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We have employed hard x-ray photoemission (HAXPES) to study a delta-doped SrTiO3 layer that consisted of a 3-nm thickness of La-doped SrTiO3 with 6% La embedded in a SrTiO3 film. Results are compared to a thick, uniformily doped La:SrTiO3 layer. We find no indication of a band offset for the delta-doped layer, but evidence of the presence of Ti3+ in both the thick sample and the delta-layer, and indications of a density of states increase near the Fermi energy in the delta-doped layer. These results further demonstrate that HAXPES is a powerful tool for the non-destructive investigation of deeply buried doped layers. [ABSTRACT FROM AUTHOR]

Background: We compared clinicopathological characteristics and survival outcomes in immigrant Asians versus USA-born Asians with endometrial cancer. Methods: Data from 2001 through 2009 were abstracted from the Surveillance, Epidemiology, and End Results Program (SEER) database. Chi-squared, Kaplan-Meier estimates, and Cox proportional hazards regression methods were used for statistical analyses. Findings: Of 4834 Asians with endometrial cancer, 1860 (38%) were immigrants from Asian countries. The median age was 56years (range 19-96). Of the immigrants, 51% (n=953) were from the Philippines and Pacific Islands, 19% (350) from China, 13% (235) from southeast Asia, 6% (117) from India, 6% (102) from Korea, and 5% (97) from Japan. In the overall study group, 16% had high disease stage and 21% had high disease grade. 3767 (78%) of patients had endometrioid, 93 (2%) had clear cell, and 285 (6%) had papillary serous histology. Compared with those born in the USA, immigrant Asians were more likely to have higher stage (33% versus 28%, p<0.01) and higher grade disease (24% versus 15%, p<0.01) disease. Immigrant Asians were also more likely to have serous (7.4% versus 5.0% p<0.01) and clear cell histologies (2.2% versus 1.7%, p<0.01). The 5-year disease-specific survival rate for immigrant versus US-born Asians was 66% versus 77% (p<0.01). 5-year survival was 77% for immigrant Asians from the Philippines and Pacific Islands, 74% for those from China, 81% for those from southeast Asia, 68% for those from India, 68% for those from Japan, and 83% for those from Korea (p=0.10). On multivariate analysis, age (hazard ratio [HR] 1.05, confidence interval [CI] 1.04-1.06, p<0.01), lower disease stage (HR 0.15, CI 0.12-0.19, p<0.01), and lower disease grade (HR 0.44, CI 0.35-0.55, p<0.01) were important predictors of survival. After adjusting for these factors, immigration status no longer predicted survival. Interpretation: Immigrant Asians with endometrial cancer have poorer survival compared with their US-born counterparts. This may be attributed to a higher proportion of advanced stage, poor histologic subtypes, and higher grade of disease. [ABSTRACT FROM AUTHOR]

Background: We investigated type I endometrioid uterine cancer in US-born Asians versus immigrant Asians. Methods: Data was obtained from the National Cancer Institute from 2001 to 2009. Chi squared, t-test, and binomial regression methods were used for statistical analyses. Findings: Of 4834 Asians with uterine cancer, 62% were born in the USA and 38% were immigrants. 2972 (61%) had type I uterine cancer (grade 1 or 2, endometrioid histology) and the remaining women had type II disease. Compared with patients with type II disease (grade 3, clear cell and serous histology), type I patients were younger (age 55 versus 59years; p<0.01) and a higher proportion had lower-stage disease (90% versus 71%; p<0.01). US-born Asians also had a significantly higher proportion of type I uterine cancers than immigrant Asians (65% versus 56%;p<0.01). Among immigrant Asians, the proportion with type I cancers was lowest in Japanese followed by Chinese and Filipino women (48% versus 52% versus 58%; p<0.01). The 5-year disease-specific survivals of US-born Asians versus immigrant Asians with type I cancer was 92% for both groups. Over three time periods (2001-2003, 2004-2006, and 2007-2009), there was an increase in type I uterine cancers among US-born Asians (61% to 65% to 68%; p<0.01). Interpretation: US-born Asians are more likely to be diagnosed with type I uterine cancer than immigrant Asians. [ABSTRACT FROM AUTHOR]

Aims: To assess the dapagliflozin exposure-response relationship in Japanese and non-Japanese patients with type 1 diabetes mellitus (T1DM) and investigate if a dose adjustment is required in Japanese patients., Materials and Methods: Data from two clinical studies were used to develop a non-linear mixed effects model describing the relationship between dapagliflozin exposure (area under the concentration curve) and response (24-hour urinary glucose excretion [UGE]) in Japanese and non-Japanese patients with T1DM. The effects of patient-level characteristics (covariates; identified using a stepwise procedure) on response was also assessed. Simulations were performed using median-normalized covariate values., Results: Data from 84 patients were included. Average self-monitored blood glucose (SMBG) at day 7, change from baseline in total insulin dose at day 7, and baseline estimated glomerular filtration rate (eGFR) all had a significant effect on 24-hours UGE, with SMBG being the most influential. Dapagliflozin systemic exposure for matching doses and baseline eGFR was similar between Japanese and non-Japanese patients; however, higher SMBG and a greater reduction in total insulin dose was observed in the Japanese population. When the significant covariates were included, the model fit the data well for both populations, and accurately predicted exposure-response in the Japanese and non-Japanese populations, in agreement with the observed data., Conclusions: There was no difference in dapagliflozin exposure-response in Japanese and non-Japanese patients with T1DM once differences in renal function, glycaemic control and insulin dose reductions between studies were considered. Therefore, no dose adjustment is recommended in Japanese patients with T1DM., (© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Cervical cancer is a malignant epithelial tumor that forms in the uterine cervix. Most cases of cervical cancer are preventable through human papilloma virus (HPV) vaccination, routine screening, and treatment of precancerous lesions. However, due to inadequate screening protocols in many regions of the world, cervical cancer remains the fourth-most common cancer in women globally. The complete NCCN Guidelines for Cervical Cancer provide recommendations for the diagnosis, evaluation, and treatment of cervical cancer. This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations. For recommendations regarding treatment of recurrent or metastatic disease, please see the full guidelines on NCCN.org., (Copyright © 2019 by the National Comprehensive Cancer Network.)

Objective: To compare the racial differences in treatment and survival of Asian-Americans and White patients with epithelial ovarian cancer., Methods: Data were obtained from the Surveillance, Epidemiology, and End Results Program between 1988 and 2009 and analyzed using Chi-squared tests, Kaplan-Meier methods, and Cox regression analysis., Results: Of the 52,260 women, 3932 (7.5%) were coded as Asian, and 48,328 (92.5%) were White. The median age of Asians at diagnosis was 56 vs. 64 years for the Whites (p<0.001). Asians were more likely to undergo primary surgery, have an earlier stage of disease, have a diagnosis of a non-serous histology, and have lower grade tumors. The 5-year disease-specific survival (DSS) of Asians was higher compared to Whites (59.1% vs. 47.3%, p<0.001). On a subset analysis, Vietnamese, Filipino, Chinese, Korean, Japanese, and Asian Indian/Pakistani ethnicities had 5-year DSS of 62.1%, 61.5%, 61.0%, 59.0%, 54.6%, and 48.2%, respectively (p=0.015). On multivariate analysis, age at diagnosis, year of diagnosis, race, surgery, stage, and tumor grade were all independent prognostic factors for survival. Asians were further stratified to U.S. born versus those who were born in Asia and immigrated. Asian immigrants presented at a younger age compared to U.S. born Asians. Immigrants were found to have an improved 5-year DSS when compared to U.S. born Asians and Whites of 55%, 52%, and 48%, respectively (p<0.001)., Conclusion: Asians were more likely to be younger, undergo primary surgery, have an earlier stage of disease, non-serous histology, lower grade tumors, and higher survival., (Copyright © 2014. Published by Elsevier Inc.)

Objective: To examine clinicopathologic variables associated with survival among women with low-grade (grade 1) serous ovarian carcinoma enrolled in a phase III study., Methods: This was an ancillary data analysis of Gynecologic Oncology Group protocol 182, a phase III study of women with stage III-IV epithelial ovarian carcinoma treated with carboplatin and paclitaxel compared with triplet or sequential doublet regimens. Women with grade 1 serous carcinoma (a surrogate for low-grade serous disease) were included in the analysis., Results: Among the 3,686 enrolled participants, 189 had grade 1 disease. The median age was 56.5 years and 87.3% had stage III disease. The median follow-up time was 47.1 months. Stratification according to residual disease after primary surgery was microscopic residual in 24.9%, 0.1-1.0 cm of residual in 51.3%, and more than 1.0 cm of residual in 23.8%. On multivariate analysis, only residual disease status (P=.006) was significantly associated with survival. Patients with microscopic residual had a significantly longer median progression-free (33.2 months) and overall survival (96.9 months) compared with those with residual 0.1-1.0 cm (14.7 months and 44.5 months, respectively) and more than 1.0 cm of residual disease (14.1 months and 42.0 months, respectively; progression-free and overall survival, P<.001). After adjustment for other variables, patients with low-grade serous carcinoma with measurable residual disease had a similar adjusted hazard ratio for death (2.12; P=.002) as their high-grade serous carcinoma counterparts with measurable disease (2.31; P<.001)., Conclusions: Surgical cytoreduction to microscopic residual was associated with improved progression-free and overall survival in women with advanced-stage low-grade serous ovarian carcinoma., Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00011986., Level of Evidence: II.

Objectives: AZD1656 is a novel glucokinase activator with a postulated dual mechanism of action by activating glucokinase in both the pancreas and the liver, and with the potential to deliver effective glucose-lowering in Type 2 diabetes mellitus. Here, we present the tolerability, pharmacokinetics and pharmacodynamics of AZD1656 in two single-blind, randomized, placebo-controlled studies, one with Western and the other with Japanese healthy adult male subjects., Methods: Both studies evaluated oral single ascending doses of AZD1656 of up to 180 mg, administered during euglycemic clamp conditions to explore a wide dose range without risking hypoglycemia. Safety, pharmacokinetics and effects on serum insulin and glucose infusion rate were assessed. A population pharmacokinetics analysis was also conducted., Results: AZD1656 was well tolerated in single doses up to 180 mg in both populations. AZD1656 was rapidly absorbed, and a dose-proportional increase in total exposure was observed for AZD1656 and the equipotent metabolite, AZD5658. Taking differences in body weight into account, there were no differences in pharmacokinetic parameters between Western and Japanese subjects. A dose-dependent blood glucose lowering effect was indirectly demonstrated by the increased glucose infusion rate required to maintain euglycemia, which was of similar magnitude in both populations. Dose-dependent increases in insulin secretion were also observed., Conclusions: No safety concerns were raised. AZD1656 displayed uncomplicated pharmacokinetics and dose-dependent pharmacodynamics effects were observed. The results suggest no ethnic differences in AZD1656 tolerability, pharmacokinetics or pharmacodynamics.