Summary Background The level of minimal residual disease during remission induction is the most important prognostic indicator in patients with acute lymphoblastic leukaemia (ALL). We aimed to ...establish the clinical significance of minimal residual disease in a prospective trial that used sequential minimal residual disease measurements to guide treatment decisions. Methods Between June 7, 2000, and Oct 24, 2007, 498 assessable patients with newly diagnosed ALL were enrolled in a clinical trial at St Jude Children's Research Hospital. We provisionally classified the risk of relapse as low, standard, or high according to patients' baseline clinical and laboratory features. Final risk assignment to establish treatment intensity was based mainly on minimal residual disease levels measured on days 19 and 46 of remission induction, and on week 7 of maintenance treatment. Additional measurements of minimal residual disease were made on weeks 17, 48, and 120 (end of treatment). The primary aim was to establish the association between event-free survival and patients' minimal residual disease levels during remission induction and sequentially post-remission. This trial was registered at ClinicalTrials.gov , number NCT00137111. Findings Irrespective of the provisional risk classification, 10-year event-free survival was significantly worse for patients with 1% or greater minimal residual disease levels on day 19 compared with patients with lower minimal residual disease levels (69·2%, 95% CI 49·6–82·4, n=36 vs 95·5%, 91·7–97·5, n=244; p<0·001 for the provisional low-risk group and 65·1%, 50·7–76·2, n=56 vs 82·9%, 75·6–88·2, n=142; p=0·01 for the provisional standard-risk group). 12 patients with provisional low-risk ALL and 1% or higher minimal residual disease levels on day 19 but negative minimal residual disease (<0·01%) on day 46 were treated for standard-risk ALL and had a 10-year event-free survival of 88·9% (43·3–98·4). For the 280 provisional low-risk patients, a minimal residual disease level of less than 1% on day 19 predicted a better outcome, irrespective of the minimal residual disease level on day 46. Of provisional standard-risk patients with minimal residual disease of less than 1% on day 19, the 15 with persistent minimal residual disease on day 46 seemed to have an inferior 10-year event-free survival compared with the 126 with negative minimal residual disease (72·7%, 42·5–88·8 vs 84·0%, 76·3–89·4; p=0·06) after receiving the same post-remission treatment for standard-risk ALL. Of patients attaining negative minimal residual disease status after remission induction, minimal residual disease re-emerged in four of 382 studied on week 7, one of 448 at week 17, and one of 437 at week 48; all but one of these six patients died despite additional treatment. By contrast, relapse occurred in only two of the 11 patients who had decreasing minimal residual disease levels between the end of induction and week 7 of maintenance therapy and were treated with chemotherapy alone. Interpretation Minimal residual disease levels during remission induction treatment have important prognostic and therapeutic implications even in the context of minimal residual disease-guided treatment. Sequential minimal residual disease monitoring after remission induction is warranted for patients with detectable minimal residual disease. Funding National Institutes of Health and American Lebanese Syrian Associated Charities.
The present exploratory cross‐sectional case–control study sought to develop a reliable and scalable screening tool for autism using a social robot. The robot HUMANE, installed with computer vision ...and linked with recognition technology, detected the direction of eye gaze of children. Children aged 3–8 (M = 5.52; N = 199) participated, 87 of whom had been confirmed with autism, 55 of whom were suspected to have autism, and 57 of whom were not considered to cause any concern for having autism. Before a session, a human experimenter instructed HUMANE to narrate a story to a child. HUMANE prompted the child to return his/her eye gaze to the robot if the child looked away, and praised the child when it re‐established its eye gaze quickly after a prompt. The reliability of eye gaze detection was checked across all pairs of human raters and HUMANE and reached 0.90, indicating excellent interrater agreement. Using the pre‐specified reference standard (Autism Spectrum Quotient), the sensitivity and specificity of the index tests (i.e., the number of robot prompts and duration of inattentiveness) reached 0.88 or above and the Diagnostic Odds Ratios were beyond 190. These results show that social robots may detect atypical eye patterns, suggesting a potential future for screening autism using social robots.
Lay summary
The present study sought to develop a feasible, scalable, and reliable screening tool that can characterize autism features and identify the children who are most in need of follow‐up by a specialist. A social robot, HUMANE, which had been installed with a vision system and linked with recognition technology, was programmed to detect eye gaze in children ages 3 to 8 while the robot was narrating stories to them. HUMANE reliably detected when children did not attend 5 s or more. In addition, the number of times HUMANE prompted the child's averted gaze (≥3 s) and the cumulative inattentive duration it detected (≥25 s) can identify predefined atypical eye contact, suggesting a potential for social robots in screening autism.
The aim of this paper is to elucidate Franz Brentano's concept of immanent object through his own words and from his own perspective. The prevalent account of Brentano's revival of intentionality, ...his initial failure to distinguish between object and content, and his wrong‐headed immanentism, is largely derived from his students. Brentano's objection to it, although well known, is seldom heeded. In fact, plenty of guidelines have been provided by Brentano himself in his writings on how his concept of immanent object is to be understood. I begin with his distinction between two senses of “object,” which, I argue, must be clearly set apart from distinction between two modes of object. I then examine three different interpretations of the term “in‐existence”: the locative, the inherentist, and the objective interpretation. In the end, after dismissing the first two interpretations, I argue that Brentano is best understood as maintaining an objective and deflationary account of mental in‐existence.
Rendezvous is a fundamental operation for cognitive users to establish communication links. In 5, we proposed a jump-stay (JS) rendezvous algorithm which was shown to have the overall best ...performance. In this work, we propose an enhanced jump-stay (EJS) algorithm. Compared with JS, EJS lowers the upper-bounds of both the maximum time-to-rendezvous (MTTR) and the expected time-to-rendezvous (E(TTR)) from O(P 3 ) to O(P 2 ) under the asymmetric model, while keeping the same order O(P) of upper-bounds of MTTR and E(TTR) under the symmetric mode, where P is the smallest prime number greater than the total number of channels.
Fetal DNA is present in the plasma of pregnant women. Massively parallel sequencing of maternal plasma DNA has been used to detect fetal trisomies 21, 18, 13 and selected sex chromosomal aneuploidies ...noninvasively. Case reports describing the detection of fetal microdeletions from maternal plasma using massively parallel sequencing have been reported. However, these previous reports were either polymorphism-dependent or used statistical analyses which were confined to one or a small number of selected parts of the genome. In this report, we reported a procedure for performing noninvasive prenatal karyotyping at 3 Mb resolution across the whole genome through the massively parallel sequencing of maternal plasma DNA. This method has been used to analyze the plasma obtained from 6 cases. In three cases, fetal microdeletions have been detected successfully from maternal plasma. In two cases, fetal microduplications have been detected successfully from maternal plasma. In the remaining case, the plasma DNA sequencing result was consistent with the pregnant mother being a carrier of a microduplication. Simulation analyses were performed for determining the number of plasma DNA molecules that would need to be sequenced and aligned for enhancing the diagnostic resolution of noninvasive prenatal karyotyping to 2 Mb and 1 Mb. In conclusion, noninvasive prenatal molecular karyotyping from maternal plasma by massively parallel sequencing is feasible and would enhance the diagnostic spectrum of noninvasive prenatal testing.
We evaluated the feasibility of existing risk assessment tools for chronic myeloid leukemia (CML) in children. Fifty-five patients with newly diagnosed CML between 1996 and 2019 were included. ...Forty-nine patients presented in chronic phase, thirty-six of whom were treated with upfront tyrosine kinase inhibitor (CP-TKI group); one presented in accelerated phase and four in blastic phase. Treatment, survival, responses, and tolerance were evaluated. All patients in the CP-TKI group received imatinib as their first TKI treatment. The 10-year overall survival (OS), progression-free survival (PFS), and event-free survival (EFS) of TKI-treated group was 97%, 91.4%, and 72.3%, respectively. At 60 months, the rates of major molecular response were 81.2% and deep molecular response was 67.5%. The EUTOS long-term survival (ELTS) risk grouping did not predict OS, PFS, or EFS. The IMAFAIL risk groups were correlated with the risk of imatinib failure. Further studies are required to modify the existing risk assessment tools for children.
A new design concept of a generalized dual-band branch-line coupler with unequal power division and four arbitrary terminated resistances is proposed in this paper. By using an external ...frequency-dependent impedance transformer, a novel dual-band branch-line coupler is obtained with a detailed analytical design method. For ease of design, maximum power-dividing ratio with varying frequency ratio for different terminated impedance values is provided. Owing to the additional design freedom, the calculation of parameters becomes much more flexible. Finally, for experimental validation and convenient measurement, a dual-band unequal microstrip branch-line coupler with four standard ports is designed, fabricated, and measured. Good agreement between the simulated and measured results can be observed.
Recently, several approaches for multiscale simulations for problems with high contrast and no scale separation are introduced. Among them is nonlocal multicontinua (NLMC) method, which introduces ...multiple macroscopic variables in each computational grid. These approaches explore the entire coarse block resolution and one can obtain optimal convergence results independent of contrast and scales. However, these approaches are not amenable to many multiscale simulations, where the subgrid effects are much smaller than the coarse-mesh resolution. For example, molecular dynamics of shale gas occurs in much smaller length scales compared to the coarse-mesh size, which is of orders of meters. In this case, one cannot explore the entire coarse-grid resolution in evaluating effective properties. In this paper, we merge the concepts of nonlocal multicontinua methods and Representative Volume Element (RVE) concepts to explore problems with extreme scale separation. The first step of this approach is to use sub-grid scale (sub to RVE) to write a large-scale macroscopic system. We call it intermediate scale macroscale system. In the next step, we couple this intermediate macroscale system to the simulation grid model, which are used in simulations. This is done using RVE concepts, where we relate intermediate macroscale variables to the macroscale variables defined on our simulation coarse grid. Our intermediate coarse model allows formulating macroscale variables correctly and coupling them to the simulation grid. We present the general concept of our approach and present details of single-phase flow. Some numerical results are presented. For nonlinear examples, we use machine learning techniques to compute macroscale parameters.
Residents of Residential Age Care Facilities (RACFs) have particularly high rates of Emergency Department (ED) visits, with up to 55% being potentially avoidable (e.g. not resulting in a hospital ...admission). This is concerning as ED visits by RACF residents are associated with negative outcomes including longer hospital stays, iatrogenic illness, complications and mortality. Limited English proficiency (LEP) has significant negative impacts on the healthcare quality and outcomes for older people but has not been studied as a factor in ED visits from RACFs. This study aimed to examine if RACF residents with LEP have a lower rate of hospital admission via the ED compared to non‐LEP controls and identify any associated factors. We hypothesised that LEP‐related communication difficulties would reduce the ability to manage minor health issues in the RACF, leading to a lower proportion of LEP ED transfers being admitted. We used a parallel mixed‐methods design, comprising a quantitative matched cohort study of ED visit data from two Local Hospital Networks (LHNs) in South‐East Melbourne, Australia and secondary thematic analysis of 25 interviews with LEP residents, family carers and staff from two RACFs in the same region. We found no differences in the proportion of hospital ED transfers that led to admission (LHN1, 87.1% LEP, 85.6% non‐LEP controls, p = 0.57; LHN2, 76.0% LEP, 76.9% non‐LEP controls, p = 0.41) and no direct qualitative evidence suggesting that resident LEP affected decisions to transfer residents to ED, despite communication difficulties being reported during the transfer process. These results may be due to the high level of family carer involvement in residents’ care identified in the qualitative study. However, additional research using different measures of LEP is recommended to further explore a broader range of cultural and linguistic factors in both rates of ED presentations and the decision‐making processes underpinning resident transfers to ED.
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