Persistence, Adaptation and Diversity

Traditions aren\u27t static. They change and adapt over time to various circumstances. Cultures and identities are always evolving. It\u27s instructive to look at what aspects of cultures and identities persist over time and what aspects of other cultures maybe \u27assimilated\u27 or \u27acculturated\u27 into the existing belief structure of another culture

The Integrated Medical Model: A Risk Assessment and Decision Support Tool for Space Flight Medical Systems

The Integrated Medical Model (IMM) is a decision support tool that is useful to mission planners and medical system designers in assessing risks and designing medical systems for space flight missions. The IMM provides an evidence based approach for optimizing medical resources and minimizing risks within space flight operational constraints. The mathematical relationships among mission and crew profiles, medical condition incidence data, in-flight medical resources, potential crew functional impairments, and clinical end-states are established to determine probable mission outcomes. Stochastic computational methods are used to forecast probability distributions of crew health and medical resource utilization, as well as estimates of medical evacuation and loss of crew life. The IMM has been used in support of the International Space Station (ISS) medical kit redesign, the medical component of the ISS Probabilistic Risk Assessment, and the development of the Constellation Medical Conditions List. The IMM also will be used to refine medical requirements for the Constellation program. The IMM outputs for ISS and Constellation design reference missions will be presented to demonstrate the potential of the IMM in assessing risks, planning missions, and designing medical systems. The implementation of the IMM verification and validation plan will be reviewed. Additional planned capabilities of the IMM, including optimization techniques and the inclusion of a mission timeline, will be discussed. Given the space flight constraints of mass, volume, and crew medical training, the IMM is a valuable risk assessment and decision support tool for medical system design and mission planning

Validation of the Nasa Integrated Medical Model: a Space Flight Medical Risk Prediction Tool

The Human Research Program funded the development of the Integrated Medical Model (IMM) to quantify the medical component of overall mission risk. The IMM uses Monte Carlo simulation methodology, incorporating space flight and ground medical data, to estimate the probability of mission medical outcomes and resource utilization. To determine the credibility of IMM output, the IMM project team completed two validation studies that compared IMM predicted output to observed medical events from a selection of Shuttle Transportation System (STS) and International Space Station (ISS) missions. The validation study results showed that the IMM underpredicted the occurrence of ~10% of the modeled medical conditions for the STS missions and overpredicted ~20% of the modeled medical conditions for the ISS missions. These findings imply that the strength of IMM predictions to inform decisions depends on simulated mission specifications including length. This discrepancy could result from medical recording differences between ISS and STS that possibly influence observed incidence rates, IMM combining all "mission type" data as constant occurrence rate or fixed proportion across both mission types, misspecification of symptoms to conditions, and gaps in the literature informing the model. Some of these issues will be alleviated by updating the IMM source data through incorporation of the observed validation data

The Integrated Medical Model

The goals of the Integrated Medical Model (IMM) are to develop an integrated, quantified, evidence-based decision support tool useful to crew health and mission planners and to help align science, technology, and operational activities intended to optimize crew health, safety, and mission success. Presentation slides address scope and approach, beneficiaries of IMM capabilities, history, risk components, conceptual models, development steps, and the evidence base. Space adaptation syndrome is used to demonstrate the model's capabilities

Validation of the NASA Integrated Medical Model: a Space Flight Medical Risk Prediction Tool

The Human Research Program funded the development of the Integrated Medical Model (IMM) to quantify the medical component of overall mission risk. The IMM uses Monte Carlo simulation methodology, incorporating space flight and ground medical data, to estimate the probability of mission medical outcomes and resource utilization. To determine the credibility of IMM output, the IMM project team completed two validation studies that compared IMM predicted output to observed medical events from a selection of Shuttle Transportation System (STS) and International Space Station (ISS) missions. The validation study results showed that the IMM underpredicted the occurrence of ~10% of the modeled medical conditions for the STS missions and overpredicted ~20% of the modeled medical conditions for the ISS missions. These findings imply that the strength of IMM predictions to inform decisions depends on simulated mission specifications including length. This discrepancy could result from medical recording differences between ISS and STS that possibly influence observed incidence rates, IMM combining all "mission type" data as constant occurrence rate or fixed proportion across both mission types, misspecification of symptoms to conditions, and gaps in the literature informing the model. Some of these issues will be alleviated by updating the IMM source data through incorporation of the observed validation data

Artificial intelligence for diagnosis and Gleason grading of prostate cancer: The PANDA challenge

Through a community-driven competition, the PANDA challenge provides a curated diverse dataset and a catalog of models for prostate cancer pathology, and represents a blueprint for evaluating AI algorithms in digital pathology. Artificial intelligence (AI) has shown promise for diagnosing prostate cancer in biopsies. However, results have been limited to individual studies, lacking validation in multinational settings. Competitions have been shown to be accelerators for medical imaging innovations, but their impact is hindered by lack of reproducibility and independent validation. With this in mind, we organized the PANDA challenge-the largest histopathology competition to date, joined by 1,290 developers-to catalyze development of reproducible AI algorithms for Gleason grading using 10,616 digitized prostate biopsies. We validated that a diverse set of submitted algorithms reached pathologist-level performance on independent cross-continental cohorts, fully blinded to the algorithm developers. On United States and European external validation sets, the algorithms achieved agreements of 0.862 (quadratically weighted kappa, 95% confidence interval (CI), 0.840-0.884) and 0.868 (95% CI, 0.835-0.900) with expert uropathologists. Successful generalization across different patient populations, laboratories and reference standards, achieved by a variety of algorithmic approaches, warrants evaluating AI-based Gleason grading in prospective clinical trials.KWF Kankerbestrijding ; Netherlands Organization for Scientific Research (NWO) ; Swedish Research Council European Commission ; Swedish Cancer Society ; Swedish eScience Research Center ; Ake Wiberg Foundation ; Prostatacancerforbundet ; Academy of Finland ; Cancer Foundation Finland ; Google Incorporated ; MICCAI board challenge working group ; Verily Life Sciences ; EIT Health ; Karolinska Institutet ; MICCAI 2020 satellite event team ; ERAPerMe

Application of In Vivo Induced Antigen Technology (IVIAT) to Bacillus anthracis

In vivo induced antigen technology (IVIAT) is an immuno-screening technique that identifies bacterial antigens expressed during infection and not during standard in vitro culturing conditions. We applied IVIAT to Bacillus anthracis and identified PagA, seven members of a N-acetylmuramoyl-L-alanine amidase autolysin family, three P60 family lipoproteins, two transporters, spore cortex lytic protein SleB, a penicillin binding protein, a putative prophage holin, respiratory nitrate reductase NarG, and three proteins of unknown function. Using quantitative real-time PCR comparing RNA isolated from in vitro cultured B. anthracis to RNA isolated from BALB/c mice infected with virulent Ames strain B. anthracis, we confirmed induced expression in vivo for a subset of B. anthracis genes identified by IVIAT, including L-alanine amidases BA3767, BA4073, and amiA (pXO2-42); the bacteriophage holin gene BA4074; and pagA (pXO1-110). The exogenous addition of two purified putative autolysins identified by IVIAT, N-acetylmuramoyl-L-alanine amidases BA0485 and BA2446, to vegetative B. anthracis cell suspensions induced a species-specific change in bacterial morphology and reduction in viable bacterial cells. Many of the proteins identified in our screen are predicted to affect peptidoglycan re-modeling, and our results support significant cell wall structural remodeling activity during B. anthracis infection. Identification of L-alanine amidases with B. anthracis specificity may suggest new potential therapeutic targets

Matrix Metalloproteinase Gene Delivery for Liver Fibrosis

The resolution of advanced liver fibrosis has been recently recognized to be possible, if the causative stimuli are successfully removed. However, whether complete resolution from cirrhosis, the end stage of liver fibrosis, can be achieved is still questionable. Delivery of interstitial collagenases, such as matrix metalloproteinase (MMP)-1, in the liver could be an attractive strategy to treat advanced hepatic fibrosis from the view point that the imbalance between too few interstitial collagenases and too many of their inhibitors is the main obstacle to the resolution from fibrosis. Remodeling of hepatic extracellular matrix by delivered interstitial collagenases also facilitates the disappearance of activated hepatic stellate cells, the main matrix-producing cells in the liver, and promotes the proliferation of hepatocytes. This review will focus on the impact of the gene delivery of MMPs for the treatment of advanced liver fibrosis while discussing other current therapeutic strategies for liver fibrosis, and on the need for the development of a safe and effective delivery system of MMPs

Persistence, Adaptation and Diversity

Traditions aren't static. They change and adapt over time to various circumstances. Cultures and identities are always evolving. It's instructive to look at what aspects of cultures and identities persist over time and what aspects of other cultures maybe 'assimilated' or 'acculturated' into the existing belief structure of another culture.This abstract is from Design for Diversity: Proceedings of the Thirty-sixth Annual Conference of the Environmental Design Research Association, ed. Habib Chaudhury (McLean, VA: Environmental Design Research Association, 2005). Posted with permission.</p