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The challenge of eradicating leukemia in patients with acute myelogenous leukemia (AML) after initial cytoreduction has motivated modern efforts to combine synergistic active modalities including immunotherapy. Recently, the ETCTN/CTEP 10026 study tested the combination of the DNA methyltransferase inhibitor decitabine together with the immune checkpoint inhibitor ipilimumab for AML/myelodysplastic syndrome (MDS) either after allogeneic hematopoietic stem cell transplantation (HSCT) or in the HSCT-naïve setting. Integrative transcriptome-based analysis of 304 961 individual marrow-infiltrating cells for 18 of 48 subjects treated on study revealed the strong association of response with a high baseline ratio of T to AML cells. Clinical responses were predominantly driven by decitabine-induced cytoreduction. Evidence of immune activation was only apparent after ipilimumab exposure, which altered CD4+ T-cell gene expression, in line with ongoing T-cell differentiation and increased frequency of marrow-infiltrating regulatory T cells. For post-HSCT samples, relapse could be attributed to insufficient clearing of malignant clones in progenitor cell populations. In contrast to AML/MDS bone marrow, the transcriptomes of leukemia cutis samples from patients with durable remission after ipilimumab monotherapy showed evidence of increased infiltration with antigen-experienced resident memory T cells and higher expression of CTLA-4 and FOXP3. Altogether, activity of combined decitabine and ipilimumab is impacted by cellular expression states within the microenvironmental niche of leukemic cells. The inadequate elimination of leukemic progenitors mandates urgent development of novel approaches for targeting these cell populations to generate long-lasting responses. This trial was registered at www.clinicaltrials.gov as #NCT02890329.

Purpose: This research note illustrates the effects of video data with nonsquare pixels on the pixel-based measures obtained from videofluoroscopic swallow studies (VFSS). Method: Six pixel-based distance and area measures were obtained from two different videoflouroscopic study units; both yielding videos with nonsquare pixels with different pixel aspect ratios (PARs). The swallowing measures were obtained from the original VFSS videos and from the videos after their pixels were squared. Results: The results demonstrated significant multivariate effects both in video type (original vs. squared) and in the interaction between video type and sample (two video recordings of different patients, different PARs, and opposing tilt angles of the external reference). A wide range of variabilities was observed on the pixel-based measures between original and squared videos with the percent deviation ranging from 0.1% to 9.1% with the maximum effect size of 7.43. Conclusions: This research note demonstrates the effect of disregarding PAR to distance and area pixel-based parameters. In addition, we present a multilevel roadmap to prevent possible measurement errors that could occur. At the planning stage, the PAR of video source should be identified, and, at the analyses stage, video data should be prescaled prior to analysis with PAR-unaware software. No methodology in prior absolute or relative pixel-based studies reports adjustment to the PAR prior to measurements nor identify the PAR as a possible source of variation within the literature. Addressing PAR will improve the precision and stability of pixel-based VFSS findings and improve comparability within and across clinical and research settings. Supplemental Material: https://doi.org/10.23641/asha.21957134

Purpose: Postswallow pharyngeal residue is a risk factor for aspiration, implies swallowing inefficiency, and increases the work of eating. The Bolus Clearance Ratio (BCR) is a derived metric that relates quantities of bolus material observed in the pharynx at two different points: before and after a swallow. The ratio provides a percentage estimate of bolus clearance. In healthy adults, mean BCR is < .05; that is, less than 5% of an ingested bolus is retained in the pharynx. The aim of this study was to compare BCR measures from patients referred for videofluoroscopic swallow studies with concerns related to stroke ( n = 100) or other neurological conditions ( n = 131, including Parkinson's disease and dementia) with BCRs for 139 healthy adults across the age range. Method: BCR for a 20 ml of thin liquid barium bolus was measured. Additional metrics included age, penetration–aspiration scale (PAS) score, and quantitative measures of timing and displacement. Correlations were explored between BCR and pharyngeal constriction ratio (PCR), pharyngoesophageal segment opening (PESmax), maximum hyoid displacement (HMax), and total pharyngeal transit time (TPT). Results: BCR values for patients with stroke ( Mdn = 9%, interquartile range [IQR]: 19%, range: 0%–73%) and other neurological conditions ( Mdn = 9%, IQR: 16%, range: 0%–96%) were significantly higher than in healthy norms ( Mdn = 2%, IQR: 4%, range: 0%–16%, p < .001). BCR was significantly correlated with age ( R s = .23, p < .01), TPT ( R s = .20, p < .01), PCR ( R s = .55, p < .01), PESmax ( R s = −.17, p < .01), HMax ( R s = −.16, p < .01), and PAS ( R s = .38, p < .01). Conclusions: BCR was elevated in patients with neurogenic dysphagia in comparison with healthy norms and was significantly associated with increased aspiration severity (i.e., PAS). BCR was also correlated with pharyngeal timing and displacement parameters, with the strongest correlation with pharyngeal constriction—a measure of pharyngeal strength. The BCR offers clinicians a simple, quantitative measure of bolus residue and, therefore, pharyngeal efficiency and may be used to assess change in patients over time and with treatment.

Purpose:Patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) have poor outcomes and require new therapies. In AML, autocrine production of hepatocyte growth factor (HGF) drives MET signaling that promotes myeloblast growth and survival, making MET an attractive therapeutic target. MET inhibition exhibits activity in AML preclinical studies, but HGF upregulation by the FGFR pathway is a common mechanism of resistance.Patients and Methods:We performed preclinical studies followed by a Phase I trial to investigate the safety and biological activity of the MET inhibitor merestinib in combination with the FGFR inhibitor LY2874455 for patients with R/R AML. Study Cohort 1 underwent a safety lead-in to determine a tolerable dose of single-agent merestinib. In Cohort 2, dose-escalation of merestinib and LY2874455 was performed following a 3+3 design. Correlative studies were conducted.Results:The primary dose-limiting toxicity (DLT) observed for merestinib alone or with LY2874455 was reversible grade 3 transaminase elevation, occurring in 2 of 16 patients. Eight patients had stable disease and one achieved complete remission (CR) without measurable residual disease. Although the MTD of combination therapy could not be determined due to drug supply discontinuation, single-agent merestinib administered at 80 mg daily was safe and biologically active. Correlative studies showed therapeutic plasma levels of merestinib, on-target attenuation of MET signaling in leukemic blood, and increased HGF expression in bone marrow aspirate samples of refractory disease.Conclusions:We provide prospective, preliminary evidence that MET and FGFR are biologically active and safely targetable pathways in AML.

Patient disposition.

Survival outcomes for the overall cohort. A, Progression-free survival. B, Overall survival.

Purpose:Patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) have poor outcomes and require new therapies. In AML, autocrine production of hepatocyte growth factor (HGF) drives MET signaling that promotes myeloblast growth and survival, making MET an attractive therapeutic target. MET inhibition exhibits activity in AML preclinical studies, but HGF upregulation by the FGFR pathway is a common mechanism of resistance.Patients and Methods:We performed preclinical studies followed by a Phase I trial to investigate the safety and biological activity of the MET inhibitor merestinib in combination with the FGFR inhibitor LY2874455 for patients with R/R AML. Study Cohort 1 underwent a safety lead-in to determine a tolerable dose of single-agent merestinib. In Cohort 2, dose-escalation of merestinib and LY2874455 was performed following a 3+3 design. Correlative studies were conducted.Results:The primary dose-limiting toxicity (DLT) observed for merestinib alone or with LY2874455 was reversible grade 3 transaminase elevation, occurring in 2 of 16 patients. Eight patients had stable disease and one achieved complete remission (CR) without measurable residual disease. Although the MTD of combination therapy could not be determined due to drug supply discontinuation, single-agent merestinib administered at 80 mg daily was safe and biologically active. Correlative studies showed therapeutic plasma levels of merestinib, on-target attenuation of MET signaling in leukemic blood, and increased HGF expression in bone marrow aspirate samples of refractory disease.Conclusions:We provide prospective, preliminary evidence that MET and FGFR are biologically active and safely targetable pathways in AML.

Two articles in this week’s issue focus on the use of ipilimumab and decitabine for patients with myelodysplasia (MDS) and acute myeloid leukemia (AML) before and after hematopoietic stem cell transplantation (HSCT) for high-risk disease. In the first article, Garcia et al report on the results of a phase 1 trial of the combination in 54 patients, demonstrating overall response rate of 52% in patients who are HSCT-naïve and 20% in patients post-HSCT; responses are usually short-lived. In the second article, Penter and colleagues characterize gene expression responses to therapy and conclude that decitabine acts directly to clear leukemic cells while ipilimumab acts on infiltrating lymphocytes in marrow and extramedullary sites. Responses are determined by leukemic cell burden and by the frequency and phenotype of infiltrating lymphocytes. Increasing bone marrow regulatory T cells is identified as a potential contributor to checkpoint inhibitor escape.

Purpose This exploratory study assessed postural control and muscle activity in children with cerebral palsy while standing barefoot (BF), in prescribed ankle-foot orthoses (AFOs) and in distal control orthoses (DCOs), which stabilized foot-ankle and deliberately aligned the shank. Methods This within-subject study evaluated 10 participants, Gross Motor Functional Classification System level III, across the 3 ankle-foot conditions in: (1) static standing duration and (2) modified Clinical Test of Sensory Interaction on Balance with electromyography (EMG) on 7 muscles. Results Participants had significantly decreased center of gravity (COG) velocity sway in DCO versus BF and AFO, decreased loss of balance (LOB), and increased standing for DCO versus BF. DCO had minimal effect on EMG activity. Conclusions DCO provided significant stabilizing effects on COG sway velocity, standing duration, and LOB. DCO may be effective in balance training. It is unclear whether benefit was derived from stabilization of the ankle joint, the resultant shank alignment, or both.

Background: CD123 is a subunit of the interleukin 3 (IL3) receptor and is expressed on the surface of blasts in most cases of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). CD123 expression is often higher on leukemia cells than normal progenitors and may be enriched in residual cells surviving chemotherapy. Uniformly high CD123 is characteristic of blastic plasmacytoid dendritic cell neoplasm (BPDCN), an uncommon leukemia related to AML. Tagraxofusp (TAG, SL-401) is a recombinant protein drug consisting of IL3 fused to a truncated diphtheria toxin payload that targets CD123. Single agent TAG is approved for treatment of BPDCN. In preclinical models and in patients who received TAG, we previously found that TAG resistance in AML and BPDCN was mediated by DNA methylation and downregulation of diphthamide genes (e.g. DPH1) and subsequent resistance to diphtheria toxin (Togami, JCI 2019). TAG resistance was reversible by the hypomethylating agent azacitidine (AZA), and TAG plus AZA was more effective than either alone in xenograft models. Therefore, we performed a phase 1b trial combining TAG with AZA or with AZA and venetoclax (VEN) in patients with AML, MDS, or BPDCN. Methods: Detection of CD123 on blasts by flow or IHC was required. Eligibility included albumin ≥3.2 g/dL, normal cardiac ejection fraction, and hospitalization in cycle 1 to mitigate risks of capillary leak syndrome (CLS). The study followed a 3+3 dose escalation, plus expansion cohorts, of 28-day cycles of TAG with fixed doses of AZA or AZA-VEN. First, we tested 5 schedules of the doublet TAG (5 or 7 μg/kg/d1-5, or 7, 9, or 12 μg/kg/d1-3) with standard doses of AZA (75 mg/m2 d1-7) in newly diagnosed AML (1L), relapsed/refractory AML (R/R), or MDS with ≥10% blasts. Next, we tested 3 doses of the triplet TAG (7, 9, or 12 μg/kg/d4-6) with AZA (75 mg/m2 d1-7) and VEN (400 mg d1-21, ramp up d1-3 in cycle 1) in 1L AML, R/R AML, or R/R BPDCN. Results: 34 patients have been enrolled and 33 are evaluable (one withdrew prior to therapy). The age range is 21-86 (median 67). Median follow up is 8.4 months [95% CI, 7.1-19.1]. 18 received TAG-AZA (5 1L AML, 9 R/R AML, 4 MDS); 15 received TAG-AZA-VEN (9 1L AML, 3 R/R AML, 3 R/R BPDCN). An MTD was not reached, and the recommended phase 2 dose of TAG was determined to be 12 μg/kg/d x3d in each combination. Adverse events (AEs) were as expected for TAG or AZA+/-VEN. Grade 3+ AEs in >10% included neutropenia (30%), thrombocytopenia (27%), anemia (18%), febrile neutropenia (18%), ALT increase (12%), and bilirubin increase (12%). Eleven of 33 (33%) experienced CLS: 8 (24%) were grade 2, 2 grade 3 (6%), and 1 grade 4 (3%). One treatment-related death occurred in a 79 year-old with AML receiving TAG-AZA-VEN who experienced tumor lysis syndrome followed by CLS and multiorgan system failure during cycle 1. Eight of 9 patients (89%) with previously untreated AML (ages 59-81, median 74; 7 of 9 ELN adverse risk) who received TAG-AZA-VEN achieved best response of complete response (CR, n=5) or complete response with incomplete count recovery (CRi, n=3), at TAG doses of 7 (n=2), 9 (n=1), or 12 μg/kg/d x3d (n=6). The 8 with CR/CRi included two AMLs with TP53 mutation and adverse karyotype, and three with secondary AML, two which had concomitant mature pDC expansion, a.k.a. "pDC-AML" (Xiao, Blood 2021). At the time of data cut off, 4 of 8 have gone to allogeneic stem cell transplantation (alloSCT) and 3 remain on therapy. Three patients with relapsed/refractory BPDCN (all had prior single agent TAG) received TAG-AZA-VEN and 2 of 3 responded (CRc=1, CRi=1), who both went to alloSCT. Four patients with previously untreated MDS and ≥10% blasts received TAG-AZA. 3 of 4 responded (all 3 with TP53 mutation) with CR (n=2) and marrow CR (n=1), and two went to alloSCT. Among 14 patients with 1L (5) or R/R (9) AML on TAG-AZA, and 3 with R/R AML on TAG-AZA-VEN, one with 1L AML (17p- and complex karyotype) achieved a CRi on TAG-AZA. Responses in all groups included patients with high and low CD123 by central flow. Conclusions: Combining TAG with AZA or AZA-VEN is feasible, with expected TAG or AZA+/-VEN toxicities. CLS is an important consideration for TAG, requiring monitoring and early implementation of supportive care. The activity of TAG-AZA-VEN in previously untreated AML and R/R BPDCN, and of TAG-AZA in MDS are encouraging, including in high-risk AML/MDS subtypes such as TP53 mutated. These data support continued development of TAG combinations in CD123+ malignancies. Figure 1 Figure 1. Disclosures Lane: Qiagen: Consultancy, Honoraria; N-of-One: Consultancy, Honoraria; Stemline Therapeutics: Research Funding; AbbVie: Research Funding. Stein: Amgen: Consultancy, Speakers Bureau; Celgene: Speakers Bureau; Stemline: Speakers Bureau. Garcia: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; AstraZeneca: Research Funding; Genentech: Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Prelude: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Stone: AbbVie: Consultancy; Syros: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Agios: Consultancy, Research Funding; Celgene: Consultancy; Astellas: Membership on an entity's Board of Directors or advisory committees; BerGen Bio: Membership on an entity's Board of Directors or advisory committees; Boston Pharmaceuticals: Consultancy; Bristol Myers Squibb: Consultancy; Foghorn Therapeutics: Consultancy; Elevate Bio: Membership on an entity's Board of Directors or advisory committees; Onconova: Consultancy; Syndax: Membership on an entity's Board of Directors or advisory committees; Syntrix/ACI: Membership on an entity's Board of Directors or advisory committees; Arog: Consultancy, Research Funding; Gemoab: Membership on an entity's Board of Directors or advisory committees; Actinium: Membership on an entity's Board of Directors or advisory committees; Innate: Consultancy; GlaxoSmithKline: Consultancy; Janssen: Consultancy; Jazz: Consultancy; Novartis: Consultancy, Research Funding; Aprea: Consultancy; Amgen: Membership on an entity's Board of Directors or advisory committees; Macrogenics: Consultancy. Winer: Novartis: Consultancy; Takeda: Consultancy; Abbvie: Consultancy. Mughal: Oxford University Press, Informa: Other: financial benefit and/or patents ; Stemline: Current Employment, Current holder of stock options in a privately-held company. Brooks: Stemline Therapeutics: Current Employment. Konopleva: KisoJi: Research Funding; Novartis: Other: research funding pending, Patents & Royalties: intellectual property rights; Rafael Pharmaceuticals: Other: grant support, Research Funding; Sanofi: Other: grant support, Research Funding; Eli Lilly: Patents & Royalties: intellectual property rights, Research Funding; Ascentage: Other: grant support, Research Funding; Stemline Therapeutics: Research Funding; Agios: Other: grant support, Research Funding; Reata Pharmaceuticals: Current holder of stock options in a privately-held company, Patents & Royalties: intellectual property rights; Ablynx: Other: grant support, Research Funding; AstraZeneca: Other: grant support, Research Funding; Cellectis: Other: grant support; Calithera: Other: grant support, Research Funding; F. Hoffmann-La Roche: Consultancy, Honoraria, Other: grant support; Forty Seven: Other: grant support, Research Funding; Genentech: Consultancy, Honoraria, Other: grant support, Research Funding; AbbVie: Consultancy, Honoraria, Other: Grant Support, Research Funding. Pemmaraju: DAVA Oncology: Consultancy; Springer Science + Business Media: Other; Samus: Other, Research Funding; MustangBio: Consultancy, Other; Incyte: Consultancy; Clearview Healthcare Partners: Consultancy; LFB Biotechnologies: Consultancy; Stemline Therapeutics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Abbvie Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Blueprint Medicines: Consultancy; Roche Diagnostics: Consultancy; Novartis Pharmaceuticals: Consultancy, Other: Research Support, Research Funding; Dan's House of Hope: Membership on an entity's Board of Directors or advisory committees; Plexxicon: Other, Research Funding; Celgene Corporation: Consultancy; ASCO Leukemia Advisory Panel: Membership on an entity's Board of Directors or advisory committees; HemOnc Times/Oncology Times: Membership on an entity's Board of Directors or advisory committees; Affymetrix: Consultancy, Research Funding; ASH Communications Committee: Membership on an entity's Board of Directors or advisory committees; Protagonist Therapeutics, Inc.: Consultancy; Sager Strong Foundation: Other; Daiichi Sankyo, Inc.: Other, Research Funding; Cellectis S.A. ADR: Other, Research Funding; Aptitude Health: Consultancy; CareDx, Inc.: Consultancy; Bristol-Myers Squibb Co.: Consultancy; ImmunoGen, Inc: Consultancy; Pacylex Pharmaceuticals: Consultancy.

Introduction Oral tyrosine kinase inhibitors (TKIs) that inhibit the constitutively active ABL1 kinase have improved outcomes for BCR-ABL1+ acute lymphoblastic leukemia (ALL) and decreased reliance on cytotoxic chemotherapy (ctx). Later generation, more potent TKIs such as dasatinib (DAS) are particularly effective (Foa et al. Blood 2011; Foa et al. N Eng J Med 2020). ABL001 (asciminib) is a STAMP (Specifically Targeting the ABL Myristoyl Pocket) allosteric inhibitor of ABL1 that binds to a site spatially distinct from all approved ATP-competitive TKIs. Combination treatment with an allosteric and an ATP-competitive TKI may deepen clinical responses and limit mutational resistance as supported by a cell line xenograft model of CML (Wylie et al. Nature 2017) and patient-derived xenograft models of BCR-ABL1+ ALL. We hypothesized that dual ABL blockade with catalytic domain and allosteric inhibitors would be tolerable and effective in BCR-ABL1+ ALL. Methods This is an investigator initiated, phase I study (NCT03595917) of ABL001 in combination with DAS plus prednisone in BCR-ABL1+ ALL. The study employs a 3+3 dose escalation design with an expansion cohort with the primary objective to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D). Secondary objectives include defining the depth and durability of responses. Patients (pts) ≥ 50 years (yrs) and younger unfit pts (18-49 yrs) with untreated BCR-ABL+ ALL or pts ≥ 18 yrs with relapsed/refractory ALL (no prior DAS or ABL001) are eligible. Pts are treated with DAS 140 mg daily and prednisone 60 mg/m2 days (d) 1-24 (max 120 mg daily, tapered d 25-32) with escalating doses of ABL001 once/d administered fasting (DL1: 40 mg; DL2: 80 mg; DL3: 160 mg). DAS plus ABL001 are given in 28-day cycles. Pts receive CNS prophylaxis with intrathecal ctx. Bone marrow transplant (BMT)-eligible pts may be consolidated with BMT after d85; BMT-ineligible pts may remain on therapy if deriving clinical benefit. Dose-limiting toxicity (DLT) was initially defined as CTCAEv4 non-heme toxicity grade (gr) 3+; the study has since been amended to assess DLT via CTCAEv5. Correlative science aims to identify biomarkers of response to combined ABL1 blockade and to define targetable biological programs enriched in minimal residual disease. Results The study has enrolled 12 pts (7 male/5 female). All 12 had untreated BCR-ABL1+ ALL. The median age at registration was 66 yrs (range 53 - 86; 4 pts 70+). DL1 (ABL001 40 mg/d) enrolled 3 pts without DLT; all have discontinued therapy (1 pt personal decision - C5, 2 pts to BMT- C5). DL2 (ABL001 80 mg daily) enrolled 3 pts without DLT (1 pt remains on study - C32, 1 pt discontinued for DAS pulmonary toxicity - C4, 1 pt discontinued for ALL progression - C11). DL3 (ABL001 160 mg daily) enrolled 3 pts with 2 pts developing asymptomatic CTCAEv4 Gr 3 amylase elevation during C1 meeting original DLT criteria (3 rd pt discontinued C2 due to DAS pulmonary toxicity and inadequate response). A 4th pt was enrolled on DL3 under protocol amendment defining asymp CTCAEv4 gr 3 amylase/lipase elevations persisting Conclusion Dual ABL1 kinase inhibition with asciminib and DAS plus prednisone in BCR-ABL1+ ALL is feasible. Primary toxicity is asymptomatic amylase and lipase elevation. Enrollment continues at DL2 under CTCAEv5 to further define safety profile and determine MTD. An expansion cohort of 10 pts (age ≥18 yrs) at the RP2D is planned. Figure 1 Figure 1. Disclosures Wang: AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; DAVA Oncology: Consultancy, Speakers Bureau; Kite Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board; Mana Therapeutics: Consultancy, Honoraria; Kura Oncology: Consultancy, Honoraria, Other: Advisory board, steering committee, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: Advisory Board; Pfizer: Consultancy, Honoraria, Other: Advisory Board, Speakers Bureau; Stemline Therapeutics: Consultancy, Honoraria, Other: Advisory board, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria, Other: Advisory Board; Takeda: Consultancy, Honoraria, Other: Advisory board; Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Rafael Pharmaceuticals: Other: Data safety monitoring committee; Gilead: Consultancy, Honoraria, Other: Advisory board; Daiichi Sankyo: Consultancy, Honoraria, Other: Advisory board; PTC Therapeutics: Consultancy, Honoraria, Other: Advisory board; Genentech: Consultancy; MacroGenics: Consultancy. Garcia: Pfizer: Research Funding; Prelude: Research Funding; AstraZeneca: Research Funding; Genentech: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Stone: AbbVie Inc, Actinium Pharmaceuticals Inc, Aprea Therapeutics, BerGenBio ASA, ElevateBio, Foghorn Therapeutics, GEMoaB, GlaxoSmithKline, Innate Pharma, Syndax Pharmaceuticals Inc, Syros Pharmaceuticals Inc, Takeda Oncology: Other: Advisory Committee; Agios Pharmaceuticals Inc, Novartis;: Research Funding; ACI Clinical, Syntrix Pharmaceuticals, Takeda Oncology: Other: Data Safety & Monitoring. DeAngelo: Autolus: Consultancy; Incyte Corporation: Consultancy; Forty-Seven: Consultancy; Agios: Consultancy; Amgen: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Consultancy; GlycoMimetics: Research Funding; Jazz: Consultancy; Shire: Consultancy; Takeda: Consultancy; Abbvie: Research Funding; Blueprint Medicines Corporation: Consultancy.

Background:The knowledge translation (KT) lecture at the Combined Sections Meeting 2014 was a personal perspective from a researcher who had been a therapist and a longtime clinician, now a PhD candidate.Objective:To better integrate research and clinical care, KT is a seamless rather than separate

The purpose of “Evidence in Practice” is to illustrate how evidence is gathered and used to guide clinical decision making. This article is not a case report. The examination, evaluation, and intervention sections are purposely abbreviated. A 28-month-old girl came to our physical therapy department with left-sided spastic hemiparesis, the result of a right cerebrovascular accident (CVA) in utero. Although she had delays in gross and fine motor development because of her hemiparesis, her cognitive and language development were typical for her age. Spontaneous use of her left upper extremity (UE) was markedly impaired in both quantity and quality of movement; however, she was able to use the left UE with prompting when she was given a 2-handed task (eg, holding a “sippy” cup with handles, holding a big ball with 2 hands) or when her right UE was therapeutically constrained. The child’s parents were well educated and well versed in therapeutic opportunities for improving left UE function, and they approached our university through their primary physical therapist to investigate the opportunity of involving their daughter in a student research project on pediatric constraint-induced therapy (PCIT). Through their support and information network, they had heard many anecdotal success stories related to the use of PCIT with children with sensory and motor impairments in the UE, and they were excited at the prospect of their daughter receiving this intervention. They contacted researchers conducting controlled clinical trials on PCIT in Alabama and New York. They put their child on a waiting list for a program at a university conducting PCIT clinical trials, but they recognized many drawbacks to attending this program, including the financial burden and the need to leave their home. The child was without any major medical complications or procedures since her diagnosis at 6 months of age. Upon diagnosis, …

The objective of this paper is to introduce a Structural Modal Identification Toolsuite (SMIT) for MATLAB that has been recently developed to facilitate system identification of structural systems. SMIT is an integrated toolbox, supporting a user-friendly Graphical User Interface (GUI) for modal identification. In this paper, the results of several system identification methods are compared in terms of accuracy and efficiency. The toolbox is capable of performing several common system identification methods with a standardized process, which is composed of input, eigenvalue estimation, and post processing procedures. The toolbox can present the estimated modal parameters graphically, and conveniently store and recall the identification results. The implemented identification methods consist of several classes of system identification algorithms, including Eigensystem Realization Algorithm (ERA), Auto-Regressive Moving-Average method with eXogenous terms (ARMAX), and Stochastic Subspace Identification (SSI). The performance of SMIT was verified by identifying the modal parameters of Northampton Steel Bridge (NSB), using five identification algorithms. A set of ambient acceleration responses was collected using a Wireless Sensor Network (WSN), and a subset of the sensing nodes was selected to identify vertical and torsional modes of NSB. The comparison of identification results to examine the accuracy and efficiency of each method supports that the SMIT is applicable to identify civil infrastructures effectively.

If Blacks and Whites are ever to engage in genuine communication, many barriers or obstacles must be removed. One of the more pervasive hindrances to authentic interracial relations is stereotyping. Blacks and Whites hold a variety of stereotypes of each other, often negative, and these racial stereotypes have generally remained unchanged over the years. Katz and Braly (1933) tackled the question of racial stereotypes early. They asked 100 White college students to choose from a prepared list of traits those that characterized certain racial groups. These-Princeton University students characterized "Negroes" as superstitious, lazy, happy-go-lucky, ignorant, musical, ostentatious, very religious, stupid, physically dirty, naive, slovenly, and unreliable. Eight years after the Katz and Braly study, Bayton (1946) suggested that, although several studies had been conducted in which White students were asked to assign traits to Blacks and other racial groups, few studies investigated how Blacks and other racial minorities viewed Whites. His study, conducted at Virginia State College, a Black school, questioned 100 students using the Katz and Braly list of traits. Bayton found that Black students characterized Whites as intelligent, industrious, scientifically minded, progressive, ambitious, peace loving, sportsmanlike, sophisticated, conceited, and neat. He also found that Black students shared many of the White stereotypes of Negroes. The Black students attributed traits to themselves such as musical, superstitious, very religious, happy-go-lucky, loud, lazy, progressive, imitative, intelligent, and