Search NASA⌕ Search

SEARCH · Search NASA

Results for “clinical assessment”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5

Noninvasive Determination of Bone Mechanical Properties Using Vibration Response: A Refined Model and Validation in vivo

Accurate non-invasive mechanical measurement of long bones is made difficult by the masking effect of surrounding soft tissues. Mechanical response tissue analysis (MRTA) offers a method for separating the effects of the soft tissue and bone; however, a direct validation has been lacking. A theoretical analysis of wave propagation through the compressed tissue revealed a strong mass effect dependent on the relative accelerations of the probe and bone. The previous mathematical model of the bone and overlying tissue system was reconfigured to incorporate the theoretical finding. This newer model (six-parameter) was used to interpret results using MRTA to determine bone cross-sectional bending stiffness, EI(sub MRTA). The relationship between EI(sub MRTA) and theoretical EI values for padded aluminum rods was R(sup 2) = 0.999. A biological validation followed using monkey tibias. Each bone was tested in vivo with the MRTA instrument. Postmortem, the same tibias were excised and tested to failure in three-point bending to determine EI(sub 3-PT) and maximum load. Diaphyseal bone mineral density (BMD) measurements were also made. The relationship between EI(sub 3-PT) and in vivo EI(sub MRTA) using the six-parameter model is strong (R(sup 2) = 0.947) and better than that using the older model (R(sup 2) = 0.645). EI(sub MRTA) and BMD are also highly correlated (R(sup 2) = 0.853). MRTA measurements in vivo and BMD ex vivo are both good predictors of scaled maximum strength (R(sup 2) = 0.915 and R(sup 2) = 0.894, respectively). This is the first biological validation of a non- invasive mechanical measurement of bone by comparison to actual values. The MRTA technique has potential clinical value for assessing long-bone mechanical properties.

Roberts, S. G.↗

Noninvasive Determination of Bone Mechanical Properties using Vibration Response: A Refined Model and Validation in vivo

Accurate non-invasive mechanical measurement of long bones is made difficult by the masking effect of surrounding soft tissues. Mechanical Response Tissue Analysis (MRTA) offers a method for separating the effects of the soft tissue and bone; however, a direct validation has been lacking. A theoretical analysis of wave propagation through the compressed tissue revealed a strong mass effect dependent on the relative accelerations of the probe and bone. The previous mathematical model of the bone and overlying tissue system was reconfigured to incorporate the theoretical finding. This newer model (six-parameter) was used to interpret results using MRTA to determine bone cross-sectional bending stiffness, EI(sub MRTA). The relationship between EI(MRTA) and theoretical EI values for padded aluminum rods was R(exp 2) = 0.999. A biological validation followed using monkey tibias. Each bone was tested in vivo with the MRTA instrument. Postmortem, the same tibias were excised and tested to failure in three-point bending to determine EI(sub 3-PT) and maximum load. Diaphyseal Bone Mineral Density (BMD) measurements were also made. The relationship between E(sub 3-PT) and in vivo EI(sub MRTA) using the six-parameter model is strong (R(exp 2) = 0.947) and better than that using the older model (R(exp 2) = 0.645). EI(MRTA) and BMD are also highly correlated (R(exp 2) = 0.853). MRTA measurements in vivo and BMD ex vivo are both good predictors of scaled maximum strength (R(exp 2) = 0.915 and R(exp 2) = 0.894, respectively). This is the first biological validation of a non-invasive mechanical measurement of bone by comparison to actual values. The MRTA technique has potential clinical value for assessing long-bone mechanical properties.

Roberts, S. G.↗

Gait variability and basal ganglia disorders: stride-to-stride variations of gait cycle timing in Parkinson's disease and Huntington's disease

The basal ganglia are thought to play an important role in regulating motor programs involved in gait and in the fluidity and sequencing of movement. We postulated that the ability to maintain a steady gait, with low stride-to-stride variability of gait cycle timing and its subphases, would be diminished with both Parkinson's disease (PD) and Huntington's disease (HD). To test this hypothesis, we obtained quantitative measures of stride-to-stride variability of gait cycle timing in subjects with PD (n = 15), HD (n = 20), and disease-free controls (n = 16). All measures of gait variability were significantly increased in PD and HD. In subjects with PD and HD, gait variability measures were two and three times that observed in control subjects, respectively. The degree of gait variability correlated with disease severity. In contrast, gait speed was significantly lower in PD, but not in HD, and average gait cycle duration and the time spent in many subphases of the gait cycle were similar in control subjects, HD subjects, and PD subjects. These findings are consistent with a differential control of gait variability, speed, and average gait cycle timing that may have implications for understanding the role of the basal ganglia in locomotor control and for quantitatively assessing gait in clinical settings.

Non-NASA Center↗

Plasma Cytokine Levels During Long-Duration Spaceflight

Determine the in-flight status of immunity, physiological stress, viral immunity/reactivation. Specific measurements include leukocyte distribution, T cell function, cytokine production profiles (mRNA, intracellular, secreted, plasma), virus-specific T cell number/function, latent herpesvirus reactivation, stress hormone levels. Determine the clinical risk related to immune dysregulation for exploration class spaceflight, as well as an appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures. Specific Study Objectives: Determine the nutritional status of astronauts before, during, and after spaceflight ensure adequate intake of energy, protein, and vitamins during missions. The Clinical Nutritional Status Assessment measures dietary intake, body composition, protein, bone, iron, mineral, vitamin, and antioxidant status (60 total analytes). Currently, it is a medical requirement for U.S. crewmembers on-board the ISS. The results of data analysis are used both to understand the connections between nutrition and human health during space flight, and to develop effective dietary strategies to reduce adverse health impacts (including bone loss, loss of important vitamins and minerals, and increased genetic damage from radiation).

Crucian, Brian E.↗

Space Technology - Game Changing Development NASA Facts: Autonomous Medical Operations

The AMO (Autonomous Medical Operations) Project is working extensively to train medical models on the reliability and confidence of computer-aided interpretation of ultrasound images in various clinical settings, and of various anatomical structures. AI (Artificial Intelligence) algorithms recognize and classify features in the ultrasound images, and these are compared to those features that clinicians use to diagnose diseases. The acquisition of clinically validated image assessment and the use of the AI algorithms constitutes fundamental baseline for a Medical Decision Support System that will advise crew on long-duration, remote missions.

Autonomous Medical Operations Project↗

Improving Medication Regimen Recommendation for Parkinson’s Disease Using Sensor Technology

Parkinson’s disease medication treatment planning is generally based on subjective data obtained through clinical, physician-patient interactions. The Personal KinetiGraph™ (PKG) and similar wearable sensors have shown promise in enabling objective, continuous remote health monitoring for Parkinson’s patients. In this proof-of-concept study, we propose to use objective sensor data from the PKG and apply machine learning to cluster patients based on levodopa regimens and response. The resulting clusters are then used to enhance treatment planning by providing improved initial treatment estimates to supplement a physician’s initial assessment. We apply k-means clustering to a dataset of within-subject Parkinson’s medication changes—clinically assessed by the MDS-Unified Parkinson’s Disease Rating Scale-III (MDS-UPDRS-III) and the PKG sensor for movement staging. A random forest classification model was then used to predict patients’ cluster allocation based on their respective demographic information, MDS-UPDRS-III scores, and PKG time-series data. Clinically relevant clusters were partitioned by levodopa dose, medication administration frequency, and total levodopa equivalent daily dose—with the PKG providing similar symptomatic assessments to physician MDS-UPDRS-III scores. A random forest classifier trained on demographic information, MDS-UPDRS-III scores, and PKG time-series data was able to accurately classify subjects of the two most demographically similar clusters with an accuracy of 86.9%, an F1 score of 90.7%, and an AUC of 0.871. A model that relied solely on demographic information and PKG time-series data provided the next best performance with an accuracy of 83.8%, an F1 score of 88.5%, and an AUC of 0.831, hence further enabling fully remote assessments. These computational methods demonstrate the feasibility of using sensor-based data to cluster patients based on their medication responses with further potential to assist with medication recommendations.

59 BASIC BIOLOGICAL SCIENCES↗

Discordant Clinical and Microbiological Outcomes Are Associated With Late Clinical Relapse in Clinical Trials for Complicated Urinary Tract Infections

Abstract Background Current US Food and Drug Administration guidance recommends that the primary endpoint for complicated urinary tract infection clinical trials be a composite of the clinical and microbiological responses, assessed at a fixed point after therapy. Although some participants meet the criteria for clinical success, they do not meet the criteria for microbiological eradication and are classified as treatment failures. These discordant outcomes have raised questions about the utility of the microbiological endpoint. Methods We analyzed participant data from 13 phase 3 clinical trials submitted to the US Food and Drug Administration (N = 4842). Outcomes were determined at the test of cure (TOC) visit, recommended to occur at least 5 days after therapy and at the late follow-up visit, recommended to occur 21 to 28 days after randomization. Clinical and microbiological success were defined as the resolution of complicated urinary tract infection symptoms present at study entry, with no new symptoms (clinical cure), and a reduction in density of the original pathogen to <103 CFU/mL on urine culture (microbiological eradication). Results Among included participants, 70.7% were concordant successes at the TOC visit, 18.0% were discordant failures (clinical cure/microbiological persistence), and 6.7% were concordant failures (clinical failure/microbiological persistence). Discordant participants were at an increased risk for clinical failure at the late follow-up visit, and the risk of late clinical failure increased with time. Conclusions Discordant clinical and microbiological outcomes at the TOC visit were associated with an increased risk of late clinical failure. Microbiological outcomes appear to be an important component of the endpoint.

Immunology↗

Xanthohumol microbiome and signature in adults with Crohn’s disease (the XMaS trial): a protocol for a phase II triple-masked, placebo-controlled clinical trial

Xanthohumol (XN), a bioactive flavonoid from Humulus lupulus with anti-inflammatory properties, has potential benefits for patients with Crohn’s disease (CD), a type of inflammatory bowel disease. We recently completed and published results of a placebo-controlled phase I clinical trial demonstrating the safety and tolerability of 24 mg XN daily for 8 weeks. The present study aims to evaluate the safety and tolerability of the same dose of XN adults with clinically active CD in a placebo-controlled phase II clinical trial. Additional aims will assess the impact of XN on inflammatory biomarkers, platelet function, CD clinical activity, and stool microbial composition. The metabolism of XN will also be evaluated. This article provides a model protocol for consideration in investigations of XN or other natural products in disease states. A triple-masked, randomized, placebo-controlled trial will be conducted in adults with clinically active CD. Participants (n ≤ 32) will be randomized to either 24 mg encapsulated XN per day or placebo and followed for 8 weeks. Throughout the trial, participants will be queried for adverse events. Biomarkers of clinical safety, blood and stool markers of inflammation, platelet function, Crohn’s Disease Activity Index score, stool microbial composition, and XN metabolite profiles in blood, urine, and stool will be assessed every 2 weeks. We describe the protocol for a phase II clinical trial that evaluates the safety and tolerability of XN in adults with active CD, as well as evaluate metabolism and mechanisms that are relevant to CD and other diseases with underlying inflammation and/or gut permeability. The effects of XN on inflammatory biomarkers, platelet function, the microbiota, and multi-omics biomarkers measured in this phase II trial of adults with CD will be compared to the effects of XN in healthy adults in our previous phase I trial. The results of the study will advance the evidence guiding the use of XN in patients with CD.

60 APPLIED LIFE SCIENCES↗

Spatial orientation perception and reflexive eye movements--a perspective, an overview, and some clinical implications

When head motion includes a linear velocity component, eye velocity required to track an earth-fixed target depends upon: a) angular and linear head velocity, b) target distance, and c) direction of gaze relative to the motion trajectory. Recent research indicates that eye movements (LVOR), presumably otolith-mediated, partially compensate for linear velocity in small head excursions on small devices. Canal-mediated eye velocity (AVOR), otolith-mediated eye velocity (LVOR), and Ocular Torsion (OT) can be measured, one by one, on small devices. However, response dynamics that depend upon the ratio of linear to angular velocity in the motion trajectory and on subject orientation relative to the trajectory are present in a centrifuge paradigm. With this paradigm, two 3-min runs yields measures of: LVOR differentially modulated by different subject orientations in the two runs; OT dynamics in four conditions; two directions of "steady-state" OT, and two directions of AVOR. Efficient assessment of the dynamics (and of the underlying central integrative processes) may require a centrifuge radius of 1.0 meters or more. Clinical assessment of the spatial orientation system should include evaluation of central integrative processes that determine the dynamics of these responses.

Review, Tutorial↗

Method and apparatus for assessing cardiovascular risk

The method for assessing risk of an adverse clinical event includes detecting a physiologic signal in the subject and determining from the physiologic signal a sequence of intervals corresponding to time intervals between heart beats. The long-time structure of fluctuations in the intervals over a time period of more than fifteen minutes is analyzed to assess risk of an adverse clinical event. In a preferred embodiment, the physiologic signal is an electrocardiogram and the time period is at least fifteen minutes. A preferred method for analyzing the long-time structure variability in the intervals includes computing the power spectrum and fitting the power spectrum to a power law dependence on frequency over a selected frequency range such as 10.sup.-4 to 10.sup.-2 Hz. Characteristics of the long-time structure fluctuations in the intervals is used to assess risk of an adverse clinical event.

Albrecht, Paul↗

Quality appraisal of clinical practice guidelines for the management of Dysphagia after acute stroke

Objectives Dysphagia is a common complication in stroke patients, widely affecting recovery and quality of life after stroke. The objective of this systematic review is to identify the gaps that between evidence and practice by critically assessing the quality of clinical practice guidelines (CPGs) for management of dysphagia in stroke. Methods We systematically searched academic databases and guideline repositories between January 1, 2014, and August 1, 2023. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was used by two authors to independently assess CPG quality. Results In a total of 14 CPGs included, we identified that three CPGs obtained a final evaluation of “high quality,” nine CPGs achieved “moderate quality” and two CPGs received “low quality.” The domain of “scope and purpose” achieved the highest mean score (91.1%) and the highest median (IQR) of 91.7% (86.1, 94.4%), while the domain of “applicability” received the lowest mean score (55.8%) and the lowest median (IQR) of 55.4% (43.2, 75.5%). Conclusion The CPG development group should pay more attention to improving the methodological quality according to the AGREE II instrument, especially in the domain of “applicability” and “stakeholder involvement;” and each item should be refined as much as possible.

Gao, Shi-Lin↗

Characterizing Long COVID: Deep Phenotype of a Complex Condition

Background: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or "long COVID"), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies. Methods: The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19. Funding: We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies. Interpretation: Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID.

60 APPLIED LIFE SCIENCES↗

Characterization of a Novel CD4 Mimetic Compound YIR-821 against HIV-1 Clinical Isolates

Small CD4-mimetic compound (CD4mc), which inhibits the interaction between gp120 with CD4, acts as an entry inhibitor and induces structural changes in the HIV-1 envelope glycoprotein trimer (Env) through its insertion within the Phe43 cavity of gp120. Here, we recently developed YIR-821, a novel CD4mc, that has potent antiviral activity and lower toxicity than the prototype NBD-556. To assess the possibility of clinical application of YIR-821, we tested its antiviral activity using a panel of HIV-1 pseudoviruses from different subtypes. YIR-821 displayed entry inhibitor activity against 53.5% (21/40) of the pseudoviruses tested and enhanced neutralization mediated by coreceptor binding site (CoRBS) antibodies in 50% (16/32) of these. Furthermore, when we assessed the antiviral effects using a panel of pseudoviruses and autologous plasma IgG, enhancement of antibody-mediated neutralization activity was observed for 48% (15/31) of subtype B strains and 51% (28/55) of non-B strains. The direct antiviral activity of YIR-821 as an entry inhibitor was observed in 53% of both subtype B (27/51) and non-B subtype (40/75) pseudoviruses. Enhancement of antibody-dependent cellular cytotoxicity was also observed with YIR-821 for all six selected clinical isolates, as well as for the transmitted/founder (T/F) CH58 virus-infected cells. The sequence diversity in the CD4 binding site as well as other regions, such as the gp120 inner domain layers or gp41, may be involved in the multiple mechanisms related to the sensitive/resistant phenotype of the virus to YIR-821. Our findings may facilitate the clinical application of YIR-821.

60 APPLIED LIFE SCIENCES↗

The use of a tracking test battery in the quantitative evaluation of neurological function

A number of tracking tasks that have proven useful to control engineers and psychologists measuring skilled performance have been evaluated for clinical use. Normal subjects as well as patients with previous diagnoses of Parkinson's disease, multiple sclerosis, and cerebral palsy were used in the evaluation. The tests that were studied included step tracking, random tracking, and critical tracking. The results of the present experiments encourage the continued use of tracking tasks as assessment precedures in a clinical environment. They have proven to be reliable, valid, and sensitive measures of neurological function.

Repa, B. S.↗

Head Tilt Posturography to Enhance Balance Control Assessment for Astronauts: A Case Study

For many years, we have used a standard clinical computerized dynamic posturography (CDP) protocol to assess recovery of integrated sensory-motor function in astronauts returning from space flight. The most reliable indications of postflight crew performance capabilities have been obtained from the sensory organization tests (SOTs) within the CDP protocol, particularly SOTs 5 (eyes closed, surface support sway referenced) and 6 (eyes open, surface support and visual surround sway referenced), which are sensitive to changes in availability and/or utilization of vestibular cues. We have observed, however, that some astronauts exhibiting visible signs of incomplete sensory-motor recovery are able to score within clinical norms on standard SOTs 5 and 6 trials, perhaps as a result of cognitive strategies driven by their naturally competitive natures. To improve the sensitivity of the CDP protocol for assessing recovery of integrated sensory-motor function and fitness to return to duties and/or activities of daily living, we have introduced pitch plane head tilt SOT trials to our protocol. In a preliminary study of 5 short duration (~11day missions) astronauts, we showed that they were unable to maintain balance on landing day when performing dynamic head tilt trials, despite scoring within the clinically normal range on the standard SOT trials. The present case report illustrates the advantages of including head tilt trials for assessing sensory-motor recovery in long duration crewmembers.

Hwang, E. Y.↗

Concurrent evaluation of autophagy induction and Burkholderia infection at the single cell level

Autophagy is a natural, regulated cellular process that "cleans up" cellular debris by degrading and recycling dysfunctional proteins. There is a high potential impact of exploiting the benefits of autophagy to complement existing treatments, but little has been done to date on bacterial pathogens of defense concern such as Burkholderia pseudomallei, a highly virulent Select Agent pathogen that is intrinsically resistant to most classes of antibiotics. Assessment of autophagy in the context of infection typically requires use of multiple technologies in combination (e.g., Western analysis paired with microscopy or flow cytometry) as applied to heterogeneous populations of cells. To address this, we have developed a dual target reporter cell line (RAW264.7 LC3-BFP:mPlum, GFP-RelA) that enables concurrent visualization of infection and autophagy induction. We assessed the effect of clinically approved small molecule inducers of autophagy on infection by Burkholderia thailendensis, a closely related but less virulent surrogate for B. pseudomallei. The reporter cells were first infected with a B. thailendensis strain that constitutively expresses GFP, then treated with one of four known autophagy inducers (rapamycin, niclosamide, bromhexine HC1, or flubendazole) for 4 hours. Confocal fluorescence imaging was used to quantify autophagy stimulation at the single cell level. Autophagy maturation was observed as a decrease in BFP LC3 puncta with a concurrent increase in mPlum LC3 puncta. B. thailendensis infection was assessed by monitoring translocation of GFP-RelA (an NFkB subunit) into the nucleus and through quantitating the intracellular bacterial presence in single cells. Preliminary results indicate that bromhexine HC1 and niclosamide may hinder B. thailendensis' ability to replicate intracellularly and reduce overall bacterial survival.

59 BASIC BIOLOGICAL SCIENCES↗

Cardiac mechanics: Physiological, clinical, and mathematical considerations

Recent studies concerning the basic physiological and biochemical principles underlying cardiac muscle contraction, methods for the assessment of cardiac function in the clinical situation, and mathematical approaches to cardiac mechanics are presented. Some of the topics covered include: cardiac ultrastructure and function in the normal and failing heart, myocardial energetics, clinical applications of angiocardiography, use of echocardiography for evaluating cardiac performance, systolic time intervals in the noninvasive assessment of left ventricular performance in man, evaluation of passive elastic stiffness for the left ventricle and isolated heart muscle, a conceptual model of myocardial infarction and cardiogenic shock, application of Huxley's sliding-filament theory to the mechanics of normal and hypertrophied cardiac muscle, and a rheological modeling of the intact left ventricle. Individual items are announced in this issue.

Mirsky, I.↗