a wavelet analysis and autocorrelation function of the light curves. Reliable rotation estimates are determined by comparing the results from the different rotation diagnostics and four data sets. We also measure the photometric activity proxy using the amplitude of the flux variations on an appropriate timescale. We report rotation periods and photometric activity proxies for about 60% of the sample, including 4431 targets for which McQuillan et al. did not report a rotation period. For the common targets with rotation estimates in this study and in McQuillan et al., our rotation periods agree within 99%. In this work, we also identify potential polluters, such as misclassified red giants and classical pulsator candidates. Within the parameter range we study, there is a mild tendency for hotter stars to have shorter rotation periods. The photometric activity proxy spans a wider range of values with increasing effective temperature. The rotation period and photometric activity proxy are also related, with being larger for fast rotators. Similar to McQuillan et al., we find a bimodal distribution of rotation periods.
While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) ...with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance.
BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs).
Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months interquartile range (IQR): 26.5-37.6 months and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination 15.4 months; 95% confidence interval (CI) 9.2-18.0 months and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), hazard ratio (HR) = 0.96; 95% CI 0.68-1.37. Median OS was 24.0 months (95% CI 17.8-32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade ≥3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively.
No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade ≥3 TRAEs were more common in patients on combination.
•A randomised trial comparing bevacizumab plus osimertinib versus osimertinib alone in EGFR-mutant NSCLC with T790M mutations.•The primary endpoint was investigator-assessed PFS.•No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone.•TRAEs of grade ≥3 were more common in patients on combination than osimertinib alone.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Probiotics, prebiotics and synbiotics have been suggested as dietary strategies to improve intestinal barrier function. This study aimed to assess the effect of two weeks synbiotic supplementation on ...intestinal permeability under basal and stressed conditions. Secondary aims were the assessment of two weeks synbiotic supplementation on systemic immune function and gastrointestinal symptoms including defecation pattern.
Twenty healthy adults completed a double-blind, controlled, randomized, parallel design study.
Groups either received synbiotic (1.5 × 1010 CFU Ecologic® 825 + 10 g fructo-oligosaccharides (FOS P6) per day) or control supplements for two weeks.
Intestinal segment specific permeability was assessed non-invasively by oral administration of multiple sugar probes and, subsequently, assessing the excretion of these probes in urine. This test was conducted at baseline and at the end of intervention, in the absence and in the presence of an indomethacin challenge. Indomethacin was applied to induce a compromised gut state. Plasma zonulin, cytokines and chemokines were measured at baseline and at the end of intervention. Gastrointestinal symptoms and stool frequency were recorded at baseline and daily during intervention.
Significantly more male subjects were in the synbiotic group compared to the control group (P = 0.025). Indomethacin significantly increased urinary lactulose/rhamnose ratio versus without indomethacin, both in the control group (P = 0.005) and in the synbiotic group (P = 0.017). Urinary sugar recoveries and ratios, plasma levels of zonulin, cytokines and chemokines, and gastrointestinal symptom scores were not significantly different after control or synbiotic intervention. Stool frequency within the synbiotic group was significantly increased during synbiotic intervention compared to baseline (P = 0.039) and higher compared to control intervention (P = 0.045).
Two weeks Ecologic® 825/FOS P6 supplementation increased stool frequency, but did not affect intestinal permeability neither under basal nor under indomethacin-induced stressed conditions, immune function or gastrointestinal symptoms in healthy adults.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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