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1.
Sci Total Environ ; 934: 172981, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38705301

ABSTRACT

Decommissioning consequences of offshore oil and gas infrastructure removal on marine population dynamics, including connectivity, are not well understood. We modelled the connectivity and metapopulation dynamics of three fish and two benthic invertebrate species inhabiting the natural rocky reefs and offshore oil and gas infrastructure located in the Bass Strait, south-east Australia. Using a network approach, we found that platforms are not major sources, destinations, or stepping-stones for most species, yet act as modest sources for connectivity of Corynactis australis (jewel anemone). In contrast, sections of subsea pipelines appear to act as stepping-stones, source and destination habitats of varying strengths for all study species, except for Centrostephanus rodgersii (long-spined sea urchin). Natural reefs were the main stepping-stones, local source, and destination habitats for all study species. These reefs were largely responsible for the overall metapopulation growth of all study species (average of 96 % contribution across all species), with infrastructure acting as a minor contributor (<2 % average contribution). Full or partial decommissioning of platforms should have a very low or negligible impact on the overall metapopulation dynamics of the species explored, except C. australis, while full removal of pipelines could have a low impact on the metapopulation dynamics of benthic invertebrate species and a moderate impact on fish species (up to 34.1 % reduction in the metapopulation growth). We recommend that the decision to remove offshore infrastructure, either in full or in-part, be made on a platform-by-platform basis and consider contributions of pipelines to connectivity and metapopulation dynamics.


Subject(s)
Population Dynamics , Animals , Oil and Gas Industry , Oil and Gas Fields , Environmental Monitoring , Coral Reefs , Fishes , Australia , Invertebrates/physiology , Ecosystem , Aquatic Organisms
2.
Sci Transl Med ; 16(747): eadl4497, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38748771

ABSTRACT

Endovascular interventions are increasingly becoming the preferred approach for treating strokes and cerebral artery diseases. These procedures rely on sophisticated angiographical imaging guidance, which encounters challenges because of limited contrast and spatial resolution. Achieving a more precise visualization of the underlying arterial pathology and neurovascular implants is crucial for accurate procedural decision-making. In a human study involving 32 patients, we introduced the clinical application of a miniaturized endovascular neuro optical coherence tomography (nOCT) imaging probe. This technology was designed to navigate the tortuous paths of the cerebrovascular circulation and to offer high-resolution imaging in situ. The nOCT probe is compatible with standard neurovascular microcatheters, integrating with the procedural workflow used in clinical routine. Equipped with a miniaturized optical fiber and a distal lens, the probe illuminates the tissue and collects the backscattered, near-infrared light. While rotating the fiber and the lens at high speed, the probe is rapidly retracted, creating a spiral-shaped light pattern to comprehensively capture the arterial wall and implanted devices. Using nOCT, we demonstrated volumetric microscopy of cerebral arteries in patients undergoing endovascular procedures. We imaged the anterior and posterior circulation of the brain, including distal segments of the internal carotid and middle-cerebral arteries, as well as the vertebral, basilar, and posterior cerebral arteries. We captured a broad spectrum of neurovascular pathologies, such as brain aneurysms, ischemic stroke, arterial stenoses, dissections, and intracranial atherosclerotic disease. nOCT offered artifact-free, high-resolution visualizations of intracranial artery pathology and neurovascular devices.


Subject(s)
Cerebral Arteries , Tomography, Optical Coherence , Tomography, Optical Coherence/methods , Humans , Cerebral Arteries/diagnostic imaging , Microscopy/methods , Miniaturization , Endovascular Procedures/instrumentation , Endovascular Procedures/methods
3.
Nat Ecol Evol ; 8(6): 1118-1128, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38769434

ABSTRACT

Many shark populations are in decline around the world, with severe ecological and economic consequences. Fisheries management and marine protected areas (MPAs) have both been heralded as solutions. However, the effectiveness of MPAs alone is questionable, particularly for globally threatened sharks and rays ('elasmobranchs'), with little known about how fisheries management and MPAs interact to conserve these species. Here we use a dedicated global survey of coral reef elasmobranchs to assess 66 fully protected areas embedded within a range of fisheries management regimes across 36 countries. We show that conservation benefits were primarily for reef-associated sharks, which were twice as abundant in fully protected areas compared with areas open to fishing. Conservation benefits were greatest in large protected areas that incorporate distinct reefs. However, the same benefits were not evident for rays or wide-ranging sharks that are both economically and ecologically important while also threatened with extinction. We show that conservation benefits from fully protected areas are close to doubled when embedded within areas of effective fisheries management, highlighting the importance of a mixed management approach of both effective fisheries management and well-designed fully protected areas to conserve tropical elasmobranch assemblages globally.


Subject(s)
Conservation of Natural Resources , Coral Reefs , Fisheries , Sharks , Skates, Fish , Animals , Conservation of Natural Resources/methods
4.
J Am Coll Emerg Physicians Open ; 5(2): e13133, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38481520

ABSTRACT

Objectives: This study presents a design framework to enhance the accuracy by which large language models (LLMs), like ChatGPT can extract insights from clinical notes. We highlight this framework via prompt refinement for the automated determination of HEART (History, ECG, Age, Risk factors, Troponin risk algorithm) scores in chest pain evaluation. Methods: We developed a pipeline for LLM prompt testing, employing stochastic repeat testing and quantifying response errors relative to physician assessment. We evaluated the pipeline for automated HEART score determination across a limited set of 24 synthetic clinical notes representing four simulated patients. To assess whether iterative prompt design could improve the LLMs' ability to extract complex clinical concepts and apply rule-based logic to translate them to HEART subscores, we monitored diagnostic performance during prompt iteration. Results: Validation included three iterative rounds of prompt improvement for three HEART subscores with 25 repeat trials totaling 1200 queries each for GPT-3.5 and GPT-4. For both LLM models, from initial to final prompt design, there was a decrease in the rate of responses with erroneous, non-numerical subscore answers. Accuracy of numerical responses for HEART subscores (discrete 0-2 point scale) improved for GPT-4 from the initial to final prompt iteration, decreasing from a mean error of 0.16-0.10 (95% confidence interval: 0.07-0.14) points. Conclusion: We established a framework for iterative prompt design in the clinical space. Although the results indicate potential for integrating LLMs in structured clinical note analysis, translation to real, large-scale clinical data with appropriate data privacy safeguards is needed.

6.
Laryngoscope ; 134(7): 3158-3164, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38294283

ABSTRACT

OBJECTIVE: While tobacco use is understood to negatively impact HPV+ oropharyngeal squamous cell carcinoma (OPSCC) outcomes, debate remains as to how this impact differs between cohorts. Multiple smoking metrics have been identified as having the greatest prognostic significance, and some recent works have found smoking to have no significant impact. Herein, we show through an analysis of four common smoking metrics that while smoking impacts overall survival (OS), it has a limited impact on recurrence-free survival (RFS) in our cohort. METHODS: We conducted a retrospective review of patients treated for HPV+ OPSCC in our health system from 2012 to 2019. Patients with metastatic disease or concurrent second primaries were excluded. Four metrics of tobacco use were assessed: current/former/never smokers, ever/never smokers, and smokers with >10 or >20 pack-year (PY) smoking histories. Our main outcomes were 3-year RFS and OS. RESULTS: Three hundred and sixty-seven patients met inclusion criteria. 37.3% of patients (137/367) were never-smokers; 13.8% of patients (51/367) were currently smoking at diagnosis and 48.8% of patients (179/367) were former smokers. No tobacco-use metric significantly impacted 3-year RFS. On univariate analysis, all smoking metrics yielded inferior OS. On multivariate analysis, current and ever smoking status significantly impacted 3-year OS. CONCLUSION: The impact of tobacco use on HPV+ OPSCC outcomes is not universal, but may instead be modulated by other cohort-specific factors. The impact of smoking may decrease as rates of tobacco use decline. LEVEL OF EVIDENCE: 3 (Cohort and case-control studies) Laryngoscope, 134:3158-3164, 2024.


Subject(s)
Oropharyngeal Neoplasms , Papillomavirus Infections , Smoking , Humans , Oropharyngeal Neoplasms/virology , Oropharyngeal Neoplasms/mortality , Male , Retrospective Studies , Female , Middle Aged , Papillomavirus Infections/complications , Papillomavirus Infections/virology , Papillomavirus Infections/diagnosis , Papillomavirus Infections/mortality , Smoking/adverse effects , Smoking/epidemiology , Aged , Prognosis , Survival Rate , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/virology , Disease-Free Survival
7.
J Anat ; 244(6): 1093-1101, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38267217

ABSTRACT

The etiology of sirenomelia is currently unknown. Data are limited in comparing external and internal abnormalities using modern imaging technologies and molecular genetic analysis. The purpose of the current study was designed to compare external and internal anatomical defects in two cases of sirenomelia and Potter's sequence. Considered rare, Potter's sequence is a fetal disorder with characteristic features of bilateral renal agenesis, obstructive uropathy, atypical facial appearance, and limb malformations. The internal and external malformations of two term fetuses with sirenomelia and Potter's sequence were compared using assessment of external features, radiography and MRI on internal structures, and molecular genetic studies on sex determination. Data reveal that both fetuses were male and manifested with an overlapping but distinct spectrum of abnormalities. Principal differences were noted in the development of the ears, brain, urogenital system, lower limbs, pelvis, and vertebral column. Defects of the axial mesoderm are likely to underlie the abnormalities seen in both fetuses. The first one, which had only caudal defects, was found to have a spectrum of abnormalities most similar to those associated with more severe forms of the small pelvic outlet syndrome, although the structure and orientation of the sacrum and iliae were different from previously reported cases. The other had both caudal and cranial defects, and was most similar to those described in the axial mesodermal dysplasia syndrome. Defects associated with sirenomelia can be evaluated with standard gross anatomy examination, radiology, MRI, and modified PCR techniques to determine anatomical abnormalities and the sex of preserved specimens, respectively. Evidence indicated that sirenomelia could be developed via various etiologies.


Subject(s)
Ectromelia , Humans , Abnormalities, Multiple/genetics , Abnormalities, Multiple/diagnostic imaging , Ectromelia/genetics , Ectromelia/diagnostic imaging , Ectromelia/pathology , Fetus/abnormalities , Fetus/diagnostic imaging , Magnetic Resonance Imaging
8.
Mar Pollut Bull ; 199: 115480, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37839912

ABSTRACT

High-intensity, impulsive sounds are used to locate oil and gas reserves during seismic exploration of the seafloor. The impacts of this noise pollution on the health and mortality of marine invertebrates are not well known, including the silverlip pearl oyster (Pinctada maxima), which comprises one of the world's last remaining significant wildstock pearl oyster fisheries, in northwestern Australia. We exposed ≈11,000 P. maxima to a four-day experimental seismic survey, plus one vessel-control day. After exposure, survival rates were monitored throughout a full two-year production cycle, and the number and quality of pearls produced at harvest were assessed. Oysters from two groups, on one sampling day, exhibited reduced survival and pearl productivity compared to controls, but 14 other groups receiving similar or higher exposure levels did not. We therefore found no conclusive evidence of an impact of the seismic source survey on oyster mortality or pearl production.


Subject(s)
Pinctada , Animals , Noise , Sound , Australia , Fisheries
9.
Otolaryngol Head Neck Surg ; 170(2): 627-629, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37855637

ABSTRACT

With the American Joint Committee on Cancer (AJCC) 8th edition staging guidelines update, human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) is now staged separately from its HPV-negative counterpart, preventing meaningful comparison of cases staged with the 7th versus 8th edition criteria. Manual restaging is time-consuming and error-prone, hindering multiyear analyses for HPV+ OPSCC. We developed an automated computational tool for re-classifying HPV+ OPSCC pathological and clinical tumor staging from AJCC 7th to 8th edition. The tool is designed to handle large data sets, ensuring comprehensive and accurate analysis of historic HPV+ OPSCC data. Validated against institutional and National Cancer Database data sets, the algorithm achieved accuracies of 100% (95% confidence interval [CI] 98.8%-100%) and 93.4% (95% CI 93.1%-93.7%), successfully restaging 326/326 and 26,505/28,374 cases, respectively. With its open-source design, this computational tool can enhance future HPV+ OPSCC research and inspire similar tools for other cancer types and subsequent AJCC editions.


Subject(s)
Head and Neck Neoplasms , Oropharyngeal Neoplasms , Papillomavirus Infections , Humans , Prognosis , Papillomavirus Infections/complications , Papillomavirus Infections/pathology , Oropharyngeal Neoplasms/pathology , Neoplasm Staging , Squamous Cell Carcinoma of Head and Neck/pathology , Head and Neck Neoplasms/pathology , Retrospective Studies
10.
J Bacteriol ; 205(10): e0020923, 2023 10 26.
Article in English | MEDLINE | ID: mdl-37787518

ABSTRACT

Cyanobacteria show an unusually complex prokaryotic cell structure including a distinct intracytoplasmic membrane system, the thylakoid membranes that are the site of the photosynthetic light reactions. The thylakoid and plasma membranes have sharply distinct proteomes, but the mechanisms that target proteins to a specific membrane remain poorly understood. Here, we investigate the locations of translation of thylakoid and plasma membrane proteins in the model unicellular cyanobacterium Synechococcus elongatus PCC 7942. We use fluorescent in situ hybridization to probe the locations of mRNAs encoding membrane-integral proteins, plus Green Fluorescent Protein tagging of the RplL subunit to reveal the location of ribosomes under different conditions. We show that membrane-integral thylakoid and plasma membrane proteins are translated in different locations. Thylakoid membrane proteins are translated in patches at the innermost thylakoid membrane surface facing the nucleoid. However, different proteins are translated in different patches, even when they are subunits of the same multiprotein complex. This implies that translation is distributed over the proximal thylakoid surface, with newly inserted proteins migrating within the membrane prior to incorporation into complexes. mRNAs encoding plasma membrane proteins form patches at the plasma membrane. Ribosomes can be observed at similar locations near the thylakoid and plasma membranes, with more ribosomes near the plasma membrane when conditions force rapid production of plasma membrane proteins. There must be routes for ribosomes and mRNAs past the thylakoids to the plasma membrane. We infer a system to chaperone plasma membrane mRNAs to prevent their translation prior to arrival at the correct membrane. IMPORTANCE Cyanobacteria have a complex and distinct membrane system within the cytoplasm, the thylakoid membranes that house the photosynthetic light reactions. The thylakoid and plasma membranes contain distinct sets of proteins, but the steps that target proteins to the two membranes remain unclear. Knowledge of the protein sorting rules will be crucial for the biotechnological re-engineering of cyanobacterial cells, and for understanding the evolutionary development of the thylakoids. Here, we probe the subcellular locations of the mRNAs that encode cyanobacterial membrane proteins and the ribosomes that translate them. We show that thylakoid and plasma membrane proteins are produced at different locations, providing the first direct evidence for a sorting mechanism that operates prior to protein translation.


Subject(s)
Cyanobacteria , Membrane Proteins , Membrane Proteins/genetics , Membrane Proteins/metabolism , In Situ Hybridization, Fluorescence , Cyanobacteria/genetics , Cyanobacteria/metabolism , Thylakoids/metabolism , Thylakoids/ultrastructure , Cell Membrane/metabolism
11.
JMIR Med Educ ; 9: e50945, 2023 Aug 14.
Article in English | MEDLINE | ID: mdl-37578830

ABSTRACT

Large language models (LLMs) such as ChatGPT have sparked extensive discourse within the medical education community, spurring both excitement and apprehension. Written from the perspective of medical students, this editorial offers insights gleaned through immersive interactions with ChatGPT, contextualized by ongoing research into the imminent role of LLMs in health care. Three distinct positive use cases for ChatGPT were identified: facilitating differential diagnosis brainstorming, providing interactive practice cases, and aiding in multiple-choice question review. These use cases can effectively help students learn foundational medical knowledge during the preclinical curriculum while reinforcing the learning of core Entrustable Professional Activities. Simultaneously, we highlight key limitations of LLMs in medical education, including their insufficient ability to teach the integration of contextual and external information, comprehend sensory and nonverbal cues, cultivate rapport and interpersonal interaction, and align with overarching medical education and patient care goals. Through interacting with LLMs to augment learning during medical school, students can gain an understanding of their strengths and weaknesses. This understanding will be pivotal as we navigate a health care landscape increasingly intertwined with LLMs and artificial intelligence.

13.
Science ; 380(6650): 1155-1160, 2023 06 16.
Article in English | MEDLINE | ID: mdl-37319199

ABSTRACT

A global survey of coral reefs reveals that overfishing is driving resident shark species toward extinction, causing diversity deficits in reef elasmobranch (shark and ray) assemblages. Our species-level analysis revealed global declines of 60 to 73% for five common resident reef shark species and that individual shark species were not detected at 34 to 47% of surveyed reefs. As reefs become more shark-depleted, rays begin to dominate assemblages. Shark-dominated assemblages persist in wealthy nations with strong governance and in highly protected areas, whereas poverty, weak governance, and a lack of shark management are associated with depauperate assemblages mainly composed of rays. Without action to address these diversity deficits, loss of ecological function and ecosystem services will increasingly affect human communities.


Subject(s)
Conservation of Natural Resources , Coral Reefs , Extinction, Biological , Sharks , Skates, Fish , Animals , Humans , Fisheries , Biodiversity
14.
Am Nat ; 201(4): 586-602, 2023 04.
Article in English | MEDLINE | ID: mdl-36958006

ABSTRACT

AbstractUnifying models have shown that the amount of space used by animals (e.g., activity space, home range) scales allometrically with body mass for terrestrial taxa; however, such relationships are far less clear for marine species. We compiled movement data from 1,596 individuals across 79 taxa collected using a continental passive acoustic telemetry network of acoustic receivers to assess allometric scaling of activity space. We found that ectothermic marine taxa do exhibit allometric scaling for activity space, with an overall scaling exponent of 0.64. However, body mass alone explained only 35% of the variation, with the remaining variation best explained by trophic position for teleosts and latitude for sharks, rays, and marine reptiles. Taxon-specific allometric relationships highlighted weaker scaling exponents among teleost fish species (0.07) than sharks (0.96), rays (0.55), and marine reptiles (0.57). The allometric scaling relationship and scaling exponents for the marine taxonomic groups examined were lower than those reported from studies that had collated both marine and terrestrial species data derived using various tracking methods. We propose that these disparities arise because previous work integrated summarized data across many studies that used differing methods for collecting and quantifying activity space, introducing considerable uncertainty into slope estimates. Our findings highlight the benefit of using large-scale, coordinated animal biotelemetry networks to address cross-taxa evolutionary and ecological questions.


Subject(s)
Aquatic Organisms , Fishes , Animals , Homing Behavior
15.
JMIR Med Educ ; 9: e45312, 2023 02 08.
Article in English | MEDLINE | ID: mdl-36753318

ABSTRACT

BACKGROUND: Chat Generative Pre-trained Transformer (ChatGPT) is a 175-billion-parameter natural language processing model that can generate conversation-style responses to user input. OBJECTIVE: This study aimed to evaluate the performance of ChatGPT on questions within the scope of the United States Medical Licensing Examination (USMLE) Step 1 and Step 2 exams, as well as to analyze responses for user interpretability. METHODS: We used 2 sets of multiple-choice questions to evaluate ChatGPT's performance, each with questions pertaining to Step 1 and Step 2. The first set was derived from AMBOSS, a commonly used question bank for medical students, which also provides statistics on question difficulty and the performance on an exam relative to the user base. The second set was the National Board of Medical Examiners (NBME) free 120 questions. ChatGPT's performance was compared to 2 other large language models, GPT-3 and InstructGPT. The text output of each ChatGPT response was evaluated across 3 qualitative metrics: logical justification of the answer selected, presence of information internal to the question, and presence of information external to the question. RESULTS: Of the 4 data sets, AMBOSS-Step1, AMBOSS-Step2, NBME-Free-Step1, and NBME-Free-Step2, ChatGPT achieved accuracies of 44% (44/100), 42% (42/100), 64.4% (56/87), and 57.8% (59/102), respectively. ChatGPT outperformed InstructGPT by 8.15% on average across all data sets, and GPT-3 performed similarly to random chance. The model demonstrated a significant decrease in performance as question difficulty increased (P=.01) within the AMBOSS-Step1 data set. We found that logical justification for ChatGPT's answer selection was present in 100% of outputs of the NBME data sets. Internal information to the question was present in 96.8% (183/189) of all questions. The presence of information external to the question was 44.5% and 27% lower for incorrect answers relative to correct answers on the NBME-Free-Step1 (P<.001) and NBME-Free-Step2 (P=.001) data sets, respectively. CONCLUSIONS: ChatGPT marks a significant improvement in natural language processing models on the tasks of medical question answering. By performing at a greater than 60% threshold on the NBME-Free-Step-1 data set, we show that the model achieves the equivalent of a passing score for a third-year medical student. Additionally, we highlight ChatGPT's capacity to provide logic and informational context across the majority of answers. These facts taken together make a compelling case for the potential applications of ChatGPT as an interactive medical education tool to support learning.

16.
Mod Pathol ; 36(2): 100003, 2023 02.
Article in English | MEDLINE | ID: mdl-36853796

ABSTRACT

The pathologic diagnosis of bone marrow disorders relies in part on the microscopic analysis of bone marrow aspirate (BMA) smears and the manual counting of marrow nucleated cells to obtain a differential cell count (DCC). This manual process has significant limitations, including the analysis of only a small subset of optimal slide areas and nucleated cells, as well as interobserver variability due to differences in cell selection and classification. To address these shortcomings, we developed an automated machine learning-based pipeline for obtaining 11-component DCCs on whole-slide BMAs. This pipeline uses a sequential process of identifying optimal BMA regions with high proportions of marrow nucleated cells, detecting individual cells within these optimal areas, and classifying these cells into 1 of 11 DCC components. Convolutional neural network models were trained on 396,048 BMA region, 28,914 cell boundary, and 1,510,976 cell class images from manual annotations. The resulting automated pipeline produced 11-component DCCs that demonstrated a high statistical and diagnostic concordance with manual DCCs among a heterogeneous group of testing BMA slides with varying pathologies and cellularities. Additionally, we demonstrated that an automated analysis can reduce the intraslide variance in DCCs by analyzing the whole slide and marrow nucleated cells within all optimal regions. Finally, the pipeline outputs of region classification, cell detection, and cell classification can be visualized using whole-slide image analysis software. This study demonstrates the feasibility of a fully automated pipeline for generating DCCs on scanned whole-slide BMA images, with the potential for improving the current standard of practice for utilizing BMA smears in the laboratory analysis of hematologic disorders.


Subject(s)
Bone Marrow , Image Processing, Computer-Assisted , Humans , Cell Count , Machine Learning , Neural Networks, Computer
17.
Front Plant Sci ; 13: 1028794, 2022.
Article in English | MEDLINE | ID: mdl-36330266

ABSTRACT

The regulatory protein CP12 can bind glyceraldehyde 3-phosphate dehydrogenase (GapDH) and phosphoribulokinase (PRK) in oxygenic phototrophs, thereby switching on and off the flux through the Calvin-Benson cycle (CBC) under light and dark conditions, respectively. However, it can be assumed that CP12 is also regulating CBC flux under further conditions associated with redox changes. To prove this hypothesis, the mutant Δcp12 of the model cyanobacterium Synechocystis sp. PCC 6803 was compared to wild type and different complementation strains. Fluorescence microscopy showed for the first time the in vivo kinetics of assembly and disassembly of the CP12-GapDH-PRK complex, which was absent in the mutant Δcp12. Metabolome analysis revealed differences in the contents of ribulose 1,5-bisphosphate and dihydroxyacetone phosphate, the products of the CP12-regulated enzymes GapDH and PRK, between wild type and mutant Δcp12 under changing CO2 conditions. Growth of Δcp12 was not affected at constant light under different inorganic carbon conditions, however, the addition of glucose inhibited growth in darkness as well as under diurnal conditions. The growth defect in the presence of glucose is associated with the inability of Δcp12 to utilize external glucose. These phenotypes could be complemented by ectopic expression of the native CP12 protein, however, expression of CP12 variants with missing redox-sensitive cysteine pairs only partly restored the growth with glucose. These experiments indicated that the loss of GapDH-inhibition via CP12 is more critical than PRK association. Measurements of the NAD(P)H oxidation revealed an impairment of light intensity-dependent redox state regulation in Δcp12. Collectively, our results indicate that CP12-dependent regulation of the CBC is crucial for metabolic adjustment under conditions leading to redox changes such as diurnal conditions, glucose addition, and different CO2 conditions in cyanobacteria.

18.
Transl Vis Sci Technol ; 11(10): 28, 2022 10 03.
Article in English | MEDLINE | ID: mdl-36259678

ABSTRACT

Purpose: Melanin plays an important function in maintaining eye health, however there are few metrics that can be used to study retinal melanin content in vivo. Methods: The slope of the spectral coefficient of variation (SSCoV) is a novel biomarker that measures chromophore concentration by analyzing the local divergence of spectral intensities using optical coherence tomography (OCT). This metric was validated in a phantom and applied in a longitudinal study of superoxide dismutase 1 knockout (SOD1-/-) mice, a model for wet and dry age-related macular degeneration. We also examined a new feature of interest in standard OCT image data, the ratio of maximum intensity in the retinal pigment epithelium to that of the choroid (RC ratio). These new biomarkers were supported by polarization-sensitive OCT and histological analysis. Results: SSCoV correlated well with depolarization metrics both in phantom and in vivo with both metrics decreasing more rapidly in SOD1-/- mice with age (P < 0.05). This finding is correlated with reduced melanin pigmentation in the choroid over time. The RC ratio clearly differentiated the SOD1-/- and control groups (P < 0.0005) irrespective of time and may indicate lower retinal pigment epithelium melanin in the SOD1-/- mice. Histological analysis showed decreased melanin content and potential differences in melanin granule shape in SOD1-/- mice. Conclusions: SSCoV and RC ratio biomarkers provided insights into the changes of retinal melanin in the SOD1-/- model longitudinally and noninvasively. Translational Relevance: These biomarkers were designed with the potential for rapid adoption by existing clinical OCT systems without requiring new hardware.


Subject(s)
Melanins , Tomography, Optical Coherence , Mice , Animals , Tomography, Optical Coherence/methods , Superoxide Dismutase-1 , Longitudinal Studies , Biomarkers
19.
World Neurosurg ; 168: e613-e620, 2022 12.
Article in English | MEDLINE | ID: mdl-36273730

ABSTRACT

BACKGROUND: Transvenous embolization is a new treatment for spinal cerebrospinal fluid (CSF)-venous fistula, with only 1 reported large case series from the center that invented this technique. METHODS: We report the clinical and radiographic data of 5 consecutive patients who were diagnosed with CSF-venous fistula at a single community-academic medical center and were treated with transvenous embolization. All patients provided consent for this report. Institutional review board approval was not required because of the retrospective nature of this study describing standards of care. RESULTS: Five patients, 3 men and 2 women, with a median age of 57 years, were diagnosed between March and December 2021with spontaneous intracranial hypotension (SIH) as a result of CSF-venous fistula. Two patients were originally referred for middle meningeal artery embolization for chronic subdural hematoma. All fistulae were in the thoracic spine at a single level in 3 patients, 2 levels in 1 patient, and multiple levels in 1 patient. Transvenous embolization was technically successful in all cases, with no significant complications. Four patients (80%) had complete or near-complete resolution of clinical symptoms and returned to baseline function and employment status. One patient (20%) has had a remitting relapsing course. Posttreatment brain magnetic resonance imaging showed resolution of spontaneous intracranial hypotension findings in 4 patients (80%) and minimal changes in 1 patient (20%), who had significant clinical improvement. CONCLUSIONS: Transvenous embolization for the treatment of CSF-venous fistula is feasible and seems effective in the short-term. The results reported by the previous case series can be reproduced in other centers with available expertise and adherence to published diagnostic and treatment protocols.


Subject(s)
Fistula , Intracranial Hypotension , Male , Humans , Female , Middle Aged , Intracranial Hypotension/etiology , Myelography/adverse effects , Cerebrospinal Fluid Leak/diagnostic imaging , Cerebrospinal Fluid Leak/therapy , Cerebrospinal Fluid Leak/complications , Retrospective Studies
20.
Ann Epidemiol ; 76: 136-142, 2022 12.
Article in English | MEDLINE | ID: mdl-36087658

ABSTRACT

PURPOSE: No method is available to systematically study SARS-CoV-2 transmission dynamics using the data that rideshare companies share with government agencies. We developed a proof-of-concept method for the analysis of SARS-CoV-2 transmissions between rideshare passengers and drivers. METHOD: To assess whether this method could enable hypothesis testing about SARS-CoV-2, we repeated ten 200-day agent-based simulations of SARS-CoV-2 propagation within the Los Angeles County rideshare network. Assuming data access for 25% of infections, we estimated an epidemiologist's ability to analyze the observable infection patterns to correctly identify a baseline viral variant A, as opposed to viral variant A with mask use (50% reduction in viral particle exchange), or a more infectious viral variant B (300% higher cumulative viral load). RESULTS: Simulations had an average of 190,387 potentially infectious rideshare interactions, resulting in 409 average diagnosed infections. Comparison of the number of observed and expected passenger-to-driver infections under each hypothesis demonstrated our method's ability to consistently discern large infectivity differences (viral variant A vs. viral variant B) given partial data from one large city, and to discern smaller infectivity differences (viral variant A vs. viral variant A with masks) given partial data aggregated across multiple cities. CONCLUSIONS: This novel statistical method suggests that, for the present and subsequent pandemics, government-facilitated analysis of rideshare data combined with diagnosis records may augment efforts to better understand viral transmission dynamics and to measure changes in infectivity associated with nonpharmaceutical interventions and emergent viral strains.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/epidemiology , Pandemics , Computer Simulation , Computers
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