Background: High tumor mutation burden (TMB-H) has been proposed as a predictive biomarker for response to immune checkpoint blockade (ICB), largely due to the potential for tumor mutations to generate immunogenic neoantigens. Despite recent pan-cancer approval of ICB treatment for any TMB-H tumor, as assessed by the targeted FoundationOne CDx assay in nine tumor types, the utility of this biomarker has not been fully demonstrated across all cancers. Patients and methods: Data from over 10 000 patient tumors included in The Cancer Genome Atlas were used to compare approaches to determine TMB and identify the correlation between predicted neoantigen load and CD8 T cells. Association of TMB with ICB treatment outcomes was analyzed by both objective response rates (ORRs, N ¼ 1551) and overall survival (OS, N ¼ 1936). Results: In cancer types where CD8 T-cell levels positively correlated with neoantigen load, such as melanoma, lung, and bladder cancers, TMB-H tumors exhibited a 39.8% ORR to ICB [95% confidence interval (CI) 34.9-44.8], which was significantly higher than that observed in low TMB (TMB-L) tumors [odds ratio (OR) ¼ 4.1, 95% CI 2.9-5.8, P < 2 Â 10 À16 ]. In cancer types that showed no relationship between CD8 T-cell levels and neoantigen load, such as breast cancer, prostate cancer, and glioma, TMB-H tumors failed to achieve a 20% ORR (ORR ¼ 15.3%, 95% CI 9.2-23.4, P ¼ 0.95), and exhibited a significantly lower ORR relative to TMB-L tumors (OR ¼ 0.46, 95% CI 0.24-0.88, P ¼ 0.02). Bulk ORRs were not significantly different between the two categories of tumors (P ¼ 0.10) for patient cohorts assessed. Equivalent results were obtained by analyzing OS and by treating TMB as a continuous variable. Conclusions: Our analysis failed to support application of TMB-H as a biomarker for treatment with ICB in all solid cancer types. Further tumor type-specific studies are warranted.

Seventy-six patients with acute promyelocytic leukemia (APL) in first complete remission after induction and consolidation by daunorubicin and cytosine arabinoside received oral arsenic trioxide (As 2 O 3 )-based maintenance. Three regimens were used: oral As 2 O 3 (10 mg/day, regimen A, n ‫؍‬ 20), oral As 2 O 3 plus alltrans retinoic acid (ATRA, 45 mg/m 2 per day, regimen AA, n ‫؍‬ 19), and oral As 2 O 3 plus ATRA plus ascorbic acid (1000 mg/ day, regimen AAA, n ‫؍‬ 37), each given for 2 weeks every 2 months for 2 years.

Aims Population surveys of Type 2 diabetes mellitus and obesity conducted in Samoa over three decades have used varying methodologies and definitions. This study standardizes measures, and trends of Type 2 diabetes mellitus and obesity for 1978-2013 are projected to 2020 for adults aged 25-64 years.Methods Unit records from eight surveys (n = 12 516) were adjusted to the previous census for Division of residence, sex and age to improve national representativeness. Type 2 diabetes mellitus is defined as a fasting plasma glucose ≥ 7.0 mmol/l and/or on medication. Obesity is defined as BMI ≥ 30 kg/m 2 . Random effects meta-regression was employed to assess time trends following logit transformation. Poisson regression from strata was used to assess the effects of mean BMI changes on Type 2 diabetes mellitus period trends.Results Over 1978-2013, Type 2 diabetes mellitus prevalence increased from 1.2% to 19.6% in men (2.3% per 5 years), and from 2.2% to 19.5% in women (2.2% per 5 years). Obesity prevalence increased from 27.7% to 53.1% in men (3.6% per 5 years) and from 44.4% to 76.7% (4.5% per 5 years) in women. Type 2 diabetes mellitus and obesity prevalences increased in all age groups. From period trends, Type 2 diabetes mellitus prevalence in 2020 is projected to be 26% in men and women. Projected obesity prevalence is projected to be 59% in men and 81% in women. Type 2 diabetes mellitus period trends attributable to BMI increase are estimated as 31% (men) and 16% (women), after adjusting for age.Conclusion This is the first study to produce trends of Type 2 diabetes mellitus and obesity in Samoa based on standardized data from population surveys. Type 2 diabetes mellitus is equally prevalent in both sexes, and obesity is widespread. Type 2 diabetes mellitus prevalence in Samoa is likely to continue to increase in the near future.

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For patients with relapsed APL, As O remained effective despite repeated As O exposures. Oral As O maintenance was an effective postremission strategy for CR2. Cancer 2018;124:2316-26. © 2018 American Cancer Society.

Background: No systematic comparison has been conducted in Fiji using all suitable surveys of type 2 diabetes mellitus (T2DM) and obesity prevalence after standardizing methodology and definitions. Methods: Unit records from six surveys of Fiji adults were variously adjusted for age, ethnicity (Fiji Melanesians, i-Taukei, and Fijians of Asian Indian descent [Indians]) and urban-rural by sex to previous censuses. Trends were assessed using meta-regression (random effect models) and estimates projected to 2020. Poisson regression of strata was used to assess the effect of body mass index (BMI) increases on T2DM period trends. Results: Over 1980-2011, T2DM prevalence increased in i-Taukei men (3.2% to 11.1%; 1.32%/5 years) and women (5.3% to 13.6%; 1.40%/5 years) and Indian men (11.1% to 17.9%; 1.24%/5 years) and women (11.2% to 19.9%; 1.71%/5 years). Projected T2DM prevalence in 2020 is 13.3% and 16.7% in i-Taukei men and women, and 23.4% and 24.1% in Indian men and women, respectively. Obesity prevalence increased in i-Taukei men (12.6% to 28.9%; 2.99%/5 years) and women (30.1% to 52.9%; 3.84%/5 years) and in Indian men (2.8% to 9.4%; 1.21%/5 years) and women (13.2% to 26.6%; 2.61%/ 5 years). Projected obesity prevalence in 2020 is 34.0% and 60.0% in i-Taukei and women, and 11.4% and 31.0% in Indian men and women, respectively. After age-adjustment, an estimated 27%, 25%, 16% and 18% of the T2DM period trend is attributable to BMI in i-Taukei men and women and Indian men and women, respectively. Conclusions: Prevalence of T2DM in Fiji is projected to continue increasing, driven by rising obesity, with consequences for premature mortality and life expectancy.

Despite that Tauc plot extrapolation has been widely adopted for extracting bandgap energies of semiconductors, there is a lack of theoretical support for applying it to nanocrystals. In this paper, direct-allowed optical transitions in semiconductor nanocrystals have been formulated based on a purely theoretical approach. This result reveals a size-dependant transition of the power factor used in Tauc plot, increasing from one half used in the 3D bulk case to one in the 0D case. This size-dependant intermediate value of power factor allows a better extrapolation of measured absorption data. Being a material characterization technique, the generalized Tauc extrapolation gives a more reasonable and accurate acquisition of the intrinsic bandgap, while the unjustified purpose of extrapolating any elevated bandgap caused by quantum confinement is shown to be incorrect.

The electronic and excitonic confinement of monoclinic silver sulfide Ag2S nanocrystals (NCs) has been investigated both theoretically and experimentally. Theoretically, the electronic band gaps and the excitonic ground-state energies of Ag2S NCs at different sizes are calculated using a hybrid method of density-functional theory (DFT) and effective mass approximation (EMA). The results have shown a good agreement with measured results, including the absorbance and photoluminescence spectra of drop-casted NC thin films. The Ag2S NCs, synthesized using wet-chemistry methods, have demonstrated a desirable size monodispersion, allowing the measurements to be sufficiently accurate. The results show that both the electronic band gap and the excitonic energy have significant blue shift only when the diameter of monodispersed NCs is reduced below 4 nm, and the excitonic Bohr radius of Ag2S is determined as being small at around 1 nm.