Water molecules can be found interacting with the surface and within cavities in proteins. However, water exchange between bulk and buried hydration sites can be slow compared to simulation ...timescales, thus leading to the inefficient sampling of the locations of water. This can pose problems for free energy calculations for computer-aided drug design. Here, we apply a hybrid method that combines nonequilibrium candidate Monte Carlo (NCMC) simulations and molecular dynamics (MD) to enhance sampling of water in specific areas of a system, such as the binding site of a protein. Our approach uses NCMC to gradually remove interactions between a selected water molecule and its environment, then translates the water to a new region, before turning the interactions back on. This approach of gradual removal of interactions, followed by a move and then reintroduction of interactions, allows the environment to relax in response to the proposed water translation, improving acceptance of moves and thereby accelerating water exchange and sampling. We validate this approach on several test systems including the ligand-bound MUP-1 and HSP90 proteins with buried crystallographic waters removed. We show that our BLUES (NCMC/MD) method enhances water sampling relative to normal MD when applied to these systems. Thus, this approach provides a strategy to improve water sampling in molecular simulations which may be useful in practical applications in drug discovery and biomolecular design.
To support public health measures during the COVID-19 pandemic, oral opioid agonist treatment (OAT) take-home doses were expanded in Western countries with positive results. Injectable OAT (iOAT) ...take-home doses were previously not an eligible option, and were made available for the first time in several sites to align with public health measures. Building upon these temporary risk-mitigating guidelines, a clinic in Vancouver, BC continued to offer two of a possible three daily doses of take-home injectable medications to eligible clients. The present study explores the processes through which take-home iOAT doses impacted clients' quality of life and continuity of care in real-life settings.
Three rounds of semi-structured qualitative interviews were conducted over a period of seventeen months beginning in July 2021 with eleven participants receiving iOAT take-home doses at a community clinic in Vancouver, British Columbia. Interviews followed a topic guide that evolved iteratively in response to emerging lines of inquiry. Interviews were recorded, transcribed, and then coded using NVivo 1.6 using an interpretive description approach.
Participants reported that take-home doses granted them the freedom away from the clinic to have daily routines, form plans, and enjoy unstructured time. Participants appreciated the greater privacy, accessibility, and ability to engage in paid work. Furthermore, participants enjoyed greater autonomy to manage their medication and level of engagement with the clinic. These factors contributed to greater quality of life and continuity of care. Participants shared that their dose was too essential to divert and that they felt safe transporting and administering their medication off-site. In the future, all participants would like more accessible treatment such as access longer take-home prescriptions (e.g., one week), the ability to pick-up at different and convenient locations (e.g., community pharmacies), and a medication delivery service.
Reducing the number of daily onsite injections from two or three to only one revealed the diversity of rich and nuanced needs that added flexibility and accessibility in iOAT can meet. Actions such as licencing diverse opioid medications/formulations, medication pick-up at community pharmacies, and a community of practice that supports clinical decisions are necessary to increase take-home iOAT accessibility.
In May 2018, St. Paul's Hospital (SPH) in Vancouver (Canada) opened an outdoor peer-led overdose prevention site (OPS) operated in partnership with Vancouver Coastal Health and RainCity Housing. At ...the end of 2020, the partnered OPS moved to a new location, which created a gap in service for SPH inpatients and outpatients. To address this gap, which was magnified by the COVID-19 pandemic, SPH opened a nurse-led OPS in February 2021. This paper describes the steps leading to the implementation of the nurse-led OPS, its impact, and lessons learned.
Four steps paved the way for the opening of the OPS: (1) identifying the problem, (2) seeking ethics guidance, (3) adapting policies and practices, and (4) supporting and training staff.
The OPS is open between 10:00 and 20:00 and staffed by two nurses per shift. It is accessible to all patients including inpatients, patients in the Emergency Department, and patients attending outpatient services. Between February 1, 2021 and October 23, 2021, the OPS recorded 1612 visits for the purpose of injection, for an average weekly visit number of 42. A total of 46 overdoses were recorded in that 9-month period. Thirty-seven (80%) required administration of naloxone and 12 (26%) required a code blue response.
Due to the unique nature of our OPS, we learned many important lessons in the process leading to the opening of the site and the months that followed. We conclude the paper with lessons learned grouped into six main categories, namely engagement, communication, access, staff education and support, data collection, and safety.
What is Mother Earth? Gill, Sam
Journal for the study of religion, nature and culture,
01/2024, Letnik:
18, Številka:
2
Journal Article
Recenzirano
Odprti dostop
A rich appreciation of Mother Earth—in the entwined contexts of Native American, Australian Aboriginal, Western intellectual, and contemporary ecological movements—is accomplished in this paper using ...new perspectives and strategies: Mother Earth as name, meme, and conspiracy. This approach is developed and illustrated to offer insight into the dynamics of identity formation of individual cultures, amalgams of cultures, academic approaches, and ecological movements that span the globe, always occurring in the context of threatening, yet creative, encounters. Projecting beyond the Mother Earth example, the paper proposes a vision of the academic study of cultures and religions that focuses on gesture and repetition demonstrating that conditions of coherence, in the presence of the constant threat of incoherence, may be more valuable than discerning meaning.
The primary goal of this paper is to increase the efficiency of criticality and burnup calculations in the ANSWERS MONK® Monte Carlo code 1. Two ways of achieving this goal are investigated as part ...of the H2020 McSAFE Project: creating a unified energy grid for all materials in the model, and reducing the spread in variances of fluxes for depletable materials using a generated optimised importance map. The average tracking speedup factor across all cycles of all burnup calculations ran using the unified energy grid, at base temperature, was found to be 1.96. For criticality calculations at 400K with runtime Doppler broadening, the unified grid approach gave a total speedup factor of 7.32. This demonstrates the potential importance of this method to reduce the calculation time with models with runtime Doppler broadening. The use of the generated optimised importance map has been demonstrated to significantly reduce the variance in the standard deviations on the fluxes in the fuel pins across two different test cases. If a solution is required in which the standard deviation in none of the fuel pins exceeds 5% it was found that the number of scoring stages required was more than halved, highlighting the potential for the outlined methodology to speedup burnup credit calculations.
Medicine Means More Than Molecules Escobar Alvarez, Sindy; Gill, Sam
Issues in science and technology,
07/2024, Letnik:
40, Številka:
4
Journal Article
In this provocative study of dancing, Sam Gill examines the interpretive styles of a variety of cultural dance traditions in discourse with the philosophic traditions of Schiller, Merleau-Ponty, ...Barbaras, Derrida, Leroi-Gourhan, and Baudrillard. As a scholar of religion, Gill provides special consideration to the importance of this emerging appreciation of dancing as a perspective inclusive of body and experience. Each chapter delves into the many factions of dancing: moving, gesturing, self-othering, playing, seducing, and masking. Gill also draws on the analysis of contemporary dance films and musicals, his experience as a dancer and dance teacher, his extensive research on dance traditions, and his interest in neurobiology and phenomenology to develop the core of this rich exploration of “dancing,” the structurality of all dances.
PDF
