Citations

Increased global connectivity has catalyzed technological development in almost all industries, in part through the facilitation of novel collaborative structures. Notably, open innovation and crowd-sourcing—of expertise and/or funding—has tremendous potential to increase the efficiency with which biomedical ecosystems interact to deliver safe, efficacious and affordable therapies to patients. Consequently, such practices offer tremendous potential in advancing development of cellular therapies. In this vein, the CASMI Translational Stem Cell Consortium (CTSCC) was formed to unite global thought-leaders, producing academically rigorous and commercially practicable solutions to a range of challenges in pluripotent stem cell translation. Critically, the CTSCC research agenda is defined through continuous consultation with its international funding and research partners. Herein, initial findings for all research focus areas are presented to inform global product development strategies, and to stimulate continued industry interaction around biomanufacturing, strategic partnerships, standards, regulation and intellectual property and clinical adoption.

This study seeks to examine the effect of level of presentation on scaling of speech intelligibility of speakers with dysarthria. Previous data [Kim et al. (2007)] reported the somewhat surprising result that different presentation levels do not cause a significant change in speech intelligibility scores of speakers with dysarthria, but do for healthy speakers. The current study reports further data using the same speech stimuli, however, with a main focus on the across-conditions effect of presentation level, since the previous data were limited to within-conditions effects. Four conditions of level of presentation were generated by varying absolute level of presentation (high and low) and normalizing each utterance for peak vowel intensity (adjusted and nonadjusted). In this presentation, we will report how scaled speech intelligibility is affected by the level of presentation of speech samples produced by speakers with various types and severity of dysarthria and by healthy speakers. The results of this study will be helpful to understand the rationale of speech therapy for dysarthria, especially considering the frequent use of speech intelligibility and speech therapy techniques designed based on intensity variation of speech. [Work supported by NIH DC00319 and internal fund from Louisiana State University.]

AbstractBackgroundIn a recent clinical trial in kidney transplant recipients, induction with alemtuzumab and rabbit‐antithymocyte globulin (r‐ATG) was equally effective in preventing rejection during the first post‐transplant year; however, this study did not include protocol biopsies.MethodsThe aim of this study was to analyze the impact of alemtuzumab induction on rejection and subclinical inflammation during the first post‐transplant year compared with a historic control group receiving induction with r‐ATG. All patients received tacrolimus and mycophenolate mofetil (MMF).ResultsThere were 361 in the alemtuzumab group and 478 in the r‐ATG groups. Rejection (excluding Banff borderline), during the first year, occurred in 14% of the alemtuzumab group and 9% of the r‐ATG group (p = 0.03). Estimated glomerular filtration rate (GFR) (chronic kidney disease (CKD)‐EPI formula) at one yr and graft survival at three yr were similar. On the protocol biopsies, interstitial inflammation (Banff i scores) and tubulitis (Banff t scores) were more likely in the r‐ATG group at one month, but at four and 12 months, both inflammation and tubulitis were more likely in the alemtuzumab group.ConclusionsWe conclude that alemtuzumab induction is associated with delayed inflammation at four and 12 months, but this inflammation did not appear to negatively impact the GFR or graft survival.

BACKGROUND Friedreich ataxia (FRDA) is caused by reduced frataxin (FXN) concentrations. A clinical diagnosis is typically confirmed by DNA-based assays for GAA-repeat expansions or mutations in the FXN (frataxin) gene; however, these assays are not applicable to therapeutic monitoring and population screening. To facilitate the diagnosis and monitoring of FRDA patients, we developed an immunoassay for measuring FXN. METHODS Antibody pairs were used to capture FXN and an internal control protein, ceruloplasmin (CP), in 15 μL of whole blood (WB) or one 3-mm punch of a dried blood spot (DBS). Samples were assayed on a Luminex LX200 analyzer and validated according to standard criteria. RESULTS The mean recovery of FXN from WB and DBS samples was 99%. Intraassay and interassay imprecision (CV) values were 4.9%–13% and 9.8%–16%, respectively. The FXN limit of detection was 0.07 ng/mL, and the reportable range of concentrations was 2–200 ng/mL. Reference adult and pediatric FXN concentrations ranged from 15 to 82 ng/mL (median, 33 ng/mL) for DBS and WB. The FXN concentration range was 12–22 ng/mL (median, 15 ng/mL) for FRDA carriers and 1–26 ng/mL (median 5 ng/mL) for FRDA patients. Measurement of the FXN/CP ratio increased the ability to distinguish between patients, carriers, and the reference population. CONCLUSIONS This assay is applicable to the diagnosis and therapeutic monitoring of FRDA. This assay can measure FXN and the control protein CP in both WB and DBS specimens with minimal sample requirements, creating the potential for high-throughput population screening of FRDA.