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Per- and polyfluoroalkyl substances (PFAS) bioaccumulate in different organ systems, including bone. While existing research highlights the adverse impact of PFAS on bone density, a critical gap remains in understanding the specific effects on the bone marrow microenvironment, especially the bone marrow adipose tissue (BMAT). Changes in BMAT have been linked to various health consequences, such as the development of osteoporosis and the progression of metastatic tumors in bone. Studies presented herein demonstrate that exposure to a mixture of five environmentally relevant PFAS compounds promotes marrow adipogenesis in vitro and in vivo. We show that among the components of the mixture, PFHxS, an alternative to PFOS, has the highest propensity to accumulate in bone and effectively promote marrow adipogenesis. Utilizing RNAseq approaches, we identified the peroxisome proliferator-activated receptor (PPAR) signaling as a top pathway modulated by PFHxS exposure. Furthermore, we provide results suggesting the activation and involvement of PPAR-gamma (PPARγ) in PFHxS-mediated bone marrow adipogenesis, especially in combination with high-fat diet. In conclusion, our findings demonstrate the potential impact of elevated PFHxS levels, particularly in occupational settings, on bone health, and specifically bone marrow adiposity. This study contributes new insights into the health risks of PFHxS exposure, urging further research on the relationship between environmental factors, diet, and adipose tissue dynamics.
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The scientific and ethical issues associated with the use of animal-derived antibodies in research can be overcome by the use of animal-free, sequence-defined recombinant antibodies, whose benefits are well documented. Here, we describe progress made following a 2019 expert meeting focused on improving the quality and reproducibility of biomedical research by accelerating the production and use of animal-free recombinant antibodies in the USA. In the five intervening years since the meeting, participants have established multifaceted initiatives to tackle the next steps outlined during the meeting. These initiatives include: prioritising the replacement of ascites-derived and polyclonal antibodies; distributing educational materials describing recombinant antibodies; fostering public-private partnerships to increase access to recombinant antibodies; and increasing the availability of funding for recombinant antibody development. Given the widescale use of antibodies across scientific disciplines, a transition to modern antibody production methods relies on a commitment from government agencies, universities, industry and funding organisations, to initiatives such as those outlined here.
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The webinar series and workshop titled "Trust Your Gut: Establishing Confidence in Gastrointestinal Models An Overview of the State of the Science and Contexts of Use" was co-organized by NICEATM, NIEHS, FDA, EPA, CPSC, DoD, and the Johns Hopkins Center for Alternatives to Animal Testing (CAAT) and hosted at the National Institutes of Health in Bethesda, MD, USA on October 11-12, 2023. New approach methods (NAMs) for assessing issues of gastrointestinal tract (GIT)- related toxicity offer promise in addressing some of the limitations associated with animal-based assessments. GIT NAMs vary in complexity, from two-dimensional monolayer cell line-based systems to sophisticated 3-dimensional organoid systems derived from human primary cells. Despite advances in GIT NAMs, challenges remain in fully replicating the complex interactions and processes occurring within the human GIT. Presentations and discussions addressed regulatory needs, challenges, and innovations in incorporating NAMs into risk assessment frameworks; explored the state of the science in using NAMs for evaluating systemic toxicity, understanding absorption and pharmacokinetics, evaluating GIT toxicity, and assessing potential allergenicity; and discussed strengths, limitations, and data gaps of GIT NAMs as well as steps needed to establish confidence in these models for use in the regulatory setting.
Non-animal methods to assess whether chemicals may be toxic to the human digestive tract promise to complement or improve on animal-based methods. These approaches, which are based on human or animal cells and/or computer models, are faced with their own technical challenges and need to be shown to predict adverse effects in humans. Regulators are tasked with evaluating submitted data to best protect human health and the environment. A webinar series and workshop brought together scientists from academia, industry, military, and regulatory authorities from different countries to discuss how non-animal methods can be integrated into the risk assessment of drugs, food additives, dietary supplements, pesticides, and industrial chemicals for gastrointestinal toxicity.
Subject(s)
Animal Testing Alternatives , Gastrointestinal Tract , Humans , Animal Testing Alternatives/methods , Animals , Models, Biological , Risk Assessment/methods , Toxicity Tests/methodsABSTRACT
Organophosphorus flame retardants (OPFRs) are abundant and persistent in the environment but have limited toxicity information. Their similarity in structure to organophosphate pesticides presents great concern for developmental neurotoxicity (DNT). However, current in vivo testing is not suitable to provide DNT information on the amount of OPFRs that lack data. Over the past decade, an in vitro battery was developed to enhance DNT assessment, consisting of assays that evaluate cellular processes in neurodevelopment and function. In this study, behavioral data of small model organisms were also included. To assess if these assays provide sufficient mechanistic coverage to prioritize chemicals for further testing and/or identify hazards, an integrated approach to testing and assessment (IATA) was developed with additional information from the Integrated Chemical Environment (ICE) and the literature. Human biomonitoring and exposure data were identified and physiologically-based toxicokinetic models were applied to relate in vitro toxicity data to human exposure based on maximum plasma concentration. Eight OPFRs were evaluated, including aromatic OPFRs (triphenyl phosphate (TPHP), isopropylated phenyl phosphate (IPP), 2-ethylhexyl diphenyl phosphate (EHDP), tricresyl phosphate (TMPP), isodecyl diphenyl phosphate (IDDP), tert-butylphenyl diphenyl phosphate (BPDP)) and halogenated FRs ((Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), tris(2-chloroethyl) phosphate (TCEP)). Two representative brominated flame retardants (BFRs) (2,2'4,4'-tetrabromodiphenyl ether (BDE-47) and 3,3',5,5'-tetrabromobisphenol A (TBBPA)) with known DNT potential were selected for toxicity benchmarking. Data from the DNT battery indicate that the aromatic OPFRs have activity at similar concentrations as the BFRs and should therefore be evaluated further. However, these assays provide limited information on the mechanism of the compounds. By integrating information from ICE and the literature, endocrine disruption was identified as a potential mechanism. This IATA case study indicates that human exposure to some OPFRs could lead to a plasma concentration similar to those exerting in vitro activities, indicating potential concern for human health.
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Significance: Hyperspectral dark-field microscopy (HSDFM) and data cube analysis algorithms demonstrate successful detection and classification of various tissue types, including carcinoma regions in human post-lumpectomy breast tissues excised during breast-conserving surgeries. Aim: We expand the application of HSDFM to the classification of tissue types and tumor subtypes in pre-histopathology human breast lumpectomy samples. Approach: Breast tissues excised during breast-conserving surgeries were imaged by the HSDFM and analyzed. The performance of the HSDFM is evaluated by comparing the backscattering intensity spectra of polystyrene microbead solutions with the Monte Carlo simulation of the experimental data. For classification algorithms, two analysis approaches, a supervised technique based on the spectral angle mapper (SAM) algorithm and an unsupervised technique based on the K-means algorithm are applied to classify various tissue types including carcinoma subtypes. In the supervised technique, the SAM algorithm with manually extracted endmembers guided by H&E annotations is used as reference spectra, allowing for segmentation maps with classified tissue types including carcinoma subtypes. Results: The manually extracted endmembers of known tissue types and their corresponding threshold spectral correlation angles for classification make a good reference library that validates endmembers computed by the unsupervised K-means algorithm. The unsupervised K-means algorithm, with no a priori information, produces abundance maps with dominant endmembers of various tissue types, including carcinoma subtypes of invasive ductal carcinoma and invasive mucinous carcinoma. The two carcinomas' unique endmembers produced by the two methods agree with each other within <2% residual error margin. Conclusions: Our report demonstrates a robust procedure for the validation of an unsupervised algorithm with the essential set of parameters based on the ground truth, histopathological information. We have demonstrated that a trained library of the histopathology-guided endmembers and associated threshold spectral correlation angles computed against well-defined reference data cubes serve such parameters. Two classification algorithms, supervised and unsupervised algorithms, are employed to identify regions with carcinoma subtypes of invasive ductal carcinoma and invasive mucinous carcinoma present in the tissues. The two carcinomas' unique endmembers used by the two methods agree to <2% residual error margin. This library of high quality and collected under an environment with no ambient background may be instrumental to develop or validate more advanced unsupervised data cube analysis algorithms, such as effective neural networks for efficient subtype classification.
Subject(s)
Algorithms , Breast Neoplasms , Mastectomy, Segmental , Microscopy , Humans , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Female , Mastectomy, Segmental/methods , Microscopy/methods , Breast/diagnostic imaging , Breast/pathology , Breast/surgery , Hyperspectral Imaging/methods , Margins of Excision , Monte Carlo Method , Image Processing, Computer-Assisted/methodsABSTRACT
PURPOSE: The purpose of this study is to identify if the local institutional shift from routine overnight observation to same-day discharge following percutaneous cryoablation (PCA) of renal tumors increases 30 day re-admission rates or serious adverse events (AEs). MATERIALS AND METHODS: This retrospective study included 133 adult patients. PCA patients in calendar years 2018-2019 were routinely observed overnight in the hospital, comprising the control group (Group A). PCA patients in calendar years 2021-2022 were routinely discharged the same day, comprising the test group (Group B). Relevant demographic information, tumor characteristics, technical outcomes, and clinical outcomes were recorded. RESULTS: 15 patients (11.3 %) from the total cohort were re-admitted to the hospital within 30 days of PCA for any reason. Seven patients (10.4 %) and eight patients (12.1 %) were re-admitted for any reason within 30 days in Group A and Group B, respectively, with no difference between the two groups (p = 0.76). Nine patients (6.8 %) from the total cohort were re-admitted to the hospital within 30 days for a diagnosis secondary to the procedure. Four patients (6 %) and five patients (7.6 %) were re-admitted within 30 days for reasons related to PCA in Group A and Group B, respectively, with no significant difference between the groups (p = 0.71). Eight patients (12 %) and four patients (6 %) had major AEs following PCA in Group A and Group B, respectively, with no difference between the two groups (p = 0.43). CONCLUSION: Overall, the change in post-procedural care after PCA did not have a deleterious effect on 30 day re-admission rates or rates of major AEs.
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OBJECTIVES: To depict the current state of global surgery opportunities in United States ACGME-approved Otolaryngology residency programs and compare the characteristics of programs with and without these opportunities. METHODS: In this cross-sectional analysis, websites of ACGME-accredited Otolaryngology residency programs were analyzed for information on program size, rank, age, and geographic region as obtained through the Doximity platform in 2023. Additional parameters were obtained for programs listing global surgery opportunities such as funding, faculty oversight, location/region, focus, and relationship to the community served. Data were tabulated and analyzed in Microsoft Excel and Stata. RESULTS: Of the 131 ACGME-accredited Otolaryngology residency programs, 26 (20%) of programs advertised a global surgery opportunity. Nine (35%) of these promoted funding, 15 (58%) offered a clinical focus, one (4%) offered a research focus, and 10 (38%) offered a combined approach. The Midwest region had the most programs with global surgery opportunities (n = 8, 31%). Less than half (42%) of programs had an established partnership with local partners within low and middle-income countries (LMICs). When comparing programs, the average Doximity rank, average program age, and average program size of programs that offered global surgery opportunities was significantly higher than those that did not (37.2 vs. 71.5, 54 vs. 41, 19.5 vs. 13.7; all p < 0.05). CONCLUSIONS: Approximately one-fifth of Otolaryngology training programs have a global surgery opportunity. Programs that offer these opportunities had a higher Doximity ranking, older program age, and a larger trainee cohort. These results highlight potential areas for expanding global surgery opportunities in academic institutions. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.
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Inhalation is a critical route through which substances can exert adverse effects in humans; therefore, it is important to characterize the potential effects that inhaled substances may have on the human respiratory tract by using fit for purpose, reliable, and human relevant testing tools. In regulatory toxicology testing, rats have primarily been used to assess the effects of inhaled substances as they-being mammals-share similarities in structure and function of the respiratory tract with humans. However, questions about inter-species differences impacting the predictability of human effects have surfaced. Disparities in macroscopic anatomy, microscopic anatomy, or physiology, such as breathing mode (e.g., nose-only versus oronasal breathing), airway structure (e.g., complexity of the nasal turbinates), cell types and location within the respiratory tract, and local metabolism may impact inhalation toxicity testing results. This review shows that these key differences describe uncertainty in the use of rat data to predict human effects and supports an opportunity to harness modern toxicology tools and a detailed understanding of the human respiratory tract to develop testing approaches grounded in human biology. Ultimately, as the regulatory purpose is protecting human health, there is a need for testing approaches based on human biology and mechanisms of toxicity.
Subject(s)
Respiratory System , Species Specificity , Toxicity Tests , Animals , Humans , Respiratory System/drug effects , Respiratory System/anatomy & histology , Rats , Toxicity Tests/methods , Inhalation Exposure/adverse effects , Risk AssessmentABSTRACT
SNAPSHOT USA is a multicontributor, long-term camera trap survey designed to survey mammals across the United States. Participants are recruited through community networks and directly through a website application (https://www.snapshot-usa.org/). The growing Snapshot dataset is useful, for example, for tracking wildlife population responses to land use, land cover, and climate changes across spatial and temporal scales. Here we present the SNAPSHOT USA 2021 dataset, the third national camera trap survey across the US. Data were collected across 109 camera trap arrays and included 1711 camera sites. The total effort equaled 71,519 camera trap nights and resulted in 172,507 sequences of animal observations. Sampling effort varied among camera trap arrays, with a minimum of 126 camera trap nights, a maximum of 3355 nights, a median 546 nights, and a mean 656 ± 431 nights. This third dataset comprises 51 camera trap arrays that were surveyed during 2019, 2020, and 2021, along with 71 camera trap arrays that were surveyed in 2020 and 2021. All raw data and accompanying metadata are stored on Wildlife Insights (https://www.wildlifeinsights.org/), and are publicly available upon acceptance of the data papers. SNAPSHOT USA aims to sample multiple ecoregions in the United States with adequate representation of each ecoregion according to its relative size. Currently, the relative density of camera trap arrays varies by an order of magnitude for the various ecoregions (0.22-5.9 arrays per 100,000 km2), emphasizing the need to increase sampling effort by further recruiting and retaining contributors. There are no copyright restrictions on these data. We request that authors cite this paper when using these data, or a subset of these data, for publication. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the US Government.
Subject(s)
Photography , United States , Animals , Mammals , EcosystemABSTRACT
OBJECTIVE: This study was undertaken to validate a set of candidate biomarkers of seizure susceptibility in a retrospective, multisite case-control study, and to determine the robustness of these biomarkers derived from routinely collected electroencephalography (EEG) within a large cohort (both epilepsy and common alternative conditions such as nonepileptic attack disorder). METHODS: The database consisted of 814 EEG recordings from 648 subjects, collected from eight National Health Service sites across the UK. Clinically noncontributory EEG recordings were identified by an experienced clinical scientist (N = 281; 152 alternative conditions, 129 epilepsy). Eight computational markers (spectral [n = 2], network-based [n = 4], and model-based [n = 2]) were calculated within each recording. Ensemble-based classifiers were developed using a two-tier cross-validation approach. We used standard regression methods to assess whether potential confounding variables (e.g., age, gender, treatment status, comorbidity) impacted model performance. RESULTS: We found levels of balanced accuracy of 68% across the cohort with clinically noncontributory normal EEGs (sensitivity =61%, specificity =75%, positive predictive value =55%, negative predictive value =79%, diagnostic odds ratio =4.64, area under receiver operated characteristics curve =.72). Group level analysis found no evidence suggesting any of the potential confounding variables significantly impacted the overall performance. SIGNIFICANCE: These results provide evidence that the set of biomarkers could provide additional value to clinical decision-making, providing the foundation for a decision support tool that could reduce diagnostic delay and misdiagnosis rates. Future work should therefore assess the change in diagnostic yield and time to diagnosis when utilizing these biomarkers in carefully designed prospective studies.
Subject(s)
Electroencephalography , Epilepsy , Humans , Electroencephalography/methods , Female , Retrospective Studies , Male , Epilepsy/diagnosis , Epilepsy/physiopathology , Case-Control Studies , Adult , Middle Aged , Young Adult , Adolescent , Aged , Child , Biomarkers , Child, Preschool , Sensitivity and SpecificityABSTRACT
Occupied between ~10,300 and 9300 years ago, the Pre-Pottery Neolithic site of Asikli Höyük in Central Anatolia went through early phases of sheep domestication. Analysis of 629 mitochondrial genomes from this and numerous sites in Anatolia, southwest Asia, Europe, and Africa produced a phylogenetic tree with excessive coalescences (nodes) around the Neolithic, a potential signature of a domestication bottleneck. This is consistent with archeological evidence of sheep management at Asikli Höyük which transitioned from residential stabling to open pasturing over a millennium of site occupation. However, unexpectedly, we detected high genetic diversity throughout Asikli Höyük's occupation rather than a bottleneck. Instead, we detected a tenfold demographic bottleneck later in the Neolithic, which caused the fixation of mitochondrial haplogroup B in southwestern Anatolia. The mitochondrial genetic makeup that emerged was carried from the core region of early Neolithic sheep management into Europe and dominates the matrilineal diversity of both its ancient and the billion-strong modern sheep populations.
Subject(s)
Genome, Mitochondrial , Animals , Sheep/genetics , Phylogeny , Sheep, Domestic/genetics , Turkey , AfricaABSTRACT
A rise in the disinfection of spaces occurred as a result of the COVID-19 pandemic as well as an increase in people wearing facial coverings. Hydrogen peroxide was among the recommended disinfectants for use against the virus. Previous studies have investigated the emissions of hydrogen peroxide associated with the disinfection of spaces and masks; however, those studies did not focus on the emitted byproducts from these processes. Here, we simulate the disinfection of an indoor space with H2O2 while a person wearing a face mask is present in the space by using an environmental chamber with a thermal manikin wearing a face mask over its breathing zone. We injected hydrogen peroxide to disinfect the space and utilized a chemical ionization mass spectrometer (CIMS) to measure the primary disinfectant (H2O2) and a Vocus proton transfer reaction time-of-flight mass spectrometer (Vocus PTR-ToF-MS) to measure the byproducts from disinfection, comparing concentrations inside the chamber and behind the mask. Concentrations of the primary disinfectant and the byproducts inside the chamber and behind the mask remained elevated above background levels for 2-4 h after disinfection, indicating the possibility of extended exposure, especially when continuing to wear the mask. Overall, our results point toward the time-dependent impact of masks on concentrations of disinfectants and their byproducts and a need for regular mask change following exposure to high concentrations of chemical compounds.
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OBJECTIVE: The PN Naloxone Nasal Swab (Pocket Naloxone Corp., Bethesda, MD) is a swab optimized for drug delivery and intended for use by non-medical personnel for the emergency treatment of opioid overdose. The aim of this study (PNC-20-003) is to determine the safety of this nasal swab in a real-world environment. METHODS: This was a single-institution, quantitative-qualitative prospective trial performed at an outpatient clinic. Patients with normal or abnormal nasal structure were recruited. A non-medically trained individual placed the nasal (soaked in fluorescein dye) on each side of the patient's nose. Endoscopy with recording was performed before and after swab placement. An independent reviewer rated degree of staining, mucosal bleeding, and trauma at nasal subsites. RESULTS: Videos from 32 nasal cavities (16 participants) were reviewed. All cavities had high intensity staining at the septum and the inferior turbinate. No patients had staining within the middle meatus, agger nasi, or olfactory regions. In patients with normal anatomy, obstructive nasal anatomy or prior nasal surgery, all cavities had staining near the nasal septum. Only 7 cavities (22 %) had minor bleeding defined as ooze that stopped in 1-2min, and 3 (9 %) had minor trauma defined as mucosal disruption less than 5mm. There were no significant differences in comparing pre- and post-swab nasal cavity, trauma, or bleeding exams. CONCLUSIONS: These study results showed that this swab is atraumatic to the nasal mucosal membranes when administered by non-medical personnel. Analysis suggests contact with targeted sites for drug absorption regardless of anatomy.
Subject(s)
Administration, Intranasal , Drug Delivery Systems , Humans , Male , Female , Adult , Middle Aged , Drug Delivery Systems/methods , Prospective Studies , Naloxone/administration & dosage , Naloxone/therapeutic use , Young Adult , Narcotic Antagonists/therapeutic use , Narcotic Antagonists/administration & dosage , Nasal Cavity , Opiate OverdoseABSTRACT
The impact of partial and full COVID lockdowns in 2020 on vehicle miles traveled (VMT) in Kuwait was estimated using data extracted from the Directions API of Google Maps and a Python script running as a cronjob. This approach was validated by comparing the predictions based on the app to measuring traffic flows for 1 week across four road segments considered in this study. VMT during lockdown periods were compared to VMT for the same calendar weeks before the pandemic. NOx emissions were estimated based on VMT and were used to simulate the spatial patterns of NOx concentrations using an air quality model (AERMOD). Compared to pre-pandemic periods, VMT was reduced by up to 25.5% and 42.6% during the 2-week partial and full lockdown episodes, respectively. The largest reduction in the traffic flow rate occurred during the middle of these 2-week periods, when the traffic flow rate decreased by 35% and 49% during the partial and full lockdown periods, respectively. The AERMOD simulation results predicted a reduction in the average maximum concentration of emissions directly related to VMT across the region by up to 38%, with the maximum concentration shifting to less populous residential areas as a result of the lockdown.
Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Vehicle Emissions/analysis , Particulate Matter/analysis , Pandemics , Environmental Monitoring/methods , Air Pollution/analysisABSTRACT
The United States Environmental Protection Agency (USEPA) uses the lethal dose 50% (LD50) value from in vivo rat acute oral toxicity studies for pesticide product label precautionary statements and environmental risk assessment (RA). The Collaborative Acute Toxicity Modeling Suite (CATMoS) is a quantitative structure-activity relationship (QSAR)-based in silico approach to predict rat acute oral toxicity that has the potential to reduce animal use when registering a new pesticide technical grade active ingredient (TGAI). This analysis compared LD50 values predicted by CATMoS to empirical values from in vivo studies for the TGAIs of 177 conventional pesticides. The accuracy and reliability of the model predictions were assessed relative to the empirical data in terms of USEPA acute oral toxicity categories and discrete LD50 values for each chemical. CATMoS was most reliable at placing pesticide TGAIs in acute toxicity categories III (>500-5000 mg/kg) and IV (>5000 mg/kg), with 88% categorical concordance for 165 chemicals with empirical in vivo LD50 values ≥ 500 mg/kg. When considering an LD50 for RA, CATMoS predictions of 2000 mg/kg and higher were found to agree with empirical values from limit tests (i.e., single, high-dose tests) or definitive results over 2000 mg/kg with few exceptions.
Subject(s)
Computer Simulation , Pesticides , Quantitative Structure-Activity Relationship , Toxicity Tests, Acute , United States Environmental Protection Agency , Animals , Risk Assessment , Pesticides/toxicity , Lethal Dose 50 , Rats , Administration, Oral , Toxicity Tests, Acute/methods , United States , Reproducibility of ResultsABSTRACT
Since the 1940s, patch tests in healthy volunteers (Human Predictive Patch Tests, HPPTs) have been used to identify chemicals that cause skin sensitization in humans. Recently, we reported the results of a major curation effort to support the development of OECD Guideline 497 on Defined Approaches (DAs) for skin sensitization (OECD in Guideline No. 497: Defined Approaches on Skin Sensitisation, 2021a. https://doi.org/10.1787/b92879a4-en ). In the course of this work, we compiled and published a database of 2277 HPPT results for 1366 unique test substances (Strickland et al. in Arch Toxicol 97:2825-2837, 2023. https://doi.org/10.1007/s00204-023-03530-3 ). Here we report a detailed analysis of the value of HPPT data for classification of chemicals as skin sensitizers under the United Nations' Globally Harmonized System of Classification and Labelling of Chemicals (GHS). As a result, we propose the dose per skin area (DSA) used for classification by the GHS to be replaced by or complemented with a dose descriptor that may better reflect sensitization incidence [e.g., the DSA causing induction of sensitization in one individual (DSA1+) or the DSA leading to an incidence of induction in 5% of the tested individuals (DSA05)]. We also propose standardized concepts and workflows for assessing individual HPPT results, for integrating multiple HPPT results and for using them in concert with Local Lymph Node Assay (LLNA) data in a weight of evidence (WoE) assessment. Overall, our findings show that HPPT results are often not sufficient for deriving unambiguous classifications on their own. However, where they are, the resulting classifications are reliable and reproducible and can be integrated well with those from other skin sensitization data, such as the LLNA.
Subject(s)
Dermatitis, Allergic Contact , Humans , Patch Tests , Dermatitis, Allergic Contact/etiology , Allergens/toxicity , Skin , Local Lymph Node AssayABSTRACT
Given the increasing prevalence of tick-borne diseases, such as Lyme disease, modeling the population and infection dynamics of tick vectors is an important public health tool. These models have applications for testing the effects of control methods or climate change on tick populations. There is an established history of tick population models, but code for them is rarely shared, especially not in a convenient format for others to modify and use. We present an R package, called IxPopDyMod, intended to function as a flexible and consistent framework for reproducible Ixodidae (hard-bodied ticks) population dynamics models. Here we focus on two key parts of the package: a function to create valid model configurations and a function to run a configured model and return the daily population over time. We provide three examples in appendices: one reproducing an existing Ixodes scapularis population model, one providing a novel Dermacentor albipictus model, and one showing Borrelia burgdorferi infection in ticks. Together these examples show the flexibility of the package to model scenarios of interest to tick researches.
Subject(s)
Borrelia burgdorferi , Ixodes , Ixodidae , Lyme Disease , Tick-Borne Diseases , Animals , Lyme Disease/epidemiology , Tick-Borne Diseases/epidemiology , PrevalenceABSTRACT
The pediatric endocrinology (PE) workforce in the United States is struggling to sustain an adequate, let alone optimal, workforce capacity. This article, one of a series of articles in a supplement to Pediatrics, focuses on the pediatric subspecialty workforce and furthers previous evaluations of the US PE workforce to model the current and future clinical PE workforce and its geographic distribution. The article first discusses the children presenting to PE care teams, reviews the current state of the PE subspecialty workforce, and presents projected headcount and clinical workforce equivalents at the national, census region, and census division level on the basis of a subspecialty workforce supply model through 2040. It concludes by discussing the educational and training, clinical practice, policy, and future workforce research implications of the data presented. Data presented in this article are available from the American Board of Pediatrics, the National Resident Matching Program, and the subspecialty workforce supply model. Aging, part-time appointments, and unbalanced geographic distribution of providers diminish the PE workforce capacity. In addition, limited exposure, financial concerns, and lifestyle perceptions may impact trainees. Additional workforce challenges are the subspecialty's increasingly complex cases and breadth of conditions treated, reliance on international medical graduates to fill fellowship slots, and high relative proportion of research careers. The recent limitations on pediatric endocrinologists providing gender-affirming care may also impact the geographic distribution of the subspecialty's workforce. Deliberate actions need to be taken now to continue serving the needs of children.
Subject(s)
Child Health , Pediatricians , Humans , Child , Aging , Dietary Supplements , WorkforceABSTRACT
Methane emission estimates for oil and gas facilities are typically based on estimates at a subpopulation of facilities, and these emission estimates are then extrapolated to a larger region or basin. Basin-level emission estimates are then frequently compared with basin-level observations. Methane emissions from oil and gas systems are inherently variable and intermittent, which make it difficult to determine whether a sample population is sufficiently large to be representative of a larger region. This work develops a framework for extrapolation of emission estimates using the case study of an operator in the Green River Basin. This work also identifies a new metric, the capture ratio, which quantifies the extent to which sources are represented in the sample population, based on the skewness of emissions for each source. There is a strong correlation between the capture ratio and extrapolation error, which suggests that understanding source-level emissions distributions can mitigate error when sample populations are selected and extrapolating measurements. The framework and results from this work can inform the selection and extrapolation of site measurements when developing methane emission inventories and establishing uncertainty bounds to assess whether inventory estimates are consistent with independent large spatial-scale observations.