Towards the re-verification of process tank calibrations

Re-verification is needed to ensure that the calibration (the relationship between measured level and measured volume) that is obtained during commissioning hasn’t changed over time. This can be achieved, in part, by metering in solution and correlating with marks identified a priori. Mark identification and correlation are discussed and possible error sources are outlined

RNA sequencing-based single sample predictors of molecular subtype and risk of recurrence for clinical assessment of early-stage breast cancer

BackgroundMultigene expression assays for molecular subtypes and biomarkers can aid clinical management of early invasive breast cancer. Based on RNA-sequencing we aimed to develop single-sample predictor (SSP) models for conventional clinical markers, molecular intrinsic subtype and risk of recurrence (ROR).MethodsA uniformly accrued breast cancer cohort of 7743 patients with RNA-sequencing data from fresh tissue was divided into a training set and a reserved test set. We trained SSPs for PAM50 molecular subtypes and ROR assigned by nearest-centroid (NC) and SSPs for conventional clinical markers from histopathology data. Additionally, SSP classifications were compared with Prosigna® in two external cohorts. Prognostic value was assessed using distant recurrence-free interval.ResultsIn the test set, agreement between SSP and NC classifications for PAM50 (five subtypes) and Subtype (four subtypes) was high (85%, Kappa=0.78) and very high (90%, Kappa=0.84) respectively. Accuracy for ROR risk category was high (84%, Kappa=0.75, weighted Kappa=0.90). The prognostic value for SSP and NC was assessed as equivalent. Agreement for SSP and histopathology was very high or high for receptor status, while moderate and poor for Ki67 status and Nottingham histological grade, respectively. SSP concordance with Prosigna® was high for subtype and moderate and high for ROR risk category. In pooled analysis, concordance between SSP and Prosigna® for emulated treatment recommendation for chemotherapy (yes vs. no) was high (85%, Kappa=0.66). In postmenopausal ER+/HER2-/N0 patients SSP application suggested changed treatment recommendations for up to 17% of patients, with nearly balanced escalation and de-escalation of chemotherapy.ConclusionsSSP models for histopathological variables, PAM50, and ROR classifications can be derived from RNA-sequencing that closely matches clinical tests. Agreement and outcome analyses suggest that NC and SSP models are interchangeable on a group-level and nearly so on a patient level. Retrospective evaluation in postmenopausal ER+/HER2-/N0 patients suggested that molecular testing could lead to a changed therapy recommendation for almost one-fifth of patients

Joint U.S./Russian plutonium disposition study: Nonproliferation issues

In an effort to establish joint activities in the disposition of fissile materials from nuclear materials, the US and Russia agreed to conduct joint work to develop consistent comparisons of various alternatives for the disposition of weapons-grade plutonium. Joint working groups were established for the analysis of alternatives for plutonium management for water reactors, fast reactors, storage, geological formations, immobilization and stabilization of solutions and other forms. In addition cross-cutting working groups were established for economic analysis and nonproliferation (NP). This paper reviews the activities of the NP working group in support of these studies. The NP working group provided integrated support in the area of nuclear NP to the other US/Russian Study teams. It involved both domestic safeguards and security and international safeguards. The analysis of NP involved consideration of the resistance to theft or diversion and resistance to retrieval, extraction or reuse

Effects of antenatal betamethasone on preterm human and mouse ductus arteriosus: comparison with baboon data.

BackgroundAlthough studies involving preterm infants ≤34 weeks gestation report a decreased incidence of patent ductus arteriosus after antenatal betamethasone, studies involving younger gestation infants report conflicting results.MethodsWe used preterm baboons, mice, and humans (≤276/7 weeks gestation) to examine betamethasone's effects on ductus gene expression and constriction both in vitro and in vivo.ResultsIn mice, betamethasone increased the sensitivity of the premature ductus to the contractile effects of oxygen without altering the effects of other contractile or vasodilatory stimuli. Betamethasone's effects on oxygen sensitivity could be eliminated by inhibiting endogenous prostaglandin/nitric oxide signaling. In mice and baboons, betamethasone increased the expression of several developmentally regulated genes that mediate oxygen-induced constriction (K+ channels) and inhibit vasodilator signaling (phosphodiesterases). In human infants, betamethasone increased the rate of ductus constriction at all gestational ages. However, in infants born ≤256/7 weeks gestation, betamethasone's contractile effects were only apparent when prostaglandin signaling was inhibited, whereas at 26-27 weeks gestation, betamethasone's contractile effects were apparent even in the absence of prostaglandin inhibitors.ConclusionsWe speculate that betamethasone's contractile effects may be mediated through genes that are developmentally regulated. This could explain why betamethasone's effects vary according to the infant's developmental age at birth

Modelling search for people in 900 scenes: A combined source model of eye guidance

How predictable are human eye movements during search in real world scenes? We recorded 14 observers’ eye movements as they performed a search task (person detection) in 912 outdoor scenes. Observers were highly consistent in the regions fixated during search, even when the target was absent from the scene. These eye movements were used to evaluate computational models of search guidance from three sources: Saliency, target features, and scene context. Each of these models independently outperformed a cross-image control in predicting human fixations. Models that combined sources of guidance ultimately predicted 94% of human agreement, with the scene context component providing the most explanatory power. None of the models, however, could reach the precision and fidelity of an attentional map defined by human fixations. This work puts forth a benchmark for computational models of search in real world scenes. Further improvements in modelling should capture mechanisms underlying the selectivity of observers’ fixations during search.National Eye Institute (Integrative Training Program in Vision grant T32 EY013935)Massachusetts Institute of Technology (Singleton Graduate Research Fellowship)National Science Foundation (U.S.) (Graduate Research Fellowship)National Science Foundation (U.S.) (CAREER Award (0546262))National Science Foundation (U.S.) (NSF contract (0705677))National Science Foundation (U.S.) (Career Award (0747120)

EEG ERP preregistration template

This preregistration template guides researchers who wish to preregister their EEG projects, more specifically studies investigating event-related potentials (ERPs) in the sensor space

Value of flow cytometry for MRD-based relapse prediction in B-cell precursor ALL in a multicenter setting

PCR of TCR/Ig gene rearrangements is considered the method of choice for minimal residual disease (MRD) quantification in BCP-ALL, but flow cytometry analysis of leukemia-associated immunophenotypes (FCM-MRD) is faster and biologically more informative. FCM-MRD performed in 18 laboratories across seven countries was used for risk stratification of 1487 patients with BCP-ALL enrolled in the NOPHO ALL2008 protocol. When no informative FCM-marker was available, risk stratification was based on real-time quantitative PCR. An informative FCM-marker was found in 96.2% and only two patients (0.14%) had non-informative FCM and non-informative PCR-markers. The overall 5-year event-free survival was 86.1% with a cumulative incidence of relapse (CIR5y) of 9.5%. FCM-MRD levels on days 15 (HzR 4.0, p 10(-4) associated with a CIR5y = 22.1%. In conclusion, FCM-MRD performed in a multicenter setting is a clinically useful method for MRD-based treatment stratification in BCP-ALL.Peer reviewe