Improved DEA Evaluation Models of IRTU Knowledge Innovation

Guided by Kraemer et al.'s (Psychological Methods, 3:257-271, 1999) framework for measuring the potency of risk factors, we sought to improve on the classification accuracy reported in Petras et al. (Journal of the American Academy of Child and Adolescent Psychiatry 43:88-96, 2004a) and Petras et al. (Journal of the American Academy of Child and Adolescent Psychiatry 44:790-797, 2005) by using multiple as opposed to single point in time assessments of early aggressive and disruptive behavior in the classification of youth who would likely benefit from targeted preventive interventions. Different from Petras et al. (2004a, 2005), the outcome used in this study included serious antisocial behavior in young adulthood as well as in adolescence. Among males, the use of multiple time points did not yield greater classification accuracy than the highest single time points, that is, third and fifth grades. For females, although fifth grade represented the best single time point in terms of classification accuracy, no significant association was found between earlier time points and the later outcome, rendering a test of the multiple time points hypothesis moot. The findings presented in this study have strong implications for the design of targeted intervention for violence prevention, indicating that the screening quality based on aggression ratings during the elementary years is rather modest, particularly for females.

Background:Identification of AML patients at high risk of relapse after achieving a complete remission (CR) with induction chemotherapy enables the use of personalized post‐remission treatment strategies to prevent relapse. Detection of molecular measurable residual disease (mMRD) by conventional next‐generation sequencing (NGS) at a single time point post‐induction has previously been associated with a higher incidence of relapse and inferior overall survival (OS).Aims:In this study, we used error‐corrected NGS (EC‐NGS) to evaluate whether changes in mMRD levels between two time points during remission provide additional prognostic information over single time point assessments.Methods:88 AML patients who received standard induction chemotherapy and achieved a CR were evaluated. Targeted NGS of 54 genes associated with myeloid malignancies was performed at diagnosis. We collected peripheral blood (PB) samples upon count recovery following induction chemotherapy and each cycle of consolidation chemotherapy. To detect mMRD, we used a custom 37‐gene hybrid‐capture panel and EC‐NGS based on the Duplex Sequencing approach. PB samples collected at two different time points during remission were analyzed for each patient. The Cox proportional hazards model was used to relate predictor variables to time to relapse and OS. P‐values <0.05 were considered significant.Results:Sequencing analysis of diagnostic samples identified at least one putative oncogenic mutation in 82 of the 88 patients (93%). EC‐NGS of samples collected at the first remission time point (T1) identified at least one persistent mutation in 63 of the 82 patients (77%); 40% of the persistent mutations were in DNMT3A, TET2, and ASXL1 (DTA). The persistence of DTA or non‐DTA mutations, when considered separately, did not correlate with risk of relapse or OS. The co‐persistence of at least one DTA and one non‐DTA mutation was associated with a higher risk of relapse (HR: 2.61; 95% CI, 1.16 to 5.83; P = 0.02) but not OS (P = 0.56). To evaluate whether changes in mMRD level correlate with clinical outcomes, we analyzed the subset of mutations that were detected at diagnosis and persisted in both T1 and T2. We calculated the fold change (FC) in variant allele frequency (VAF) between T1 and T2 for each mutation and used the maximum FC among all mutations of each patient (maxFC) as a continuous variable for regression analysis. High maxFC values restricted to mutations found at diagnosis (maxFCD) were significantly correlated with a higher risk of relapse (P = 0.002) and inferior OS (P = 0.003). We extended the analysis to all non‐synonymous mutations that were detected in T1 and T2 including ones that were not identified at diagnosis. The mutations were predominantly in DNMT3A, TET2, ASXL1, and TP53. Higher maxFC values among mutations found in remission samples (maxFCR) was strongly associated with an increased risk of relapse (P < 0.0001; Fig 1A) and inferior OS (P < 0.0001; Fig 1B). In multivariable regression analysis, maxFCR remained an independent risk factor for relapse after adjustment for age, WBC, ELN 2017 risk group, maxFCD, MRD by flow cytometry, and persistence of mutations found at diagnosis (Table 1).Summary/Conclusion:Our analysis demonstrates that assessment of mMRD kinetics using EC‐NGS provides additional prognostic information over mMRD monitoring at a single time point. We developed an analytical framework to analyze mMRD results in remission and identified a novel parameter (maxFCR) that is independently associated with risk of relapse and OS.image

The aim of this study was to compare the accuracy of two abbreviated approaches for estimating Gross Motor Function Measure 66 (GMFM-66) scores against the full GMFM-66 and to explore their strengths and limitations. An existing dataset (n=224) comprising children aged 1 to 13years (mean age 6y 11mo, SD 4y 6mo; 132 males, 92 females) with cerebral palsy (CP) of all Gross Motor Function Classification System (GMFCS) levels was used to compare the validity of the item set version (GMFM-66-IS) and the basal and ceiling version (GMFM-66-B&C) with the full GMFM-66 scores. Follow-up assessment at 1year (n=109) allowed evaluation of change scores and accuracy at a single point in time. The cross-sectional agreement was excellent for both abbreviated measures (all intraclass correlation coefficients [ICCs] >0.98). When measuring change over time, both the GMFM-66-IS and the GMFM-66-B&C showed good agreement for children with bilateral CP (ICCs >0.9). However, the GMFM-66-IS assessed change over 1year more accurately than the GMFM-66-B&C in children with unilateral CP (ICC=0.89 vs ICC=0.58; 95% confidence intervals do not overlap). Both approaches for estimating GMFM-66 scores are accurate at a single point in time. If the primary goal of assessment is to measure change, the full GMFM-66 should still be regarded as the criterion standard. The GMFM-66-IS should be the preferred shortened measure for children with unilateral CP.

Chromothripsis under the microscope: a cytogenetic perspective of two cases of AML with catastrophic chromosome rearrangement

Using cross-sectional data from the Framingham Heart Study including nondemented middle-aged adults, Echouffo-Tcheugui et al. identified an association between higher serum cortisol levels and lower brain volume and poorer performance on a variety of cognitive assessments. Although the serum cortisol measurement was acquired at a single point in time, and may not be reflective of chronic elevations in cortisol as Barbosa et al. assert, the data are strongly suggestive of a correlation. The investigators also agree that hair cortisol might be a better indicator of long-term cortisol levels; however, these data were not available in this observational cohort. Drs. Jimenez-Pavon and Carbonell-Baeza comment on the role that physical activity (PA) and cardiorespiratory fitness (CRF) may have on structural brain integrity and cognitive performance. Some of these associations from the Framingham Heart Study have been previously published in Neurology ® in 2016. Although analysis of these physiologic variables may be worthy of further investigation, Echouffo-Tcheugi et al. argue that PA and CRF may alter cortisol levels (and thereby, neural structure and function), but that such a mediation could lead to an overadjustment. Based on the results of this analysis, the investigators emphasize that cortisol levels may be the bridge the between PA/CRF and brain volume and cognitive performance. Using cross-sectional data from the Framingham Heart Study including nondemented middle-aged adults, Echouffo-Tcheugui et al. identified an association between higher serum cortisol levels and lower brain volume and poorer performance on a variety of cognitive assessments. Although the serum cortisol measurement was acquired at a single point in time, and may not be reflective of chronic elevations in cortisol as Barbosa et al. assert, the data are strongly suggestive of a correlation. The investigators also agree that hair cortisol might be a better indicator of long-term cortisol levels; however, these data were not available in this observational cohort. Drs. Jimenez-Pavon and Carbonell-Baeza comment on the role that physical activity (PA) and cardiorespiratory fitness (CRF) may have on structural brain integrity and cognitive performance. Some of these associations from the Framingham Heart Study have been previously published in Neurology ® in 2016. Although analysis of these physiologic variables may be worthy of further investigation, Echouffo-Tcheugi et al. argue that PA and CRF may alter cortisol levels (and thereby, neural structure and function), but that such a mediation could lead to an overadjustment. Based on the results of this analysis, the investigators emphasize that cortisol levels may be the bridge the between PA/CRF and brain volume and cognitive performance.

Life-course socioeconomic positions and subclinical atherosclerosis in the multi-ethnic study of atherosclerosis

The purpose of this study was to define and document the interior design profession's body of knowledge at a single point in time. This was done using a career cycle approach and a health, safety, and welfare framework. The method and framework used to define the body of knowledge are presented in the article. The body of knowledge was defined from a career cycle approach using the four stages of a professional interior designer's career cycle: education, experience, examination, and legal regulation (NCIDQa, 2003). A content analysis was conducted of the written documents of the organizations that represent each stage in the cycle. Eighty–one knowledge areas were identified from this content analysis and placed into one of seven categories: Codes; Communication; Design; Furnishings, Fixtures, and Equipment; Human Needs; Interior Building Construction; and Professional Practice. These categories and knowledge areas are what defined the interior design profession's body of knowledge based on this approach. Next, each knowledge area was analyzed using a health, safety, and welfare framework to determine its benefit to the public. Finally, a review of literature was conducted to document that the knowledge areas comprise the specialized knowledge necessary for the professional interior designer to protect the public's health, safety, and welfare. The method used to define the interior design profession's body of knowledge assessed several limited bodies of knowledge that had been developed for a specific purpose, such as education or examination. While this comprehensive body of knowledge reflects a single point in time, it provides a venue for dialogue from which revision can occur and updating can continue, leading to further development of the profession.

177 Lu-PSMA-617-radioligand therapy (RLT) has shown promising therapeutic role in patients with metastatic castration-resistant prostate cancer. However, off-target action in salivary glands often presents with xerostomia. Personalized dosimetry can help in optimizing the treatment, however, has so far been tedious due to multiple time-point imaging. In this prospective study, we intended to estimate the absorbed dose delivered to the salivary glands in patients undergoing 177 Lu-PSMA-617-RLT using quantitative SPECT/CT at a single time point. Patients undergoing 177 Lu-PSMA-617 RLT were included in this prospective study. Post-therapy whole-body images and regional quantitative single time-point SPECT/CT were acquired at 24 h with high-energy collimator. The data was processed and analyzed using Q.Metrix software. A scaling factor, that is, the time-integrated activity conversion factor was applied for the image acquired at 24 h. Absorbed doses were computed using MIRD scheme and OLINDA software. A total of 21 patients (mean age: 66 ± 9 years) were included. The value of mean absorbed dose for the parotid glands was 1.90 ± 1.31Gy (range: 0.26-6.23) and that for the submandibular glands was 1.37 ± 0.94Gy (range: 0.16-3.65). The mean absorbed doses per administered activity for the parotid and submandibular glands were 0.26 ± 0.18 Gy/GBq and 0.19 ± 0.12 Gy/GBq, respectively. The absorbed doses were estimated for one cycle of therapy and were well within acceptable limits. None of the patients experienced dryness of mouth. Single time-point dosimetry with quantitative SPECT/CT is feasible and can be standardized to estimate the absorbed dose to salivary glands instead of multiple time-point acquisitions.

Participant noncompliance, in which participants do not follow their assigned treatment protocol, has long complicated the interpretation of randomized clinical trials. No gold standard has been identified for detecting noncompliance, but in some trials participants' biomarkers can provide objective information that suggests exposure to non-study treatments. However, existing methods are limited to retrospectively detecting noncompliance at a single time point based on a single biomarker measurement. We propose a novel method that can leverage participants' full biomarker history to detect noncompliance across multiple time points. Conditional on longitudinal biomarker data, our method can estimate the probability of compliance at (1) a single time point of the trial, (2) all time points, and (3) a future time point. Across time points, we model the biomarker as a mixture density with (latent) components corresponding to longitudinal patterns of compliance. To estimate the mixture density, we fit mixed effects models for both compliance and the biomarker. We use the mixture density to derive compliance probabilities that condition on the longitudinal biomarker data. We evaluate our compliance probabilities by simulation and apply them to a trial in which current smokers were asked to only smoke low nicotine study cigarettes (Center for the Evaluation of Nicotine in Cigarettes Project 1 Study 2). In the simulation, we investigated three different effects of compliance on the biomarker, as well as the effect of misspecification of the covariance structures. We compared probability estimators (1) and (2) to those that ignore the longitudinal correlation in the data according to area under the receiver operating characteristic curve. We evaluated estimator (3) by plotting its calibration lines. For Center for the Evaluation of Nicotine in Cigarettes Project 1 Study 2, we compared estimators (1) and (3) to a probability estimator of compliance at the last time point that ignores the longitudinal correlation. In the simulation, for both compliance at the last time point and at all time points, conditioning on the longitudinal biomarker data uniformly raised area under the receiver operating characteristic curve across all three compliance effect scenarios. The gains in area under the receiver operating characteristic curve were smaller under misspecification. The calibration lines for the prediction of compliance closely followed 45°, though with additional variability under misspecification. For compliance at the last time point of Center for the Evaluation of Nicotine in Cigarettes Project 1 Study 2, conditioning on participants' full biomarker history boosted area under the receiver operating characteristic curve by three percentage points. The prediction probabilities somewhat accurately approximated the non-longitudinal compliance probabilities. Compared to existing methods that only use a single biomarker measurement, our method can account for the longitudinal correlation in the biomarker and compliance to more accurately identify noncompliant participants. Our method can also use participants' biomarker history to predict compliance at a future time point.

A significant heritability has been documented for articular osteochondrosis. Selection against osteochondrosis has historically been based on macroscopic evaluation, but as computed tomography (CT) now is used to select boars with optimal body composition it can potentially also be used to screen for osteochondrosis. False negative diagnosis will occur if defects have not developed or have resolved prior to screening at a single time point. The aim of the current study was to assess the suitability of the use of CT at a single point in time as a screening tool in piglets for articular osteochondrosis, which is known to be a highly dynamic condition in which lesions develop and resolve over time. Male Landrace piglets (n = 18) were serial CT scanned from 2-8 times at biweekly intervals from 70-180 days of age. At each interval, 1-2 piglets were euthanased and the left distal femur processed for histological validation. A total of 795 defects were identified in the 112 available CT scans. Within the hind and fore limbs, the incidence of defects was highest in the stifle (n = 321) and elbow joints (n = 110), respectively. Ninety-eight per cent of the defects in the stifle and elbow joints had developed by the 7th examination interval when the piglets were a mean age of 159 days old. The proportion of defects that resolved was lowest in the stifle joint at 51% and highest in the elbow joint at 69%. Scanning of the current piglets at an age of 159 days resulted in detection of 98% of the total number of defects that developed up to the maximum age of 180 days. The proportion of defects that resolved ranged from 51-69% for different joints, but may not adversely affect prevalence as this category of false negative diagnosis will result in selection of pigs that are disposed for healing. Optimally timed CT is a powerful screening tool for osteochondrosis.

Dynamic Consistency in Denmark: A Longitudinal Field Experiment

Cockroach-induced IL9, IL13, and IL31 expression and the development of allergic asthma in urban children

(P27) Rate of Change in Quantitative PET/CT Metrics Prior to Definitive Chemoradiotherapy for Cervical Cancer Does not Add Prognostic Information Over Single Time Point Metrics

Purpose: The aim of the study was to establish the moderating effect of project environment on the relationship between constrained programming and project outcomes in United Nations Agencies in Kenya.Methodology: A cross sectional survey is a method that involves the analysis of data collected from a population, or a representative subset, at one specific point in time (Orodho, 2011). This design is used to gather data on more than one case at a single point in time in order to collect a body of quantitative data in connection to the variables. The study picked data for projects and sought to investigate the concept trends and status of project outcomes at a particular period (2014-2018).Results: The results indicated that the geographical environment affect project outcomes (4.565); Social Cultural environment inhibit project outcomes (3.875); Beliefs and traditions affect project outcomes (4.670); Political instability hinders success of project outcomes (3.734) and technological changes affect project outcomes (3.713). The findings revealed the moderating effect of project environment on the relationship between constrained programming and project outcomes in UN agencies in Kenya.Contribution to policy, practice and theory: Humanitarian projects should realize that in the present project environment, constrained programming forms an important element of intangible assets of the UN agencies. These should be reconfigured to ensure that the projects seize opportunities, are proactive in the market place, make new product and process innovations.

An intention to act has different onsets when it is measured in different ways. When participants provide a self-initiated report on the onset of their awareness of intending to act, the report occurs around 150 ms prior to action. However, when the same participants are repeatedly asked about their awareness of intending at different points in time, the onset of intending is found up to 2 s prior to action. This ‘probed’ awareness has its onset around the same time as the brain starts preparing the act, as measured using EEG. First of all, this undermines straightforward interpretations about the temporal relation between unconscious brain states and conscious intentions and actions. Secondly, we suggest that these results present a problem for the view that intentions are mental states occurring at a single point in time. Instead, we suggest the results to support the interpretation of an intention to act as a multistage process developing over time. This process of intending seems to develop during the process of acting, leaving reportable traces in consciousness at certain points along the road.Electronic supplementary materialThe online version of this article (doi:10.1007/s00221-016-4600-1) contains supplementary material, which is available to authorized users.