Project description:This paper evaluates the current state of life cycle impact assessment (LCIA) methods used to estimate potential eutrophication impacts in freshwater and marine ecosystems and presents a critical review of the underlying surface water quality, watershed, marine, and air fate and transport (F&T) models. Using a criteria rubric, we assess the potential of each method and model to contribute to further refinements of life cycle assessment (LCA) eutrophication mechanisms and nutrient transformation processes as well as model structure, availability, geographic scope, and spatial and temporal resolution. We describe recent advances in LCIA modeling and provide guidance on the best available sources of fate and exposure factors, with a focus on midpoint indicators. The critical review identifies gaps in LCIA characterization modeling regarding the availability and spatial resolution of fate factors in the soil compartment and identifies strategies to characterize emissions from soil. Additional opportunities are identified to leverage detailed F&T models that strengthen existing approaches to LCIA or that have the potential to link LCIA modeling more closely with the spatial and temporal realities of the effects of eutrophication.
Project description:ObjectiveHealthcare data such as clinical notes are primarily recorded in an unstructured manner. If adequately translated into structured data, they can be utilized for health economics and set the groundwork for better individualized patient care. To structure clinical notes, deep-learning methods, particularly transformer-based models like Bidirectional Encoder Representations from Transformers (BERT), have recently received much attention. Currently, biomedical applications are primarily focused on the English language. While general-purpose German-language models such as GermanBERT and GottBERT have been published, adaptations for biomedical data are unavailable. This study evaluated the suitability of existing and novel transformer-based models for the German biomedical and clinical domain.Materials and methodsWe used 8 transformer-based models and pre-trained 3 new models on a newly generated biomedical corpus, and systematically compared them with each other. We annotated a new dataset of clinical notes and used it with 4 other corpora (BRONCO150, CLEF eHealth 2019 Task 1, GGPONC, and JSynCC) to perform named entity recognition (NER) and document classification tasks.ResultsGeneral-purpose language models can be used effectively for biomedical and clinical natural language processing (NLP) tasks, still, our newly trained BioGottBERT model outperformed GottBERT on both clinical NER tasks. However, training new biomedical models from scratch proved ineffective.DiscussionThe domain-adaptation strategy's potential is currently limited due to a lack of pre-training data. Since general-purpose language models are only marginally inferior to domain-specific models, both options are suitable for developing German-language biomedical applications.ConclusionGeneral-purpose language models perform remarkably well on biomedical and clinical NLP tasks. If larger corpora become available in the future, domain-adapting these models may improve performances.
Project description:Background and purposeKnowledge-Based Planning (KBP) is increasingly used to standardize and optimize radiotherapy planning. This study aims to develop, refine, and compare multicentric KBP models for craniospinal irradiation (CSI) in pediatric patients.Materials and methodsA total of 113 CSI treatments from three Italian centers were collected, comprising Computed Tomography scans, target and organ contours, and treatment plans. Treatment techniques included Helical Tomotherapy (HT) and Volumetric Modulated Arc Therapy (VMAT). Three KBP models were developed: a full model (F-model) using data from 87 patients, a reduced model (R-model) based on a subset of the same sample, and a replanned model (RP-model) using KBP re-optimized plans. Models' quality was evaluated using goodness-of-fit and goodness-of-prediction metrics, and their performance was assessed on a validation set of 26 patients through dose-volume histogram (DVH) comparisons, prediction bias, and variance analysis.ResultsThe F-model and R-model exhibited similar quality and predictive ability, reflecting the variability of the original dataset and resulting in broad prediction intervals in low to mid-dose ranges. The RP-model achieved the highest quality, with narrower prediction bands. The RP-model is preferable for standardizing planning across centers, while the F-model is better suited for quality assurance as it captures clinical variability.ConclusionsKBP models can effectively predict DVHs despite extreme geometric variability. However, models trained on highly variable datasets cannot simultaneously achieve high precision and accuracy. Comparing KBP models is essential for establishing benchmarks to meet specific clinical goals, particularly for complex pediatric CSI treatments.
Project description:MotivationMicrobial gene catalogs are data structures that organize genes found in microbial communities, providing a reference for standardized analysis of the microbes across samples and studies. Although gene catalogs are commonly used, they have not been critically evaluated for their effectiveness as a basis for metagenomic analyses.ResultsAs a case study, we investigate one such catalog, the Integrated Gene Catalog (IGC), however, our observations apply broadly to most gene catalogs constructed to date. We focus on both the approach used to construct this catalog and on its effectiveness when used as a reference for microbiome studies. Our results highlight important limitations of the approach used to construct the IGC and call into question the broad usefulness of gene catalogs more generally. We also recommend best practices for the construction and use of gene catalogs in microbiome studies and highlight opportunities for future research.Availability and implementationAll supporting scripts for our analyses can be found on GitHub: https://github.com/SethCommichaux/IGC.git. The supporting data can be downloaded from: https://obj.umiacs.umd.edu/igc-analysis/IGC_analysis_data.tar.gz.Supplementary informationSupplementary data are available at Bioinformatics online.
Project description:BackgroundData on emergency and critical care (ECC) capacity in low-income countries (LICs) are needed to improve outcomes and make progress towards realizing the goal of Universal Health Coverage.MethodsWe developed a novel research instrument to assess public sector ECC capacity and service readiness in LICs. From January 20th to February 18th, 2020 we administered the instrument at all four central hospitals and a simple random sample of nine of 24 district hospitals in Malawi, a landlocked and predominantly rural LIC of 19·1 million people in Southern Africa. The instrument contained questions on the availability of key resources across three domains and was administered to hospital administrators and clinicians from outpatient departments, emergency departments, and inpatient units. Results were used to generate an ECC Readiness Score, with a possible range of 0 to 1, for each facility.FindingsA total of 114 staff members across 13 hospitals completed interviews for this study. Three (33%) district hospitals and all four central hospitals had ECC Readiness Scores above 0·5 (p-value 0·070). Absent equipment was identified as the most common barrier to ECC Readiness. Central hospitals had higher median ECC Readiness Scores with less variability 0·82 (interquartile range: 0·80-0·89) than district hospitals (0·33, 0·23 to 0·50, p-value 0·021).InterpretationThis is the first study to employ a systematic approach to assessing ECC capacity and service readiness at both district and central hospitals in Malawi and provides a framework for measuring ECC capacity in other LICs. Prior ECC assessments potentially overestimated equipment availability and our methodology may provide a more accurate approach. There is an urgent need for investments in ECC services, particularly at district hospitals which are more accessible to Malawi's predominantly rural population. These findings highlight the need for long-term investments in health systems strengthening and underscore the importance of understanding capacity in LIC settings to inform these efforts.FundingDivision of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Department of Emergency Medicine, Brigham and Women's Hospital.
Project description:ObjectivesCharacterize current practices for PICU-based rehabilitation, and physician perceptions and attitudes, barriers, resources, and outcome assessment in contemporary PICU settings.DesignInternational, self-administered, quantitative, cross-sectional survey.SettingOnline survey distributed from March 2017 to April 2017.Patients or subjectsPediatric critical care physicians who subscribed to email distribution lists of the Pediatric Acute Lung Injury and Sepsis Investigators, the Pediatric Neurocritical Care Research Group, or the Prevalence of Acute Critical Neurological Disease in Children: A Global Epidemiological Assessment study group, and visitors to the World Federation of Pediatric Intensive and Critical Care Societies website.InterventionsNone.Measurements and main resultsOf the 170 subjects who began the survey, 148 completed it. Of those who completed the optional respondent information, most reported working in an academic medical setting and were located in the United States. The main findings were 1) a large majority of PICU physicians reported working in institutions with no guidelines for PICU-based rehabilitation, but expressed interest in developing and implementing such guidelines; 2) despite this lack of guidelines, an overwhelming majority of respondents reported that their current practices would involve consultation of multiple rehabilitation services for each case example provided; 3) PICU physicians believed that additional research evidence is needed to determine efficacy and optimal implementation of PICU-based rehabilitation; 4) PICU physicians reported significant barriers to implementation of PICU-based rehabilitation across centers; and 5) low routine assessment of long-term functional outcomes of PICU patients, although some centers have developed multidisciplinary follow-up programs.ConclusionsPhysicians lack PICU-based rehabilitation guidelines despite great interest and current practices involving a high degree of PICU-based rehabilitation consultation. Data are needed to identify best practices and necessary resources in the delivery of ICU-based multidisciplinary rehabilitation and long-term functional outcomes assessment to optimize recovery of children and families affected by critical illness.
Project description:Destruxin A (DA), a major secondary metabolite of Metarhizium anisopliae, has anti-immunity to insects. However, the detailed mechanism and its interactions with target proteins are elusive. Previously, three immunophilins, peptidyl-prolyl cis-trans isomerase (BmPPI), FK506 binding-protein 45 (BmFKBP45) and BmFKBP59 homologue, were isolated from the silkworm, Bombyx mori Bm12 cell line following treatment with DA, which suggested that these proteins were possible DA-binding proteins. To validate the interaction between DA and the three immunophilins, we performed bio-layer interferometry (BLI) assay, and the results showed that DA has interaction with BmPPI, whose affinity constant value is 1.98 × 10-3 M and which has no affinity with FKBP45 and FKBP59 homologue in vitro. Furthermore, we investigated the affinity between DA and human PPI protein (HsPPIA) and the affinity constant (KD) value is 2.22 × 10-3 M. Additionally, we compared the effects of silkworm and human PPI proteins produced by DA and immunosuppressants, cyclosporine A (CsA), and tacrolimus (FK506), by employing I2H (insect two-hybrid) in the SF-9 cell line. The results indicated that in silkworm, the effects created by DA and CsA were stronger than FK506. Furthermore, the effects created by DA in silkworm were stronger than those in humans. This study will offer new thinking to elucidate the molecular mechanism of DA in the immunity system of insects.
Project description:Immunophilins are protein chaperones with peptidylprolyl isomerase activity that belong to one of two large families, the cyclosporin-binding cyclophilins (CyPs) and the FK506-binding proteins (FKBPs). Each family displays characteristic and conserved sequence features that differ between the two families. We report a novel group of dual-family immunophilins that contain both CyP and FKBP domains for which we propose the name FCBP (FK506- and cyclosporin-binding protein). The FCBP of Toxoplasma gondii, a protozoan parasite, contained N-terminal FKBP and C-terminal CyP domains joined by tetratricopeptide repeats. Structure-function analysis revealed that both domains were functional and exhibited family-specific drug sensitivity. The individual domains of FCBP inhibited calcineurin (protein phosphatase 2B) in the presence of the appropriate drugs. In binding studies, FCBP recruited calcineurin in the presence of FK506 and a putative target of rapamycin homolog in the presence of rapamycin. Two additional FCBP sequences in Flavobacterium and one in Treponema (spirochete) were also identified in which the CyP and FKBP domains were in the reverse order. T. gondii growth was inhibited by cyclosporin and FK506 in a moderately synergistic manner. The knockdown of FCBP by RNA interference revealed its essentiality for T. gondii growth. Clearly, the FCBPs are novel chaperones and potential targets of multiple immunosuppressant drugs.
Project description:Invasive listeriosis, due to its severe nature in susceptible populations, has been the focus of many quantitative risk assessment (QRA) models aiming to provide a valuable guide in future risk management efforts. A review of the published QRA models of Listeria monocytogenes in seafood was performed, with the objective of appraising the effectiveness of the control strategies at different points along the food chain. It is worth noting, however, that the outcomes of a QRA model are context-specific, and influenced by the country and target population, the assumptions that are employed, and the model architecture itself. Studies containing QRA models were retrieved through a literature search using properly connected keywords on Scopus and PubMed®. All 13 QRA models that were recovered were of short scope, covering, at most, the period from the end of processing to consumption; the majority (85%) focused on smoked or gravad fish. Since the modelled pathways commenced with the packaged product, none of the QRA models addressed cross-contamination events. Many models agreed that keeping the product's temperature at 4.0-4.5 °C leads to greater reductions in the final risk of listeriosis than reducing the shelf life by one week and that the effectiveness of both measures can be surpassed by reducing the initial occurrence of L. monocytogenes in the product (at the end of processing). It is, therefore, necessary that future QRA models for RTE seafood contain a processing module that can provide insight into intervention strategies that can retard L. monocytogenes' growth, such as the use of bacteriocins, ad hoc starter cultures and/or organic acids, and other strategies seeking to reduce cross-contamination at the facilities, such as stringent controls for sanitation procedures. Since risk estimates were shown to be moderately driven by growth kinetic parameters, namely, the exponential growth rate, the minimum temperature for growth, and the maximum population density, further work is needed to reduce uncertainties.
Project description:A review of quantitative risk assessment (QRA) models of Listeria monocytogenes in produce was carried out, with the objective of appraising and contrasting the effectiveness of the control strategies placed along the food chains. Despite nine of the thirteen QRA models recovered being focused on fresh or RTE leafy greens, none of them represented important factors or sources of contamination in the primary production, such as the type of cultivation, water, fertilisers or irrigation method/practices. Cross-contamination at processing and during consumer's handling was modelled using transfer rates, which were shown to moderately drive the final risk of listeriosis, therefore highlighting the importance of accurately representing the transfer coefficient parameters. Many QRA models coincided in the fact that temperature fluctuations at retail or temperature abuse at home were key factors contributing to increasing the risk of listeriosis. In addition to a primary module that could help assess current on-farm practices and potential control measures, future QRA models for minimally processed produce should also contain a refined sanitisation module able to estimate the effectiveness of various sanitisers as a function of type, concentration and exposure time. Finally, L. monocytogenes growth in the products down the supply chain should be estimated by using realistic time-temperature trajectories, and validated microbial kinetic parameters, both of them currently available in the literature.