15 research outputs found
Bound by the Bounty: Collaboratively Shaping Evaluation Processes for Queer AI Harms
Bias evaluation benchmarks and dataset and model documentation have emerged
as central processes for assessing the biases and harms of artificial
intelligence (AI) systems. However, these auditing processes have been
criticized for their failure to integrate the knowledge of marginalized
communities and consider the power dynamics between auditors and the
communities. Consequently, modes of bias evaluation have been proposed that
engage impacted communities in identifying and assessing the harms of AI
systems (e.g., bias bounties). Even so, asking what marginalized communities
want from such auditing processes has been neglected. In this paper, we ask
queer communities for their positions on, and desires from, auditing processes.
To this end, we organized a participatory workshop to critique and redesign
bias bounties from queer perspectives. We found that when given space, the
scope of feedback from workshop participants goes far beyond what bias bounties
afford, with participants questioning the ownership, incentives, and efficacy
of bounties. We conclude by advocating for community ownership of bounties and
complementing bounties with participatory processes (e.g., co-creation).Comment: To appear at AIES 202
Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies
CELSR3 codes for a planar cell polarity protein. We describe twelve affected individuals from eleven independent families with bi-allelic variants in CELSR3. Affected individuals presented with an overlapping phenotypic spectrum comprising central nervous system (CNS) anomalies (7/12), combined CNS anomalies and congenital anomalies of the kidneys and urinary tract (CAKUT) (3/12) and CAKUT only (2/12). Computational simulation of the 3D protein structure suggests the position of the identified variants to be implicated in penetrance and phenotype expression. CELSR3 immunolocalization in human embryonic urinary tract and transient suppression and rescue experiments of Celsr3 in fluorescent zebrafish reporter lines further support an embryonic role of CELSR3 in CNS and urinary tract formation.</p
Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies
CELSR3 codes for a planar cell polarity protein. We describe twelve affected individuals from eleven independent families with bi-allelic variants in CELSR3. Affected individuals presented with an overlapping phenotypic spectrum comprising central nervous system (CNS) anomalies (7/12), combined CNS anomalies and congenital anomalies of the kidneys and urinary tract (CAKUT) (3/12) and CAKUT only (2/12). Computational simulation of the 3D protein structure suggests the position of the identified variants to be implicated in penetrance and phenotype expression. CELSR3 immunolocalization in human embryonic urinary tract and transient suppression and rescue experiments of Celsr3 in fluorescent zebrafish reporter lines further support an embryonic role of CELSR3 in CNS and urinary tract formation.</p
Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial
Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial
Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose
Study of the Engage New England Initiative Cross-Site Learning Brief 3: Improving Instructional Systems
SRI Education, the research partner for the Barr Engage New England (ENE) initiative, captured the ENE school and program grantees' learnings about improving instructional systems through interviews of school leaders, school staff members, and external partners; student focus groups; and staff surveys during the 2019-20 school year. This brief describes common facilitators and challenges experienced by grantees as they worked to further their instructional systems. It also provides some promising practices that grantees used to support these efforts or to address challenges
Recurrent Superior Vena Cava Syndrome in a Patient with Sarcoidosis and Pancreatic Adenocarcinoma: A Case Report and Literature Review
Background: Superior vena cava (SVC) syndrome may result from extravascular compression or intravascular obstruction such as thrombosis. Recurrent venous thrombosis is typically associated with a hypercoagulable state such as malignancy, and inheritable or acquired coagulopathy. Sarcoidosis is a derangement of the immune system, and it has been associated with malignant diseases and hypercoagulation. The association of pancreatic cancer and sarcoidosis with SVC syndrome has not been reported previously. Here, we present a case of recurrent venous thrombosis causing SVC syndrome in a patient with pancreatic ductal adenocarcinoma and underlying thoracic sarcoidosis. Methods: The patient’s electronic health record was retrospectively analyzed. Results: A 66-year-old woman with pancreatic adenocarcinoma was treated with neoadjuvant chemotherapy followed by Whipple procedure, before developing tumor recurrence in the liver. Her treatment course was complicated with repeated incidents of venous thrombosis in the presence of a central venous catheter leading to recurrent SVC syndrome, which resolved with anti-coagulation. Conclusions: This case raises a plausible inter-relationship between sarcoidosis, pancreatic cancer, and hypercoagulable state. We suggest that patients with multiple risk factors for developing venous thrombosis should be carefully monitored for any thrombotic event, and they may benefit from prophylactic anti-coagulation