Abstract
Front-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) therapy is the standard of care for lung cancer patients with sensitising EGFR mutations (exon 19 deletion or ...L858R mutation). Several phase III studies have demonstrated the superiority of gefitinib, erlotinib (first generation of TKIs) or afatinib (second generation) to chemotherapy in progression-free survival and response rates. Drug-related toxicities, such as diarrhoea, acneiform skin rash, mucositis, and paronychia, are frequently encountered in patients who receive EGFR TKIs. Other rare side-effects, such as hepatic impairment and interstitial lung disease, should be identified early and managed carefully. Patients with uncommon EGFR mutations, such as G719X, S768I, and L861Q, may require special selection of EGFR TKIs. The combination of erlotinib plus bevacizumab has been accepted in certain parts of the world as an alternative front-line treatment. This review article summarizes the studies leading to the establishment of EGFR TKIs in EGFR-mutant lung cancer patients. The side-effect profiles of the current EGFR TKIs in these large trials are listed, and the management of uncommon EGFR mutations is discussed. Finally, the potential role of combination front-line treatment is discussed.
Interstellar dust (ISD) is the condensed phase of the interstellar medium. In situ data from the Cosmic Dust Analyzer on board the Cassini spacecraft reveal that the Saturnian system is passed by ISD ...grains from our immediate interstellar neighborhood, the local interstellar cloud. We determine the mass distribution of 36 interstellar grains, their elemental composition, and a lower limit for the ISD flux at Saturn. Mass spectra and grain dynamics suggest the presence of magnesium-rich grains of silicate and oxide composition, partly with iron inclusions. Major rock-forming elements (magnesium, silicon, iron, and calcium) are present in cosmic abundances, with only small grain-to-grain variations, but sulfur and carbon are depleted. The ISD grains in the solar neighborhood appear to be homogenized, likely by repeated processing in the interstellar medium.
Summary
Tranexamic acid is an effective treatment to reduce blood loss. We performed a retrospective observational study to evaluate safety in unilateral total knee arthroplasty. We utilised Taiwan's ...national health insurance database to identify relevant patients and to retrieve information on peri‐operative blood transfusions and tranexamic acid administration within 60 days of follow‐up. We examined changes in the rate of transfusions and adverse events with respect to tranexamic acid administration using logistic regression. We observed a total of 226,719 knee arthroplasty cases during 2010–2019. Transfusion and tranexamic acid administration rates were 38.9% (88,258) and 42.9% (97,237), respectively. Tranexamic acid was associated with a 50% decrease in blood transfusions (RR: 0.50, 95%CI: 0.48–0.51). After propensity‐score matching, tranexamic acid was not associated with pulmonary embolism; deep vein thromboembolism; artery vein thromboembolism; acute myocardial infarction; ischaemic stroke; or in‐hospital mortality, but was significantly associated with acute kidney injury. Patients with existing chronic kidney disease suffered a high absolute risk of kidney injury irrespective of tranexamic acid administration (832 per 10,000, 95%CI 797–869). Tranexamic acid was also associated with surgical site infection. There was strong interaction between blood transfusion; tranexamic aid administration; and development of surgical site infection. In conclusion, tranexamic acid use was associated with decreased blood transfusion and was not associated with thromboembolic events. However, careful consideration is required before use in patients with pre‐existing renal disease. Further, our observed interaction between patients given tranexamic acid who subsequently require transfusion requires careful consideration with respect to enhanced prophylaxis against surgical site infection.
The unique characteristic of head and neck squamous cell carcinoma (HNSCC) is that local invasion rather than distant metastasis is the major route for dissemination. Therefore, targeting the locally ...invasive cancer cells is more important than preventing systemic metastasis in HNSCC and other invasive-predominant cancers. We previously demonstrate a specific mechanism for HNSCC local invasion: the epithelial-mesenchymal transition (EMT) regulator Twist1 represses microRNA let-7i expression, leading to the activation of the small GTPase Rac1 and engendering the mesenchymal-mode movement in three-dimensional (3D) culture. However, targeting the EMT regulator is relatively difficult because of its transcription factor nature and the strategy for confining HNSCC invasion to facilitate local treatment is limited. Imipramine blue (IB) is a newly identified anti-invasive compound that effectively inhibits glioma invasion. Here we demonstrate that in HNSCC cells, a noncytotoxic dose of IB represses mesenchymal-mode migration in two-and-a-half-dimensional/3D culture system. IB suppresses EMT and stemness of HNSCC cells through inhibition of Twist1-mediated let-7i downregulation and Rac1 activation and the EMT signalling. Mechanistically, IB inhibits reactive oxygen species-induced nuclear factor-κB pathway activation. Importantly, IB promotes degradation of the EMT inducer Twist1 by enhancing F-box and leucine-rich repeat protein 14 (FBXL14)-mediated polyubiquitination of Twist1. Together, this study demonstrates the potent anti-invasion and EMT-inhibition effect of IB, suggesting the potential of IB in treating local invasion-predominant cancers.
Background
Use of polysomnography (PSG) is the gold standard of diagnosis and measurement of treatment effectiveness for paediatric obstructive sleep apnoea (OSA). Although adenotonsillectomy (T&A) ...is effective in diminishing the apnoea–hypopnoea index (AHI), a meta‐analysis of postoperative changes for all other PSG parameters and outcome comparisons between obese and non‐obese children following T&A have never been conducted.
Objective of review
To comprehensively review polysomnographic findings after surgery for obese and non‐obese children with OSA.
Search strategy
Study protocol was registered on PROSPERO (CRD42013004737). Two authors independently searched databases including PubMed, MEDLINE, EMBASE and Cochrane Review from January 1997 to July 2014. The keywords used included the following: sleep apnea, OSA, sleep apnea syndromes, tonsillectomy, adenoidectomy, infant, child, adolescent, and Humans.
Evaluation method
A comprehensive systematic review and meta‐analysis for literature for OSA children treated by T&A with polysomnography data. Random‐effects model was applied to determine postoperative sleep parameter changes and the surgical success rate between obese and non‐obese groups. The quality of studies was assessed using the Newcastle–Ottawa Scale.
Results
In total, 51 studies with 3413 subjects were enrolled. After surgery, sleep architecture was altered by a significant decrease in sleep stage 1, and an increase in slow‐wave sleep and the rapid eye movement stage, and enhanced sleep efficiency. The mean difference between pre‐ and postoperative was a significant reduction of 12.4 event/h in AHI, along with a reduction of obstructive index, hypopnoea index, central index and arousal index. Mean and minimum oxygen saturation increased significantly after surgery. The overall success rate was 51% for postoperative AHI <1 (obese versus non‐obese versus combined, 34% versus 49% versus 56%), and 81% for AHI <5 (obese versus non‐obese versus combined, 61% versus 87% versus 84%). Meta‐regression analyses demonstrate that postoperative AHI was positively correlated with AHI and body mass index z score before surgery.
Conclusions
Meta‐analysis of current literature shows T&A offers prominent improvement in a variety of sleep parameters. Improvements in non‐obese children exceeded those for obese children. Postoperative residual OSA remained in roughly half of the children, especially those with severe disease and obesity, making additional treatment strategies and/or long‐term follow‐up highly desirable.
We report on laboratory experiments to shed light on dust charging and transport that have been suggested to explain a variety of unusual phenomena on the surfaces of airless planetary bodies. We ...have recorded micron‐sized insulating dust particles jumping to several centimeters high with an initial speed of ~0.6 m/s under ultraviolet illumination or exposure to plasmas, resulting in an equivalent height of ~0.11 m on the lunar surface that is comparable to the height of the so‐called lunar horizon glow. Lofted large aggregates and surface mobilization are related to many space observations. We experimentally show that the emission and re‐absorption of photoelectron and/or secondary electron at the walls of microcavities formed between neighboring dust particles below the surface are responsible for generating unexpectedly large negative charges and intense particle‐particle repulsive forces to mobilize and lift off dust particles.
Key Points
Micron‐sized insulating dust particles are recorded to hop and mobilize under UV illumination or exposure to plasmas in laboratory
The emission and re‐absorption of photoelectron/secondary electron at dusty surfaces generate unexpectedly large charges and repulsive forces
Electrostatic processes are efficient on the surfaces of all airless bodies in space to redistribute fine dust particles
Abstract
In this first paper in the SUPER GOODS series on powerfully star-forming galaxies in the two GOODS fields, we present a deep SCUBA-2 survey of the GOODS-N at both 850 and 450
μ
m (central ...rms noise of 0.28 mJy and 2.6 mJy, respectively). In the central region, the 850
μ
m observations cover the GOODS-N to near the confusion limit of ∼1.65 mJy, while over a wider 450 arcmin
2
region—well complemented by
Herschel
far-infrared imaging—they have a median
limit of 3.5 mJy. We present
catalogs of 186 850
μ
m and 31 450
μ
m selected sources. We use interferometric observations from the Submillimeter Array (SMA) and the Karl G. Jansky Very Large Array (VLA) to obtain precise positions for 114 SCUBA-2 sources (28 from the SMA, all of which are also VLA sources). We present new spectroscopic redshifts and include all existing spectroscopic or photometric redshifts. We also compare redshifts estimated using the 20 cm/850
μ
m and the 250 cm/850
μ
m flux ratios. We show that the redshift distribution increases with increasing flux, and we parameterize the dependence. We compute the star formation history and the star formation rate (SFR) density distribution functions in various redshift intervals, finding that they reach a peak at
before dropping to higher redshifts. We show that the number density per unit volume of
galaxies measured from the SCUBA-2 sample does not change much relative to that of lower SFR galaxies from UV selected samples over
, suggesting that, apart from changes in the normalization, the shape in the number density as a function of SFR is invariant over this redshift interval.
The associated risk of phthalate exposure, both parent compounds in the home and their metabolites in urine, to childhood allergic and respiratory morbidity, after adjusting for exposures of indoor ...pollutants, especially bioaerosols, was comprehensively assessed. Levels of five phthalates in settled dust from the homes of 101 children (3–9 years old) were measured, along with their corresponding urinary metabolites. Other environmental risk factors, including indoor CO2, PM2.5, formaldehyde, 1,3‐β‐d‐glucan, endotoxin, allergen and fungal levels, were concomitantly examined. Subject’s health status was verified by pediatricians, and parents recorded observed daily symptoms of their children for the week that the home investigation visit took place. Significantly increased level of benzylbutyl phthalate, in settled dust, was associated with test case subjects (allergic or asthmatic children). Higher levels of dibutyl phthalate and its metabolites, mono‐n‐butyl phthalate, and mono‐2‐ethylhexyl phthalate were found to be the potential risk factors for the health outcomes of interest. Similarly, indoor fungal exposure remained a significant risk factor, especially for reported respiratory symptoms. The relative contribution from exposure to phthalates and indoor biocontaminants in childhood allergic and respiratory morbidity is, for the first time, quantitatively assessed and characterized.
Practical Implications
For asthmatic and allergic children living in subtropical and highly developed environments like homes in Taiwan, controlling environmental exposure of phthalates may be viewed as equally important as avoiding indoor microbial burdens, for the management of allergy‐related diseases. It is also recognized that multidisciplinary efforts will be critical in realizing the true underlying mechanisms associated with these observations.
The sizes of Saturn's ring particles range from meters (boulders) to nanometers (dust). Determination of the rings' ages depends on loss processes, including the transport of dust into Saturn's ...atmosphere. During the Grand Finale orbits of the Cassini spacecraft, its instruments measured tiny dust grains that compose the innermost D-ring of Saturn. The nanometer-sized dust experiences collisions with exospheric (upper atmosphere) hydrogen and molecular hydrogen, which forces it to fall from the ring into the ionosphere and lower atmosphere. We used the Magnetospheric Imaging Instrument to detect and characterize this dust transport and also found that diffusion dominates above and near the altitude of peak ionospheric density. This mechanism results in a mass deposition into the equatorial atmosphere of ~5 kilograms per second, constraining the age of the D-ring.
Current methods of chemical vapour deposition (CVD) of graphene on copper are complicated by multiple processing steps and by high temperatures required in both preparing the copper and inducing ...subsequent film growth. Here we demonstrate a plasma-enhanced CVD chemistry that enables the entire process to take place in a single step, at reduced temperatures (<420 °C), and in a matter of minutes. Growth on copper foils is found to nucleate from arrays of well-aligned domains, and the ensuing films possess sub-nanometre smoothness, excellent crystalline quality, low strain, few defects and room-temperature electrical mobility up to (6.0±1.0) × 10(4) cm(2) V(-1) s(-1), better than that of large, single-crystalline graphene derived from thermal CVD growth. These results indicate that elevated temperatures and crystalline substrates are not necessary for synthesizing high-quality graphene.
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