Building Socio-culturally Inclusive Stereotype Resources with Community Engagement

With rapid development and deployment of generative language models in global settings, there is an urgent need to also scale our measurements of harm, not just in the number and types of harms covered, but also how well they account for local cultural contexts, including marginalized identities and the social biases experienced by them. Current evaluation paradigms are limited in their abilities to address this, as they are not representative of diverse, locally situated but global, socio-cultural perspectives. It is imperative that our evaluation resources are enhanced and calibrated by including people and experiences from different cultures and societies worldwide, in order to prevent gross underestimations or skews in measurements of harm. In this work, we demonstrate a socio-culturally aware expansion of evaluation resources in the Indian societal context, specifically for the harm of stereotyping. We devise a community engaged effort to build a resource which contains stereotypes for axes of disparity that are uniquely present in India. The resultant resource increases the number of stereotypes known for and in the Indian context by over 1000 stereotypes across many unique identities. We also demonstrate the utility and effectiveness of such expanded resources for evaluations of language models. CONTENT WARNING: This paper contains examples of stereotypes that may be offensive

Science Diplomacy - A New Chapter in IISF2020

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Knowledge and perceptions regarding Coronavirus (COVID-19) among pediatric dentists during lockdown period

Aim: To assess the knowledge and perceptions of COVID-19 among pediatric dentists based on their dependent source of information. Methods: A descriptive-analytical cross-sectional survey using a self-administered questionnaire with 23 questions was sent via Google forms to pediatric dentists. All participants were divided into three groups [postgraduate residents (PGs), private practitioners (PP), and faculty (F)]. The comparison of knowledge and perception scores was made based on occupation, source of information, and descriptive statistics used for the analysis using SPSS 21.0 (IBM, Armonk, NY, USA). Results: A total of 291 pediatric dentists completed the survey, and the majority of them were females (65%). Overall, good mean scores were obtained for knowledge (9.2 ± 1.07) and perceptions (5.6 ± 1.5). The majority of the participants used health authorities (45%) to obtain updates on COVID-19, while social media (35.1%) and both (19.6%) accounted for the next two. A statistically significant difference (p < 0.05) was found among different pediatric dentists groups for relying on the source of information. Conclusion: Overall good pediatric dentists showed sufficient knowledge regarding COVID-19. The pediatric dentists’ age, occupation, and source of information influenced knowledge regarding COVID-19, whereas perceptions were influenced by age and gender of the participants. Health authorities successfully educated pediatric dentists than the social medi

Development of a sensitive trial-ready poly(GP) CSF biomarker assay for C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis

Objective A GGGGCC repeat expansion in the C9orf72 gene is the most common cause of genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). As potential therapies targeting the repeat expansion are now entering clinical trials, sensitive biomarker assays of target engagement are urgently required. Our objective was to develop such an assay. Methods We used the single molecule array (Simoa) platform to develop an immunoassay for measuring poly(GP) dipeptide repeat proteins (DPRs) generated by the C9orf72 repeat expansion in cerebrospinal fluid (CSF) of people with C9orf72-associated FTD/ALS. Results and conclusions We show the assay to be highly sensitive and robust, passing extensive qualification criteria including low intraplate and interplate variability, a high precision and accuracy in measuring both calibrators and samples, dilutional parallelism, tolerance to sample and standard freeze-thaw and no haemoglobin interference. We used this assay to measure poly(GP) in CSF samples collected through the Genetic FTD Initiative (N=40 C9orf72 and 15 controls). We found it had 100% specificity and 100% sensitivity and a large window for detecting target engagement, as the C9orf72 CSF sample with the lowest poly(GP) signal had eightfold higher signal than controls and on average values from C9orf72 samples were 38-fold higher than controls, which all fell below the lower limit of quantification of the assay. These data indicate that a Simoa-based poly(GP) DPR assay is suitable for use in clinical trials to determine target engagement of therapeutics aimed at reducing C9orf72 repeat-containing transcripts

Development of a sensitive trial-ready poly(GP) CSF biomarker assay for <i>C9orf72</i>-associated frontotemporal dementia and amyotrophic lateral sclerosis

Data availability statement: Data are available upon reasonable request.Supplementary Data: This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content. Data supplement 1 available at: https://jnnp.bmj.com/highwire/filestream/214878/field_highwire_adjunct_files/0/jnnp-2021-328710supp001_data_supplement.pdf .Copyright © Author(s) (or their employer(s)) 2022. Objective: A GGGGCC repeat expansion in the C9orf72 gene is the most common cause of genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). As potential therapies targeting the repeat expansion are now entering clinical trials, sensitive biomarker assays of target engagement are urgently required. Our objective was to develop such an assay. Methods: We used the single molecule array (Simoa) platform to develop an immunoassay for measuring poly(GP) dipeptide repeat proteins (DPRs) generated by the C9orf72 repeat expansion in cerebrospinal fluid (CSF) of people with C9orf72-associated FTD/ALS. Results and conclusions: We show the assay to be highly sensitive and robust, passing extensive qualification criteria including low intraplate and interplate variability, a high precision and accuracy in measuring both calibrators and samples, dilutional parallelism, tolerance to sample and standard freeze–thaw and no haemoglobin interference. We used this assay to measure poly(GP) in CSF samples collected through the Genetic FTD Initiative (N=40 C9orf72 and 15 controls). We found it had 100% specificity and 100% sensitivity and a large window for detecting target engagement, as the C9orf72 CSF sample with the lowest poly(GP) signal had eightfold higher signal than controls and on average values from C9orf72 samples were 38-fold higher than controls, which all fell below the lower limit of quantification of the assay. These data indicate that a Simoa-based poly(GP) DPR assay is suitable for use in clinical trials to determine target engagement of therapeutics aimed at reducing C9orf72 repeat-containing transcripts.This work was funded by Wave Life Sciences, the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (648716 - C9ND) (AMI), the UK Dementia Research Institute, which receives its funding from UK DRI, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. The Dementia Research Centre is supported by Alzheimer's Research UK, Alzheimer's Society, Brain Research UK and The Wolfson Foundation. This work was supported by the NIHR UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility and the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. AK is supported by a Weston Brain Institute and Selfridges Group Foundation award (UB170045). JMS is supported by Engineering and Physical Sciences Research Council (EP/J020990/1), British Heart Foundation (PG/17/90/33415), EU’s Horizon 2020 research and innovation programme (666992). HZ is a Wallenberg Scholar. Simoa instruments used were funded by Wellcome Trust, Fidelity International Foundation and UK DRI. JDR is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Bluefield Project and the JPND GENFI-PROX grant (2019-02248). Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Performance and Development Effectiveness of Sardar Sarovar Project

The Tata institute of Social Sciences (TISS), Mumbai, was the official agency for Monitoring and Evaluation of Resettlement and Rehabilitation of people displaced in Maharashtra by the Sardar Sarovar Project (SSP) from 1987 to 1994. During this period, the TISS developed baseline data on social, demographic, economic, cultural and environmental aspects of individuals, families and communities in 33 villages in Akkalkuwa and Akrani tehsils of Dhule (now Nandurbar) district, and tracked changes in the habitat and life conditions of people shifted from Manibeli, Dhankhedi, and Chimalkhedi villages to Parveta (one of the earliest resettlement sites in Gujarat)