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Deterministic chemical assembly in nanophotonic chips.
performance. The findings demonstrated the benefits of using assessments that simultaneously evaluate multiple domains of neurologic function (eg, upper extremity and postural control) after SRC.
Measurement of postural movements during the object-hit task revealed impairments in postural stability that were not related to impairments in upper extremity performance. The findings demonstrated the benefits of using assessments that simultaneously evaluate multiple domains of neurologic function (eg, upper extremity and postural control) after SRC.Inhalation and ingestion of 137Cs and other long-lived radionuclides can occur after large-scale accidental or malicious radioactive contamination incidents, resulting in a complex temporal pattern of radiation dose/dose rate, influenced by radionuclide pharmacokinetics and chemical properties. GBD-9 High-throughput radiation biodosimetry techniques for such internal exposure are needed to assess potential risks of short-term toxicity and delayed effects (e.g., carcinogenesis) for exposed individuals. Previously, we used γ-H2AX to reconstruct injected 137Cs activity in experimentally-exposed mice, and converted activity values into radiation doses based on time since injection and 137Cs elimination kinetics. In the current study, we sought to assess the feasibility and possible advantages of combining γ-H2AX with transcriptomics to improve 137Cs activity reconstructions. We selected five genes (Atf5, Hist2h2aa2, Olfr358, Psrc1, Hist2h2ac) with strong statistically-significant Spearman's correlations with injected activity and stable expression over time after 137Cs injection. The geometric mean of log-transformed signals of these five genes, combined with γ-H2AX fluorescence, are used as predictors in a nonlinear model for reconstructing injected 137Cs activity. The coefficient of determination (R2) comparing actual and reconstructed activities was 0.91 and root mean squared error (RMSE) was 0.95 MBq. These metrics remained stable when the model was fitted to a randomly-selected half of the data and tested on the other half, repeated 100 times. Model performance was significantly better when compared to our previous analysis using γ-H2AX alone, and when compared to an analysis where genes are used without γ-H2AX, suggesting that integrating γ-H2AX with gene expression provides an important advantage. Our findings show a proof of principle that integration of radiation-responsive biomarkers from different fields is promising for radiation biodosimetry of internal emitters.Patients with hereditary rare bleeding disorders (RBDs) present with diverse hemorrhagic symptoms. Correlation between factor activity levels and clinical bleeding severity is poor for most RBDs. Threshold factor activity levels have been previously described in relation to bleeding severity but have not yet been validated. The Rare Bleeding Disorders in the Netherlands (RBiN) study is a nationwide cross-sectional study of patients registered in all 6 Dutch Haemophilia Treatment Centers with a known RBD and who are age 1 to 99 years. Bleeding scores were determined, and laboratory and clinical data were extracted from patient files. In all, 263 patients were included, of whom 202 (77%) attended the scheduled study visit. The median International Society of Thrombosis and Haemostasis (ISTH) bleeding assessment tool (BAT) score was 9. Correlations between baseline factor activity levels and ISTH BAT scores were strong for deficiencies in factor II (FII) (r = -0.792) and FX (r = -0.838) and were moderate for deficiencies of fibrinogen (r = -0.683), FV (r = -0.623), FVII (r = -0.516), FXIII (r = -0.516), and α2-antiplasmin (r = -0.594). There was no correlation for FXI deficiency (r = -0.218). The RBD BAT identified more women (94% vs 83%) and children (100% vs 71%) with an RBD than the ISTH BAT did. Importantly, 48% of patients had more severe bleeding than predicted for their baseline factor activity level. In addition, 34% of patients were predicted to be asymptomatic, but they actually had grade 2 (31%) or 3 (3%) bleeding. Bleeding severity in patients with RBDs is more pronounced than previously anticipated. The previously determined threshold factor activity levels to ensure no (spontaneous) bleeding in patients with an RBD are inaccurate. This trial was registered at www.clinicaltrials.gov as #NCT03347591.The limits of radiation tolerance, which often deter the use of large doses, have been a major challenge to the treatment of bulky primary and metastatic cancers. A novel technique using spatial modulation of megavoltage therapy beams, commonly referred to as spatially fractionated radiation therapy (SFRT) (e.g., GRID radiation therapy), which purposefully maintains a high degree of dose heterogeneity across the treated tumor volume, has shown promise in clinical studies as a method to improve treatment response of advanced, bulky tumors. Compared to conventional uniform-dose radiotherapy, the complexities of megavoltage GRID therapy include its highly heterogeneous dose distribution, very high prescription doses, and the overall lack of experience among physicists and clinicians. Since only a few centers have used GRID radiation therapy in the clinic, wide and effective use of this technique has been hindered. To date, the mechanisms underlying the observed high tumor response and low toxicity are still not nical management of bulky and advanced tumors by providing improved treatment response, and to alter our current radiobiology models and parameters of radiation therapy design.Neuroimaging has identified individual brain regions, but not yet whole-brain patterns, that correlate with the population impact of health messaging. We used neuroimaging to measure whole-brain responses to health news articles across two studies. Beyond activity in core reward value-related regions (ventral striatum, ventromedial prefrontal cortex), our approach leveraged whole-brain responses to each article, quantifying expression of a distributed pattern meta-analytically associated with reward valuation. The results indicated that expression of this whole-brain pattern was associated with population-level sharing of these articles beyond previously identified brain regions and self-report variables. Further, the efficacy of the meta-analytic pattern was not reducible to patterns within core reward value-related regions but rather depended on larger-scale patterns. Overall, this work shows that a reward-related pattern of whole-brain activity is related to health information sharing, advancing neuroscience models of the mechanisms underlying the spread of health information through a population.
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