Prognostic value of desaturation during a six minute walk test in Idiopathic Interstitial Pneumonia

Exercise-induced hypoxia is an index of the severity of interstitial lung disease. We hypothesized that desaturation during a 6-minute walk test would predict mortality for patients with usual interstitial pneumonia (n = 83) and nonspecific interstitial pneumonia (n = 22). Consecutive patients with biopsy-proven disease performed a 6-minute walk test between January 1996 and December 2001. Desaturation was defined as a fall in oxygen saturation to 88% or less during the 6-minute walk test. Desaturation was common (44 of 83 usual interstitial pneumonia and 8 of 22 nonspecific interstitial pneumonia; chi square, p = 0.39). Patients with usual interstitial pneumonia or nonspecific interstitial pneumonia who desaturated had a significantly higher mortality than patients who did not desaturate (respective log-rank tests, p = 0.0018, p = 0.0089). In patients with usual interstitial pneumonia, the presence of desaturation was associated with an increased hazard of death (hazard ratio, 4.2; 95% confidence interval, 1.40, 12.56; p = 0.01) after adjusting for age, sex, smoking, baseline diffusion capacity for carbon monoxide, FVC, and resting saturation.Weconclude that knowledge of desaturation during a 6-minute walk test adds prognostic information for patients with usual interstitial pneumonia and nonspecific interstitial pneumonia.Supported in part by National Institutes of Health NHLBI Grant #P50HL46487, NHLBI, 1 K24 HL04212, and 1 K23 HL68713.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91972/1/2003 AJRCCM - Prognostic value of desaturation during a six minute walk test in Idiopathic Interstitial Pneumonia.pd

Promising effect of Ayurveda in the management of Gridhrasi - A Case Study

Nowadays, the most prevalent ailment affecting human body is backache, which has an impact on everyday routine. Human life styles have altered dramatically over time due to over exertion, improper sitting and standing postures in work place, jerky movements during travel etc invariably causes jerks to the spinal column leading to Sciatica etc. spinal disorders. Its prevalence is 1.2% to 43% Worldwide which affects person’s age group of 30-60 years. Currently it seen in younger adults also with equal ratio in both genders. In Ayurveda it can be correlated with Gridhrasi. The word Gridhrasi is derived from - Gridhramapi Syathi. So, which means the disease where gait of the affected person resembles like a Gridhra which means Vulture. Gridhra is a bird which is fond of meat. This bird pierces the meat with its beak and pulls out; which gives severe pain to the prey similarly this type of pain is felt by affected person hence it is named as Gridhrasi. The present case is single case study which is about 20 days, where patient came with complaints of pain and stiffness in lower back region radiating to right lower leg, difficulty to sit normally, etc. since 3 months. The Patient was treated with peculiar combinations like only Niruhabasti, Kukkutanda Sweda along with Shamanaushadhis and reported with evident result in this case

Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction after Lung Transplant

RATIONALE: Primary graft dysfunction (PGD) is a form of acute lung injury that occurs after lung transplantation. The definition of PGD was standardized in 2005. Since that time, clinical practice has evolved, and this definition is increasingly used as a primary endpoint for clinical trials; therefore, validation is warranted. OBJECTIVES: We sought to determine whether refinements to the 2005 consensus definition could further improve construct validity. METHODS: Data from the Lung Transplant Outcomes Group multicenter cohort were used to compare variations on the PGD definition, including alternate oxygenation thresholds, inclusion of additional severity groups, and effects of procedure type and mechanical ventilation. Convergent and divergent validity were compared for mortality prediction and concurrent lung injury biomarker discrimination. MEASUREMENTS AND MAIN RESULTS: A total of 1,179 subjects from 10 centers were enrolled from 2007 to 2012. Median length of follow-up was 4 years (interquartile range = 2.4-5.9). No mortality differences were noted between no PGD (grade 0) and mild PGD (grade 1). Significantly better mortality discrimination was evident for all definitions using later time points (48, 72, or 48-72 hours; P < 0.001). Biomarker divergent discrimination was superior when collapsing grades 0 and 1. Additional severity grades, use of mechanical ventilation, and transplant procedure type had minimal or no effect on mortality or biomarker discrimination. CONCLUSIONS: The PGD consensus definition can be simplified by combining lower PGD grades. Construct validity of grading was present regardless of transplant procedure type or use of mechanical ventilation. Additional severity categories had minimal impact on mortality or biomarker discrimination

FAIRification of Geospatial Data

FAIRification (Findability, Accessibility, Interoperability, and Reusability) of geospatial and temporal data from the United States Geological Survey (USGS) is crucial for the continuance of the National Science Foundation (NSF) Engineering Research Center for Advancing Sustainable and Distributed Fertilizer Production (CASFER) whose aim is to aid in the development of eco-friendly fertilizers. The USGS data contains key information about water quality and contaminants, which are important metrics for our geospatial project since our work aims to track the contaminants\u27 flow and work towards their reduction and subsequent elimination. FAIR principles refer to - Findability, Accessibility, Interoperability, and Reusability. This is important for the safeguarding and preservation of the data collected. Often, the data that has been extracted and worked on will be needed by someone else in the same project for a different purpose. The person working on the data will have their philosophies behind naming and storing the data which could become a problem for anyone else trying to use the data down the line if they do not have a guidebook or a manual to the initial person’s pointers. This is why FAIRification of data is crucial in academia and industry. The FAIR principles have been designed to create a standardized and globally recognized nomenclature for the storage of data. Findability refers to assigning the data an identifier that is global and unique and the data is indexed in a searchable database. Accessibility means that the data can be retrieved by its identifier using a universally implementable protocol with authentication procedures wherever required. It also refers to the fact that the metadata will be accessible even when the data is not available. Interoperability means that the metadata uses a formal, accessible, and applicable language for knowledge representation and uses vocabularies that follow FAIR principles. Reusability refers to the fact that the metadata is extensively described with relevant attributes and released with a clear and accessible data usage license

Geospatial Analysis of Hydrologic Nitrogen in Ohio Using Terrain Ruggedness Index (TRI) and Terrain Position Index (TPI)

Hydrologic nitrogen in ecosystems can significantly impact water quality. Excessive nitrogen, often originating from agricultural runoff, wastewater discharge, and industrial activities, can lead to eutrophication – the over-enrichment of water bodies with nutrients, resulting in excessive algal growth and depleted oxygen levels. This study aims to use geospatial analytics to identify areas in Ohio that are more susceptible to high nitrogen levels due to their topographic characteristics. Terrain Ruggedness Index (TRI) and Terrain Position Index (TPI) are two key metrics derived from Digital Elevation Models (DEMs) that can help characterize the landscape. TRI measures the variability in elevation of adjacent parts of a DEM, while TPI compares a data point in a DEM to its neighbors. By analyzing terrain ruggedness and position, we can statistically identify locations that are more likely to have higher nitrogen levels. Nitrogen tends to flow towards areas with lower elevation relative to their neighbors. By using geospatial techniques to identify points on the DEM with lower TPI and TRI values, we can locate areas that could have higher nitrogen runoff compared to others. If left unchecked, hydrologic nitrogen can cause disastrous consequences for ecosystems, as evidenced by the algal blooms in Lake Erie caused by nitrogen runoff from fertilizers. In this study, we propose to use geospatial analytics to estimate areas in Ohio that are more likely to have higher nitrogen levels based on their topographic characteristics. We will visualize our findings using a Shiny App to effectively communicate the spatial distribution of potential high-nitrogen areas

Immunogenicity Risk Assessment of Spontaneously Occurring Therapeutic Monoclonal Antibody Aggregates

Aggregates of therapeutic proteins have been associated with increased immunogenicity in pre-clinical models as well as in human patients. Recent studies to understand aggregates and their immunogenicity risks use artificial stress methods to induce high levels of aggregation. These methods may be less biologically relevant in terms of their quantity than those that occur spontaneously during processing and storage. Here we describe the immunogenicity risk due to spontaneously occurring therapeutic antibody aggregates using peripheral blood mononuclear cells (PBMC) and a cell line with a reporter gene for immune activation: THP-1 BLUE NFκB. The spontaneously occurring therapeutic protein aggregates were obtained from process intermediates and final formulated drug substance from stability retains. Spontaneously occurring aggregates elicited innate immune responses for several donors in a PBMC assay with cytokine and chemokine production as a readout for immune activation. Meanwhile, no significant adaptive phase responses to spontaneously occurring aggregate samples were detected. While the THP-1 BLUE NFκB cell line and PBMC assays both responded to high stress induced aggregates, only the PBMC from a limited subset of donors responded to processing-induced aggregates. In this case study, levels of antibody aggregation occurring at process relevant levels are lower than those induced by stirring and may pose lower risk in vivo. Our methodologies can further inform additional immunogenicity risk assessments using a pre-clinical in vitro risk assessment approach utilizing human derived immune cells

Idiopathic pulmonary fibrosis: Prognostic value of changes in physiology and six minute hallwalk.

Rationale and Hypothesis: Idiopathic pulmonary fibrosis is a fatal disease with a variable rate of progression. We hypothesized that changes in distance walked and quantity of desaturation during a six-minute-walk test (6MWT) would add prognostic information to changes in FVC or diffusing capacity for carbon monoxide. Methods: One hundred ninety-seven patients with idiopathic pulmonary fibrosis were evaluated. Desaturation during the 6MWT was associated with increased mortality even if a threshold of 88% was not reached. Baseline walk distance predicted subsequent walk distance but was not a reliable predictor of subsequent mortality in multivariate survival models. The predictive ability of serial changes in physiology varied when patients were stratified by the presence/absence of desaturation 88% during a baseline 6MWT. For patients with a baseline saturation 88% during a 6MWT, the strongest observed predictor of mortality was serial change in diffusing capacity for carbon monoxide. For patients with saturation 88% during their baseline walk test, serial decreases in FVC and increases in desaturation area significantly predicted subsequent mortality, whereas decreases in walk distance and in diffusing capacity for carbon monoxide displayed less consistent statistical evidence of increasing mortality in our patients. Conclusion: These data highlight the importance of stratifying patients by degree of desaturation during a 6MWT before attributing prognostic value to serial changes in other physiologic variables.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91940/1/2006 AJRCCM Idiopathic pulmonary fibrosis - Prognostic value of changes in physiology and six minute hallwalk.pd

Soluble P-Selectin and the Risk of Primary Graft Dysfunction After Lung Transplantation

Background - Platelet activation with subsequent neutrophilic adherence to the vasculature initiates ischemia-reperfusion injury. We hypothesized that higher plasma P-selectin levels reflecting platelet activation would therefore be associated with primary graft dysfunction (PGD) after lung transplantation. Methods - In a prospective, multicenter cohort study of 376 patients who had undergone lung transplantation between 2002 and 2007, we measured soluble P-selectin levels before lung transplantation and at 6 and 24 h after lung reperfusion in 20 patients with grade III PGD (Pao2/fraction of inspired oxygen, < 200 mm Hg [with alveolar infiltrates seen on chest radiographs]) at 72 h after transplantation and 61 control subjects without PGD. Results - Higher postoperative soluble P-selectin levels were associated with an increased risk of PGD at 72 h after transplantation (odds ratio [OR] per 1 natural log increase in soluble P-selectin at 6 h after lung allograft reperfusion, 3.5; 95% confidence interval [CI], 1.01 to 11.8; p = 0.048) and at 24 h after lung allograft reperfusion (OR, 4.8; 95% CI, 1.4 to 16.1; p = 0.01). Higher preoperative mean pulmonary artery pressure and the use of cardiopulmonary bypass were also associated with an increased risk of PGD. Conclusion - Higher postoperative soluble P-selectin levels were associated with an increased risk of PGD at 72 h following lung transplantation