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PURPOSE: Transgender (TG) individuals are a historically understudied and underserved patient population. Although clinical guidelines for the care of TG patients exist, quality measures (QMs) specific to this population are lacking. The goal of this study was to obtain expert input on aspects of care for which quality measurement may be appropriate and describe feedback on candidate QMs. METHODS: We convened a virtual technical expert panel in September 2020 with six experts in TG medical care. Experts participated in a guided discussion and provided numeric ratings on dimensions of measure suitability (importance, validity/reliability, feasibility, and ease of understanding) for eight candidate QMs spanning multiple care domains (e.g., laboratory testing/monitoring, cancer screening, and sexually transmitted infection screening). RESULTS: Panelists acknowledged high importance and potential to improve care for some candidate QMs, particularly those related to laboratory testing before initiating and during hormone therapy. Numeric ratings of QMs varied but tended to be higher for testing-focused QMs. Experts raised concerns about overly prescriptive language for some QMs and emphasized the importance of considering more flexible specifications to accommodate diverse care scenarios—including care provided to nonbinary individuals—and align with the individualized nature of gender-affirming care. CONCLUSION: These preliminary findings support a potential role for QMs in improving quality of care for TG patients. Measures related to laboratory testing/monitoring for patients who receive or plan to initiate hormone therapy may be feasible and promising to explore in the future. Additional larger-scale efforts are needed to develop and test QMs for the care of TG individuals.

Anal dysplasia can lead to anal cancer, which affects persons living with HIV (PLWH) more than people in the general population. Screening for anal dysplasia is recommended to detect anal cancer at an early stage. The aim of our process improvement project was to improve compliance and consistency in implementing anal dysplasia screening for PLWH receiving care at a Ryan White facility covering 18 counties in western North Carolina. There were 291 PLWH screened for anal dysplasia during the 9-month data-gathering period. The compliance rate significantly increased from a preintervention rate of 31.3% to 57.5% (p .001). There were 109 (37.5%) abnormal screening results. PLWH who had abnormal screening results were more likely to be White. Gender and age were not significantly associated with abnormal screening results. Anal dysplasia screening is a simple procedure to detect precursors to cancer that can be integrated into the primary care of PLWH.

In order to develop non-ATP competitive CDK2/cyclin A inhibitors, the REPLACE strategy has been applied to generate fragment alternatives for the N-terminal tetrapeptide of the cyclin binding motif (HAKRRLIF) involved in substrate recruitment prior to phosphotransfer. The docking approach used for the prediction of small molecule mimics for peptide determinants was validated through reproduction of experimental binding modes of known inhibitors and provides useful information for evaluating binding to protein-protein interaction sites. Further to this, potential arginine isosteres predicted using the validated LigandFit docking method were ligated to the truncated C-terminal peptide, RLIF using solid phase synthesis and evaluated in a competitive binding assay. After testing, identified fragments were shown to represent not only appropriate mimics for a critical arginine residue but also to interact effectively with a minor hydrophobic pocket present in the binding groove. Further evaluation of binding modes was undertaken to optimize the potency of these compounds. Through further application of the REPLACE strategy in this study, peptide-small molecule hybrid CDK2 inhibitors were identified that are more drug-like and suitable for further optimization as anti-tumor therapeutics.

Cryptococcus neoformans causes an estimated 600,000 AIDS-related deaths annually that occur primarily in resource-limited countries. Fluconazole and amphotericin B are currently available for the treatment of cryptococcal-related infections. However, fluconazole has limited clinical efficacy and amphotericin B requires intravenous infusion and is associated with high renal toxicity. Therefore, there is an unmet need for a new orally administrable anti-cryptococcal drug. We have developed a high-throughput screening assay for the measurement of C. neoformans viability in 1,536-well plate format. The signal-to-basal ratio of the ATP content assay was 21.9 fold with a coefficient of variation and Z' factor of 7.1 % and 0.76, respectively. A pilot screen of 1,280 known compounds against the wild-type C. neoformans (strain H99) led to the identification of four active compounds including niclosamide, malonoben, 6-bromoindirubin-3′-oxime, and 5-[(4-ethylphenyl)methylene]-2-thioxo-4-thiazolidinone. These compounds were further tested against nine clinical isolates of C. neoformans, and their fungicidal activities were confirmed. The results demonstrate that this miniaturized C. neoformans assay is advantageous for the high-throughput screening of large compound collections to identify lead compounds for new anti-cryptococcal drug development.

This documentary is based on the book The Corporation: The Pathological Pursuit of Power and Profit, written by one of the film's coauthors, Joel Bakan (2004). The filmmakers present narrative interviews with 40 CEOs and executives from a variety of industries, economists, academics, and a host of o

In an extensive series of experiments Sternberg, Monsell, Knoll, and Wright (1978) reported that simple RT increased as a linear function of the number of items to be pronounced or typed. The present experiments replicate a portion of these results, but show that the effect is less general than may have been supposed. Since the effect does not occur in every case in which a response programming interpretation would predict it, this interpretation must be rejected. This conclusion is consistent with the viewpoint that response programming should be investigated in a choice- rather than simple-RT paradigm. In this view, motivated subjects can program responses in advance of the simple-RT interval because the particular response to be made has been precued. Effects of response parameters which are observed for motivated subjects in the simple-RT paradigm, such as those reported by Sternberg et al. (1978), should be attributed to processes other than programming motor responses.