Development of the Soft X-ray AGM-AGS RIXS beamline at the Taiwan Photon Source.

We report on the development of a high-resolution and highly efficient beamline for soft X-ray resonant inelastic X-ray scattering (RIXS) located at the Taiwan Photon Source. This beamline adopts an optical design that uses an active grating monochromator (AGM) and an active grating spectrometer (AGS) to implement the energy compensation principle of grating dispersion. Active gratings are utilized to diminish defocus, coma and higher-order aberrations, as well as to decrease the slope errors caused by thermal deformation and optical polishing. The AGS is mounted on a rotatable granite platform to enable momentum-resolved RIXS measurements with scattering angles over a wide range. Several high-precision instruments developed in-house for this beamline are described briefly. The best energy resolution obtained from this AGM-AGS beamline was 12.4 meV at 530 eV, achieving a resolving power of 4.2 × 104, while the bandwidth of the incident soft X-rays was kept at 0.5 eV. To demonstrate the scientific impact of high-resolution RIXS, we present an example of momentum-resolved RIXS measurements on a high-temperature superconducting cuprate, i.e. La2-xSrxCuO4. The measurements reveal the A1g buckling phonons in superconducting cuprates, opening a new opportunity to investigate the coupling between these phonons and charge-density waves.

Population-based study of environmental lead exposure and hearing loss: a systematic review and meta-analysis.

OBJECTIVES: Multiple studies suggest that there is an association between environmental lead exposure and hearing loss. However, the results of studies exploring the relationship between lead exposure and the occurrence of hearing loss are inconsistent. To clarify this issue, we conducted a meta-analysis to determine the association between lead exposure and hearing loss. STUDY DESIGN: This study was a meta-analysis. METHODS: A comprehensive literature search was performed using PubMed, Web of Knowledge, Elsevier ScienceDirect, and Springer databases. Eight articles involving 10 studies were included, and a random effect model was used for the meta-analysis. The Agency for Healthcare Research and Quality was used for judging the quality of the articles. RESULTS: Environmental lead exposure was significantly and substantially associated with hearing loss (combined odds ratio [OR] 1.42; 95% confidence interval [CI] 1.22-1.67) with mild heterogeneity (I2 = 47.0%, P = 0.049). Subgroup and sensitivity analyses confirmed the results; however, publication bias was evident. After the 'fill and trim' method, the recalculated OR was 1.36 (95% CI 1.12-1.64). CONCLUSIONS: The results of this study suggest an association between lead exposure and hearing loss. Exposure to a high concentration of lead was positively proportional to the risk of hearing loss. To eliminate the effects of other confounding factors, larger prospective cohort studies are required to further elucidate the relationship between lead exposure and hearing loss.

Downregulation of miR-506-3p Facilitates EGFR-TKI Resistance through Induction of Sonic Hedgehog Signaling in Non-Small-Cell Lung Cancer Cell Lines.

Non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation eventually develop resistance to EGFR-targeted tyrosine kinase inhibitors (TKIs). Treatment resistance remains the primary obstacle to the successful treatment of NSCLC. Although drug resistance mechanisms have been studied extensively in NSCLC, the regulation of these mechanisms has not been completely understood. Recently, increasing numbers of microRNAs (miRNAs) are implicated in EGFR-TKI resistance, indicating that miRNAs may serve as novel targets and may hold promise as predictive biomarkers for anti-EGFR therapy. MicroRNA-506 (miR-506) has been identified as a tumor suppressor in many cancers, including lung cancer; however, the role of miR-506 in lung cancer chemoresistance has not yet been addressed. Here we report that miR-506-3p expression was markedly reduced in erlotinib-resistant (ER) cells. We identified Sonic Hedgehog (SHH) as a novel target of miR-506-3p, aberrantly activated in ER cells. The ectopic overexpression of miR-506-3p in ER cells downregulates SHH signaling, increases E-cadherin expression, and inhibits the expression of vimentin, thus counteracting the epithelial-mesenchymal transition (EMT)-mediated chemoresistance. Our results advanced our understanding of the molecular mechanisms underlying EGFR-TKI resistance and indicated that the miR-506/SHH axis might represent a novel therapeutic target for future EGFR mutated lung cancer treatment.

Hypereosinophilia (HE) in acute myeloid leukemia (AML) with normal karyotype: A report of two cases.

We present two rare cases of hypereosinophilia (HE) in acute myeloid leukemia with normal karyotype (NK-AML) at diagnosis. The first case is a 29-year-old female who presented with HE. On evaluation, she was found to have NK-AML. She failed to achieve complete remission (CR) after the first induction therapy with standard idarubicin and cytarabine (IA). She achieved CR after two cycles of reinduction chemotherapy with cytarabine, aclarubicin, and granulocyte colony-stimulating factor (G-CSF) (CAG) but had early relapsed. Reinduction chemotherapy with fludarabine, Ara-C, and G-CSF (FLAG) led to her second remission, followed by unrelated umbilical cord hematopoietic stem cell transplantation (HSCT). Unfortunately, she died of thrombotic thrombocytopenic purpura. The second case is a 23-year-old male who was diagnosed as NK-AML with HE. IA regimen was successively used in two cycles treatment achieving CR. He underwent haploidentical HSCT but had a relapse after 17 months of sustained remission and died 4 months later. The presence of HE may be a poor prognostic feature in NK-AML.

[Coexisting mutations in NPM1-mutated elderly adults with acute myeloid leukemia].

Objective: To explore the coexisting mutations in NPM1 mutated elderly patients with acute myeloid leukemia(AML). Methods: The clinical data of 152 elderly adults(aged≥60 years) and 49 young adults(aged 18-45 years) with AML between June 2013 and December 2018 in outpatient and hospitalized patients of Changzhou Second People's Hospital and Wuxi Second People's Hospital were retrospectively analyzed. A total of 51 gene mutations were detected using targeted next-generation sequencing (NGS) and sanger sequencing. The general clinical characteristics, the occurrence of coexistence gene mutations, the correlation between coexistence gene mutations and some clinical parameters, and the initial induction remission rate between elderly and young adult AML patients with NPM1 mutations were analyzed and compared. Results: NPM1 mutations were detected in 46 of 152 elderly AML patients. Thirty eight patients (82.6%) with NPM1 mutations carried other gene mutations at the same time, among whom 8 patients (17.4%) carried NPM1 mutations alone, while 14(30.4%) carried 2, 16 (34.8%) carried 3, and 8 (17.4%) carried ≥ 4 mutations. NPM1 mutations frequently co-occurred with FLT3-ITD15 cases (32.6%) , DNMT3A10 (21.7%) , TET26 (13.4%) and FLT3-TKD5 (10.9%) . Compared with young adults with NPM1 mutations, elderly patients had higher TP53, FLT3-TKD rates, lower incidence of DNMT3A, RAS mutation (all P<0.05) and lower coexistence rate of 4 gene mutations (P=0.002).The presence of ≥ 4 mutations was found to be significantly associated with higher white blood level than those in patients with single, double and 3 mutations coexisted in elderly adults AML patients(all P<0.05). With the increase of the amount of mutations, the complete remission(CR) rate decreased gradually after the initial induction. Patients who carried 3 or more mutations showed a lower CR rate than those with single gene mutations (all P<0.05) . Patients who carried>4 genes also showed a significantly lower CR rate than those with double gene mutations (P=0.031). Patients with FLT3-ITD mutations exhibited higher white blood level and lower CR rate than that in nonmutant type group (all P<0.05). The CR rate of patients with DNMT3A mutation was also significantly lower than that with nonmutant type (P=0.033). However, patients with FLT3-TKD mutations showed a higher platelet level than that with nonmutant type (P=0.019). There was no significant difference in CR rate and peripheral blood cell level between TET2 mutated and nonmutant type. Conclusion: NPM1 mutated elderly patients with AML commonly show additional mutations, and the amount and type of coexisting mutations have an influence on the clinical features and CR rate of elderly patients with AML.

[Analysis of sleep quality of a prison police].

Objective: To investigate the sleep quality of prison policemen and explore its influencing factors, so as to provide reference for improving the sleep quality of prison policemen. Methods: In August 2013, 177 policemen in a prison were selected by cluster sampling. The sleep quality of 177 prison policemen was investigated by Pittsburgh Sleep Quality Index Scale and General Situation Questionnaire, and the influencing factors were analyzed. Results: The PSQI scores of 177 prison policemen were (7.47+3.80). There were significant differences between the PSQI scores of prison policemen and the normal adult norm (P<0.05). According to the standard of poor sleep quality, 84 prison policemen (47.46%) had poor sleep quality, and the prison policemen scored higher on daytime dysfunction, subjective sleep quality, sleeping time and sleeping time components. Single factor t test and single factor variance analysis showed that there were significant differences in sleep quality among prison policemen in gender, age, educational level and job classification (P <0.05). The results of multiple stepwise regression analysis showed that gender, age and job classification entered the regression equation with PSQI total score as dependent variable (ß=0.167, 0.270, 0.222) . Conclusion: The sleep quality of prison policemen is worse than that of normal adults, and is affected by gender, age, job classification and other factors, which should be paid attention to by prison administrators.

Alpha-enolase regulates hepatitis B virus replication through suppression of the interferon signalling pathway.

Persistent chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of HBV-related diseases. The molecular mechanisms that underlie HBV infection and associated carcinogenesis are not fully understood. The aim of this study was to explore the role of ENO1 in HBV replication processes. Here, we examined ENO1 expression levels in HBV-infected and non-HBV-infected liver tissues and cells by Western blot analysis, real-time PCR and immunohistochemistry. In addition, HBsAg and HBeAg in the media of transfected HepG2.2.15 cells were detected using an electrochemical luminescence analyser within 48 hours after ENO1-specific siRNA transfection. The expression levels of HBV DNA, type I interferon and 5 downstream IFN-stimulated genes in HepG2.2.15 cells were examined using real-time PCR. We found ENO1 expression was upregulated in the HBV-infected liver tissues and cells. Silencing of ENO1 resulted in a significant reduction in HBV replication, and this siRNA-mediated reaction also caused the upregulation of expression of type I interferon and downstream IFN-stimulated genes. Therefore, we come to the conclusion ENO1 is involved in HBV replication. It is therefore likely that HBV replication is enhanced following suppression of the IFN signalling pathway. However, the mechanisms that underpin ENO1-mediated modulation of the IFN signalling pathway remain to be elucidated.

Simultaneous biodegradation of three mononitrophenol isomers by a tailor-made microbial consortium immobilized in sequential batch reactors.

The ortho-nitrophenol (ONP)-utilizing Alcaligenes sp. strain NyZ215, meta-nitrophenol (MNP)-utilizing Cupriavidus necator JMP134 and para-nitrophenol (PNP)-utilizing Pseudomonas sp. strain WBC-3 were assembled as a consortium to degrade three nitrophenol isomers in sequential batch reactors. Pilot test was conducted in flasks to demonstrate that a mixture of three mononitrophenols at 0·5 mol l-1 each could be mineralized by this microbial consortium within 84 h. Interestingly, neither ONP nor MNP was degraded until PNP was almost consumed by strain WBC-3. By immobilizing this consortium into polyurethane cubes, all three mononitrophenols were continuously degraded in lab-scale sequential reactors for six batch cycles over 18 days. Total concentrations of ONP, MMP and PNP that were degraded were 2·8, 1·5 and 2·3 mol l-1 during this time course respectively. Quantitative real-time PCR analysis showed that each member in the microbial consortium was relatively stable during the entire degradation process. This study provides a novel approach to treat polluted water, particularly with a mixture of co-existing isomers. SIGNIFICANCE AND IMPACT OF THE STUDY: Nitroaromatic compounds are readily spread in the environment and pose great potential toxicity concerns. Here, we report the simultaneous degradation of three isomers of mononitrophenol in a single system by employing a consortium of three bacteria, both in flasks and lab-scale sequential batch reactors. The results demonstrate that simultaneous biodegradation of three mononitrophenol isomers can be achieved by a tailor-made microbial consortium immobilized in sequential batch reactors, providing a pilot study for a novel approach for the bioremediation of mixed pollutants, especially isomers present in wastewater.

The Role of Compounds Derived from Natural Supplement as Anticancer Agents in Renal Cell Carcinoma: A Review.

Renal Cell Carcinoma (RCC) is the most prominent kidney cancer derived from renal tubules and accounts for roughly 85% of all malignant kidney cancer. Every year, over 60,000 new cases are registered, and about 14,000 people die from RCC. The incidence of this has been increasing significantly in the U.S. and other countries. An increased understanding of molecular biology and the genomics of RCC has uncovered several signaling pathways involved in the progression of this cancer. Significant advances in the treatment of RCC have been reported from agents approved by the Food and Drug Administration (FDA) that target these pathways. These agents have become drugs of choice because they demonstrate clinical benefit and increased survival in patients with metastatic disease. However, the patients eventually relapse and develop resistance to these drugs. To improve outcomes and seek approaches for producing long-term durable remission, the search for more effective therapies and preventative strategies are warranted. Treatment of RCC using natural products is one of these strategies to reduce the incidence. However, recent studies have focused on these chemoprevention agents as anti-cancer therapies given they can inhibit tumor cell grow and lack the severe side effects common to synthetic compounds. This review elaborates on the current understanding of natural products and their mechanisms of action as anti-cancer agents. The present review will provide information for possible use of these products alone or in combination with chemotherapy for the prevention and treatment of RCC.

[A survey of sleep quality of employed nurses in military hospitals].

Objective: To investigate the sleep quality of the employed nurses in three grade A tertiary military hospitals in Beijing, China and its influential factors and to provide a reference for improving the sleep quality of employed nurses. Methods: From January 2014 to January 2017, a questionnaire survey was carried out to investigate the sleep quality of 253 employed nurses in three grade A tertiary military hospitals in Beijing, China using the Pittsburgh Sleep Quality Index (PSQI) and a general status questionnaire. The results were compared with the adult norms to analyze the influential factors for sleep quality of the employed nurses. Results: The global PSQI score of the 253 employed nurses was 7.76 ± 3.53. Their global PSQI score and PSQI component scores were significantly higher than the adults norms (P<0.05) . And 54.94% of the employed nurses had poor sleep quality; they had high scores of daytime dysfunction (1.39±0.83) , sleep latency (1.67±0.94) , sleep quality (1.33±0.88) , and sleep time (1.23±0.78) . The one-way analysis of variance showed that the sleep quality of the employed nurses was associated with nursing age, educational background, professional title, whether to have children, frequency of night shifts, and department (P<0.05) . The multivariate logistic regression analysis showed that the risk factors for sleep quality of the employed nurses were technical secondary school education (OR=4.292) and emergency department and intensive care unit (OR=2.582) ; the protective factors for sleep quality of the employed nurses were outpatient department and assistant department (OR=0.312) , no children (OR=0.318) , and no night shift (OR=0.332) . Conclusion: The employed nurses in military hospitals have poorer sleep quality than the normal adults. The influential factors for sleep quality of employed nurses are educational background, department, whether to have children, and frequency of night shifts.

[Relationship between personality characteristics and turnover intention of medical staff in an infectious disease hospital].

Objective: To investigate the relationship between personality characteristics and turnover intention of the medical staff in an infectious diseases hospital. Methods: Using the cluster sampling method, a total of 366 members of medical staff were selected from different departments in an infectious disease hospital from May to August, 2013. The general information, such as sex, age, education level, and professional title, were collected and they were subjected to a survey using Cattell's 16 Personality Factor Questionnaire and Turnover Intention Scale. The data were subjected to logistic regression analysis. Results: Compared with the Chinese norm, the medical staff in the infectious disease hospital had significantly higher scores of intelligence, stability, bullying, excitability, perseverance, social boldness, fantasy, privateness, independence, and self-discipline and significantly lower scores of gregariousness, sensitivity, suspicion, anxiety, and tension (P<0.05). Of the 366 members of medical staff, 22 (6.01%) had a very low turnover intention, low in 152 (41.53%) , high in 61 (16.67%) , and very high in 131 (35.79%). The logistic regression analysis showed that sensitivity, suspicion, fantasy, privateness, anxiety, openness to change, and independence were the risk factors for turnover intention (P<0.05) . Conclusion: Compared with the Chinese norm, the medical staff in the infectious disease hospital have a better mental quality and a higher turnover intention. The individuals with sensitivity, suspicion, fantasy, and anxiety are prone to having turnover intention.

Renal depletion of myo-inositol is associated with its increased degradation in animal models of metabolic disease.

Renal depletion of myo-inositol (MI) is associated with the pathogenesis of diabetic nephropathy in animal models, but the underlying mechanisms involved are unclear. We hypothesized that MI depletion was due to changes in inositol metabolism and therefore examined the expression of genes regulating de novo biosynthesis, reabsorption, and catabolism of MI. We also extended the analyses from diabetes mellitus to animal models of dietary-induced obesity and hypertension. We found that renal MI depletion was pervasive across these three distinct disease states in the relative order: hypertension (-51%)>diabetes mellitus (-35%)>dietary-induced obesity (-19%). In 4-wk diabetic kidneys and in kidneys derived from insulin-resistant and hypertensive rats, MI depletion was correlated with activity of the MI-degrading enzyme myo-inositol oxygenase (MIOX). By contrast, there was decreased MIOX expression in 8-wk diabetic kidneys. Immunohistochemistry localized the MI-degrading pathway comprising MIOX and the glucuronate-xylulose (GX) pathway to the proximal tubules within the renal cortex. These findings indicate that MI depletion could reflect increased catabolism through MIOX and the GX pathway and implicate a common pathological mechanism contributing to renal oxidative stress in metabolic disease.

Overexpression of the methanol dehydrogenase gene mxaF in Methylobacterium sp. MB200 enhances L-serine production.

UNLABELLED: Increase in L-serine production is of interest for industry. Here, we describe a metabolic engineering approach to increase the production of L-serine in a methylotrophic bacterium. mxaF, the gene encoding the large subunit of a methanol dehydrogenase, was cloned from Methylobacterium sp. MB200 through transposon mutagenesis. Deletion of mxaF gene prevented the strain to grow on methanol, suggesting that mxaF is involved in methanol metabolism. Overexpression of mxaF gene in the strain MB200 resulted in a fivefold increase in methanol dehydrogenase activity compared to the wild-type. Resting cell assays showed that the recombinant strain accumulated 6·6 mg ml(-1) L-serine in 72 h with 30 mg ml(-1) wet cells from 50 mg ml(-1) glycine and 50 mg ml(-1) methanol, representing a 1·5-fold increment for L-serine production in contrast to the wild-type strain. These results demonstrate that the potential for improving the production of L-serine can be achieved by overexpressing mxaF gene in methylotrophic bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: The amount of L-serine produced each year worldwide is relatively small compared with the amounts of the other amino acids and hence it is in great demand. Here, we describe a metabolic engineering approach to increase the production of L-serine in a methylotrophic bacterium Methylobacterium sp. MB200. The result demonstrates that raising the output of L-serine can be achieved by overexpressing mxaF gene in methylotrophic bacteria.

Effects of Gender Difference and Caffeine Supplementation on Anaerobic Muscle Performance.

The primary purpose of this study was to investigate the effects of gender difference and caffeine supplementation to maximal voluntary isometric contractions (MVIC) and submaximal voluntary isometric contractions (T(lim)). 10 male (age: 20.10 ± 2.18 years, BMI: 22.23±1.96 kg/m(2)) and 10 female (age: 19.90±0.99 years, BMI: 21.76±2.65 kg/m(2)) elite collegiate athletes were recruited. Subjects ingested caffeine (6 mg/kg) or a placebo in a randomized, double-blind, placebo-control, and counter-balanced fashion. MVIC and T(lim) were measured after supplementations. T(lim) result was calculated based on the time to exhaustion of isometric contraction with 50% MVIC. Fatigue index (FI%) referred to the MVIC tested 20 s after the cessation of T(lim) test, and was indexed by the percentage of MVIC decline. No significant interaction effect was found between the gender factor and the supplementation factor for all dependent variables. Compared to the placebo, caffeine supplementation significantly increased MVIC (5.9%) and T(lim) (15.5%) (p<0.05) whereas it had no significant effect on FI%. This study demonstrates that caffeine supplementation at a 6 mg/kg dosage facilitates performances in MVIC and T(lim). The ergogenic effect of caffeine on muscle power and muscle endurance does not show a gender bias.

The distribution of homogeneously grafted nanoparticles in polymer thin films and blends.

Polymer nanocomposites are an important and growing class of materials where nanoparticles are mixed in a polymer matrix. Much of the interest in polymer nanocomposites is derived from the nanoparticles' ability to impart properties to the polymer not commonly found in polymer materials, such as tunable optical, electrical, and mechanical properties. Grafting polymer chains to the surface of a nanoparticle is one of the most common routes towards promoting dispersion of nanoparticles in a polymer matrix. However, we only understand the thermodynamics of grafted nanoparticles in a polymer matrix in the simplest of cases, and this problem is exacerbated by the lack of theoretical and computational tools capable of efficiently predicting the structure of phase separated grafted nanoparticle/polymer blends. In this work, we extend a recently developed field theoretic framework to study the distribution of homogeneously grafted nanoparticles in homopolymer thin films and blends. We demonstrate that our method reproduces trends observed experimentally in homopolymer thin films, and then we examine how the nanoparticle size, grafting density, and the length of the grafted chains relative to the matrix chains affects the distribution of the grafted nanoparticles in phase separated polymer blends. We find that position of the nanoparticles relative to the interface in the blends is sensitive to the brush conformation, even when the nanoparticles are miscible in one of the two homopolymer phases.

Dosimetric and efficiency comparison of high-dose radiotherapy for esophageal cancer: volumetric modulated arc therapy versus fixed-field intensity-modulated radiotherapy.

The aim of this study was to compare high-dose volumetric modulated arc therapy (VMAT) and fixed-field intensity-modulated radiotherapy (ff-IMRT) plans for the treatment of patients with middle-thoracic esophageal cancer. Eight patients with cT2-3N0M0 middle-thoracic esophageal cancer were enrolled. The treatment planning system was the version 9 of the Pinnacle(3) with SmartArc (Philips Healthcare, Fitchburg, WI, USA). VMAT and ff-IMRT treatment plans were generated for each case, and both techniques were used to deliver 50 Gy to the planning target volume (PTV(50)) and then provided a 16-Gy boost (PTV(66)). The VMAT plans provided superior PTV(66) coverage compared with the ff-IMRT plans (P = 0.034), whereas the ff-IMRT plans provided more appropriate dose homogeneity to the PTV(50) (P = 0.017). In the lung, the V(5) and V(10) were lower for the ff-IMRT plans than for the VMAT plans, whereas the V(20) was lower for the VMAT plans. The delivery time was significantly shorter for the VMAT plans than for the ff-IMRT plans (P = 0.012). In addition, the VMAT plans delivered fewer monitor units. The VMAT technique required a shorter planning time than the ff-IMRT technique (3.8 ± 0.8 hours vs. 5.4 ± 0.6 hours, P = 0.011). The major advantages of VMAT plans are higher efficiency and an approximately 50% reduction in delivery time compared with the ff-IMRT plans, with comparable plan quality. Further clinical investigations to evaluate the use of high-dose VMAT for the treatment of esophageal cancer are warranted.

Biomechanical analysis of the longitudinal ligament of upper cervical spine in maintaining atlantoaxial stability.

STUDY DESIGN: In vitro human cadaveric biomechanical study. OBJECTIVES: To investigate the roles of transverse atlantal ligament (TAL) and longitudinal ligament (LL) of the upper cervical spine (UCS) in maintaining atlantoaxial stability. SETTING: China. METHODS: Six intact UCS specimens were harvested and embedded in polymethylmethacrylate. Three-dimensional movements including flexion, extension, right and left lateral bending, and axial rotation, as well as the C1-C2 displacement in flexion (atlantodental interval, ADI), were tested on specimens with the following state sequentially: (1) intact (intact group), (2) TAL transected (TAL group) and (3) TAL and LL disrupted (TAL+LL group) using an electromechanical testing machine. RESULTS: Compared with intact group, the flexion/extension motion range and ADI were significantly higher in TAL group when the loading was 10 N or >100 N. However, no significant differences were detected between the two groups within a range of physiological loading (10-100 N). Similarly, significant differences in right-left lateral bending and axial rotation between TAL and intact groups occurred only when the loading was 150 N. However, when both of the TAL and LL were resected, the atlantoaxial joint showed obvious instability compared with TAL or intact group, which were further demonstrated in the analyses of the three-dimensional movements (significant differences at any loading). CONCLUSION: Within physiological loading range, the LLs have sufficient capacities to maintain the stability of atlantoaxial joint even if there are TAL injuries in atlas fractures.

Evolution of beam distribution in crossing a Walkinshaw resonance.

The third-integer coupling resonance at ν(x)-2ν(z)=ℓ, known as the Walkinshaw resonance, is important in high-power accelerators. We find that, when the betatron tunes ramp through a Walkinshaw resonance the fractional emittance growth (FEG) is a universal function of the effective resonance strength: G(1,-2,ℓ)√[ε(xi)]|Δ(ν(x)-2ν(z))/Δn|(-1/2), where G(1,-2,ℓ) is the resonance strength; ε(xi) and ε(zi) are the initial horizontal and vertical emittances, respectively; and |Δ(ν(x)-2ν(z))/Δn| is the resonance crossing rate per revolution. At large effective resonance strengths, the FEG reaches an asymptotic maximum value (FEG)(max)~2ε(xi)/ε(zi) for ε(xi)>>1/2ε(zi) or ε(zi)/(2ε(xi)) for ε(xi)<<1/2ε(zi). There is little emittance exchange at ε(xi)=1/2ε(z), which can be used to minimize emittance growth in crossing a Walkinshaw resonance.

Computed tomography has low sensitivity for the diagnosis of early colon cancer.

AIM: The accuracy of computed tomography (CT) in detecting local invasion (T status) and nodal metastasis (N status) of colon cancer was determined. METHOD: Data on the preoperative CT scan of 153 lesions from 152 patients with colon cancer were reviewed retrospectively. Evaluation included the T stage and N stage of the TNM system. The results were compared with those obtained by histopathological examination of the resected tumour. RESULTS: Of the 153 tumours, 117 (76.5%) were correctly classified as Stage T1 and T2 (33 tumours) and Stage T3 and T4 (84 tumours) by CT. The sensitivity and specificity were 70.2% and 79.2%, respectively, and the positive and negative predictive values were 85.7% and 60.0%. When analysed according to the individual T stage (Tx/Tis, T1, 2, 3, 4) and N stage (N0, 1, 2), the kappa coefficient with linear weighting was 0.208 (fair agreement) for T stage and 0.154 (slight agreement) for N stage. The estimation of tumour size showed good agreement with histopathology (Spearman correlation coefficient 0.865). CONCLUSION: CT scanning of colonic cancer showed 75% accuracy in identifying T1 and T2 cancers combined, but gave poor agreement between CT and histopathology for individual T stages.

Phase II Randomized Trial of Carboplatin, Pemetrexed, and Bevacizumab With and Without Atezolizumab in Stage IV Nonsquamous Non-Small-Cell Lung Cancer Patients Who Harbor a Sensitizing EGFR Mutation or Have Never Smoked.

INTRODUCTION: Patients with non-small-cell lung cancer (NSCLC) who have never smoked or have tumors with mutations in EGFR generally derive minimal benefit from single-agent PD-1/PD-L1 checkpoint inhibitors. Prior data indicate that adding PD-L1 inhibition to anti-VEGF and cytotoxic chemotherapy may be a promising approach to overcoming immunotherapy resistance in these patients, however prospective validation is needed. This trial in progress (NCT03786692) is evaluating patients with stage IV NSCLC who have never smoked or who have tumors with sensitizing EGFR alterations to determine if a 4-drug combination of atezolizumab, carboplatin, pemetrexed, and bevacizumab can improve outcomes compared to carboplatin, pemetrexed and bevacizumab without atezolizumab. METHODS: This is a randomized, phase II, multicenter study evaluating carboplatin, pemetrexed, bevacizumab with and without atezolizumab in 117 patients with stage IV nonsquamous NSCLC. Randomization is 2 to 1 favoring the atezolizumab containing arm. Eligible patients include: 1) those with tumors with sensitizing EGFR alterations in exons 19 or 21 or 2) patients who have never smoked and have wild-type tumors (ie, no EGFR, ALK or ROS1 alterations). Patients are defined as having never smoked if they have smoked less than 100 cigarettes in a lifetime. Patients with EGFR-mutated tumors must have disease progression or intolerance to prior tyrosine kinase inhibitor (TKI) therapy. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), response rate, duration of response, and time to response. CONCLUSION: This phase II trial is accruing patients at U.S. sites through the National Comprehensive Cancer Network (NCCN). The trial opened in August 2019 and accrual is expected to be completed in the Fall of 2024.