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Abstract Surgery remains the primary treatment modality in the management of early-stage invasive breast cancer. Artificial intelligence (AI)-powered visualization platforms offer the compelling potential to aid surgeons in evaluating the tumor’s location and morphology within the breast and accordingly optimize their surgical approach. We sought to validate an AI platform that employs dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to render three-dimensional (3D) representations of the tumor and 5 additional chest tissues, offering clear visualizations as well as functionalities for quantifying tumor morphology, tumor-to-landmark structure distances, excision volumes, and approximate surgical margins. This retrospective study assessed the visualization platform’s performance on 100 cases with ground-truth labels vetted by 2 breast-specialized radiologists. We assessed features including automatic AI-generated clinical metrics (e.g., tumor dimensions) as well as visualization tools including convex hulls at desired margins around the tumor to help visualize lumpectomy volume. The statistical performance of the platform’s automated features was robust and within the range of inter-radiologist variability. These detailed 3D tumor and surrounding multi-tissue depictions offer both qualitative and quantitative comprehension of cancer topology and may aid in formulating an optimal surgical approach for breast cancer treatment. We further establish the framework for broader data integration into the platform to enhance precision cancer care.

Summary: Complement proteins contribute to neurodegeneration in Alzheimer’s disease (AD) and are secreted by glia surrounding beta-amyloid (Aβ) plaques. We present an optimized protocol for Aβ plaque detection with tyramide-digoxigenin signal amplification. This is combined with a multiplex mRNA fluorescence in situ hybridization (FISH) panel to assay glial-specific complement expression proximal to Aβ plaques in TauPS2APP mice. We describe steps for tissue preparation and mRNA detection. We then detail steps for the detection of Aβ plaques, image acquisition, and analysis. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Summary: Background: Schizophrenia, a debilitating psychiatric disorder, displays considerable interindividual variation in clinical presentations. The ongoing debate revolves around whether this heterogeneity signifies a continuum of severity linked to a singular causative factor or a collection of distinct subtypes with unique origins. Within the realm of schizophrenia, the functional impairment of GluN2A, a subtype of the NMDA receptor, has been associated with an elevated risk. Despite GluN2A’s expression across various neuronal types throughout the brain, its specific contributions to schizophrenia and its involvement in particular cell types or brain regions remain unexplored. Methods: We generated age-specific, cell type-specific or brain region-specific conditional knockout mice targeting GluN2A and conducted a comprehensive analysis using tests measuring phenotypes relevant to schizophrenia. Findings: Through the induction of germline ablation of GluN2A, we observed the emergence of numerous schizophrenia-associated abnormalities in adult mice. Intriguingly, GluN2A knockout performed at different ages, in specific cell types and within distinct brain regions, we observed overlapping yet distinct schizophrenia-related phenotypes in mice. Interpretation: Our interpretation suggests that the dysfunction of GluN2A is sufficient to evoke heterogeneous manifestations associated with schizophrenia, indicating that GluN2A stands as a prominent risk factor and a potential therapeutic target for schizophrenia. Funding: This project received support from the Shanghai Municipal Science and Technology Major Project (Grant No. 2019SHZDZX02) awarded to Y.C. and the Natural Science Foundation of Shanghai (Grant No. 19ZR1468600 and 201409003800) awarded to G.Y.

Abstract The nasal and bronchial epithelium are unified parts of the respiratory tract that are affected in the monogenic disorder cystic fibrosis (CF). Recent studies have uncovered that nasal and bronchial tissues exhibit intrinsic variability, including differences in mucociliary cell composition and expression of unique transcriptional regulatory proteins which relate to germ layer origin. In the present study, we explored whether intrinsic differences between nasal and bronchial epithelial cells persist in cell cultures and affect epithelial cell functioning in CF. Comparison of air–liquid interface (ALI) differentiated epithelial cells from subjects with CF revealed distinct mucociliary differentiation states of nasal and bronchial cultures. Moreover, using RNA sequencing we identified cell type-specific signature transcription factors in differentiated nasal and bronchial epithelial cells, some of which were already poised for expression in basal progenitor cells as evidenced by ATAC sequencing. Analysis of differentiated nasal and bronchial epithelial 3D organoids revealed distinct capacities for fluid secretion, which was linked to differences in ciliated cell differentiation. In conclusion, we show that unique phenotypical and functional features of nasal and bronchial epithelial cells persist in cell culture models, which can be further used to investigate the effects of tissue-specific features on upper and lower respiratory disease development in CF.

Abstract Sea turtles are migratory with nesting and foraging areas in distinct and often widely separated habitats. Telemetry has been a vital tool for tracking sea turtle migrations between these areas, but tagging efforts are often focused on only a few large rookeries in a given region. For instance, turtle tagging in the Red Sea has been focused in the north of the basin. We tagged five green turtles (Chelonia mydas) at a nesting site in the central-southern Red Sea and tracked them for 72–243 days. During the inter-nesting period, the turtles showed high site-fidelity, with a maximum home range of 161 km2. After the nesting season, the turtles migrated up to 1100 km to five distinct foraging locations in three countries (Saudi Arabia, Sudan, and Eritrea). Movements within foraging habitats were more wide-ranging compared to inter-nesting movements, with home ranges varying between 1.19 and 931 km2. The tracking data revealed that the creation of a relatively small marine reserve could protect the critical inter-nesting habitat in the Farasan Banks. The results also highlight the need for multinational collaboration to protect migratory corridors and foraging sites of this endangered species.

Abstract Semi‐enclosed seas are often associated with elevated local threats and distinct biogeographic patterns among marine fishes, but our understanding of how fish assemblage dynamics vary in relation to relatively small semi‐enclosed seas (e.g., the Gulf of Aqaba) remains limited. Baited remote underwater video surveys (n = 111) were conducted across ~300 km of coral reef habitats in the Gulf of Aqaba and the northern Red Sea. A total of 55 predatory fish species were detected, with less than half of all species (n = 23) observed in both basins. Relative abundance patterns between the Gulf of Aqaba and the northern Red Sea were variable among taxa, but nearly twice as many predatory fish were observed per unit of effort in the northern Red Sea. In general, assemblages in both basins were dominated by three taxa (Epinephelinae, Carangidae, and Lethrinidae). Large‐bodied and threatened species were recorded at very low abundances. Multivariate analysis revealed distinct assemblage structuring of coral reef predators between the Gulf of Aqaba and the northern Red Sea. Most of the species driving these differences were recorded in both basins, but occurred at varying levels of abundance. Environmental factors were largely unsuccessful in explaining variation in assemblage structuring. These findings indicate that biological assemblages in the Gulf of Aqaba are more distinct than previously reported and that reef fish assemblage structuring can occur even within a relatively small semi‐enclosed sea. Despite inter‐basin assemblage structuring, the overall low abundance of vulnerable fish species is suggestive of overexploitation in both the Gulf of Aqaba and the northern Red Sea of Saudi Arabia. As the region surveyed is currently undergoing large‐scale coastal development, the results presented herein aim to guide spatial management and recovery plans for these coral reef systems in relation to this development.

Background: No objective radiographic scoring system exists to classify metaphyseal cone stability. Our purpose was to create a novel, systematic method to radiographically evaluate metaphyseal cone fixation based on radiographic findings suggestive of cone stability. Methods: A retrospective analysis was conducted of revision total knee arthroplasty patients (6/2015-12/2017) using porous titanium femoral or tibial metaphyseal cones in conjunction with short cemented stems (50 mm-75 mm). Minimum follow-up was 2 years. Survivorship free of aseptic loosening and reoperation, as well as radiographic evaluation using a novel cone zone scoring system were analyzed. Results: Forty-nine revision total knee arthroplasties were included in the study (12 femoral, 48 tibial cones), the majority, performed for aseptic loosening (25/49, 51%). Median follow-up was 39 months (range 25-58). Using the radiographic cone zone scoring method, >90% of all femoral cones were classified as likely stable or stable with strong, statistically significant intraclass correlations between all 3 reviewers. Similarly, >97% of all tibial cones were classified as likely stable or stable, with moderate, statistically significant intraclass correlations between all 3 reviewers. Only 1 femoral and 1 tibial cone were considered at risk of loosening. The study sample demonstrated 100% survivorship free of revision for aseptic loosening without evidence of radiographic loosening in any case. Conclusions: Using a novel systematic cone zone scoring and classification method, the overwhelming majority of femoral and tibial cones were classified as likely stable or stable, with no identified cases of aseptic loosening or related revision. Further studies are needed to validate this objective classification method.

Background:. There is limited information about minority representation throughout the plastic and reconstructive surgery (PRS) pipeline. The aim of this study was to examine trends in representation among minorities at different stages of the PRS training pathway, starting with potential candidates in high school through practicing physicians. Methods:. The PRS pipeline was defined as high school; college; medical school applicants, matriculants, and graduates; PRS residency applicants, matriculants, and active residents; and PRS practicing physicians. Racial data for each stage were obtained from the US Census and Association of American Medical Colleges. The proportion of races at each stage were divided by their US population counterpart proportions to produce representation quotients (RQs). Medians and interquartile ranges (IQRs) are reported. Mann–Whitney U tests compared RQ values within identities between successive stages. Results:. Black students had high representation in high school (RQ = 1.26 [IQR: 1.21–1.29]) but had significant, stepwise decreases in representation in subsequent stages. A similar trend was observed for Hispanic individuals, who had their highest representation in high school (1.43 [1.37–1.50]), followed by significant decreases in RQ at nearly every subsequent stage up to and including practicing physicians (0.30 [0.28–0.31). Asian individuals were overrepresented at every stage (high school RQ: 1.01 [1.00–1.03]; practicing physician RQ: 2.30 [2.27–2.32]). White individuals were underrepresented before residency but had an RQ that approximated 1 in subsequent stages. Conclusions:. Racial minorities experienced decreases in representation at each successive stage in the PRS pipeline following high school. Ongoing diversity efforts should focus on premedical recruitment and professional support for minority students.

Abstract Background Attributes defining the Social Determinants of Health (SDoH) are associated with disproportionate exposures to environmental hazards and differential health outcomes among communities. The dynamics between SDoH, disproportionate environmental exposures, and differential health outcomes are often specific to micro-geographic areas. Methods This study focused on children less than 20 years of age who lived in Douglas County, Nebraska, during 2016–2019. To assess the role of SDoH in differential exposures, we evaluated the association between SDoH metrics and criteria pollutant concentrations and the association between SDoH and pediatric asthma exacerbations to quantify the role of SDoH in differential pediatric asthma outcomes. The Bayesian Poisson regression model with spatial random effects was used to evaluate associations. Results We identified significant positive associations between the annual mean concentration of criteria pollutants (carbon monoxide, particulate matter2.5, nitrogen dioxide, sulfur dioxide) with race (Non-Hispanic Black and Hispanic/Latino), financial stability, and literacy. Additionally, there were significant positive associations between higher rates of pediatric asthma emergency department visits and neighborhoods with more Non-Hispanic Black children, children without health insurance coverage, and households without access to a vehicle. Conclusions Non-Hispanic Black and Hispanic/Latino children living in Douglas County, NE experience disproportionately higher exposure to criteria pollutant concentrations. Additionally, higher rates of asthma exacerbations among Non-Hispanic Black children could be due to reduced access to respiratory care that is potentially the result of financial instability and vehicle access. These results could inform city planners and health care providers to mitigate respiratory risks among these higher at-risk populations.

Abstract Background Hawksbill turtles (Eretmochelys imbricata) are Critically Endangered throughout their global range, and concerningly little is known about this species in the Red Sea. With large-scale coastal development projects underway in the northern Red Sea, it is critical to understand the movement and habitat use patterns of hawksbill turtles in this environmentally unique region, so that effective conservation strategies can be implemented. We satellite tagged three hawksbill turtles, one 63 cm curved carapace length adult male captured near Wahlei Island, one 55 cm turtle captured in the Gulf of Aqaba, and one 56 cm turtle suffering from a floating syndrome which was captured at Waqqadi Island, rehabilitated, and released at Waqqadi Island. Turtles were tracked for 156, 199, and 372 days between October 2020 and November 2021. Results We calculated the home ranges and core use areas of hawksbill turtles using kernel-density estimations and found that each turtle showed high fidelity to their foraging sites. Home ranges calculated with GPS-derived locations ranged between 13.6 and 2.86 km2, whereas home ranges calculated with Argos-derived locations ranged from 38.98 to 286.45 km2. GPS-derived locations also revealed a higher proportion of time spent in coral and rock habitats compared to Argos, based on location overlap with the Allen Coral Reef Atlas. We also found that turtles were making shallow dives, usually remaining between 0 and 5 m. Conclusions While the number of tracked turtles in this study was small, it represents an important contribution to the current understanding of spatial ecology among foraging hawksbill turtles globally, and provides the first-ever reported hawksbill turtle tracking data from the Red Sea. Our results suggest that protecting coral reef habitats and implementing boating speed limits near reefs could be effective conservation measures for foraging hawksbill turtles in the face of rapid coastal development.

Tumor progression locus 2 (TPL2) (MAP3K8) is a central signaling node in the inflammatory response of peripheral immune cells. We find that TPL2 kinase activity modulates microglial cytokine release and is required for microglia-mediated neuron death in vitro. In acute in vivo neuroinflammation settings, TPL2 kinase activity regulates microglia activation states and brain cytokine levels. In a tauopathy model of chronic neurodegeneration, loss of TPL2 kinase activity reduces neuroinflammation and rescues synapse loss, brain volume loss, and behavioral deficits. Single-cell RNA sequencing analysis indicates that protection in the tauopathy model was associated with reductions in activated microglia subpopulations as well as infiltrating peripheral immune cells. Overall, using various models, we find that TPL2 kinase activity can promote multiple harmful consequences of microglial activation in the brain including cytokine release, iNOS (inducible nitric oxide synthase) induction, astrocyte activation, and immune cell infiltration. Consequently, inhibiting TPL2 kinase activity could represent a potential therapeutic strategy in neurodegenerative conditions.

Many children and adolescents with congenital and acquired heart disease (CHD) are physically inactive and participate in an insufficient amount of moderate-to-vigorous intensity exercise. Although physical activity (PA) and exercise interventions are effective at improving short- and long-term physiological and psychosocial outcomes in youth with CHD, several barriers including resource limitations, financial costs, and knowledge inhibit widespread implementation and dissemination of these beneficial programs. New and developing eHealth, mHealth, and remote monitoring technologies offer a potentially transformative and cost-effective solution to increase access to PA and exercise programs for youth with CHD, yet little has been written on this topic. In this review, a cardiac exercise therapeutics (CET) model is presented as a systematic approach to PA and exercise, with assessment and testing guiding three sequential PA and exercise intervention approaches of progressive intensity and resource requirements: (1) PA and exercise promotion within a clinical setting; (2) unsupervised exercise prescription; and (3) medically supervised fitness training intervention (i.e., cardiac rehabilitation). Using the CET model, the goal of this review is to summarize the current evidence describing the application of novel technologies within CET in populations of children and adolescents with CHD and introduce potential future applications of these technologies with an emphasis on improving equity and access to patients in low-resource settings and underserved communities.

Drought is considered among the most devastating climate hazards impacting civilizations, including human health, throughout history. It causes cumulative damages based on the five generally categorized meteorological, hydrological, agricultural, socioeconomic, and ecological droughts. Reducing damages at the local, regional, and global levels requires a better understanding of human (health) vulnerability to drought. While there are different studies to distinguish and measure vulnerabilities for the five aforementioned conditions, there is minimal effort to identify vulnerabilities to health impacts from drought. Our study aims to develop an analysis of vulnerability for Nebraska based on the established health effects associated with drought. We considered vulnerability as the interaction between exposure to drought and different sensitivity measures for a timespan, including the highest drought levels in the 21st century. To calculate the total sensitivities, we extracted ten initial variables and applied two well-known methods of dimensionality reduction and (Weighted) Additive Overlays of percentile-ranked values. The result showed the inadequacy of the former method for our study. We also grouped the sensitivity variables into socioeconomic, environmental, and water-related intervention categories and developed related intensity maps showing different spatial patterns. We calculated the drought exposure levels by adding the intensity, duration, and frequency of drought over the study period (2012–2016) and developed total vulnerability maps to determine the ten most vulnerable counties, of which nine are rural. The resulting three intervention category maps can help related experts find priority areas within Nebraska, and the final vulnerability maps can help distinguish the areas of concern for general state-wide planning. While the results and some sensitivity variables are unique to Nebraska, the provided framework and the inclusion of two different methods can guide other regions in similar studies.

Low frequency acoustic methods are a common tool for seabed stratigraphy mapping. Due to the efficiency in seabed mapping compared to geotechnical methods, estimating geotechnical sediment properties from acoustic surveying is attractive for many applications. In this study, co-located geotechnical and geoacoustic measurements of different seabed sediment types in shallow water environments (su < 3 kPa) and loose sands (~20% relative density). This is a step towards validating the ability of acoustic methods to capture geotechnical properties in the topmost seabed layers.

Abstract Background Reef manta ray (Mobula alfredi) populations along the Northeastern African coastline are poorly studied. Identifying critical habitats for this species is essential for future research and conservation efforts. Dungonab Bay and Mukkawar Island National Park (DMNP), a component of a UNESCO World Heritage Site in Sudan, hosts the largest known M. alfredi aggregation in the Red Sea. Methods A total of 19 individuals were tagged using surgically implanted acoustic tags and tracked within DMNP on an array of 15 strategically placed acoustic receivers in addition to two offshore receivers. Two of these acoustically monitored M. alfredi were also equipped with satellite linked archival tags and one individual was fitted with a satellite transmitting tag. Together, these data are used to describe approximately two years of residency and seasonal shifts in habitat use. Results Tagged individuals were detected within the array on 96% of monitored days and recorded an average residence index of 0.39 across all receivers. Detections were recorded throughout the year, though some individuals were absent from the receiver array for weeks or months at a time, and generalized additive mixed models showed a clear seasonal pattern in presence with the highest probabilities of detection occurring in boreal fall. The models indicated that M. alfredi presence was highly correlated with increasing chlorophyll-a levels and weakly correlated with the full moon. Modeled biological factors, including sex and wingspan, had no influence on animal presence. Despite the high residency suggested by acoustic telemetry, satellite tag data and offshore acoustic detections in Sanganeb Atoll and Suedi Pass recorded individuals moving up to 125 km from the Bay. However, all these individuals were subsequently detected in the Bay, suggesting a strong degree of site fidelity at this location. Conclusions The current study adds to growing evidence that M. alfredi are highly resident and site-attached to coastal bays and lagoons but display seasonal shifts in habitat use that are likely driven by resource availability. This information can be used to assist in managing and supporting sustainable ecotourism within the DMNP, part of a recently designated UNESCO World Heritage Site.

Abstract Ecological disturbance regimes across the globe are being altered via direct and indirect human influences. Biodiversity loss at multiple scales can be a direct outcome of these shifts. Fire, especially in dry forests, is an ecological disturbance that is experiencing dramatic changes due to climate change, fire suppression, increased human population in fire‐prone areas, and alterations to vegetation composition and structure. Dry western conifer forests that historically experienced frequent, low‐severity fires are now increasingly burning at high severity. Relatively little work has been done looking at the effects of this novel disturbance type on affected plant communities, and little is known about how these impacts change over time. To fill in these knowledge gaps, we examined a fire that burned in a yellow pine and mixed conifer forest in the central Sierra Nevada in California, USA. We sampled at five time steps across the nine years following the fire (1, 3, 5, 8, and 9 years postfire). We found a generally unimodal relationship between fire severity and plant alpha and gamma diversity, but found that areas that burned at high severity supported progressively lower plant diversity as time since fire increased. Similarly, beta diversity decreased drastically through time for the high‐severity areas, while remaining more static in the other severity classes. The combination of these findings indicates that significant floristic homogenization can result from high‐severity fire in this ecosystem type. We also saw consistently lower diversity in unburned areas in comparison to area burned at low and moderate severity, underlining that both lack of fire and high‐severity fire can have negative impacts on postfire plant diversity. Unburned areas that experienced forest thinning after the first sample year saw an increase in plant diversity over time, suggesting that some—but not all—of the effects of fire on plant diversity can be approximated through forest management.

Background: Current literature does not provide conclusive evidence on whether routine pathologic examination of femoral heads from total hip arthroplasty is indicated or cost-effective. As a result, there is substantial variation in opinion among surgeons related to this issue. Our study aim was to determine factors that impact surgeon propensity to order pathologic examination of femoral heads. Methods: A 12-question survey was created to evaluate surgeon practices, indications, and patient care implications surrounding routine pathologic examination of femoral heads. The email survey was distributed to all members of the American Association of Hip and Knee Surgeons (n = 2598). Results: There were 572 survey respondents. Out of all respondents, 28.4% always send femoral heads to pathology, and 27.6% reported an institutional requirement to do so. Of the 572 surgeons, 73.6% report femoral head pathology has never resulted in a change in patient disease course. Factors that increase the likelihood of surgeons ordering femoral head pathologic examination include institutional requirements, medicolegal concern, and prior experience with femoral head pathologic examination changing patients' disease course (P < .001). Cost concern decreases the likelihood of surgeons ordering femoral head pathologic examination (P = .0012). Conclusions: A minority of surgeons routinely send femoral heads from total hip arthroplasty for pathologic examination, mostly because of institutional requirement. The majority of surgeons feel that femoral head pathologic examination never changes patient management, although others have infrequently detected malignancy and infection. Institutional policy, concern for litigation, and prior experience with discordant pathologic diagnoses increase femoral head pathologic examinations, while cost concern decreases them.

Background Cystic fibrosis (CF) is a rare hereditary disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Recent therapies enable effective restoration of CFTR function of the most common F508del CFTR mutation. This shifts the unmet clinical need towards people with rare CFTR mutations such as nonsense mutations, of which G542X and W1282X are most prevalent. CFTR function measurements in patient-derived cell-based assays played a critical role in preclinical drug development for CF and may play an important role to identify new drugs for people with rare CFTR mutations. Methods Here, we miniaturised the previously described forskolin-induced swelling (FIS) assay in intestinal organoids from a 96-well to a 384-well plate screening format. Using this novel assay, we tested CFTR increasing potential of a 1400-compound Food and Drug Administration (FDA)-approved drug library in organoids from donors with W1282X/W1282X CFTR nonsense mutations. Results The 384-well FIS assay demonstrated uniformity and robustness based on coefficient of variation and Z’-factor calculations. In the primary screen, CFTR induction was limited overall, yet interestingly, the top five compound combinations that increased CFTR function all contained at least one statin. In the secondary screen, we indeed verified that four out of the five statins (mevastatin, lovastatin, simvastatin and fluvastatin) increased CFTR function when combined with CFTR modulators. Statin-induced CFTR rescue was concentration-dependent and W1282X-specific. Conclusions Future studies should focus on elucidating genotype specificity and mode-of-action of statins in more detail. This study exemplifies proof of principle of large-scale compound screening in a functional assay using patient-derived organoids.

Abstract Climate change is known to increase the frequency and intensity of hot days (daily maximum temperature ≥30°C), both globally and locally. Exposure to extreme heat is associated with numerous adverse human health outcomes. This study estimated the burden of heat‐related illness (HRI) attributable to anthropogenic climate change in North Carolina physiographic divisions (Coastal and Piedmont) during the summer months from 2011 to 2016. Additionally, assuming intermediate and high greenhouse gas emission scenarios, future HRI morbidity burden attributable to climate change was estimated. The association between daily maximum temperature and the rate of HRI was evaluated using the Generalized Additive Model. The rate of HRI assuming natural simulations (i.e., absence of greenhouse gas emissions) and future greenhouse gas emission scenarios were predicted to estimate the HRI attributable to climate change. Over 4 years (2011, 2012, 2014, and 2015), we observed a significant decrease in the rate of HRI assuming natural simulations compared to the observed. About 3 out of 20 HRI visits are attributable to anthropogenic climate change in Coastal (13.40% [IQR: −34.90,95.52]) and Piedmont (16.39% [IQR: −35.18,148.26]) regions. During the future periods, the median rate of HRI was significantly higher (78.65%: Coastal and 65.85%: Piedmont), assuming a higher emission scenario than the intermediate emission scenario. We observed significant associations between anthropogenic climate change and adverse human health outcomes. Our findings indicate the need for evidence‐based public health interventions to protect human health from climate‐related exposures, like extreme heat, while minimizing greenhouse gas emissions.

Although females have a higher rate of primary total joint arthroplasty (TJA), males have a higher rate of revision. The literature lacks studies examining the relationship between sex and outcomes following single and two-stage exchange for periprosthetic joint infection (PJI). The purpose of this study was to examine if differences exist in outcomes following revision for chronic PJI between sexes. A retrospective review was performed on all patients with an MSIS confirmed PJI who underwent a single or two-stage exchange at our institution from January 2010 to January 2021. Patient demographics, comorbidity characteristics, and outcomes were collected and compared between males and females. The primary outcome variable was disease-free survival at 1 year following definitive revision. Multivariable logistic regression analysis was performed to determine risk factors for failure. Of the 470 patients meeting final eligibility criteria, 250 were male and 226 were female (2 males and 4 females had a joint infection of either the contralateral side or a different joint and were treated as separate records). Of the patients in the cohort, 80% of the males (200/250) and 80% of the females (181/226) were found to be disease-free at 1-year follow-up (p > 0.99). Multivariable logistic regression analysis showed that nicotine use and diabetes, but not sex, were significant predictors of failure. Our study did not find a relationship between sex and outcome of revision for PJI. Further research is required to determine whether differences exist between males and females in the expression of PJI and outcomes following treatment.

Background: The COVID-19 pandemic led to cancelation of all elective surgeries for a time period in the vast majority of the United States. We compiled a questionnaire to determine the physical and mental toll of this delay on elective total joint arthroplasty patients. Methods: All patients whose primary or revision total hip or knee arthroplasty was canceled because of the COVID-19 pandemic at a large academic-private practice were identified. An 11-question survey was administered to these patients via email. All data were deidentified and stored in a REDCAP database. Results: Of 367 total patients identified, 113 responded to the survey. Seventy-seven percent of patients had their surgery postponed at least 5 weeks, and 20% were delayed longer than 12 weeks. Forty-one percent of patients reported an average visual analog scale pain score greater than 7.5. Forty percent of respondents experienced increased anxiety during the delay. Thirty-four percent of patients felt their surgery was not elective. Sixteen percent experienced a fall during the delay, and 1 patient sustained a hip fracture. Level of pain reported was significantly associated with negative emotions, negative effects of delay, and whether patients felt their surgery was indeed elective. Seventy-six percent reported trust in their surgeon’s judgment regarding appropriate timing of surgery. Communication was listed as the number one way in which patients felt their surgeon could have improved during this time. Conclusion: Surgical delay due to the COVID-19 pandemic resulted in increased pain and anxiety for many total joint arthroplasty patients. While most patients maintained trust in their surgeon during the delay, methods to improve communication may benefit the patient experience in future delays. Level of Evidence: Level II.

Background: There is mounting evidence that smoking, abnormal body mass index (BMI), uncontrolled diabetes, and poor nutritional status are associated with complications after total hip arthroplasty (THA). The goal of the present study was to evaluate the consequences of failure to medically optimize Medicare-eligible patients with respect to these key modifiable health targets by assessing complications in the early postoperative period after THA. Methods: The National Surgical Quality Improvement Program database was queried for all primary THAs performed in 2018. Data were collected on preoperative serum albumin, BMI, diabetes, and tobacco use as well as postoperative infections, readmissions, complications, and mortality. We identified 47,924 THA patients with a median BMI of 29 kg/m2 and age of 72 years, and 60% of whom were female. Results: We found that preoperative albumin

The world’s largest extant fish, the whale shark Rhincodon typus, is one of the most-studied species of sharks globally. The discovery of predictable aggregation sites where these animals gather seasonally or are sighted year-round – most of which are coastal and juvenile-dominated – has allowed for a rapid expansion of research on this species. The most common method for studying whale sharks at these sites is photographic identification (photo-ID). This technique allows for long-term individual-based data to be collected which can, in turn, be used to evaluate population structure, build population models, identify long-distance movements, and assess philopatry and other population dynamics. Lagged identification rate (LIR) models have fewer underlying assumptions than more traditional capture mark recapture approaches, making them more broadly applicable to marine taxa, especially far-ranging megafauna species like whale sharks. However, the increased flexibility comes at a cost. Parameter estimations based on LIR can be difficult to interpret and may not be comparable between areas with different sampling regimes. Using a unique data-set from the Philippines with ~8 years of nearly continuous survey effort, we were able to derive a metric for converting LIR residency estimates into more intuitive days-per-year units. We applied this metric to 25 different sites allowing for the first quantitatively-meaningful comparison of sightings-derived residence among the world’s whale shark aggregations. We validated these results against the only three published acoustic residence metrics (falling within the ranges established by these earlier works in all cases). The results were then used to understand residency behaviours exhibited by the sharks at each site. The adjusted residency metric is an improvement to LIR-based population modelling, already one of the most widely used tools for describing whale shark aggregations. The standardised methods presented here can serve as a valuable tool for assessing residency patterns of whale sharks, which is crucial for tailored conservation action, and can cautiously be tested in other taxa.

Background: There is considerable disparity in institutional practices surrounding routine pathologic examination of femoral heads removed during total hip arthroplasty (THA). Multiple groups have studied the merits of routine femoral head pathology in THA, without clear consensus. We sought to further investigate the existing evidence on routine pathologic examination of femoral heads retrieved during THA to determine if this practice provides additional clinical value and is cost-effective. Material and methods: To conduct a systematic review of the literature, a medical librarian was consulted to develop and perform comprehensive searches in PubMed (1809-present), Embase (embase.com 1974-present), CINAHL (EBSCO, 1937-present), and the Cochrane Central Register of Controlled Trials (Wiley). Final searches resulted in 727 references. Through multiple reviewer screenings and assessments of eligible full-text articles, we included 14 articles for review. Results: Our systematic review yielded pathologic examination results from 17,388 femoral head specimens collected during THA. In 0.85% of cases, the pathologic diagnosis differed in a meaningful way from the preoperative clinical diagnosis. Routine pathology changed patient management in approximately 0.0058% of cases. The average cost for pathologic examination of each specimen was $126.38. Conclusion: Routine pathologic examination of femoral heads retrieved during THA has limited impact on patient management. With an estimated 500,000 THAs performed in 2019, the economic feasibility of routine femoral head pathology is limited at an annual cost of up to $63,000,000 and cost per quality-adjusted life-year approaching infinity. However, surgeon discretion on a patient-specific or practice-specific basis should be used to make the final determination on the need for femoral head pathology.

Background: The prevalence of an abnormal spinopelvic relationship in patients presenting for primary total hip arthroplasty (THA) is not well known. The purpose of this study was to identify the prevalence of abnormal spinopelvic relationships in patients presenting for primary THA. Methods: A retrospective chart review of 338 consecutive, nonselected patients undergoing primary THA from the practice of 2 fellowship-trained adult reconstruction surgeons was performed (J.E.O. and T.S.B.). Sitting and standing radiographs were measured for lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SSstand), and pelvic tilt; the sacral slope was also measured on sitting radiographs (SSsit). Patients were assessed for the presence of spinopelvic imbalance, defined as PI–LL>10°, and decreased spinopelvic motion, defined as SSstand–SSsit< 10°. Descriptive statistics were reported. Results: A cohort of 338 patients was identified; 110 were excluded. In total, 228 unique patients underwent measurement. One hundred one of 228 patients (44.3%) in the cohort were female. The mean age of the cohort was 60.0 ± 13 years, with the mean body mass index of 31 ± 7 mg/kg2. Spinopelvic imbalance (PI–LL > 10°) was present in 142 of 228 patients (62.3%). Decreased motion at the spinopelvic junction (SSstand–SSsit < 10°) was present in 78 of 228 patients (34.2%). Fifty (21.9%) patients had both spinopelvic imbalance and decreased spinopelvic motion. Conclusions: In a cohort of 228 patients presenting for primary THA, the prevalence of spinopelvic imbalance was 62.3%, the prevalence of decreased spinopelvic motion was 34.2%, and the prevalence of both spinopelvic imbalance and decreased spinopelvic motion was 22%. Hip surgeons are likely to encounter patients with abnormal spinopelvic relationships.

Chondrocytes have altered cellular metabolism in the context of osteoarthritis, but whether and how these changes are associated with inflammation is a controversial area. Here the authors show that inflammatory NF-κB signalling drives a glycolytic shift in chondrocytes and the production of ROS, which drives cartilage catabolism.

Abstract Background Little is known about the effect of drought on all-cause mortality, especially in higher income countries such as the United States. As the frequency and severity of droughts are likely to increase, understanding the connections between drought and mortality becomes increasingly important. Methods Our exposure variable was an annual cumulative drought severity score based on the 1-month, county-level Standardized Precipitation Evapotranspiration Index. The outcome variables of demographic subgroup-specific all-cause mortality count data per year were obtained from the National Vital Statistics System. Any counts below 10 deaths were censored in that demographic group per county. We modeled county-stratum-year mortality using interval-censored negative binomial regression with county-level random intercepts, for each combined age-race-sex stratum either with or without further stratification by climate regions. Fixed effects meta-regression was used to test the associations between age, race, sex, and region with the drought-mortality regression coefficients. Predictive margins were then calculated from the meta-regression model to estimate larger subgroup (e.g., ‘race’ or ‘sex’) associations of drought with mortality. Results Most of the results were null for associations between drought severity and mortality, across joint strata of race, age, sex and region, but incidence rate ratios (IRRs) for 17 subgroups were significant after accounting for the multiple testing; ten were

Abstract This study was conducted to examine, at the county level, the relationship between pediatric cancer incidence rate and atrazine and nitrate mean concentrations in surface and groundwater. A negative binomial regression analysis was performed to investigate the association between central nervous system (CNS) tumors, leukemia, lymphoma, and atrazine and nitrate mean concentrations in groundwater. The age‐adjusted brain and other CNS cancer incidence was higher than the national average in 63% of the Nebraska counties. After controlling for the counties socio‐economic status and nitrate concentrations in groundwater, counties with groundwater atrazine concentrations above 0.0002 µg/L had a higher incidence rate for pediatric cancers (brain and other CNS, leukemia, and lymphoma) compared to counties with groundwater atrazine concentrations in the reference group (0.0000–0.0002 µg/L). Additionally, compared to counties with groundwater nitrate concentrations between 0 and 2 mg/L (reference group), counties with groundwater nitrate concentrations between 2.1 and 5 mg/L (group 2) had a higher incidence rate for pediatric brain and other CNS cancers (IRR = 8.39; 95% CI: 8.24–8.54), leukemia (IRR = 7.35; 95% CI: 7.22–7.48), and lymphoma (IRR = 5.59; CI: 5.48–5.69) after adjusting for atrazine groundwater concentration and the county socio‐economic status. While these findings do not indicate a causal relationship, because other contaminants or cancer risk factors have not been accounted for, they suggest that atrazine and nitrate may pose a risk relative to the genesis of pediatric brain and CNS cancers, leukemia, and lymphoma.

The bacterial genus Myroides, like other members of the Flavobacteriaceae family, consists of aerobic, non-motile, Gram-negative bacilli. Myroides spp. is considered predominantly opportunistic pathogens as, historically, most documented infections have been in immunocompromised individuals. Along with advancements in molecular assay testing, there are growing reports of clinically relevant Myroides spp. infections in immunocompetent individuals. These organisms display broad antimicrobial resistance, and while research into their mechanisms of resistance is progressing, genetic testing has revealed metallo-β-lactamases present in their genome. The sporadic identification of Myroides spp. and ongoing clarification of resistance patterns make empiric treatment difficult. This report documents two cases of extensively drug-resistant Myroides odoratus isolated from critically ill but otherwise immunocompetent patients followed by a review of available literature on Myroides spp. antibiotic sensitivities. Our findings indicate that minocycline and moxifloxacin have the highest documented in vitro activity against Myroides spp.

Selective autophagy is a conserved subcellular process that maintains the health of eukaryotic cells by targeting damaged or toxic cytoplasmic components to the vacuole/lysosome for degradation. A key player in the initiation of selective autophagy in S. Cerevisiae (baker’s yeast) is a large adapter protein called Atg11. Atg11 has multiple predicted coiled-coil domains and intrinsically disordered regions, is known to dimerize, and binds and organizes other essential components of the autophagosome formation machinery, including Atg1 and Atg9. We performed systematic directed mutagenesis on the coiled-coil 2 domain of Atg11 in order to map which residues were required for its structure and function. Using yeast-2-hybrid and coimmunoprecipitation, we found only three residues to be critical: I562, Y565, and I569. Mutation of any of these, but especially Y565, could interfere with Atg11 dimerization and block its interaction with Atg1 and Atg9, thereby inactivating selective autophagy.

Abstract The whale shark Rhincodon typus is found throughout the world's tropical and warm‐temperate ocean basins. Despite their broad physical distribution, research on the species has been concentrated at a few aggregation sites. Comparing DNA sequences from sharks at different sites can provide a demographically neutral understanding of the whale shark's global ecology. Here, we created genetic profiles for 84 whale sharks from the Saudi Arabian Red Sea and 72 individuals from the coast of Tanzania using a combination of microsatellite and mitochondrial sequences. These two sites, separated by approximately 4500 km (shortest over‐water distance), exhibit markedly different population demographics and behavioral ecologies. Eleven microsatellite DNA markers revealed that the two aggregation sites have similar levels of allelic richness and appear to be derived from the same source population. We sequenced the mitochondrial control region to produce multiple global haplotype networks (based on different alignment methodologies) that were broadly similar to each other in terms of population structure but suggested different demographic histories. Data from both microsatellite and mitochondrial markers demonstrated the stability of genetic diversity within the Saudi Arabian aggregation site throughout the sampling period. These results contrast previously measured declines in diversity at Ningaloo Reef, Western Australia. Mapping the geographic distribution of whale shark lineages provides insight into the species’ connectivity and can be used to direct management efforts at both local and global scales. Similarly, understanding historical fluctuations in whale shark abundance provides a baseline by which to assess current trends. Continued development of new sequencing methods and the incorporation of genomic data could lead to considerable advances in the scientific understanding of whale shark population ecology and corresponding improvements to conservation policy.

The Red Sea is particularly biodiverse, hosting high levels of endemism and numerous populations whose extinction risk is heightened by their relative isolation. Elasmobranchs and sea turtles have likely suffered recent declines in this region, although data on their distribution and biology are severely lacking, especially on the eastern side of the basin in Saudi Arabian waters. Here, we present sightings of elasmobranchs and sea turtles across the north-eastern Red Sea and Gulf of Aqaba collected through a combination of survey methods. Over 455 survey hours, we recorded 407 sightings belonging to 26 elasmobranch species and two sea turtle species, more than 75% of which are of conservation concern. We identified 4 species of rays and 9 species of sharks not previously recorded in Saudi Arabia and report a range extension for the pink whipray (Himantura fai) and the round ribbontail ray (Taeniurops meyeni) into the Gulf of Aqaba. High density of sightings of conservation significance, including green and hawksbill sea turtles and halavi guitarfish were recorded in bay systems along the eastern Gulf of Aqaba and the Saudi Arabian coastline bordering the north-eastern Red Sea, and many carcharhinid species were encountered at offshore seamounts in the region. Our findings provide new insights into the distribution patterns of megafaunal assemblages over smaller spatial scales in the region, and facilitate future research and conservation efforts, amidst ongoing, large-scale coastal developments in the north-eastern Red Sea and Gulf of Aqaba.

(1) Background: Plastic pollution is a major environmental concern confronting marine animals. Sea turtles are considered a bio-indicator of plastic pollution, but there is little information regarding plastic ingestion by turtles in the Red Sea. With large-scale development projects being built along the Saudi Arabian coast, it is important to have a baseline for plastic ingestion before construction is complete. (2) Methods: Ten deceased sea turtles (four hawksbill and six green turtles) were collected along the Saudi Arabian coastline. Necropsies were conducted, and the entire gastrointestinal tracts were extracted and the contents were passed through a 1 mm mesh sieve. (3) Results: We found that 40% of the turtles in this study had ingested plastics. Thread-like plastics were the most common plastic category, and multi-colored was the most prevalent color category. (4) Conclusions: Monitoring of the plastic ingestion by marine megafauna should be conducted as a long-term assessment of the developments’ impacts. Additionally, conservation efforts should be focused on removing plastics (namely ghost nests and fishing lines) from the reefs and reducing the amount of plastic entering the sea.

Abstract Heatwaves cause excess mortality and physiological impacts on humans throughout the world, and climate change will intensify and increase the frequency of heat events. Many adaptation and mitigation studies use spatial distribution of highly vulnerable local populations to inform heat reduction and response plans. However, most available heat vulnerability studies focus on urban areas with high heat intensification by Urban Heat Islands (UHIs). Rural areas encompass different environmental and socioeconomic issues that require alternate analyses of vulnerability. We categorized Nebraska census tracts into four urbanization levels, then conducted factor analyses on each group and captured different patterns of socioeconomic vulnerabilities among resultant Heat Vulnerability Indices (HVIs). While disability is the major component of HVI in two urbanized classes, lower education, and races other than white have higher contributions in HVI for the two rural classes. To account for environmental vulnerability of HVI, we considered different land type combinations for each urban class based on their percentage areas and their differences in heat intensifications. Our results demonstrate different combinations of initial variables in heat vulnerability among urban classes of Nebraska and clustering of high and low heat vulnerable areas within the highest urbanized sections. Less urbanized areas show no spatial clustering of HVI. More studies with separation on urbanization level of residence can give insights into different socioeconomic vulnerability patterns in rural and urban areas, while also identifying changes in environmental variables that better capture heat intensification in rural settings.

Background: Readmission following total joint arthroplasty has become a closely watched metric for many hospitals in the United States due to financial penalties imposed by Centers for Medicare and Medicaid Services. The purpose of this study was to identify both preoperative and postoperative reasons for readmission within 30 days following primary total hip and total knee arthroplasty (TKA). Methods: Retrospective data were collected for patients who underwent elective primary total hip arthroplasty (THA; CPT code 27130) and TKA (27447) from 2008 to 2013 at our institution. The sample was separated into readmitted and nonreadmitted cohorts. Demography, comorbidities, Charlson comorbidity index (CCI), operative parameters, readmission rates, and causes of readmission were compared between the groups using univariate and multivariate regression analysis. Results: There were 42 (3.4%) and 28 (2.2%) readmissions within 30 days for THA and TKA, respectively. The most common cause of readmission within 30 days following total joint arthroplasty was infection. Trauma was the second most common reason for readmission of a THA while wound dehiscence was the second most common cause for readmission following TKA. With univariate regression, there were multiple associated factors for readmission among THA and TKA patients, including body mass index, metabolic equivalent (MET), and CCI. Multivariate regression revealed that hospital length of stay was significantly associated with 30-day readmission after THA and TKA. Conclusion: Patient comorbidities and preoperative functional capacity significantly affect 30-day readmission rate following total joint arthroplasty. Adjustments for these parameters should be considered and we recommend the use of CCI and METs in risk adjustment models that use 30-day readmission as a marker for quality of patient care. Level of Evidence: Level III/Retrospective cohort study

Highly mobile marine megafauna species, while widely distributed and frequently threatened, often aggregate in distinct localized habitats. Implementation of local management initiatives within these hotspots is more achievable than developing effective conservation strategies that encompass their entire distributions. Such measures have the potential for disproportionate population-level benefits but rely on a detailed understanding of spatiotemporal habitat use. To that end, we examined the residency and small-scale habitat use of 51 whale sharks (Rhincodon typus) over 5 years at an aggregation site in Tanzania using passive acoustic telemetry. Whale sharks were highly resident within and across years, with a combined maximum residency index of 0.39. Although fewer sharks were detected from March to September, residency was high throughout the year. Ancillary photographic-identification data showed that individual residency persisted before and after tag attachment. Kernel utilization distributions (KUD) and movement networks both revealed the same spatiotemporal pattern of habitat use, with a small core habitat (50% KUD area for all sharks combined = 12.99 km2) that predictably changed on a seasonal basis. Activity spaces did not differ with time of day, sex, or size of the sharks, indicating a population-level pattern driven by prey availability. The small and predictable core habitat area at this site means that site-based management options to reduce shark injuries and mortality from boat strike and fishing gear entanglement can be spatially targeted for maximum effectiveness and compliance by human users.

Background The routine use of angiotensin‐converting enzyme inhibitors (ACEI) during palliation of hypoplastic left heart syndrome is controversial. We sought to describe ACEI prescription in the interstage between stage 1 palliation (stage I Norwood procedure) discharge and stage 2 palliation (stage II superior cavopulmonary anastomosis procedure) admission using the NPC‐QIC (National Pediatric Cardiology Quality Improvement Collaborative) registry. Methods and Results Analysis of all patients (n=2180) enrolled in NPC‐QIC from 2008 to 2016 included preoperative anatomy, risk factors, and echocardiographic data. ACEI were prescribed at stage I Norwood procedure discharge in 38% of patients. ACEI prescription declined from 2011 to 2016 compared with pre‐2010 (36.8% versus 45%; P=0.005) with significant variation across centers (range 7–100%; P

Herein, we discuss a case of a 39-year-old male with hemophilia B, who developed end-stage liver disease secondary to nonalcoholic steatohepatitis, that underwent orthotopic liver transplantation (OLT) as a curative means for his liver disease and coagulation disorder. Existing case reports have demonstrated favorable outcomes in patients outside of the United States who received continuous infusions of recombinant factor IX replacement in the perioperative setting after liver transplant. Given limitations in the stability of the recombinant factor IX products in the United States, a dosing strategy was comprised of once daily bolus dosing to achieve satisfactory factor IX levels. Within 48 hours of initial surgery, the patient had sustained factor IX levels above 70% of normal and the patient required no further dosing of factor IX products to date. This strategy helped facilitate less frequent dosing as well as achieved targeted factor levels while synthetic function of the transplanted liver recovered.

Summary: NMDA receptors (NMDARs) play subunit-specific roles in synaptic function and are implicated in neuropsychiatric and neurodegenerative disorders. However, the in vivo consequences and therapeutic potential of pharmacologically enhancing NMDAR function via allosteric modulation are largely unknown. We examine the in vivo effects of GNE-0723, a positive allosteric modulator of GluN2A-subunit-containing NMDARs, on brain network and cognitive functions in mouse models of Dravet syndrome (DS) and Alzheimer’s disease (AD). GNE-0723 use dependently potentiates synaptic NMDA receptor currents and reduces brain oscillation power with a predominant effect on low-frequency (12–20 Hz) oscillations. Interestingly, DS and AD mouse models display aberrant low-frequency oscillatory power that is tightly correlated with network hypersynchrony. GNE-0723 treatment reduces aberrant low-frequency oscillations and epileptiform discharges and improves cognitive functions in DS and AD mouse models. GluN2A-subunit-containing NMDAR enhancers may have therapeutic benefits in brain disorders with network hypersynchrony and cognitive impairments. : Hanson et al. examine the therapeutic effects of enhancing GluN2A-subunit-containing NMDAR function in Dravet syndrome and Alzheimer’s disease mice. GNE-0723 treatment reduces aberrant low-frequency oscillations and epileptiform discharges and improves cognitive functions in both disease models. GluN2A NMDAR enhancers may benefit brain disorders with network hypersynchrony and cognitive impairments. Keywords: J20, epilepsy, learning, memory, APP, Nav1.1, SCN1A, interneuron, EEG, MK-801

High air pollution events spanning multiple months and caused by environmental perturbations such as droughts and wildfires are increasing in frequency, intensity and duration due to climate change. While both daily and annual exposure to fine particulate matter (PM _2.5 ) have regulatory standards in the United States, mid-scale exposure at the monthly interval remains unregulated and the public health impacts of mid-duration ambient air pollution exposure are poorly understood. These present a new public health challenge in mitigating harmful effects of persistent ambient air pollution on community health. We executed an ecological study of the associations between monthly mean PM _2.5 exposure with total, cardiovascular and respiratory mortality counts, stratified by age, sex and race, in 698 counties in the conterminous United States from 1999 to 2018. A two-stage model was used to estimate the risk and number of deaths associated with this exposure timescale reported as incidence rate ratios (IRRs) and absolute risk differences per million persons (ARDs). Increased mortality of all types was positively associated with a 10 μ g m ^−3 monthly change in PM _2.5 exposure (total mortality IRR: 1.011, 95% confidence interval (CI): (1.009, 1.013), ARD: 8.558, 95% CI: (6.869, 10.247); cardiovascular mortality IRR: 1.014, 95% CI: (1.011, 1.018), ARD: 3.716, 95% CI: (2.924, 4.509); respiratory mortality IRR: 1.016, 95% CI: (1.011, 1.023), ARD: 1.676, 95% CI: (1.261, 2.091)). Our results suggest elderly, non-black minorities and males to be the most impacted subgroups along with metropolitan and highly socially vulnerable communities. Heterogeneities in the magnitude and direction of association were also detected across climate regions of the United States. These results elucidate potential effects of monthly PM _2.5 on mortality and demonstrate a need for future health policies for this currently unregulated interval of ambient air pollution exposure.

Inhibitory interneurons play important roles in brain circuits and in several neuropsychiatric disorders. Here, the authors show that excitatory synapses onto interneurons vs. excitatory neurons differ in their ambient synaptic glutamate level, a finding with important implications for selective pharmacological targeting of inhibitory neuron NMDA receptors.

Abstract The use of generalized linear models in Bayesian phylogeography has enabled researchers to simultaneously reconstruct the spatiotemporal history of a virus and quantify the contribution of predictor variables to that process. However, little is known about the sensitivity of this method to the choice of the discrete state partition. Here we investigate this question by analyzing a data set containing 299 sequences of the West Nile virus envelope gene sampled in the United States and fifteen predictors aggregated at four spatial levels. We demonstrate that although the topology of the viral phylogenies was consistent across analyses, support for the predictors depended on the level of aggregation. In particular, we found that the variance of the predictor support metrics was minimized at the most precise level for several predictors and maximized at more sparse levels of aggregation. These results suggest that caution should be taken when partitioning a region into discrete locations to ensure that interpretable, reproducible posterior estimates are obtained. These results also demonstrate why researchers should use the most precise discrete states possible to minimize the posterior variance in such estimates and reveal what truly drives the diffusion of viruses.

Background: With the increased number of influenza cases observed during the 2017 – 2018 season, patients may be at a greater risk of cardiac related complications as a sequela of viral illness. We described the frequency of troponin elevations in patients with influenza infection during the 2017 – 2018 influenza season. Methods: This was a retrospective, single-center observational study. All patients aged 18 years or older and had laboratory confirmed influenza viral infection were included in the study. Troponins were considered elevated if greater than 0.3 ng/mL. Electronic health records were reviewed for demographics, laboratory values, coronary artery disease history, electrocardiography, echocardiography results, and incidence of inpatient mortality. Results: A total of 1,131 patients had lab confirmed influenza infection. Majority of the influenza strains were influenza A, 76.2% (n = 863), and the rest of the influenza strains comprised of influenza B, 23.8% (n = 270). Thirty three (2.9%) patients had elevation of troponin levels greater than 0.3 ng/mL. Most of the patients with elevated troponin levels had influenza A infection (90.9%, n = 30), of which H3 subtype was the most common (48.5%, n = 16). Fifteen patients (45.5%) had a myocardial infarction, 20 (60.6%) had left ventricular abnormalities visualized on echocardiogram, and four (12.1%) died while inpatient. Conclusions: Our results describe the frequency of troponin elevations in patients with influenza infection at our institution during the 2017 – 2018 influenza season. Keywords: Troponin elevations, Influenza, 2017–2018 influenza season, Myocardial infarction

Agrichemicals, chemicals used to maximize crop and animal production, can lead to water quality concerns when these chemicals run off into surface and groundwater after precipitation events. In Nebraska, one such chemical is atrazine, a suspected carcinogen. This study evaluated the association between atrazine in surface and groundwater, in relation to the incidence of pediatric cancer in Nebraska watersheds over 30 years (1 January 1987 to 31 December 2016). The watersheds were grouped into four categories based on the average atrazine concentration over the study period, using quantile classification. The associations between atrazine (ground/surface) and pediatric cancer after adjusting for social vulnerability index (SVI) variables, using pediatric population as offset, were compared using a generalized linear model (GLM) assuming a negative binomial distribution. The results from the GLM approach suggested positive associations between watersheds with higher atrazine concentration and a higher pediatric cancer incidence rate ratio. In this study, the associations were evaluated using atrazine measurements obtained from non-drinking water sources as a proxy measure. Further research is necessary to establish the causal relationship between atrazine and pediatric cancer.

Human land-use legacies have long-term effects on plant community composition and ecosystem function. While ancient and historical land use is known to affect biodiversity patterns, it is unknown whether such legacies affect other plant community properties such as the diversity of functional traits. Functional traits are a critical tool for understanding ecological communities because they give insights into community assembly processes as well as potential species interactions and other ecosystem functions. Here, we present the first systematic study evaluating how plant functional trait distributions and functional diversity are affected by ancient and historical Indigenous forest management in the Pacific Northwest. We compare forest garden ecosystems - managed perennial fruit and nut communities associated exclusively with archaeological village sites - with surrounding periphery conifer forests. We find that forest gardens have substantially greater plant and functional trait diversity than periphery forests even more than 150 years after management ceased. Forests managed by Indigenous peoples in the past now provide diverse resources and habitat for animals and other pollinators and are more rich than naturally forested ecosystems. Although ecological studies rarely incorporate Indigenous land-use legacies, the positive effects of Indigenous land use on contemporary functional and taxonomic diversity that we observe provide some of the strongest evidence yet that Indigenous management practices are tied to ecosystem health and resilience.