Automating Intended Target Identification for Paraphasias in Discourse using a large language model

Purpose: To date, there are no automated tools for the identification and fine-grained classification of paraphasias within discourse, the production of which is the hallmark characteristic of most people with aphasia (PWA). In this work, we fine-tune a large language model (LLM) to automatically predict paraphasia targets in Cinderella story retellings. Method: Data consisted of 332 Cinderella story retellings containing 2,489 paraphasias from PWA, for which research assistants identified their intended targets. We supplemented these training data with 256 sessions from control participants, to which we added 2,415 synthetic paraphasias. We conducted four experiments using different training data configurations to fine-tune the LLM to automatically “fill in the blank” of the paraphasia with a predicted target, given the context of the rest of the story retelling. We tested the experiments\u27 predictions against our human-identified targets and stratified our results by ambiguity of the targets and clinical factors. Results: The model trained on controls and PWA achieved 50.7% accuracy at exactly matching the human-identified target. Fine-tuning on PWA data, with or without controls, led to comparable performance. The model performed better on targets with less human ambiguity and on paraphasias from participants with fluent or less severe aphasia. Conclusions: We were able to automatically identify the intended target of paraphasias in discourse using just the surrounding language about half of the time. These findings take us a step closer to automatic aphasic discourse analysis. In future work, we will incorporate phonological information from the paraphasia to further improve predictive utility

A randomized, controlled trial of endovenous thermal ablation using the 810-nm wavelength laser and the ClosurePLUS radiofrequency ablation methods for superficial venous insufficiency of the great saphenous vein

BackgroundGreat saphenous vein (GSV) incompetence is the most common cause of superficial venous insufficiency. Radiofrequency catheter ablation (RFA) is superior to conventional ligation and stripping, and endovenous laser treatment (EVL) has emerged as an effective alternative to RFA. This randomized study evaluated RFA and EVL for superficial venous insufficiency due to GSV incompetence and compared early and 1-year results.MethodsBetween June 2006 and May 2008, patients with symptomatic primary venous insufficiency due to GSV incompetence were randomized to RFA or EVL. Patients with bilateral disease were randomized for treatment of the first leg and received the alternative method on the other. Pretreatment examination included a leg assessment using the Venous Clinical Severity Score (VCSS) and CEAP classification. Patients completed the Chronic Venous Insufficiency Questionnaire 2 (CIVIQ2). RFA was performed with the ClosurePlus system (VNUS Medical Technologies, Sunnyvale, Calif). EVL was performed with the EVLT system (AngioDynamics Inc, Queensbury, NY). Early (1-week and 1-month) postoperative results of pain, bruising, erythema, and hematoma were recorded. Duplex ultrasound (DU) imaging was used at 1 week and 1 year to evaluate vein status. VCSS scores and CEAP clinical class were recorded at each postoperative visit, and quality of life (QOL) using CIVIQ2 was assessed at 1 month and 1 year.ResultsThe study enrolled 118 patients (141 limbs): 46 (39%) were randomized to RFA and 48 (40%) to EVL, and 24 (20%) had bilateral GSV incompetence. At 1 week, one patient in the RFA group had an open GSV and was deemed a failure. More bruising occurred in the EVL group (P = .01) at 1 week, but at 1 month, there was no difference in bruising between groups. At 1 year, DU imaging showed evidence of recanalization with reflux in 11 RFA and 2 EVL patients (P = .002). The mean VCSS score change from baseline to 1 week postprocedure was higher for RFA than EVL (P = .002), but there was no difference between groups at 1 month (P = .07) and 1 year (P = .9). Overall QOL mean score improved over time for all patients (P < .001). CEAP clinical class scores of ≥3 were recorded in 21 RFA (44%) and 24 EVL patients (44%) pretreatment, but at 1-year, 9 RFA (19%) and 12 EVL patients (24%) had scores of ≥3 (P < .001). This represented a significant improvement in all patients compared with baseline.ConclusionBoth methods of endovenous ablation effectively reduce symptoms of superficial venous insufficiency. EVL is associated with greater bruising and discomfort in the perioperative period but may provide a more secure closure over the long-term than RFA

The most used and most helpful facilitators for patient-centered medical home implementation

Background: Like other transformative healthcare initiatives, patient-centered medical home (PCMH) implementation requires substantial investments of time and resources. Even though PCMH and PCMH-like models are being implemented by multiple provider practices and health systems, little is known about what facilitates their implementation. The purpose of this study was to assess which PCMH-implementation resources are most widely used, by whom, and which resources primary care personnel find most helpful. Methods: This study is an analysis of data from a cross-sectional survey of primary care personnel in the Veterans Health Administration in 2012, in which respondents were asked to rate whether they were aware of and accessed PCMH-implementation resources, and to rate their helpfulness. Logistic regression was used to produce odds ratios for the outcomes (1) resource use and (2) resource helpfulness. Respondents were nested within clinics, nested, in turn, within 135 parent hospitals. Results: Teamlet huddles were the most widely accessed (80.4% accessed) and most helpful (90.4% rated helpful) resource; quality-improvement methods to conduct small tests of change were the least frequently accessed (42.4% accessed) resource though two-thirds (66.7%) of users reported as helpful. Supervisors were significantly more likely (ORs, 1.46 to 1.86) to use resources than non-supervisors but were less likely to rate the majority (8 out of 10) of resources as "somewhat/very helpful" than non-supervisors (ORs, 0.72 to 0.84). Longer-tenured employees tended to rate resources as more helpful. Conclusions: These findings are the first in the PCMH literature that we are aware of that systematically assesses primary care staff's access to and the helpfulness of PCMH implementation resources. Supervisors generally reported greater access to resources, relative to non-supervisors, but rated resources as less helpful, suggesting that information about them may not have been optimally disseminated. Knowing what resources primary care staff use and find helpful can inform administrators' and policymakers' investments in PCMH-implementation resources. The implications of our model extend beyond just PCMH implementation but also to considerations when providing implementation resources for other complex quality-improvement initiatives.KEYWORDS: Provider self-efficacy, Patient-centered medical home, Implementation resourcesThis is the publisher’s final pdf. The published article is copyrighted by BioMed Central and can be found at: http://www.implementationscience.co

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus.

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability

Compound Semiconductor Materials and Devices

Contains table of contents for Part I, table of contents for Section 1, reports on fourteen research projects and a list of publications.Defense Advanced Research Projects Agency/National Center for Integrated Photonics TechnologyFannie and John Hertz Foundation Graduate FellowshipJoint Services Electronics Program Grant DAAH04-95-1-0038National Science Foundation Graduate FellowshipNTT CorporationNational Science FoundationU.S. Navy - Office of Naval ResearchToshiba CorporationAT&T Bell Laboratories Graduate Fellowshi

Functional Characterization of FLT3 Receptor Signaling Deregulation in Acute Myeloid Leukemia by Single Cell Network Profiling (SCNP)

Molecular characterization of the FMS-like tyrosine kinase 3 receptor (FLT3) in cytogenetically normal acute myeloid leukemia (AML) has recently been incorporated into clinical guidelines based on correlations between FLT3 internal tandem duplications (FLT3-ITD) and decreased disease-free and overall survival. These mutations result in constitutive activation of FLT3, and FLT3 inhibitors are currently undergoing trials in AML patients selected on FLT3 molecular status. However, the transient and partial responses observed suggest that FLT3 mutational status alone does not provide complete information on FLT3 biological activity at the individual patient level. Examination of variation in cellular responsiveness to signaling modulation may be more informative.Using single cell network profiling (SCNP), cells were treated with extracellular modulators and their functional responses were quantified by multiparametric flow cytometry. Intracellular signaling responses were compared between healthy bone marrow myeloblasts (BMMb) and AML leukemic blasts characterized as FLT3 wild type (FLT3-WT) or FLT3-ITD. Compared to healthy BMMb, FLT3-WT leukemic blasts demonstrated a wide range of signaling responses to FLT3 ligand (FLT3L), including elevated and sustained PI3K and Ras/Raf/Erk signaling. Distinct signaling and apoptosis profiles were observed in FLT3-WT and FLT3-ITD AML samples, with more uniform signaling observed in FLT3-ITD AML samples. Specifically, increased basal p-Stat5 levels, decreased FLT3L induced activation of the PI3K and Ras/Raf/Erk pathways, decreased IL-27 induced activation of the Jak/Stat pathway, and heightened apoptotic responses to agents inducing DNA damage were observed in FLT3-ITD AML samples. Preliminary analysis correlating these findings with clinical outcomes suggests that classification of patient samples based on signaling profiles may more accurately reflect FLT3 signaling deregulation and provide additional information for disease characterization and management.These studies show the feasibility of SCNP to assess modulated intracellular signaling pathways and characterize the biology of individual AML samples in the context of genetic alterations

Compound Semiconductor Materials and Devices

Contains table of contents for Part I, table of contents for Section 1, an introduction, reports on fourteen research projects and a list of publications.Defense Advanced Research Projects Agency/National Center for Integrated Photonics TechnologyJoint Services Electronics Program Grant DAAH04-95-1-0038MIT Lincoln LaboratoryNational Science Foundation Graduate FellowshipU.S. Navy - Office of Naval ResearchAT&T Bell Laboratories FellowshipU.S. Army - Ft. MeadeNTT CorporationNational Science FoundationLockheed-Martin Corporatio

Expression and Functional Roles of Angiopoietin-2 in Skeletal Muscles

Angiopoietin-1 (ANGPT1) and angiopoietin-2 (ANGPT2) are angiogenesis factors that modulate endothelial cell differentiation, survival and stability. Recent studies have suggested that skeletal muscle precursor cells constitutively express ANGPT1 and adhere to recombinant ANGPT1 and ANGPT2 proteins. It remains unclear whether or not they also express ANGPT2, or if ANGPT2 regulates the myogenesis program of muscle precursors. In this study, ANGPT2 regulatory factors and the effects of ANGPT2 on proliferation, migration, differentiation and survival were identified in cultured primary skeletal myoblasts. The cellular networks involved in the actions of ANGPT2 on skeletal muscle cells were also analyzed.Primary skeletal myoblasts were isolated from human and mouse muscles. Skeletal myoblast survival, proliferation, migration and differentiation were measured in-vitro in response to recombinant ANGPT2 protein and to enhanced ANGPT2 expression delivered with adenoviruses. Real-time PCR and ELISA measurements revealed the presence of constitutive ANGPT2 expression in these cells. This expression increased significantly during myoblast differentiation into myotubes. In human myoblasts, ANGPT2 expression was induced by H(2)O(2), but not by TNFα, IL1β or IL6. ANGPT2 significantly enhanced myoblast differentiation and survival, but had no influence on proliferation or migration. ANGPT2-induced survival was mediated through activation of the ERK1/2 and PI-3 kinase/AKT pathways. Microarray analysis revealed that ANGPT2 upregulates genes involved in the regulation of cell survival, protein synthesis, glucose uptake and free fatty oxidation.Skeletal muscle precursors constitutively express ANGPT2 and this expression is upregulated during differentiation into myotubes. Reactive oxygen species exert a strong stimulatory influence on muscle ANGPT2 expression while pro-inflammatory cytokines do not. ANGPT2 promotes skeletal myoblast survival and differentiation. These results suggest that muscle-derived ANGPT2 production may play a positive role in skeletal muscle fiber repair

Missing steps in a staircase: a qualitative study of the perspectives of key stakeholders on the use of adaptive designs in confirmatory trials

Background Despite the promising benefits of adaptive designs (ADs), their routine use, especially in confirmatory trials, is lagging behind the prominence given to them in the statistical literature. Much of the previous research to understand barriers and potential facilitators to the use of ADs has been driven from a pharmaceutical drug development perspective, with little focus on trials in the public sector. In this paper, we explore key stakeholders’ experiences, perceptions and views on barriers and facilitators to the use of ADs in publicly funded confirmatory trials. Methods Semi-structured, in-depth interviews of key stakeholders in clinical trials research (CTU directors, funding board and panel members, statisticians, regulators, chief investigators, data monitoring committee members and health economists) were conducted through telephone or face-to-face sessions, predominantly in the UK. We purposively selected participants sequentially to optimise maximum variation in views and experiences. We employed the framework approach to analyse the qualitative data. Results We interviewed 27 participants. We found some of the perceived barriers to be: lack of knowledge and experience coupled with paucity of case studies, lack of applied training, degree of reluctance to use ADs, lack of bridge funding and time to support design work, lack of statistical expertise, some anxiety about the impact of early trial stopping on researchers’ employment contracts, lack of understanding of acceptable scope of ADs and when ADs are appropriate, and statistical and practical complexities. Reluctance to use ADs seemed to be influenced by: therapeutic area, unfamiliarity, concerns about their robustness in decision-making and acceptability of findings to change practice, perceived complexities and proposed type of AD, among others. Conclusions There are still considerable multifaceted, individual and organisational obstacles to be addressed to improve uptake, and successful implementation of ADs when appropriate. Nevertheless, inferred positive change in attitudes and receptiveness towards the appropriate use of ADs by public funders are supportive and are a stepping stone for the future utilisation of ADs by researchers