Life expectancy in older adults with advanced cancer: Evaluation of a geriatric assessment-based prognostic model

Objectives: Oncologists estimate patients' prognosis to guide care. Evidence suggests oncologists tend to overestimate life expectancy, which can lead to care with questionable benefits. Information obtained from geriatric assessment may improve prognostication for older adults. In this study, we created a geriatric assessment-based prognostic model for older adults with advanced cancer and compared its performance to alternative models. Materials and methods: We conducted a secondary analysis of a trial (URCC 13070; PI: Mohile) capturing geriatric assessment and vital status up to one year for adults age ≥ 70 years with advanced cancer. Oncologists estimated life expectancy as 0–6 months, 7–12 months, and > 1 year. Three statistical models were developed: (1) a model including age, sex, cancer type, and stage (basic model), (2) basic model + Karnofsky Performance Status (≤50, 60–70, and 80+) (KPS model), and (3) basic model +16 binary indicators of geriatric assessment impairments (GA model). Cox regression was used to model one-year survival; c-indices and time-dependent c-statistics assessed model discrimination and stratified survival curves assessed model calibration. Results: We included 484 participants; mean age was 75; 48% had gastrointestinal or lung cancer. Overall, 43% of patients died within one year. Oncologists classified prognosis accurately for 55% of patients, overestimated for 35%, and underestimated for 10%. C-indices were 0.61 (basic model), 0.62 (KPS model), and 0.63 (GA model). The GA model was well-calibrated. Conclusions: The GA model showed moderate discrimination for survival, similar to alternative models, but calibration was improved. Further research is needed to optimize geriatric assessment-based prognostic models for use in older adults with advanced cancer

Solving an Avionics Real-Time Scheduling Problem by Advanced IP-Methods

We report on the solution of a real-time scheduling problem that arises in the design of software-based operation control of aircraft. A set of tasks has to be distributed on a minimum number of machines and offsets of the tasks have to be computed. The tasks emit jobs periodically starting at their offset and then need to be executed on the machines without any delay. Also, further constraints in terms of memory usage and redundancy requirements have to be met. Approaches based on standard integer programming formulations fail to solve our real-world instances. By exploiting structural insights of the problem we obtain an IP-formulation and primal heuristics that together solve the real-world instances to optimality and outperform text-book approaches by several orders of magnitude. Our methods lead, for the first time, to an industry strength tool to optimally schedule aircraft sized problems

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10-11 to 5.0 × 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

Dust in Supernovae and Supernova Remnants I : Formation Scenarios

Supernovae are considered as prime sources of dust in space. Observations of local supernovae over the past couple of decades have detected the presence of dust in supernova ejecta. The reddening of the high redshift quasars also indicate the presence of large masses of dust in early galaxies. Considering the top heavy IMF in the early galaxies, supernovae are assumed to be the major contributor to these large amounts of dust. However, the composition and morphology of dust grains formed in a supernova ejecta is yet to be understood with clarity. Moreover, the dust masses inferred from observations in mid-infrared and submillimeter wavelength regimes differ by two orders of magnitude or more. Therefore, the mechanism responsible for the synthesis of molecules and dust in such environments plays a crucial role in studying the evolution of cosmic dust in galaxies. This review summarises our current knowledge of dust formation in supernova ejecta and tries to quantify the role of supernovae as dust producers in a galaxy.Peer reviewe

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap

Impacts of sedimentation on soft-bottom benthic communities in the southern islands of Singapore

10.1023/B:HYDR.0000027321.23230.2fHydrobiologia51591-106HYDR

Highly Unsaturated Fatty Acid (HUFA) Retention in the Freshwater Cladoceran, Moina macrocopa, Enriched With Lipid Emulsions

Fatty acid profiles of Moina macrocopa enriched with lipids from inexpensive squid or canola oil were compared with profiles of Moina enriched with a commercial enrichment diet, A1 DHA Selco® (ADS). Arachidonic acid (AA) significantly increased from <0.01 to 0.28 mg/g body weight in Moina enriched with ADS at 1 g/l for 12 h and to 0.38 mg/g in Moina enriched in 2 g/l canola oil for 12 h. The highest increase in eicosapentaenoic acid (EPA; from 0.15 to 0.38 mg/g) was obtained when Moina were enriched in 1 g/l ADS for 12 h. The highest increases in docosahexaenoic acid (DHA; originally <0.01) were obtained in Moina enriched in 1 g/l ADS for 12 h (increased to 0.09) or in 2 g/l ADS for 24 h (rose to 0.8 mg/g). The AA:EPA ratio was highest in Moina treated with 2 g/l canola oil for 12 h or 2 g/l squid oil for 24 h. The AA:DHA ratio was highest in Moina enriched with 2 g/l canola oil for 12 h while the DHA:EPA ratio was highest in Moina enriched with 2 g/l squid oil for 24 h

The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges

10.3390/cells8101118Cells81

Guanidine-catalyzed enantioselective desymmetrization of meso-aziridines

10.1039/c0cc05840hChemical Communications47133897-3899CHCO

Evaluation of paper-based and web-based food frequency questionnaires for 7-year-old children in Singapore

10.1017/S0007114521004517British Journal of Nutritio