Development of Good Manufacturing Practice-Compatible Isolation and Culture Methods for Human Olfactory Mucosa-Derived Mesenchymal Stromal Cells.

Demyelination in the central nervous system (CNS) resulting from injury or disease can cause loss of nerve function and paralysis. Cell therapies intended to promote remyelination of axons are a promising avenue of treatment, with mesenchymal stromal cells (MSCs) a prominent candidate. We have previously demonstrated that MSCs derived from human olfactory mucosa (hOM-MSCs) promote myelination to a greater extent than bone marrow-derived MSCs (hBM-MSCs). However, hOM-MSCs were developed using methods and materials that were not good manufacturing practice (GMP)-compliant. Before considering these cells for clinical use, it is necessary to develop a method for their isolation and expansion that is readily adaptable to a GMP-compliant environment. We demonstrate here that hOM-MSCs can be derived without enzymatic tissue digestion or cell sorting and without culture antibiotics. They grow readily in GMP-compliant media and express typical MSC surface markers. They robustly produce CXCL12 (a key secretory factor in promoting myelination) and are pro-myelinating in in vitro rodent CNS cultures. GMP-compliant hOM-MSCs are comparable in this respect to those grown in non-GMP conditions. However, when assessed in an in vivo model of demyelinating disease (experimental autoimmune encephalitis, EAE), they do not significantly improve disease scores compared with controls, indicating further pre-clinical evaluation is necessary before their advancement to clinical trials.

Analysis of protected species observer data: Strengths, weaknesses, and application in the assessment of marine mammal responses to seismic surveys in the northern Gulf of Mexico 2002-2015.

Visual observation data collected by protected species observers (PSOs) is required per regulations stipulated in Notices to Lessees (NTLs) and geophysical survey Permits (Form BOEM-0328) issued to seismic operators in the Gulf of Mexico (GOM). Here, data collected by certified and trained PSOs during seismic surveys conducted between 2002-2015 were compiled and analyzed to assess utility in assessing marine mammal responses to seismic noise and effectiveness of required mitigation measures. A total of 3,886 agency-required bi-weekly PSO Effort and Sightings reports were analyzed comprising 598,319 hours of PSO visual effort and 15,117 visual sighting records of marine mammals. The observed closest point of approach (CPA) distance was statistically compared across five species groupings for four airgun activity levels (full, minimum source, ramp up, silent). Whale and dolphin detections were significantly farther from airgun array locations during full power operations versus silence, indicating some avoidance response to full-power operations. Dolphin CPA distances were also significantly farther from airguns operating at minimum source than silence. Blackfish were observed significantly farther from the airgun array during ramp up versus both full and minimum source activities. Blackfish were observed significantly closer to the airgun array during silent activities versus at full, minimum source, and ramp up activities. Beaked whales had the largest mean CPA for detection distance compared to all other species groups. Detection distances for beaked whales were not significantly differences between full and silent operations; however, the sample size was very low. Overall results are consistent with other studies indicating that marine mammals may avoid exposure to airgun sounds based on observed distance from the seismic source during specified source activities. There was geographic variability in sighting rates associated with specific areas of interest within the GOM. This study demonstrates that agency required PSO reports provide a robust and useful data set applicable to impact assessments; management, policy and regulatory decision making; and qualitative input for regional scientific, stock assessment and abundance studies. However, several improvements in content and consistency would facilitate finer-scale analysis of some topics (e.g., effort associated with specific activities, observer biases, sound field estimation) and support statistical comparisons that could provide further insight into marine mammal responses and mitigation efficacy.

Concordance of randomised controlled trials for artificial intelligence interventions with the CONSORT-AI reporting guidelines.

The Consolidated Standards of Reporting Trials extension for Artificial Intelligence interventions (CONSORT-AI) was published in September 2020. Since its publication, several randomised controlled trials (RCTs) of AI interventions have been published but their completeness and transparency of reporting is unknown. This systematic review assesses the completeness of reporting of AI RCTs following publication of CONSORT-AI and provides a comprehensive summary of RCTs published in recent years. 65 RCTs were identified, mostly conducted in China (37%) and USA (18%). Median concordance with CONSORT-AI reporting was 90% (IQR 77-94%), although only 10 RCTs explicitly reported its use. Several items were consistently under-reported, including algorithm version, accessibility of the AI intervention or code, and references to a study protocol. Only 3 of 52 included journals explicitly endorsed or mandated CONSORT-AI. Despite a generally high concordance amongst recent AI RCTs, some AI-specific considerations remain systematically poorly reported. Further encouragement of CONSORT-AI adoption by journals and funders may enable more complete adoption of the full CONSORT-AI guidelines.