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Clinical Decision Support - Concepts of Operation

We are entering a new era in space exploration to return to the moon and explore Mars. Crew members operating independently during long duration space exploration missions will require a clinical decision support system (CDSS) to increase autonomy by augmenting their knowledge, skills and abilities in different scenarios. Significant changes to in-flight and habitat medical care due to constraints on mass, volume, power, crew time and medical evacuation capabilities are needed to increase crew autonomy and self-reliance in decision making and task performance. The Exploration Medical Capability (ExMC) Element of the Human Research Program (HRP) pushes the boundary of space medical systems to advance the care of astronauts on future exploration missions beyond low Earth orbit by identifying and testing next-generation medical care and crew health maintenance technologies. Clinical decision support (CDS) presents knowledge and data in a context aware manner to augment a crew members’ knowledge, skills and abilities during the process of observation, orientation, decisions and action. A comprehensive crew health and performance CDSS is required to augment crew capability and will be used in different scenarios for several reasons. In general, the CDSS’s role is to assist the crew in prevention, detection, diagnosis and treatment of crew health and performance related conditions that may arise in exploration spaceflight. For example, CDSS would assist a high acuity scenario such as a heart attack by supplying clear instructions, vital signs and treatment reminders. A lower severity scenario such as kidney stone risk could interface to vehicle systems and display more complex predictive data during a diagnosis. A CDSS needs to contribute to successful missions by maintaining a high performing crew who can potentially exhibit countless medical conditions related to derangements from the space environment (sleep, cognition, nutrition and exercise) as well as conditions intrinsic to humans anywhere. While supporting the crew’s ability to make sound clinical decisions is desirable in any mission, it is essential for exploration missions with significant communication delays, no evacuation capability, and extended exposure to the flight environment. Such missions correspond with medical Level of Care V (LOC V), the highest level specified in NASA-STD-3001. The project focuses on CDS implementation research to derive requirements for LOC V, where the need for increased autonomy results in new practices and the inclusion of non-clinical data, such as vehicle environmental measures and physical exercise results, from other human and vehicle domains and advanced analytics. The CDS project describes how the CDSS is intended to be used by defining concepts of operations (ConOps). The process to derive ConOps focuses on increased autonomy that reduces the likelihood and consequences of accepted medical conditions. These crew health and performance inputs are grouped by common datasets and analysis models. Use cases are derived to research new clinical scenarios, architectural development and workflows. Implementation research is conducted with protypes to inform assumptions and derive requirements. The project also establishes how externally developed analysis and approaches can be added to expand a clinical decision support system and thus highlight how a comprehensive system can be globally developed with collaborators. This presentation will cover example scenarios from the CDS ConOps and the method to derive them. One example scenario will be CDSS alerting an increased kidney stone risk during a mission, with diagnosis and treatment options provided during the intervention.

clinical decision support↗

Meteorite Sample Section Repair at NASA Johnson Space Center

Introduction: Meteorite thin and thick sections are routinely shipped from NASA Johnson Space Center to fulfill sample allocation requests from principle investigators around the world. Sections are also re-turned to JSC when researchers are finished studying them since, in most cases, they can be reused for other studies. The sections are very fragile unfortunately, and sometimes return to us needing repairs. The fol-lowing should give you an idea of how we repair sections here in the very lab where they were created. NOTE: Please do not attempt to repair ANSMET meteorite sections that are in your possession. We will perform the repairs for you at NASA JSC if you send the section back to us. Section Delamination: The majority of the meteorite sections that we produce here are secured to the glass slide using a high quality, two-part epoxy. Occasionally, we are asked to use superglue if the researcher wishes to dismount the section from the slide. Both epoxy and superglue are excellent adhesives, but they both tend to embrittle with time which results in delamination from the slide. Exposure to vacuum can also degrade the adhesion between the sample section and the glass slide. Repeated handling of the slide edges can accelerate delamination and, as a preventive measure, the outer 1-2 mm of epoxy is trimmed from newly created sections at JSC. If conductive tapes (copper, carbon, etc.) are used on the section during analysis, great care must be taken in removing the tape so that the epoxy is not pulled up with it. If in doubt, the tape can be left on the section when it is returned to JSC. Before we perform any repairs to sample sections, carbon, gold, or other coatings are removed. We accomplish this using a slurry of 0.05 micron alumina and 190 proof ethyl alcohol applied to a felt polishing pad fitted to a rotating lap wheel. Coatings are re-moved in this manner from all sections that are re-turned to JSC. The extent of the delamination determines how we proceed with the section repair. If the meteorite sample area of the section is not disturbed, then we carefully remove the delaminated epoxy. This is done using a binocular microscope with a 6X zoom, cut-proof gloves, and a very sharp, single edged razor blade. We cut the delaminated epoxy with the blade angled away from the sample area and using very light pressure. The trimmed section is then cleaned in an ultrasonic bath of 200 proof ethyl alcohol for no more than 10 seconds and carefully dried using a lint-free clean room wipe. The section is then placed into a lab oven at 110o F in preparation for epoxy. We mix the resin and hardener components of the low viscosity epoxy and very small amounts are applied to the cut edges of the section using a needle probe and the binocular microscope. Warming the epoxy helps secure the existing section by filling any voids between the glass slide and the section. After the new epoxy cures, we give the section a light polish on a lap wheel fitted with cotton polishing paper that is charged with 1 micron diamond paste. If the section has delaminated to the point of sample area being lifted from the glass, then it may be irreparable. We employ the above technique along with clamping the section in a Teflon pad arrangement in order to flatten the sample while the epoxy cures. Otherwise, the sample will tend to curl. This works to some degree, but once the sample area curls, it seldom re-turns to the original flatness without cracking or bending. Canada Balsam and Crystalbond: We repair damaged sections that had originally been prepared using Canada Balsam or Crystalbond adhesives through the gradual application of heat. We take great care with these samples since these bonding materials tend to get brittle with age. The section is heated in gradual steps (40-50o F per hour) to the melting point of the adhesive. We repair the sample while the adhesive is fluid and then the section is cooled in the same gradual manner in which it was heated. Slide Cracks and Breaks: Accidents happen. Especially with something as small and fragile as a thin/thick section. We all know someone who has driven a microscope objective into a section. As bad as the damage may look, the section can be repaired in most instances. NOTE: Please do not try to tape or glue section pieces back together prior to returning the dam-aged section. This practice usually renders the section irreparable. If the glass slide is cracked but the section is still in one piece, we repair it by infilling the crack with the low viscosity epoxy mentioned earlier. If the slide is in pieces, we can reassemble it with epoxy on a new backer slide. This is a tricky task as the pieces need to be in the correct plane with respect to each other, especially if the sample area is split among several pieces.

Meteorite↗

Harnessing Artificial Intelligence for Medical Diagnosis and Treatment During Space Exploration Missions

From May 8th to June 9th, 2023, I had the opportunity to participate in an experiential learning experience at Johnson Space Center in Houston, TX with Exploration Medical Capability (ExMC), an element of the NASA Human Research Program. During this research experience, I was not only able to work on the above titled research project, but also gain an immense exposure to the field of aerospace medicine, make numerous connections within the field, tour NASA facilities, as well as travel to the Aerospace Medical Association Annual Conference (AsMA) in New Orleans. To briefly introduce my project, it is well understood that the medical capabilities available to crew medical officers (CMOs) on the International Space Station will be different than the capabilities available and needed during deep space exploration missions to the Moon, Mars, and beyond. Ground support is particularly limited due to distance, communication delays (or lack of communication), and lack of resupply. Therefore, to support medical care by CMOs on these missions, robust clinical decision support systems (CDSSs) must be designed. The recent publication and public launch of generative artificial intelligence (AI) tools based upon large language models (LLM) such as ChatGPT provides the opportunity to create a smart assistant for onboard triage, diagnosis, and treatment of medical conditions. Ultimately, the overall purpose of the project was to research what AI tools currently exist or are in development, and to see how they might be implemented onboard during exploration class spaceflights of the future. The ExMC element is actively developing several tools to be used in preparation for and during deep space exploration missions. One of those tools, known as IMPACT, is a probabilistic risk assessment model which can be used to propose a desired medical system (based on mass and volume) and suggest the clinical outcomes likely to occur for a design reference mission (DRM). The group recently presented the IMPACT model and a DRM of interest titled “Modified Long Duration Lunar Orbital and Lunar Surface” (mLDLOLS) at the recent AsMA conference. The mLDLOLS mock mission is a 9 month and 6-day deep space exploration mission consisting of time in Moon’s orbit (3 months on the Gateway space station), on the lunar surface (3 months within habitat), and another 3 months on Gateway before return to Earth. For this DRM, IMPACT ultimately outlined a preferred medical system that was then associated with medical conditions considered to be most likely based on frequency, most likely to cause astronaut task time loss (TTL), most likely to cause return to definitive care (RTDC), and most likely cause loss of crew life (LOCL). IMPACT also highlighted the medical capabilities/skills that would be required to care for those medical conditions, such as performing a history of present illness or musculoskeletal exam with ultrasound. The primary objective of the project was to perform a survey of the AI tools and systems applicable to the conditions outlined for the proposed mLDLOLS mission. Using PubMed (including most relevant MeSH terms) and Google Scholar, we then created a robust annotated bibliography organized by condition. The 56-page and over 500 reference annotated bibliography was subsequently used to create a review outline that would become the basis for drafting of a future publication. For the review outline, we took those medical conditions researched within the annotated bibliography (condition-based approach) and deployed a systems-based approach, combining those medical conditions and related tools into ten categories. These categories included general/all-purpose CDSSs, tools to diagnose or manage respiratory, dermatologic, neurologic, auditory and vestibular, ophthalmic, musculoskeletal, infection-associated, and gynecologic conditions, as well as tools that could be deployed in the setting of trauma/emergency. With the completion of the 30-page outline, we then began drafting the review paper. To conclude the research experience, I presented the findings from our survey to the ExMC Clinical and Science team. With these objectives, I ultimately learned about the number of AI tools that exist today to assist medical professionals with the triage, diagnosis, and management of several medical conditions. These tools can span from chatbot assistants to help triage knee pain to vision transformer models that can identify ophthalmic conditions based on ocular surface images captured with a cell phone. We also highlighted the current gaps that exist in the literature alongside the advancements that are needed to make the desired CDSS for deep space exploration missions. With this experience, I certainly confirmed an existing career goal and identified several additional skills needed to become an aerospace medical doctor including knowledge of critical care in an extreme medicine setting, aerospace engineering and human integration systems, artificial intelligence, machine learning, and risk models. I also identified numerous transferable skills for this career goal including the basic knowledge of medicine (MD), deployment of the scientific method for critical thought about new scientific questions (PhD), review of published literature, including creating an annotated bibliography (PhD), as well as detailed scientific writing (PhD). The results of my research will likely guide the design of an all-encompassing onboard medical assistant for use during deep space exploration missions of the future. I plan on sharing the outcomes from this experience with my peers at a student seminar in the Fall semester on August 30th. During the seminar, I will detail the project, my experience at NASA and AsMA, as well as offer best practice guidelines for students entertaining similar experiences or careers. In conclusion, I would like to thank the WVU School of Medicine, Research and Graduate Education office, as well as NASA ExMC for the unwavering support of this life-changing experience.

Ryan A. Lacinski↗

Task Load Management in Earth Independent Medical Operations

BACKGROUND: Medical care in spaceflight carries a high task load and can easily overwhelm a small crew. Present day operations in low Earth orbit (LEO) offload most medical tasks to ground teams in mission control. This team includes dozens of flight surgeons, specialists, and engineers and supports the on-orbit crew in monitoring environmental systems, tracking medications, guiding procedures, providing expert advice, and many other tasks. However, the physical limitations of the speed of light and technical limitations of bandwidth, channel capacity, and signal processing mean that missions beyond LEO cannot rely on this level of telemedical support. The further we travel from Earth the more these tasks will fall on the shoulders of the crew and the greater the risk of task saturation to the wellbeing of the crew and the success of the mission. Exploration class space crews will need progressively more robust systems for managing task load as they progress further out in space. OVERVIEW: Medical task management systems will need to assist with two broad categories of tasks; cognitively intensive tasks and procedure execution tasks. In both cases the goal is for the systems to operate in the background with minimal human-in-the-loop intervention. To accomplish this such systems will need to be designed with careful consideration for human factors and human systems integration to maximize efficiency, minimize alarm fatigue, and avoid inadvertently increasing task loads. Finally, the key domains of space medicine tasking can be used to map present day and near future technologies to the areas where they are best suited to support and identify gaps which can be targeted for research and development. DISCUSSION: Task load is a major challenge for Earth Independent Medical Operations to overcome. It will require careful coordination between experts in a variety of fields paying attention to human factors and human systems integration as well as technical and medical expertise. If done well medical task management systems can handle many of the tasks currently run by humans in mission control and enable human crews to maintain terrestrial standards of care in the extraterrestrial environment.

Dana Levin↗

Developing Mars-Based Clinical Scenarios for an Earth Independent Medical Operations (EIMO) – Based Decision Support Service

As crewed missions move beyond Low-Earth Orbit, pre-mission planning cannot fully buy down the medical risks of exploration-class missions. Martian missions, where increased hazards exist, (such as long-duration spaceflight, surface-level EVA operations, and communications delays) will require a paradigm shift in the structure of a medical system. An Earth-Independent Medical Operations-based Medical System (EIMO-MS) will need to optimize four critical domains to help provide medical care: utilization of Pre-Mission Planning, augmentation of Acute and Prolonged Medical Decision Making, automated tracking of Resource Management, and assistance in Task Load Balance. The ideal EIMO-MS will be able to accomplish this goal by having an interactive, adaptable interface that will be able to provide real-time medical services. It must respond based on the level of crewmember training, medical situation, and available medical and non-medical resources. To showcase the capabilities and requirements of such a sophisticated automated MS, a series of clinical scenarios of escalating complexity were developed with clinical and systems engineering input. These scenarios describe in clinical detail what a theoretical future medical system, enhanced with multiple information streams (such as a medical database, an AI-based Decision Support System, real-time monitoring, enhanced in-situ laboratory imaging, etc.) can achieve in conjunction with a trained and experienced crew. Scenarios are comprised of: a context section including objectives and applicable spaceflight environment, a highlighted assumptions section, a clinical narrative section, and a systems engineering activity diagram demonstrating the integrated Medical System (MS). The “swim lanes” of the activity diagram act as the logistical core of each scenario and show how the MS will interact with the crew, ground support, and other in-flight systems. The Design Reference Mission that is used for the scenarios is based on existing reference mission profiles [1] with a projected 30-sol stay on the Martian surface. Scenarios span the spectrum from planned evaluations, minor medical care, urgent care, surgical guidance, critical and expectant management, and behavioral health care. Mission complexity will exponentially increase during deep space and Mars exploration-class missions, and medical support for these missions will likewise need to increase in autonomy and adaptability. The integrated system that will support these missions will need to provide assistance in a variety of anticipated and unforeseen scenarios. These medical scenarios, guided by clinician input, are initial steps in crafting the requirements for an EIMO-based medical system. By working in a systems engineering framework, requirements and capabilities can be extracted and mapped while maintaining a clinical core.

Prashant Parmar↗

Earth-Independent Medical Operations (EIMO) Concept of Operations

In contrast to the current crew health paradigm for low-Earth orbit and Lunar missions, which depends on real-time communication with Mission Control, deep-space exploration missions will require a significant shift in medical operations. This shift is driven by the constraints of operating at a considerable distance from Earth, such as resource limitations—lack of resupply, restricted mass, power, volume, and data—as well as communication delays and the inability to evacuate back to Earth during emergencies. To move toward a more self-reliant medical model, a strategy is needed to gradually increase space-based crew autonomy and reduce risks to mission success in the challenging environment of deep space. This transformative change, known as "Earth-Independent Medical Operations" (EIMO), explores the gradual transfer of medical care and decision-making from Earth-based support to space-based systems. The goal of this transition is to enhance astronaut health and performance while minimizing mission risks. EIMO requires the development of a medical system that integrates seamlessly with mission planning, vehicle and spacesuit design, and data architecture. This integration is crucial for building a robust medical infrastructure that not only safeguards astronaut well-being but also ensures overall mission success. The Human Research Program (HRP) Exploration Medical Capability (ExMC) Element has revised the EIMO model-based Concept of Operations (ConOps) which outlines an initial vision for EIMO. The ConOps, which is built on the stakeholders’ need, system goals, and objectives (NGOs), presents an array of in-mission scenarios that span a wide range of medical conditions demonstrating the system’s capabilities from basic to complex events. Developed by a multidisciplinary team of systems engineers, scientists, and clinicians within ExMC, the ConOps revision includes two new scenarios(Barotrauma and Self-Medical Management and Behavioral Health and Chronic Medical Care), and implementation of findings from EIMO technical interchange meetings that focused on data and training. The envisioned EIMO Medical System (MS) operates as a system of systems, gathering data from various sources such as reference databases, real-time wearable sensors, point-of-care diagnostics, and environmental controls. The MS also incorporates advanced training tools to support autonomous medical care, assisting the Crew Medical Officer (CMO) during medical events where Ground Support is either unavailable or communication-delayed beyond practicality. Furthermore, MS functions and capabilities were decomposed from the scenarios to establish foundational requirements for EIMO and traced to the NASA Spaceflight Human-System Standard(NASA-STD-3001, Volumes 1 and 2). These traces were performed to gain insights on the alignment of EIMO requirements with the NASA standard. This work serves as an initial recommendation to increase crew autonomy gradually and safely for Mars missions and future deep-space exploration.

medical system↗

Development and Validation of a Non-Invasive, Chairside Oral Cavity Cancer Risk Assessment Prototype Using Machine Learning Approach

Oral cavity cancer (OCC) is associated with high morbidity and mortality rates when diagnosed at late stages. Early detection of increased risk provides an opportunity for implementing prevention strategies surrounding modifiable risk factors and screening to promote early detection and intervention. Historical evidence identified a gap in the training of primary care providers (PCPs) surrounding the examination of the oral cavity. The absence of clinically applicable analytical tools to identify patients with high-risk OCC phenotypes at point-of-care (POC) causes missed opportunities for implementing patient-specific interventional strategies. This study developed an OCC risk assessment tool prototype by applying machine learning (ML) approaches to a rich retrospectively collected data set abstracted from a clinical enterprise data warehouse. We compared the performance of six ML classifiers by applying the 10-fold cross-validation approach. Accuracy, recall, precision, specificity, area under the receiver operating characteristic curve, and recall–precision curves for the derived voting algorithm were: 78%, 64%, 88%, 92%, 0.83, and 0.81, respectively. The performance of two classifiers, multilayer perceptron and AdaBoost, closely mirrored the voting algorithm. Integration of the OCC risk assessment tool developed by clinical informatics application into an electronic health record as a clinical decision support tool can assist PCPs in targeting at-risk patients for personalized interventional care.

60 APPLIED LIFE SCIENCES↗

Simple Bioparticle Filtration Device Based on an Ultralow-Fouling Zwitterionic Polyurethane Membrane for Rapid Large-Volume Separation of Plasma and Viruses from Whole Blood

Plasma separation from whole blood is oftent required as an essential first step when performing blood tests with a viral assay. However, developing a point-of-care plasma extraction device with a large output and high virus recovery remains a significant obstacle to the success of on-site viral load tests. Here, we report a portable, easy-to-use, cost-efficient, membrane-filtration-based plasma separation device that enables rapid large-volume plasma extraction from whole blood, designed for point-of-care virus assays. The plasma separation is realized by a low-fouling zwitterionic polyurethane-modified cellulose acetate (PCBU-CA) membrane. The zwitterionic coating on the cellulose acetate membrane can decrease surface protein adsorption by 60% and increase plasma permeation by 46% compared with a pristine membrane. The PCBU-CA membrane, with its ultralow-fouling properties, enables rapid plasma separation. The device can yield a total of 1.33 mL plasma from 10 mL whole blood in 10 min. The extracted plasma is cell-free and exhibits a low hemoglobin level. In addition, our device demonstrated a 57.8% T7 phage recovery in the separated plasma. The results of real-time polymerase chain reaction analysis confirmed that the nucleic acid amplification curve of the plasma extracted by our device is comparable to that obtained by centrifugation. With its high plasma yield and good phage recovery, our plasma separation device provides an excellent replacement for traditional plasma separation protocols for point-of-care virus assays and a broad spectrum of clinical tests.

36 MATERIALS SCIENCE↗

Some approaches to medical support for Martian expedition

Medical support in a Martian expedition will be within the scope of crew responsibilities and maximally autonomous. Requirements to the system of diagnostics in this mission include considerable use of means and methods of visualization of the main physiological parameters, telemedicine, broad usage of biochemical analyses (including "dry" chemistry), computerized collection, measurement, analysis and storage of medical information. The countermeasure system will be based on objective methods of crew fitness and working ability evaluation, individual selection of training regimens, and intensive use of computer controlled training. Implementation of the above principles implies modernization and refinement of the countermeasures currently used by space crews of long-term missions (LTM), and increases of the assortment of active and passive training devices, among them a short-arm centrifuge. The system of medical care with the functions of prevention, clinical diagnostics and timely treatment will be autonomous, too. The general requirements to medical care during the future mission are the following: availability of conditions and means for autonomous urgent and special medical aid and treatment of the most possible states and diseases, "a hospital", and assignment to the crew of one or two doctors. To ensure independence of medical support and medical care in an expedition to Mars an automated expert system needs to be designed and constructed to control the medical situation as a whole. c2003 Published by Elsevier Science Ltd.

Mars↗

A reinvestigation into Munson’s model for room closure in bedded rock salt

Accurate predictions of room closure are important for hazardous waste repositories in rock salt formations, such as the Waste Isolation Pilot Plant (WIPP). When Munson and co-workers simulated several room closure experiments conducted at the WIPP during the 1980’s and 1990’s, their simulated closure curves closely agreed with the closure measurements. A careful review of their work, however, raised concerns and prompted the reinvestigation in this paper. Here, to begin the reinvestigation, Munson’s legacy Room D closure simulation was reasonably recreated in a current-day finite element code. Next, special care was taken to obtain numerically converged results, re-introduce the anhydrite strata intermittently ignored by Munson, and calibrate the Munson–Dawson (M–D) constitutive model for salt as much as possible from laboratory test measurements. When this new model was used to simulate Room D’s closure, it under-predicted the horizontal and vertical closure rates by 2.34x and 3.10x, respectively, at 5.7 years after room excavation. As a result, the M–D model was extended to capture the newly established creep behavior at low equivalent stresses (<8 MPa) and replace the Tresca with the Hosford equivalent stress. Simulations using the new M–D model over-predicted the horizontal closure rate by 1.15x and under-predicted the vertical closure rate by 1.08x at 5.7 years, averaged over three room closure experiments. Although further improvements could be made, the new model has a stronger scientific foundation than Munson’s legacy model and appears ready for careful engineering use.

58 GEOSCIENCES↗

Costs of Definitive Chemoradiation, Surgery, and Adjuvant Radiation Versus De-Escalated Adjuvant Radiation per MC1273 in HPV+ Cancer of the Oropharynx

De-escalated treatment for human papillomavirus (HPV)+ oropharynx squamous cell carcinoma (OPSCC) has shown promising initial results. Health-care policy is increasingly focusing on high-value care. This analysis compares the cost of care for HPV+ OPSCC treated with definitive chemoradiation (CRT), surgery and adjuvant radiation (RT), and surgery and de-escalated CRT on MC1273.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Medication abortion via digital health in the United States: a systematic scoping review

Digital health, including telemedicine, has increased access to abortion care. The convenience, flexibility of appointment times, and ensured privacy to abortion users may make abortion services via telemedicine preferable. This scoping review systematically mapped studies conducted on abortion services via telemedicine, including their effectiveness and acceptability for abortion users and providers. All published papers included abortion services via telemedicine in the United States were considered. Articles were searched in PubMed, CINAHL, and Google Scholar databases in September 2022. The findings were synthesized narratively, and the PRISMA-ScR guidelines were used to report this study. Out of 757 retrieved articles, 33 articles were selected based on the inclusion criteria. These studies were published between 2011 and 2022, with 24 published in the last 3 years. The study found that telemedicine increased access to abortion care in the United States, especially for people in remote areas or those worried about stigma from in-person visits. The effectiveness of abortion services via telemedicine was comparable to in-clinic visits, with 6% or fewer abortions requiring surgical intervention. Both care providers and abortion seekers expressed positive perceptions of telemedicine-based abortion services. However, abortion users reported mixed emotions, with some preferring in-person visits. The most common reasons for choosing telemedicine included the distance to the abortion clinic, convenience, privacy, cost, flexibility of appointment times, and state laws imposing waiting periods or restrictive policies. Telemedicine offered a preferable option for abortion seekers and providers. The feasibility of accessing abortion services via telemedicine in low-resource settings needs further investigation.

60 APPLIED LIFE SCIENCES↗

Elucidating ion capture and transport mechanisms of Preyssler anions in aqueous solutions using biased MACE-accelerated MD simulations

Equilibrium and biased multi-atomic cluster expansion (MACE) accelerated molecular dynamics (MD) simulations in aqueous solutions are performed to investigate the ion capture and transport mechanisms of the {P 5 W 30 } Preyssler anion (PA) as the smallest representative member of the extended polyoxometalate (POM) family with an internal cavity. The unique interatomic interactions present in the internal cavity vs the exterior of PA are carefully investigated using equilibrium MACE MD simulations for two representative Na(H 2 O)@PA and Na@PA complexes in aqueous solutions. Our careful analyses of radial distribution functions and coordination numbers show that the presence of confined water in Na(H 2 O)@PA has profound modulating effects on the nature of the interactions of the encapsulated ion with the oxygens of the PA cavity. Using well-converged MACE-accelerated multiple walker well-tempered metadynamics simulations with nanosecond timescales, two different associative (ion exchange) and dissociative (ion ejection) ion transport mechanisms were carefully investigated for Na + as one of the most abundant and representative ions present in seawater and saline solutions. By comparing systems with and without confined water, it was found that the presence of only one pre-encapsulated confined water in Na(H 2 O)@PA dramatically changes the free energy landscape of ion transport processes. It was also found that the contraction and dilation of the two windows present in PA directly influence the Na + and H 2 O transport. Furthermore, the results from this work are helpful, as they show a viable path toward tuning the ion exchange and transport phenomena in aqueous solutions of POM molecular clusters and frameworks.

25 ENERGY STORAGE↗

An Improved Boosting to Amplify Signal with Isobaric Labeling (iBASIL) Strategy for Precise Quantitative Single-cell Proteomics

Mass spectrometry (MS)-based proteomics has great potential for overcoming the limitations of antibody-based immunoassays for antibody-independent, comprehensive, and quantitative proteomic analysis of single cells. Indeed, recent advances in nanoscale sample preparation have enabled effective processing of single cells. In particular, the concept of using boosting/carrier channels in isobaric labeling to increase the sensitivity in MS detection has also been increasingly used for quantitative proteomic analysis of small-sized samples including single cells. However, the full potential of such boosting/carrier approaches has not been significantly explored, nor has the resulting quantitation quality been carefully evaluated. Herein, we have further evaluated and optimized our recent boosting to amplify signal with isobaric labeling (BASIL) approach, originally developed for quantifying phosphorylation in small number of cells, for highly effective analysis of proteins in single cells. This improved BASIL (iBASIL) approach enables reliable quantitative single-cell proteomics analysis with greater proteome coverage by carefully controlling the boosting-to-sample ratio (e.g. in general <100×) and optimizing MS automatic gain control (AGC) and ion injection time settings in MS/MS analysis (e.g. 5E5 and 300 ms, respectively, which is significantly higher than that used in typical bulk analysis). By coupling with a nanodroplet-based single cell preparation (nanoPOTS) platform, iBASIL enabled identification of ~2500 proteins and precise quantification of ~1500 proteins in the analysis of 104 FACS-isolated single cells, with the resulting protein profiles robustly clustering the cells from three different acute myeloid leukemia cell lines. This study highlights the importance of carefully evaluating and optimizing the boosting ratios and MS data acquisition conditions for achieving robust, comprehensive proteomic analysis of single cells.

59 BASIC BIOLOGICAL SCIENCES↗

The lifetime risk and impact of vitiligo across sociodemographic groups: a UK population-based cohort study

Abstract Background Vitiligo is an autoimmune skin disorder characterized by depigmented patches of skin, which can have significant psychological impacts. Objectives To estimate the lifetime incidence of vitiligo, overall, by ethnicity and across other sociodemographic subgroups, and to investigate the impacts of vitiligo on mental health, work and healthcare utilization. Methods Incident cases of vitiligo were identified in the Optimum Patient Care Database of primary care records in the UK between 1 January 2004 and 31 December 2020. The lifetime incidence of vitiligo was estimated at age 80 years using modified time-to-event models with age as the timescale, overall and stratified by ethnicity, sex and deprivation. Depression, anxiety, sleep disturbance, healthcare utilization and work-related outcomes were assessed in the 2 years after vitiligo diagnosis and compared with matched controls without vitiligo. The study protocol for this retrospective observational study was registered with ClinicalTrials.gov (NCT06097494). Results In total, 9460 adults and children were newly diagnosed with vitiligo during the study period. The overall cumulative lifetime incidence was 0.92% at 80 years of age [95% confidence interval (CI) 0.90–0.94]. Cumulative incidence was similar in female (0.94%, 95% CI 0.92–0.97) and male patients (0.89%, 95% CI 0.86–0.92). There were substantial differences in lifetime incidence across ethnic groups, listed by Office for National Statistics criteria [Asian 3.58% (95% CI 3.38–3.78); Black 2.18% (95% CI 1.85–2.50); Mixed/multiple 2.03% (95% CI 1.58–2.47); Other 1.05% (95% CI 0.94–1.17); and White 0.73% (95% CI 0.71–0.76)]. Compared with matched controls, people with vitiligo had an increased risk of depression [adjusted odds ratio (aOR) 1.08, 95% CI 1.01–1.15]; anxiety (aOR 1.19, 95% CI 1.09–1.30); depression or anxiety (aOR 1.10, 95% CI 1.03–1.17); and sleep disturbance [adjusted hazard ratio (aHR) 1.15, 95% CI 1.02–1.31]. People with vitiligo also had a greater number of primary care encounters (adjusted incidence rate ratio 1.29, 95% CI 1.26–1.32) and a greater risk of time off work (aHR 1.15, 95% CI 1.06–1.24). There was little evidence of disparities in vitiligo-related impacts across ethnic subgroups. Conclusions Clinicians should be aware of the markedly increased incidence of vitiligo in people belonging to Asian, Black, Mixed/multiple and Other groups. The negative impact of vitiligo on mental health, work and healthcare utilization highlights the importance of monitoring people with vitiligo to identify those who need additional support.

Eleftheriadou, Viktoria↗

Standardized perioperative management in acute abdominal surgery: Swedish SMASH controlled study

Abstract Background Acute high-risk abdominal surgery is common, as are the attendant risks of organ failure, need for intensive care, mortality, or long hospital stay. This study assessed the implementation of standardized management. Methods A prospective study of all adults undergoing emergency laparotomy over an interval of 42 months (2018–2021) was undertaken; outcomes were compared with those of a retrospective control group. A new standardized clinical protocol was activated for all patients including: prompt bedside physical assessment by the surgeon and anaesthetist, interprofessional communication regarding location of resuscitation, elimination of unnecessary factors that might delay surgery, improved operating theatre competence, regular epidural, enhanced recovery care, and frequent early warning scores. The primary endpoint was 30-day mortality. Secondary endpoints were duration of hospital stay, need for intensive care, and surgical complications. Results A total of 1344 patients were included, 663 in the control group and 681 in the intervention group. The use of antibiotics increased (81.4 versus 94.7 per cent), and the time from the decision to operate to the start of surgery was reduced (3.80 versus 3.22 h) with use of the new protocol. Fewer anastomoses were performed (22.5 versus 16.8 per cent). The 30-day mortality rate was 14.5 per cent in the historical control group and 10.7 per cent in the intervention group (P = 0.045). The mean duration of hospital (11.9 versus 10.2 days; P = 0.007) and ICU (5.40 versus 3.12 days; P = 0.007) stays was also reduced. The rate of serious surgical complications (grade IIIb–V) was lower (37.6 versus 27.3 per cent; P = <0.001). Conclusion Standardized management protocols improved outcomes after emergency laparotomy.

Timan, Terje J.↗

Molecular and Epidemiological Investigation of Fluconazole-resistant Candida parapsilosis —Georgia, United States, 2021

Abstract Background Reports of fluconazole-resistant Candida parapsilosis bloodstream infections are increasing. We describe a cluster of fluconazole-resistant C parapsilosis bloodstream infections identified in 2021 on routine surveillance by the Georgia Emerging Infections Program in conjunction with the Centers for Disease Control and Prevention. Methods Whole-genome sequencing was used to analyze C parapsilosis bloodstream infections isolates. Epidemiological data were obtained from medical records. A social network analysis was conducted using Georgia Hospital Discharge Data. Results Twenty fluconazole-resistant isolates were identified in 2021, representing the largest proportion (34%) of fluconazole-resistant C parapsilosis bloodstream infections identified in Georgia since surveillance began in 2008. All resistant isolates were closely genetically related and contained the Y132F mutation in the ERG11 gene. Patients with fluconazole-resistant isolates were more likely to have resided at long-term acute care hospitals compared with patients with susceptible isolates (P = .01). There was a trend toward increased mechanical ventilation and prior azole use in patients with fluconazole-resistant isolates. Social network analysis revealed that patients with fluconazole-resistant isolates interfaced with a distinct set of healthcare facilities centered around 2 long-term acute care hospitals compared with patients with susceptible isolates. Conclusions Whole-genome sequencing results showing that fluconazole-resistant C parapsilosis isolates from Georgia surveillance demonstrated low genetic diversity compared with susceptible isolates and their association with a facility network centered around 2 long-term acute care hospitals suggests clonal spread of fluconazole-resistant C parapsilosis. Further studies are needed to better understand the sudden emergence and transmission of fluconazole-resistant C parapsilosis.

Misas, Elizabeth (ORCID:0000000162437716)↗

Materials Data on CaReH4ClO6 by Materials Project

(CaRe(H2O3)2)2Cl2 crystallizes in the orthorhombic Cmcm space group. The structure is three-dimensional and consists of four hydrochloric acid molecules and one CaRe(H2O3)2 framework. In the CaRe(H2O3)2 framework, Ca2+ is bonded in a 8-coordinate geometry to eight O2- atoms. There are a spread of Ca–O bond distances ranging from 2.40–2.61 Å. Re7+ is bonded in a tetrahedral geometry to four O2- atoms. All Re–O bond lengths are 1.75 Å. H1+ is bonded in a single-bond geometry to one O2- atom. The H–O bond length is 1.00 Å. There are three inequivalent O2- sites. In the first O2- site, O2- is bonded in a distorted linear geometry to one Ca2+ and one Re7+ atom. In the second O2- site, O2- is bonded in a water-like geometry to two equivalent Ca2+ and two equivalent H1+ atoms. In the third O2- site, O2- is bonded in a linear geometry to one Ca2+ and one Re7+ atom.

36 MATERIALS SCIENCE↗