Ulysses at 100

The year 2022 marked the 100th anniversary of the publication of Ulysses. The following reflections express different sentiments and thoughts about the novel that gave T. S. Eliot “all the surprise, delight, and terror that I can require.

Improving quality of care through routine, successful implementation of evidence-based practice at the bedside: an organizational case study protocol using the Pettigrew and Whipp model of strategic change

BACKGROUND: Evidence-based practice (EBP) is an expected approach to improving the quality of patient care and service delivery in health care systems internationally that is yet to be realized. Given the current evidence-practice gap, numerous authors describe barriers to achieving EBP. One recurrently identified barrier is the setting or context of practice, which is likewise cited as a potential part of the solution to the gap. The purpose of this study is to identify key contextual elements and related strategic processes in organizations that find and use evidence at multiple levels, in an ongoing, integrated fashion, in contrast to those that do not. METHODS: The core theoretical framework for this multi-method explanatory case study is Pettigrew and Whipp's Content, Context, and Process model of strategic change. This framework focuses data collection on three entities: the Why of strategic change, the What of strategic change, and the How of strategic change, in this case related to implementation and normalization of EBP. The data collection plan, designed to capture relevant organizational context and related outcomes, focuses on eight interrelated factors said to characterize a receptive context. Selective, purposive sampling will provide contrasting results between two cases (departments of nursing) and three embedded units in each. Data collection methods will include quantitative tools (e.g., regarding culture) and qualitative approaches including focus groups, interviews, and documents review (e.g., regarding integration and “success”) relevant to the EBP initiative. DISCUSSION: This study should provide information regarding contextual elements and related strategic processes key to successful implementation and sustainability of EBP, specifically in terms of a pervasive pattern in an acute care hospital-based health care setting. Additionally, this study will identify key contextual elements that differentiate successful implementation and sustainability of EBP efforts, both within varying levels of a hospital-based clinical setting and across similar hospital settings interested in EBP

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Cheech and Chong

Utopianism in the Eightie

A 10mg Dose of Amiloride Increases Time to Failure During Blood-Flow-Restricted Plantar Flexion in Healthy Adults Without Influencing Blood Pressure.

Amiloride has been shown to inhibit acid-sensing ion channels (ASIC\u27s), which contribute to ischemia related muscle pain during exercise. Purpose. To determine if a single oral dose of amiloride would improve exercise tolerance and attenuate blood pressure during blood-flow-restricted (BFR) exercise in healthy adults. Methods. Ten subjects (4 female) performed isometric plantar flexion exercise with BFR (30% maximal voluntary contraction) after ingesting either a 10mg dose of amiloride or a volume-matched placebo (random order). Time to failure, time-tension index (TTI) and perceived pain (visual analog scale) were compared between the amiloride and placebo trials. Mean blood pressure, heart rate, blood pressure index (BPI), and BPI normalized to TTI (BPInorm) were also compared between trials using both time matched (TM50 and TM100) and effort matched (T50 and T100) comparisons. Results. Time to failure (+69.4 ± 63.2 seconds, P\u3c0.01) and TTI (+1,441 ± 633 Kg*sec, P=0.02) were both significantly increased in the amiloride trial compared to placebo, despite no increase in pain (+0.4 ± 1.7 cm, P=0.46). In contrast, amiloride had no significant influence on the mean blood pressure or heart rate responses, nor were there any significant differences in BPI or BPInorm between trials when matched for time (all P\u3e0.13). When matched for effort, BPI was significantly greater in the amiloride trial (+5300 ± 1798 mmHg*sec, P=0.01), likely owing to an increase in total exercise duration. Conclusions. A 10mg oral dose of amiloride appears to significantly improve the tolerance to BFR exercise in healthy adults without influencing blood pressure responses