Augmentative communication device design, implementation and evaluation

The ultimate aim of this thesis was to design and implement an advanced software based Augmentative Communication Device (ACD) , or Voice Output Communication Aid NOCA), for non-vocal Learning Disabled individuals by applying current psychological models, theories, and experimental techniques. By taking account of potential user's cognitive and linguistic abilities a symbol based device (Easy Speaker) was produced which outputs naturalistic digitised human speech and sound and makes use of a photorealistic symbol set. In order to increase the size of the available symbol set a hypermedia style dynamic screen approach was employed. The relevance of the hypermedia metaphor in relation to models of knowledge representation and language processing was explored.Laboratory based studies suggested that potential user's could learn to productively operate the software, became faster and more efficient over time when performing set conversational tasks. Studies with unimpaired individuals supported the notion that digitised speech was less cognitively demanding to decode, or listen to.With highly portable, touch based, PC compatible systems beginning to appear it is hoped that the otherwise silent will be able to use the software as their primary means of communication with the speaking world. Extensive field trials over a six month period with a prototype device and in collaboration with user's caregivers strongly suggested this might be the case.Off-device improvements were also noted suggesting that Easy Speaker, or similar software has the potential to be used as a communication training tool. Such training would be likely 10 improve overall communicative effectiveness.To conclude, a model for successful ACD development was proposed

Work and Welfare in the American States: Analyzing the Effects of the JOBS Program

This research seeks to determine whether the Job Opportunities and Basic Skills GOBS) program (established under the 1988 Family Support Act) was successful in reducing the number of welfare recipients among U.S. states for the period 1984 to 1996. Within the context of two theoretical perspectives-developmental and rational choice-we assess the impact of JOBS on AFDC participation rates using a pooled time-series design. At best, JOBS had a minimal effect. We estimate that states with higher proportions of their AFDC populations enrolled in JOBS programs had only slightly lower rates of participation in AFDC. Other forces were far more influential in reducing welfare participation. In particular, states with higher per capita income, lower female unemployment rates, lower poverty rates, and higher wages for low-paying jobs had the lowest welfare recipiency The AFDC participation rates of neighboring states had a significant effect, as well. The analysis showed that more generous AFDC benefits exerted strong upward pressure on a state's welfare rolls.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis

Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10-8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3′ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10-11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry. © 2013 Cui et al

Comparability: manufacturing, characterization and controls, report of a UK Regenerative Medicine Platform Pluripotent Stem Cell Platform Workshop, Trinity Hall, Cambridge, 14–15 September 2015

This paper summarizes the proceedings of a workshop held at Trinity Hall, Cambridge to discuss comparability and includes additional information and references to related information added subsequently to the workshop. Comparability is the need to demonstrate equivalence of product after a process change; a recent publication states that this ‘may be difficult for cell-based medicinal products’. Therefore a well-managed change process is required which needs access to good science and regulatory advice and developers are encouraged to seek help early. The workshop shared current thinking and best practice and allowed the definition of key research questions. The intent of this report is to summarize the key issues and the consensus reached on each of these by the expert delegates

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on twelve research projects.National Institutes of Health Grant 5 R01 DC00117National Institutes of Health Contract 2 P01 DC00361National Institutes of Health Grant 5 R01 DC00126National Institutes of Health Grant R01-DC00270U.S. Air Force - Office of Scientific Research Contract AFOSR-90-0200National Institutes of Health Grant R29-DC00625U.S. Navy - Office of Naval Research Grant N00014-88-K-0604U.S. Navy - Office of Naval Research Grant N00014-91-J-1454U.S. Navy - Office of Naval Research Grant N00014-92-J-1814U.S. Navy - Naval Training Systems Center Contract N61339-93-M-1213U.S. Navy - Naval Training Systems Center Contract N61339-93-C-0055U.S. Navy - Naval Training Systems Center Contract N61339-93-C-0083U.S. Navy - Office of Naval Research Grant N00014-92-J-4005U.S. Navy - Office of Naval Research Grant N00014-93-1-119

Treatment with a corticotrophin releasing factor 2 receptor agonist modulates skeletal muscle mass and force production in aged and chronically ill animals

<p>Abstract</p> <p>Background</p> <p>Muscle weakness is associated with a variety of chronic disorders such as emphysema (EMP) and congestive heart failure (CHF) as well as aging. Therapies to treat muscle weakness associated with chronic disease or aging are lacking. Corticotrophin releasing factor 2 receptor (CRF2R) agonists have been shown to maintain skeletal muscle mass and force production in a variety of acute conditions that lead to skeletal muscle wasting.</p> <p>Hypothesis</p> <p>We hypothesize that treating animals with a CRF2R agonist will maintain skeletal muscle mass and force production in animals with chronic disease and in aged animals.</p> <p>Methods</p> <p>We utilized animal models of aging, CHF and EMP to evaluate the potential of CRF2R agonist treatment to maintain skeletal muscle mass and force production in aged animals and animals with CHF and EMP.</p> <p>Results</p> <p>In aged rats, we demonstrate that treatment with a CRF2R agonist for up to 3 months results in greater extensor digitorum longus (EDL) force production, EDL mass, soleus mass and soleus force production compared to age matched untreated animals. In the hamster EMP model, we demonstrate that treatment with a CRF2R agonist for up to 5 months results in greater EDL force production in EMP hamsters when compared to vehicle treated EMP hamsters and greater EDL mass and force in normal hamsters when compared to vehicle treated normal hamsters. In the rat CHF model, we demonstrate that treatment with a CRF2R agonist for up to 3 months results in greater EDL and soleus muscle mass and force production in CHF rats and normal rats when compared to the corresponding vehicle treated animals.</p> <p>Conclusions</p> <p>These data demonstrate that the underlying physiological conditions associated with chronic diseases such as CHF and emphysema in addition to aging do not reduce the potential of CRF2R agonists to maintain skeletal muscle mass and force production.</p

Sensory Communication

Contains table of contents for Section 2 and reports on five research projects.National Institutes of Health Contract 2 R01 DC00117National Institutes of Health Contract 1 R01 DC02032National Institutes of Health Contract 2 P01 DC00361National Institutes of Health Contract N01 DC22402National Institutes of Health Grant R01-DC001001National Institutes of Health Grant R01-DC00270National Institutes of Health Grant 5 R01 DC00126National Institutes of Health Grant R29-DC00625U.S. Navy - Office of Naval Research Grant N00014-88-K-0604U.S. Navy - Office of Naval Research Grant N00014-91-J-1454U.S. Navy - Office of Naval Research Grant N00014-92-J-1814U.S. Navy - Naval Air Warfare Center Training Systems Division Contract N61339-94-C-0087U.S. Navy - Naval Air Warfare Center Training System Division Contract N61339-93-C-0055U.S. Navy - Office of Naval Research Grant N00014-93-1-1198National Aeronautics and Space Administration/Ames Research Center Grant NCC 2-77

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on fifteen research projects.National Institutes of Health Grant RO1 DC00117National Institutes of Health Grant RO1 DC02032National Institutes of Health Contract P01-DC00361National Institutes of Health Contract N01-DC22402National Institutes of Health/National Institute on Deafness and Other Communication Disorders Grant 2 R01 DC00126National Institutes of Health Grant 2 R01 DC00270National Institutes of Health Contract N01 DC-5-2107National Institutes of Health Grant 2 R01 DC00100U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-94-C-0087U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-95-K-0014U.S. Navy - Office of Naval Research/Naval Air Warfare Center Grant N00014-93-1-1399U.S. Navy - Office of Naval Research/Naval Air Warfare Center Grant N00014-94-1-1079U.S. Navy - Office of Naval Research Subcontract 40167U.S. Navy - Office of Naval Research Grant N00014-92-J-1814National Institutes of Health Grant R01-NS33778U.S. Navy - Office of Naval Research Grant N00014-88-K-0604National Aeronautics and Space Administration Grant NCC 2-771U.S. Air Force - Office of Scientific Research Grant F49620-94-1-0236U.S. Air Force - Office of Scientific Research Agreement with Brandeis Universit

Oral Abstracts 7: RA ClinicalO37. Long-Term Outcomes of Early RA Patients Initiated with Adalimumab Plus Methotrexate Compared with Methotrexate Alone Following a Targeted Treatment Approach

Background: This analysis assessed, on a group level, whether there is a long-term advantage for early RA patients treated with adalimumab (ADA) + MTX vs those initially treated with placebo (PBO) + MTX who either responded to therapy or added ADA following inadequate response (IR). Methods: OPTIMA was a 78- week, randomized, controlled trial of ADA + MTX vs PBO + MTX in MTX-naïve early (<1 year) RA patients. Therapy was adjusted at week 26: ADA + MTX-responders (R) who achieved DAS28 (CRP) <3.2 at weeks 22 and 26 (Period 1, P1) were re-randomized to withdraw or continue ADA and PBO + MTX-R continued randomized therapy for 52 weeks (P2); IR-patients received open-label (OL) ADA + MTX during P2. This post hoc analysis evaluated the proportion of patients at week 78 with DAS28 (CRP) <3.2, HAQ-DI <0.5, and/or ΔmTSS ≤0.5 by initial treatment. To account for patients who withdrew ADA during P2, an equivalent proportion of R was imputed from ADA + MTX-R patients. Results: At week 26, significantly more patients had low disease activity, normal function, and/or no radiographic progression with ADA + MTX vs PBO + MTX (Table 1). Differences in clinical and functional outcomes disappeared following additional treatment, when PBO + MTX-IR (n = 348/460) switched to OL ADA + MTX. Addition of OL ADA slowed radiographic progression, but more patients who received ADA + MTX from baseline had no radiographic progression at week 78 than patients who received initial PBO + MTX. Conclusions: Early RA patients treated with PBO + MTX achieved comparable long-term clinical and functional outcomes on a group level as those who began ADA + MTX, but only when therapy was optimized by the addition of ADA in PBO + MTX-IR. Still, ADA + MTX therapy conferred a radiographic benefit although the difference did not appear to translate to an additional functional benefit. Disclosures: P.E., AbbVie, Merck, Pfizer, UCB, Roche, BMS—Provided Expert Advice, Undertaken Trials, AbbVie—AbbVie sponsored the study, contributed to its design, and participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the final version. R.F., AbbVie, Pfizer, Merck, Roche, UCB, Celgene, Amgen, AstraZeneca, BMS, Janssen, Lilly, Novartis—Research Grants, Consultation Fees. S.F., AbbVie—Employee, Stocks. A.K., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, UCB—Research Grants, Consultation Fees. H.K., AbbVie—Employee, Stocks. S.R., AbbVie—Employee, Stocks. J.S., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, GlaxoSmithKline, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, UCB—Research Grants, Consultation Fees. R.V., AbbVie, BMS, GlaxoSmithKline, Human Genome Sciences, Merck, Pfizer, Roche, UCB Pharma—Consultation Fees, Research Support. Table 1.Week 78 clinical, functional, and radiographic outcomes in patients who received continued ADA + MTX vs those who continued PBO + MTX or added open-label ADA following an inadequate response ADA + MTX, n/N (%)a PBO + MTX, n/N (%)b Outcome Week 26 Week 52 Week 78 Week 26 Week 52 Week 78 DAS28 (CRP) <3.2 246/466 (53) 304/465 (65) 303/465 (65) 139/460 (30)*** 284/460 (62) 300/460 (65) HAQ-DI <0.5 211/466 (45) 220/466 (47) 224/466 (48) 150/460 (33)*** 203/460 (44) 208/460 (45) ΔmTSS ≤0.5 402/462 (87) 379/445 (86) 382/443 (86) 330/459 (72)*** 318/440 (72)*** 318/440 (72)*** DAS28 (CRP) <3.2 + ΔmTSS ≤0.5 216/462 (47) 260/443 (59) 266/443 (60) 112/459 (24)*** 196/440 (45) 211/440 (48)*** DAS28 (CRP) <3.2 + HAQ-DI <0.5 + ΔmTSS ≤0.5 146/462 (32) 168/443 (38) 174/443 (39) 82/459 (18)*** 120/440 (27)*** 135/440 (31)** aIncludes patients from the ADA Continuation (n = 105) and OL ADA Carry On (n = 259) arms, as well as the proportional equivalent number of responders from the ADA Withdrawal arm (n = 102). bIncludes patients from the MTX Continuation (n = 112) and Rescue ADA (n = 348) arms. Last observation carried forward: DAS28 (CRP) and HAQ-DI; Multiple imputations: ΔmTSS. ***P < 0.001 and **iP < 0.01, respectively, for differences between initial treatments from chi-squar

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on fourteen research projects.National Institutes of Health Grant RO1 DC00117National Institutes of Health Grant RO1 DC02032National Institutes of Health/National Institute on Deafness and Other Communication Disorders Grant R01 DC00126National Institutes of Health Grant R01 DC00270National Institutes of Health Contract N01 DC52107U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-95-K-0014U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-96-K-0003U.S. Navy - Office of Naval Research Grant N00014-96-1-0379U.S. Air Force - Office of Scientific Research Grant F49620-95-1-0176U.S. Air Force - Office of Scientific Research Grant F49620-96-1-0202U.S. Navy - Office of Naval Research Subcontract 40167U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-96-K-0002National Institutes of Health Grant R01-NS33778U.S. Navy - Office of Naval Research Grant N00014-92-J-184