Can Computer-Assisted Training of Prerequisite Motor Skills Help Enable Communication in People with Autism?

Our and others' research indicates that in fully a third of people with autism who lack communicative speech, the communication deficit may actually be a deficit in motor skills necessary to move the mouth and the vocal tract. These individuals have difficulties in fine, gross and especially oral motor skills, and a disparity between impaired expressive language and relatively intact receptive language: that is to say, they can listen but not speak. Because involvement in research and receipt of the fullest educational, occupational and other services demands ability to interact verbally and to control one's movements and actions, these people get the short end of the stick when it comes to scientific enquiry and pedagogic and therapeutic practice. Point OutWords, tablet-based software designed in collaboration with autistic clients and their communication therapists, exploits the autistic fascination with parts and details to motivate attention to learning manual motor and oral motor skills essential for communication. Along the way, autistic clients practise pointing and dragging at objects, then pointing at sequences of letters on a keyboard, and even speaking the syllables represented by these letters. Whereas many teaching and learning strategies adapted from methods for non-autistic people end up working against autistic cognition by asking people with autism to do what they cannot easily do, Point OutWords works with autistic cognition, by beginning from the autistic skill at manipulating parts and details. Users and their parents or guardians can opt into collection of data on motor interactions with Point OutWords; these internal measures of motor skills development are complemented by external, standardised tests of motor, oral motor and communicative development. These quantitative measures are collected alongside reports on Point OutWords's acceptability to users, and users' fidelity to a recommended treatment regime, so as to evaluate feasibility of a larger randomised controlled trial

Critical parameters influencing the EUV-induced damage of Ru-capped multilayer mirrors

Ongoing endurance testing of Ru-capped multilayer mirrors (MLMs) at the NIST synchrotron facility has revealed that the damage resulting from EUV irradiation does not always depend on the exposure conditions in an intuitive way. Previous exposures of Ru-capped MLMs to EUV radiation in the presence of water vapor demonstrated that the mirror damage rate actually decreases with increasing water pressure. We will present results of recent exposures showing that the reduction in damage for partial pressures of water up to 5 x 10{sup -6} Torr is not the result of a spatially uniform decrease in damage across the Gaussian intensity distribution of the incident EUV beam. Instead we observe a drop in the damage rate in the center of the exposure spot where the intensity is greatest, while the reflectivity loss in the wings of the intensity distribution appears to be independent of water partial pressure. (See Fig. 1.) We will discuss how the overall damage rate and spatial profile can be influenced by admixtures of carbon-containing species (e.g., CO, CO{sub 2}, C{sub 6}H{sub 6}) at partial pressures one-to-two orders of magnitude lower than the water vapor partial pressure. An investigation is underway to find the cause of the non-Gaussian damage profile. Preliminary results and hypotheses will be discussed. In addition to high-resolution reflectometry of the EUV-exposure sites, the results of surface analysis such as XPS will be presented. We will also discuss how the bandwidth and time structure of incident EUV radiation may affect the rate of reflectivity degradation. Although the observations presented here are based on exposures of Ru-capped MLMs, unless novel capping layers are similarly characterized, direct application of accelerated testing results could significantly overestimate mirror lifetime in the production environment

EUV testing of multilayer mirrors: critical issues

Recently, while performing extensive EUV irradiation endurance testing on Ru-capped multilayer mirrors in the presence of elevated partial pressures of water and hydrocarbons, NIST has observed that the amount of EUV-induced damage actually decreases with increasing levels of water vapor above {approx} 5 x 10{sup -7} Torr. It is thought that the admitted water vapor may interact with otherwise stable, condensed carbonaceous species in an UHV vacuum system to increase the background levels of simple gaseous carbon-containing molecules. Some support for this hypothesis was demonstrated by observing the mitigating effect of very small levels of simple hydrocarbons with the intentional introduction of methyl alcohol in addition to the water vapor. It was found that the damage rate decreased by at least an order of magnitude when the partial pressure of methyl alcohol was just one percent of the water partial pressure. These observations indicate that the hydrocarbon components of the vacuum environment under actual testing conditions must be characterized and controlled to 10{sup -11} Torr or better in order to quantify the damage caused by high levels of water vapor. The possible effects of exposure beam size and out-of-band radiation on mirror lifetime testing will also be discussed

Centrosome clustering and Cyclin D1 gene amplification in double minutes are common events in chromosomal unstable bladder tumors

Background: Aneuploidy, centrosome abnormalities and gene amplification are hallmarks of chromosome instability (CIN) in cancer. Yet there are no studies of the in vivo behavior of these phenomena within the same bladder tumor. Methods: Twenty-one paraffin-embedded bladder tumors were analyzed by conventional comparative genome hybridization and fluorescence in situ hybridization (FISH) with a cyclin D1 gene (CCND1)/centromere 11 dual-color probe. Immunofluorescent staining of α, β and γ tubulin was also performed. Results: Based on the CIN index, defined as the percentage of cells not displaying the modal number for chromosome 11, tumors were classified as CIN-negative and CIN-positive. Fourteen out of 21 tumors were considered CIN-positive. All T1G3 tumors were included in the CIN-positive group whereas the majority of Ta samples were classified as CIN-negative tumors. Centrosome clustering was observed in six out of 12 CIN-positive tumors analyzed. CCND1 amplification in homogeneously staining regions was present in six out of 14 CIN-positive tumors; three of them also showed amplification of this gene in double minutes. Conclusions: Complex in vivo behavior of CCND1 amplicon in bladder tumor cells has been demonstrated by accurate FISH analysis on paraffin-embedded tumors. Positive correlation between high heterogeneity, centrosome abnormalities and CCND1 amplification was found in T1G3 bladder carcinomas. This is the first study to provide insights into the coexistence of CCND1 amplification in homogeneously staining regions and double minutes in primary bladder tumors. It is noteworthy that those patients whose tumors showed double minutes had a significantly shorter overall survival rate (p < 0.001)

Distributed collaborative writing: a comparison of spoken and written modalities for reviewing and revising documents

Previous research indicates that voice annotation helps reviewers to express the more complex and social aspects of a collaborative writing task. Little direct evidence exists, however, about the effect of voice annotations on the writers who must use such annotations. To test the effect, we designed an interface intended to alleviate some of the problems associated with the voice modality and undertook a study with two goals; to compare the nature and quantity of voice and written comments, and to evaluate how writers responded to comments produced in each mode. Writers were paired with reviewers who made either written or spoken annotations from which the writers revised. The study provides direct evidence that the greater expressivity of the voice modality, which previous research suggested benefits reviewers, produces annotations that writers also find usable. Interactions of modality with the type of annotation suggest specific advantages of each mode for enhancing the processes of review and revision

Assoc. Computer Support for Distributed Collaborative Writing: A Coordination Science Perspective

The goal of our research is to provide computer support for distributed collaborative writing. Writers can be said to be distributed when they have distributed knowledge and skill, and they share that knowledge and skill in order to develop a draft; or, even when they have significant overlap in knowledge and skill, they distribute the work of producing the draft itself among them. But in this sense, all collaborative writing is distributed. In the sense we will use the term here, distributed collaborative writing refers to, additionally, situations in which the writers are distributed in time (i.e., they do not work on the artifact at the same time) or place (i.e., they do not meet face-to-face). The central research questions in distributed collaborative writing are &amp;quot;What does the process of producing a written product look like when it is divided among writers who coordinate to produce it over time and space? &amp;quot; and &amp;quot;What is the relationship of these processes to success? &amp;quot; When the process includes &amp;quot;active agents, &amp;quot; the scope of the first question shifts slightly to include not only people, but computers as well. This question is, of course, the central question of &amp;quot;distributed cognition &amp;quot; or &amp;quot;coordination science, &amp;quot; applied to collaborative writing. In analogy with the way cognitive scientists (psychologists, AI researchers, etc.) are interested in identifying strategies and representations involved in individual cognition, coordination scientists are intereste

Outcomes for Hispanic Patients with Acute Leukemia Treated at Academic Centers

Abstract Introduction: Health disparities for underrepresented U.S. minority populations with hematologic cancers contribute to differential treatment and higher death rates. The Hispanic population (including people of Mexican, South/Central American, Cuban, Puerto Rican, or other Spanish-speaking cultures, regardless of race) collectively constitutes the largest minority group in the United States. Hispanic patients have been reported to have an increased incidence of B-cell acute lymphoblastic lymphoma (B-ALL) and acute promyelocytic leukemia (APL). While APL is associated with favorable outcomes compared to other acute leukemias, registry data suggest poorer outcomes in Hispanic patients with both acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML). The Hispanic paradox is an epidemiological paradox that refers to the finding that Hispanic patients have paradoxically comparable, or better, health outcomes compared to their U.S. non-Hispanic White counterparts despite barriers to care such as lower socioeconomic status. This paradox has also been reported in hematologic malignancies. Definitive data regarding differences in outcome between Hispanic and non-Hispanic patients with acute leukemias (AL) are lacking. We sought to compare outcomes of Hispanic patients and non- Hispanic patients with acute leukemia with access to care, and examine whether the Hispanic paradox reported in hematologic malignancies is attributable to enrichment of patients with highly curable disease such as APL. Methods: Using data from a Vizient Clinical Data Base, a healthcare claims database, we identified patients with leukemia using ICD 10 codes for acute leukemia. Adult patients with AL, ages 18-89 who were treated between January 2020 and June 2021 were evaluated. Data from 121 academic centers was included. We focused on academic centers to limit the impact of access to care . Demographic information was obtained from the registry, to which ethnicity was self-reported. Patients were stratified by age, and we compared complication rates, number of complications, number of deaths, percent deaths and mortality index between Hispanic and non-Hispanic patients. The key metric used to compare outcomes of Hispanic patients with non-Hispanic patients was the severity adjusted mortality index, which is the ratio of observed mortality over expected mortality for patients with the same diagnosis in this registry. Chi-squared test is used for to determine the statistical significance of differences in mortality (by age group) in Hispanics v. non-Hispanic patients. Initial analysis included all patients with acute leukemias, and the data was subsequently reanalyzed excluding patients with APL, as APL is known to portend a favorable prognosis. Results: A total of 29,967 patients were with acute leukemia were evaluated; of these patients, 2903 identified as Hispanic and 27,064 were non- Hispanic. As seen in table 1, patients of Hispanic origin generally had lower treatment related complication rates in all age groups compared to their age matched non-Hispanic counterparts. Except for the 51-64 and 80-84 age groups the mortality index was lower in Hispanic patients compared to non-Hispanic peers. Differences in mortality between Hispanic and non-Hispanic patients in all age groups were not statistically significant. Trends to a lower mortality index in Hispanic patients are highlighted in green in table 1. When patients with APL were excluded from the analysis, the trend lower mortality in Hispanic patients in most age groups persisted. Again, the mortality index was comparatively higher in hispanic patients in the 51-64 and 80-84 age groups, but differences in mortality between Hispanic and non- Hispanic patients were not statistically significant. Exclusion of APL patients did not have a significant impact on the complication rate or mortality supporting that the Hispanic paradox is independent of higher rates of very favorable risk myeloid malignacies in this population. Conclusions: Hispanic patients with access to academic cancer centers have the potential for non-inferior outcomes compared to non-Hispanic patients. Equivalent outcomes as assessed by mortality index were not attributable solely to the higher incidence of very favorable risk disease such as APL in the Hispanic population. Figure 1 Figure 1. Disclosures Watts: Takeda: Consultancy, Research Funding; Genentech: Consultancy; Rafael Pharma: Consultancy; Celgene/BMS: Consultancy. Bradley: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Sekeres: Takeda/Millenium: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees

Real World Outcomes of Liposomal Daunorubicin and Cytarabine Versus 7+3 in Patients with Secondary Acute Myeloid Leukemia

Introduction: Liposomal daunorubicin and cytarabine (CPX-351) was approved based on data which showed improved overall survival (9.56 v 5.95 months; p = .003) and remission rates (47.7% v 33.3%; p = .016) compared to conventional cytarabine and daunorubicin (7+3) chemotherapy in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). Patients receiving CPX-351 had prolonged time to neutrophil and platelet count recovery compared to 7+3, which was not associated with adverse outcomes (Lancet et al, JCO 2018). Based on these data, our center adopted CPX-351 as a first-line agent in this patient population. Considering the significant cost differences and delays in count recovery, we conducted a comparison of outcomes in patients who received CPX-351 versus 7+3 at our center. Methods: The objective of this study was to compare efficacy and safety of CPX-351 versus 7+3 in patients with sAML. Primary outcome was response rate as defined by CR or CRi. Secondary outcomes included duration of neutropenia, incidence of invasive fungal infections (IFIs), and number of patients proceeding to allogeneic hematopoietic cell transplant (HCT). Patients with sAML receiving induction with 7+3 (daunorubicin dosed at 60 or 90 mg/m2 per treating physician's discretion) or CPX-351 from July 2014 to April 2020 were reviewed. Secondary AML was defined as: AML with a history of myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML), AML with myelodysplasia-related changes, or therapy-related AML. Patients with prior myeloproliferative neoplasms, myelofibrosis, or FLT3 mutations were excluded. Patient characteristics were summarized using descriptive statistics (TABLE 1) including mean for continuous measures and proportions and frequencies for categorical measures. The association between continuous variables and patient groups were assessed using ANOVA or Student's t-test. The associations between categorical variables and patient groups were evaluated using Chi-square test. Results: Over the study period, 65 patients with sAML received induction therapy with either CPX-351 (n = 31) or 7+3 (n = 34). Of these, 61 patients had an evaluable bone marrow biopsy at count recovery. The data is summarized in Table 2. The response rates (CR or CRi) were no different (36% 7+3 vs 36% CPX-351, p = 0.958) among the study population. Longer duration of neutropenia was observed with CPX-351 (33 days 7+3 vs 47 days CPX-351, p = 0.026). More patients in the 7+3 arm proceeded to allogeneic HCT; however, this was not statistically significant (59% 7+3 vs 39% CPX-351, p = 0.105). In an efficacy subgroup analysis of patients with TP53 mutation, there was no difference in response rates (33% 7+3 vs 11% CPX-351, p = 0.224). There was no difference in IFI between the groups (38% 7+3 vs 42% CPX-351, p = 0.761). Upon further analysis of IFI characteristics, there was no difference in choice of mold-active vs non mold-active prophylaxis (ppx) and the incidence of IFIs (40% mold ppx vs 39% non-mold ppx, p = 0.91). Patients with baseline neutropenia prior to induction did not have increased risk of IFIs (65% 7+3 vs 74% CPX-351, p = 0.626). Additionally, there were no between group differences in incidence of IFIs in patients who were neutropenic prior to induction. Conclusions: In the evaluable dataset of patients receiving 7+3 or CPX-351, there was no difference in CR/CRi rate between the two subgroups. There was a longer duration of neutropenia in the CPX-351 group without increased incidence of IFI. However, we report a higher incidence of IFI compared to the study population in Lancet et al (18% Lancet vs 40% Miami) despite appropriate anti-fungal prophylaxis, which may be due to patient selection on the clinical trial, demographic differences (e.g., age, ethnicity), or locoregional environmental factors. In our population, a greater percentage of patients who received 7+3 proceeded to allogeneic HCT. While this study was not powered to detect a significant difference between the two regimens and these findings require validation in larger cohorts, they do not support superior outcomes in patients who receive CPX-351. Data on differences in hospital costs will also be presented. Future directions include a larger multi-center real-world analysis to evaluate patient outcomes, safety, and the financial implications of these two regimens. Disclosures Watts: Genentech: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Rafael Pharma: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Aptevo Therapeutics: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees