A Multimodal Analysis of Vocal and Visual Backchannels in Spontaneous Dialogs

Backchannels (BCs) are short vocal and visual listener responses that signal attention, interest, and understanding to the speaker. Previous studies have investigated BC prediction in telephone-style dialogs from prosodic cues. In contrast, we consider spontaneous face-to-face dialogs. The additional visual modality allows speaker and listener to monitor each other's attention continuously, and we hypothesize that this affects the BC-inviting cues. In this study, we investigate how gaze, in addition to prosody, can cue BCs. Moreover, we focus on the type of BC performed, with the aim to find out whether vocal and visual BCs are invited by similar cues. In contrast to telephone-style dialogs, we do not find rising/falling pitch to be a BC-inviting cue. However, in a face-to-face setting, gaze appears to cue BCs. In addition, we find that mutual gaze occurs significantly more often during visual BCs. Moreover, vocal BCs are more likely to be timed during pauses in the speaker's speech

Backchannel Strategies for Artificial Listeners

We evaluate multimodal rule-based strategies for backchannel (BC) generation in face-to-face conversations. Such strategies can be used by artificial listeners to determine when to produce a BC in dialogs with human speakers. In this research, we consider features from the speaker’s speech and gaze. We used six rule-based strategies to determine the placement of BCs. The BCs were performed by an intelligent virtual agent using nods and vocalizations. In a user perception experiment, participants were shown video fragments of a human speaker together with an artificial listener who produced BC behavior according to one of the strategies. Participants were asked to rate how likely they thought the BC behavior had been performed by a human listener. We found that the number, timing and type of BC had a significant effect on how human-like the BC behavior was perceived

Enhancing mHealth Technology in the Patient-Centered Medical Home Environment to Activate Patients With Type 2 Diabetes: A Multisite Feasibility Study Protocol.

BackgroundThe potential of mHealth technologies in the care of patients with diabetes and other chronic conditions has captured the attention of clinicians and researchers. Efforts to date have incorporated a variety of tools and techniques, including Web-based portals, short message service (SMS) text messaging, remote collection of biometric data, electronic coaching, electronic-based health education, secure email communication between visits, and electronic collection of lifestyle and quality-of-life surveys. Each of these tools, used alone or in combination, have demonstrated varying degrees of effectiveness. Some of the more promising results have been demonstrated using regular collection of biometric devices, SMS text messaging, secure email communication with clinical teams, and regular reporting of quality-of-life variables. In this study, we seek to incorporate several of the most promising mHealth capabilities in a patient-centered medical home (PCMH) workflow.ObjectiveWe aim to address underlying technology needs and gaps related to the use of mHealth technology and the activation of patients living with type 2 diabetes. Stated differently, we enable supporting technologies while seeking to influence patient activation and self-care activities.MethodsThis is a multisite phased study, conducted within the US Military Health System, that includes a user-centered design phase and a PCMH-based feasibility trial. In phase 1, we will assess both patient and provider preferences regarding the enhancement of the enabling technology capabilities for type 2 diabetes chronic care management. Phase 2 research will be a single-blinded 12-month feasibility study that incorporates randomization principles. Phase 2 research will seek to improve patient activation and self-care activities through the use of the Mobile Health Care Environment with tailored behavioral messaging. The primary outcome measure is the Patient Activation Measure scores. Secondary outcome measures are Summary of Diabetes Self-care Activities Measure scores, clinical measures, comorbid conditions, health services resource consumption, and technology system usage statistics.ResultsWe have completed phase 1 data collection. Formal analysis of phase 1 data has not been completed. We have obtained institutional review board approval and began phase 1 research in late fall 2016.ConclusionsThe study hypotheses suggest that patients can, and will, improve their activation in chronic care management. Improved activation should translate into improved diabetes self-care. Expected benefits of this research to the scientific community and health care services include improved understanding of how to leverage mHealth technology to activate patients living with type 2 diabetes in self-management behaviors. The research will shed light on implementation strategies in integrating mHealth into the clinical workflow of the PCMH setting.Trial registrationClinicalTrials.gov NCT02949037. https://clinicaltrials.gov/ct2/show/NCT02949037. (Archived by WebCite at http://www.webcitation.org/6oRyDzqei)

A rare sequence variant in intron 1 of THAP1 is associated with primary dystonia

Although coding variants in THAP1 have been causally associated with primary dystonia, the contribution of noncoding variants remains uncertain. Herein, we examine a previously identified Intron 1 variant (c.71+9C>A, rs200209986). Among 1672 subjects with mainly adult-onset primary dystonia, 12 harbored the variant in contrast to 1/1574 controls (P < 0.01). Dystonia classification included cervical dystonia (N = 3), laryngeal dystonia (adductor subtype, N = 3), jaw-opening oromandibular dystonia (N = 1), blepharospasm (N = 2), and unclassified (N = 3). Age of dystonia onset ranged from 25 to 69 years (mean = 54 years). In comparison to controls with no identified THAP1 sequence variants, the c.71+9C>A variant was associated with an elevated ratio of Isoform 1 (NM_018105) to Isoform 2 (NM_199003) in leukocytes. In silico and minigene analyses indicated that c.71+9C>A alters THAP1 splicing. Lymphoblastoid cells harboring the c.71+9C>A variant showed extensive apoptosis with relatively fewer cells in the G2 phase of the cell cycle. Differentially expressed genes from lymphoblastoid cells revealed that the c.71+9C>A variant exerts effects on DNA synthesis, cell growth and proliferation, cell survival, and cytotoxicity. In aggregate, these data indicate that THAP1 c.71+9C>A is a risk factor for adult-onset primary dystonia

Assessing the efficacy and safety of magnesium sulfate for management of autonomic nervous system dysregulation in Vietnamese children with severe hand foot and mouth disease.

BACKGROUND: Brainstem encephalitis is a serious complication of hand foot and mouth disease (HFMD) in children. Autonomic nervous system (ANS) dysregulation and hypertension may occur, sometimes progressing to cardiopulmonary failure and death. Vietnamese national guidelines recommend use of milrinone if ANS dysregulation with Stage 2 hypertension develops. We wished to investigate whether magnesium sulfate (MgSO4) improved outcomes in children with HFMD if used earlier in the evolution of the ANS dysregulation (Stage 1 hypertension). METHODS: During a regional epidemic we conducted a randomized, double-blind, placebo-controlled trial of MgSO4 in children with HFMD, ANS dysregulation and Stage 1 hypertension, at the Hospital for Tropical Diseases in Ho Chi Minh city. Study participants received an infusion of MgSO4 or matched placebo for 72 h. We also reviewed data from non-trial HFMD patients in whom milrinone failed to control hypertension, some of whom received MgSO4 as second line therapy. The primary outcome for both analyses was a composite of disease progression within 72 h - addition of milrinone (trial participants only), need for ventilation, shock, or death. RESULTS: Between June 2014 and September 2016, 14 and 12 participants received MgSO4 or placebo respectively, before the trial was stopped due to futility. Among 45 non-trial cases with poorly controlled hypertension despite high-dose milrinone, 33 received MgSO4 while 12 did not. There were no statistically significant differences in the composite outcome between the MgSO4 and the placebo/control groups in either study (adjusted relative risk (95%CI) of [6/14 (43%) vs. 6/12 (50%)], 0.84 (0.37, 1.92), p = 0.682 in the trial and [1/33 (3%) vs. 2/12 (17%)], 0.16 (0.01, 1.79), p = 0.132 in the observational cohort). The incidence of adverse events was similar between the groups. Potentially toxic magnesium levels occurred very rarely with the infusion regime used. CONCLUSION: Although we could not demonstrate efficacy in these studies, there were no safety signals associated with use of 30-50 mg/kg/hr. MgSO4 in severe HFMD. Intermittent outbreaks of HFMD are likely to continue across the region, and an adequately powered trial is still needed to evaluate use of MgSO4 in controlling hypertension in severe HFMD, potentially involving a higher dose regimen. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01940250 (Registered 22 AUG 2013). Trial sponsor: University of Oxford

Angiogenesis induced by tumor necrosis factor-agr; is mediated by α4 integrins

Tumor necrosis factor-α (TNF-α) and fibroblast growth factor-2 (FGF-2 or bFGF) are potent stimulators of angiogenesis. TNF-α, but not FGF-2, can induce the expression of vascular cell adhesion molecule-1 (VCAM-1) on the surface of endothelial cells. The soluble form of VCAM-1 has recently been demonstrated to function as an angiogenic mediator. Here we demonstrate that monoclonal antibodies directed against VCAM-1 or its α4 integrin counter-receptor inhibited TNF-α-induced endothelial cell migration in vitro. Angiogenesis induced in vivo in rat corneas by TNF-α was inhibited by a neutralizing antibody directed against the rat α4 integrin subunit. A peptide antagonist of the a4 integrins blocked TNF-α-induced endothelial cell migration in vitro and angiogenesis in rat corneas in vivo. No inhibition by the antibodies or peptide antagonist was observed either in vitro or in vivo when FGF-2 was used as the stimulus. The peptide antagonist did not inhibit TNF-a binding to its receptor nor did it block the function of αvβ3, an integrin previously implicated in TNF-a and FGF-2 mediated angiogenesis. These results demonstrate that angiogenic processes induced by TNF-α are mediated in part by agr;4 integrins possibly by a mechanism involving the induction of soluble VCAM-1.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41761/1/10456_2004_Article_188219.pd

High-throughput mutational analysis of TOR1A in primary dystonia

<p>Abstract</p> <p>Background</p> <p>Although the c.904_906delGAG mutation in Exon 5 of <it>TOR1A </it>typically manifests as early-onset generalized dystonia, DYT1 dystonia is genetically and clinically heterogeneous. Recently, another Exon 5 mutation (c.863G>A) has been associated with early-onset generalized dystonia and some ΔGAG mutation carriers present with late-onset focal dystonia. The aim of this study was to identify <it>TOR1A </it>Exon 5 mutations in a large cohort of subjects with mainly non-generalized primary dystonia.</p> <p>Methods</p> <p>High resolution melting (HRM) was used to examine the entire <it>TOR1A </it>Exon 5 coding sequence in 1014 subjects with primary dystonia (422 spasmodic dysphonia, 285 cervical dystonia, 67 blepharospasm, 41 writer's cramp, 16 oromandibular dystonia, 38 other primary focal dystonia, 112 segmental dystonia, 16 multifocal dystonia, and 17 generalized dystonia) and 250 controls (150 neurologically normal and 100 with other movement disorders). Diagnostic sensitivity and specificity were evaluated in an additional 8 subjects with known ΔGAG DYT1 dystonia and 88 subjects with ΔGAG-negative dystonia.</p> <p>Results</p> <p>HRM of <it>TOR1A </it>Exon 5 showed high (100%) diagnostic sensitivity and specificity. HRM was rapid and economical. HRM reliably differentiated the <it>TOR1A </it>ΔGAG and c.863G>A mutations. Melting curves were normal in 250/250 controls and 1012/1014 subjects with primary dystonia. The two subjects with shifted melting curves were found to harbor the classic ΔGAG deletion: 1) a non-Jewish Caucasian female with childhood-onset multifocal dystonia and 2) an Ashkenazi Jewish female with adolescent-onset spasmodic dysphonia.</p> <p>Conclusion</p> <p>First, HRM is an inexpensive, diagnostically sensitive and specific, high-throughput method for mutation discovery. Second, Exon 5 mutations in <it>TOR1A </it>are rarely associated with non-generalized primary dystonia.</p