Objectives
To identify successful strategies for retention of participants in multi-year, community-based randomized controlled trials (RCTs) aiming to reduce early childhood caries in health disparities populations from diverse racial/ethnic backgrounds and across diverse geographic settings.
Methods
Four RCTs conducted by the Early Childhood Caries Collaborating Centers (EC4), an initiative of the National Institute of Dental and Craniofacial Research, systematically collected information on the success of various strategies implemented to promote participant retention in each RCT. The observational findings from this case series of four RCTs were tabulated and the strategies rated by study staff.
Results
Participant retention at 12 months of follow-up ranged from 52.8% to 91.7%, and at 24 months ranged from 53.6% to 85.9, across the four RCT. For the three RCT that had a 36 month follow-up, retention ranged from 53.6% to 85.1%. Effectiveness of different participant retention strategies varied widely across the RCT.
Conclusions
Findings from this case series study may help to guide the design of future RCTs to maximize retention of study participants and yield needed data on effective interventions to reduce oral health disparities.
Purpose
Flourine-18-flortaucipir tau positron emission tomography (PET) was developed for the detection for Alzheimer’s disease. Human imaging studies have begun to investigate its use in chronic traumatic encephalopathy (CTE). Flortaucipir-PET to autopsy correlation studies in CTE are needed for diagnostic validation. We examined the association between end-of-life flortaucipir PET and postmortem neuropathological measurements of CTE-related tau in six former American football players.
Methods
Three former National Football League players and three former college football players who were part of the DIAGNOSE CTE Research Project died and agreed to have their brains donated. The six players had flortaucipir (tau) and florbetapir (amyloid) PET prior to death. All brains from the deceased participants were neuropathologically evaluated for the presence of CTE. On average, the participants were 59.0 (SD = 9.32) years of age at time of PET. PET scans were acquired 20.33 (SD = 13.08) months before their death. Using Spearman correlation analyses, we compared flortaucipir standard uptake value ratios (SUVRs) to digital slide-based AT8 phosphorylated tau (p-tau) density in a priori selected composite cortical, composite limbic, and thalamic regions-of-interest (ROIs).
Results
Four brain donors had autopsy-confirmed CTE, all with high stage disease (n = 3 stage III, n = 1 stage IV). Three of these four met criteria for the clinical syndrome of CTE, known as traumatic encephalopathy syndrome (TES). Two did not have CTE at autopsy and one of these met criteria for TES. Concomitant pathology was only present in one of the non-CTE cases (Lewy body) and one of the CTE cases (motor neuron disease). There was a strong association between flortaucipir SUVRs and p-tau density in the composite cortical (ρ = 0.71) and limbic (ρ = 0.77) ROIs. Although there was a strong association in the thalamic ROI (ρ = 0.83), this is a region with known off-target binding. SUVRs were modest and CTE and non-CTE cases had overlapping SUVRs and discordant p-tau density for some regions.
Conclusions
Flortaucipir-PET could be useful for detecting high stage CTE neuropathology, but specificity to CTE p-tau is uncertain. Off-target flortaucipir binding in the hippocampus and thalamus complicates interpretation of these associations. In vivo biomarkers that can detect the specific p-tau of CTE across the disease continuum are needed.
Cancer screening and timely follow-up of abnormal results can reduce mortality. One barrier to follow-up is the failure to identify abnormal results. While EHRs have coded results for certain tests, cancer screening results are often stored in free-text reports, which limit capabilities for automated decision support. As part of the multilevel Follow-up of Cancer Screening (mFOCUS) trial, we developed and implemented a natural language processing (NLP) tool to assist with real-time detection of abnormal cancer screening test results (including mammograms, low-dose chest CT scans, and Pap smears) and identification of gynecological follow-up for higher risk abnormalities (i.e. colposcopy) from free-text reports. We demonstrate the integration and implementation of NLP, within the mFOCUS system, to improve the follow-up of abnormal cancer screening results in a large integrated healthcare system. The NLP pipelines have detected scenarios when guideline-recommended care was not delivered, in part because the provider mis-identified the text-based result reports.
A series of thiourea derivatives bearing pendant hydroxyl groups was synthesized. These quadruply nucleophilic compounds underwent cyclization reactions with bromoacyl bromides, yielding two isomeric iminothiozolidinones. While the remote hydroxyl group in functionalized thioureas was not directly involved in the cyclization, it allowed us to establish control over the product formation through the choice of temperature and/or solvent. The new mode of temperature‐dependent control over the product distribution was different from the classical kinetic vs thermodynamic control. A number of synthesized iminothiozolidinones underwent an unprecedented termolecular decyclization reaction in the presence of an external nucleophile and a proton to yield aminooxoethylcarbamothionates. In addition to the theoretical importance of this newly discovered reaction, there is also a practical need for these decyclized products as they are known privileged structures in the family of HIV‐1 transcriptase inhibitors.
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