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Background: Geographic distance promotes phenotypic variation by facilitating environmental distance, limiting gene flow, and exposing plants to different pollen vectors. Therefore, understanding how plant morphology changes across a geographic range improves our understanding of the drivers of morphological diversification both on a macro- and micro-evolutionary scale. Questions: 1) How do geographic location and abiotic factors affect flower morphology between populations? 2) Is there a geographic pattern of flower morphology variation? and 3) How does yearly variation in temperature and precipitation affect flower morphology within populations? Studied species: Penstemon albidus, P. fruticosus, P. glandulosus, P. speciosus, and P. whippleanus Study site and dates: The continental USA, summers of 2017 and 2018 Methods: Fifty-seven populations and 496 individuals were selected at random to measure ten floral traits. Bioclimatic variables were extracted from the WorldClim database and NOAA. Linear models, partial least squares regression, Mantel tests and canonical correlation analysis were used to analyze the data. Results: Geographic variables alone explained a significant portion of the variation in flower morphology in two species, while in others, flower morphology did not vary despite large geographic distances. Penstemon albidus and P. whippleanus flowers increase in size from south-north, while P. glandulosus and P. speciosus exhibited an east-west increasing trend. Additionally, mean annual precipitation was the most important variable influencing P. glandulosusflower morphology. Conclusions: Geographic distance facilitates isolation-by-distance and isolation-by-phenology as well as abiotic differences between populations; however, other factors such as pollinators might be keeping populations morphologically homogeneous despite large geographic distance.

Purpose: To compare the incidence and visual outcomes of endophthalmitis after injection of an intravitreal dexamethasone implant and injection of intravitreal ranibizumab. Methods: This retrospective cohort study assessed endophthalmitis in eyes receiving an intravitreal injection of a 0.7 mg dexamethasone implant (DEX group), 0.5 mg ranibizumab (R5 group), or 0.3 mg ranibizumab (R3 group) between January 1, 2016, and May 31, 2018, at 2 large retina practices in the United States. Results: Suspected endophthalmitis occurred in 5 eyes after 4973 DEX injections, 43 eyes after 163 974 R5 injections, and 6 eyes after 18 954 R3 injections. Suspected endophthalmitis was significantly more common in the DEX group (1/995) than in the R5 group (1/3813) ( P = .008) but not than in the R3 group (1/3159) ( P = .10). Visual acuity outcomes were similar in the 3 groups. Conclusions: Suspected endophthalmitis might be more common after 0.7 mg dexamethasone injections than after 0.5 mg ranibizumab injections. Culture-positive endophthalmitis rates were similar across all 3 medications.

Background/Objective Investigate real-world patients receiving faricimab for the treatment of neovascular age-related macular degeneration (nAMD). Subjects/Methods Multicenter, retrospective chart review was conducted on patients treated with faricimab for nAMD from February 2022 to September 2022. Collected data includes background demographics, treatment history, best-corrected visual acuity (BCVA), anatomic changes, and adverse events as safety markers. The main outcome measures are changes in BCVA, changes in central subfield thickness (CST) and adverse events. Secondary outcome measures included treatment intervals and presence of retinal fluid. Results After one injection of faricimab, all eyes (n = 376), previously-treated (n = 337) and treatment-naïve (n = 39) eyes demonstrated a + 1.1 letter (p = 0.035), a + 0.7 letter (p = 0.196) and a + 4.9 letter (p = 0.076) improvement in BCVA, respectively, and a − 31.3 μM (p p p n = 94), previously-treated (n = 81) and treatment-naïve (n = 13) eyes demonstrated a + 3.4 letter (p = 0.03), a + 2.7 letter (p = 0.045) and a + 8.1 letter (p = 0.437) improvement in BCVA, and a − 43.4 μM (p p p Conclusions Faricimab has demonstrated improvement or maintenance of visual acuity for patients with nAMD, along with rapid improvement of anatomical parameters. It has been well-tolerated with low incidence of treatable intraocular inflammation. Future data will continue to investigate faricimab for real-world patients with nAMD.

The Palos Verdes fault zone (PVFZ) extends across the southwestern Los Angeles basin and Inner Continental Borderland, California, and is considered capable of generating large (Mw>7), damaging earthquakes with short recurrence intervals. The 110 km long fault zone is composed of vertical and moderately dipping segments that accommodate oblique, right-lateral reverse displacement. Onshore, there is a counterclockwise reorientation in the PVFZ’s strike, which produces a major restraining bend that generates the Palos Verdes Peninsula. Here, we use well and seismic reflection data to develop kinematic models that show folding of the PVFZ by the Wilmington blind thrust led to formation of the restraining bend. North of the peninsula in Santa Monica Bay, debate persists over the extent, geometry, and activity of the PVFZ. Here, we analyze a dense grid of high-resolution seismic reflection data and present a new mapping of the Santa Monica Bay segment of the PVFZ, including multiple active splays (e.g., Redondo Canyon fault zone) that occur within a broad damage zone at the northern termination of the fault system. Based on these insights and prior studies, we develop a new, comprehensive 3D model of the PVFZ including its Santa Monica Bay, San Pedro Bay, and Lasuen Knoll segments. The sizes of these segments indicate that PVFZ is capable of larger events than previously reported—Mw 7.1–7.4 for single-segment ruptures and Mw 7.4–7.8 for multisegment ruptures. Based on a reported slip rate of 1.1–5.9 mm/yr, average recurrence intervals for these single- and multisegment rupture scenarios are 580–610 and 760–1170 yr, respectively.

To review how private equity entities generate profit for investors and ophthalmologists.There is a preponderance of private equity acquisitions and consolidation in ophthalmology. These private equity entities generate revenue by growth, profit improvement, and efficient use of capital structure. Physician partners sell their revenue and assets to a private equity entity while retaining a percentage of future profit. In general, a greater percentage going forward, will result in a smaller initial buyout. Partners typically receive payment in the form of cash and stock in the private equity entity, aligning incentives of both parties to grow and succeed. Junior associates and future partners typically do not benefit from the cash buyout but might have opportunity to buy shares in the private equity entity.The ophthalmology job market has changed significantly with the rise in private equity. Private equity investors profit from organic growth, economies of scale, and future revenue of ophthalmology practices. Ophthalmology partners benefit from often sizeable buyouts and potentially profitable shares in the private equity entity. Junior and future ophthalmologist may be less likely to succeed financially compared with their contemporaries. Some private equity entities will thrive and other may fail, particularly if they are unable to attract talented new ophthalmologists.

The Energy Exascale Earth System Model (E3SM) is a state-of-the-science Earth system model (ESM) with the ability to focus horizontal resolution of its multiple components in specific areas. Regionally refined global ESMs are motivated by the need to explicitly resolve, rather than parameterize, relevant physics within the regions of refined resolution, while offering significant computational cost savings relative to the respective cost of configurations with high-resolution (HR) everywhere on the globe. In this paper, we document results from the first Arctic regionally refined E3SM configuration for the ocean and sea-ice components (E3SM-Arctic-OSI), while employing data-based atmosphere, land, and hydrology components. Our aim is an improved representation of the Arctic coupled ocean and sea-ice state, its variability and trends, and the exchanges of mass and property fluxes between the Arctic and the sub-Arctic. We find that E3SM-Arctic-OSI increases the realism of simulated Arctic ocean and sea-ice conditions compared to a similar low-resolution E3SM simulation without the Arctic regional refinement in ocean and sea-ice components (E3SM-LR-OSI). In particular, exchanges through the main Arctic gateways are greatly improved with respect to E3SM-LR-OSI. Other aspects, such as the Arctic freshwater content variability and sea-ice trends, are also satisfactorily simulated. Yet, other features, such as the upper-ocean stratification and the sea-ice thickness distribution, need further improvements, involving either more advanced parameterizations, model tuning, or additional grid refinements. Overall, E3SM-Arctic-OSI offers an improved representation of the Arctic system relative to E3SM-LR-OSI, at a fraction (15 %) of the computational cost of comparable global high-resolution configurations, while permitting exchanges with the lower-latitude oceans that cannot be directly accounted for in Arctic regional models.

To evaluate the visual outcomes and the affect of timing of surgical repair of fovea-splitting rhegmatogenous retinal detachments.A retrospective, consecutive cohort from multiple surgeons at a single center. Fovea status (fovea-on, fovea-splitting, or fovea-off) was classified by preoperative optical coherence tomography. The primary outcome measure was the visual acuity at the last follow-up that was further correlated with the timing of surgical repair.One hundred and ninety-five eyes were included with 62 fovea-on, 65 fovea-splitting, and 68 fovea-off detachments. The mean preoperative logarithm of the minimum angle of resolution visual acuity for fovea-on, fovea-splitting, and fovea-off groups was 0.16 ± 0.21, 0.70 ± 0.56, and 1.67 ± 0.87, respectively (P =0.001). Mean postoperative logarithm of the minimum angle of resolution visual acuity for fovea-on, fovea-splitting, and fovea-off groups were 0.07 ± 0.13, 0.10 ± 0.15, and 0.20 ± 0.22, respectively (P =0.001). A statistically significant difference in mean postoperative logMAR visual acuity was found between fovea-off and fovea-on groups (P = 0.003) and between fovea-off and fovea-splitting groups (P = 0.013), however not between fovea-on and fovea-splitting groups (P = 0.827). Visual acuity improved when repair was performed earlier after presentation for fovea-on (R = 0.378, P = 0.002) and fovea-off groups (R = 0.277, P = 0.022), but not for the fovea-splitting group (R = 0.089, P = 0.481).We described the favorable visual outcomes of surgery for fovea-splitting rhegmatogenous retinal detachment and correlated these with the timing of surgical repair, which may help guide the management of this urgent, vision-threatening condition.

Supplementary Methods, Figures 1-2 from Zoledronic Acid Reduces Bone Loss and Tumor Growth in an Orthotopic Xenograft Model of Osteolytic Oral Squamous Cell Carcinoma

This is the peer reviewed version of the following article: [Human impacts on mammal communities in Rio Campo Nature Reserve, Equatorial Guinea. African Journal of Ecology 61, 2 p262-276 (2023)], which has been published in final form at https://doi.org/10.1111/aje.13108. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions: https://authorservices.wiley.com/author-resources/Journal-Authors/licensing/self-archiving.html#3. Deposited by shareyourpaper.org and openaccessbutton.org. We've taken reasonable steps to ensure this content doesn't violate copyright. However, if you think it does you can request a takedown by emailing help@openaccessbutton.org.

Faculty retention is a prominent topic in academic medicine. Investment in faculty career development supports faculty vitality, advancement, and retention. Academic physicians in community-based settings far from their academic affiliate may find identifying local career advancement mentorship challenging.In June 2018, a career advancement in-service day at The Children's Hospital of San Antonio and Baylor College of Medicine-Houston was convened to design a peer mentoring circle (PMC). Using self-determination theory, this program aimed to help PMC members develop goals; schedule and attend regular meetings; format, review, and critique member curricula vitae and portfolios; and hold one another accountable to submitting award and promotion applications.Eleven inaugural PMC cohort members attended regular monthly meetings from July 2018 to June 2019 (median, 6 members per meeting). All members were competent in accessing the PMC repository of materials. Statistically significant improvement (P.01) was seen in self-reported knowledge and skills relevant to award or academic promotion support and resources. compared with no patient care or teaching awards and 1 academic promotion among non-PMC faculty, 5 PMC members (45.5%) earned a patient care award, 4 (36.4%) earned a teaching award, and 5 of 10 faculty members (50.0%) achieved academic promotion (P.001 for all). On the retrospective pre-post survey, members endorsed several PMC strengths, including personal and emotional support, professional support, and accountability.Next steps include establishing a local faculty development office, convening a second cohort, revising evaluation methods, expanding membership, and offering 1-on-1 career counseling. Community-based academicians who aim to replicate this program should organize a career advancement and faculty development in-service day; identify local faculty members to manage meetings; retain a repository of resources; set deadlines and hold one another accountable to them; and celebrate achievements and support one another in failure.

This work documents version two of the Department of Energy's Energy Exascale Earth System Model (E3SM). E3SMv2 is a significant evolution from its predecessor E3SMv1, resulting in a model that is nearly twice as fast and with a simulated climate that is improved in many metrics. We describe the physical climate model in its lower horizontal resolution configuration consisting of 110 km atmosphere, 165 km land, 0.5° river routing model, and an ocean and sea ice with mesh spacing varying between 60 km in the mid-latitudes and 30 km at the equator and poles. The model performance is evaluated with Coupled Model Intercomparison Project Phase 6 Diagnosis, Evaluation, and Characterization of Klima simulations augmented with historical simulations as well as simulations to evaluate impacts of different forcing agents. The simulated climate has many realistic features of the climate system, with notable improvements in clouds and precipitation compared to E3SMv1. E3SMv1 suffered from an excessively high equilibrium climate sensitivity (ECS) of 5.3K. In E3SMv2, ECS is reduced to 4.0K which is now within the plausible range based on a recent World Climate Research Program assessment. However, a number of important biases remain including a weak Atlantic Meridional Overturning Circulation, deficiencies in the characteristics and spectral distribution of tropical atmospheric variability, and a significant underestimation of the observed warming in the second half of the historical period. An analysis of single-forcing simulations indicates that correcting the historical temperature bias would require a substantial reduction in the magnitude of the aerosol-related forcing.

This paper provides an overview of the United States (US) Department of Energy's (DOE's) Energy Exascale Earth System Model version 2 (E3SMv2) fully coupled Regionally Refined Model (RRM) and documents the overall atmosphere, land, and river results from the Coupled Model Intercomparison Project 6 (CMIP6) DECK (Diagnosis, Evaluation, and Characterization of Klima) and historical simulations – a first-of-kind set of climate production simulations using RRM. The North American (NA) RRM (NARRM) is developed as the high-resolution configuration of E3SMv2 with the primary goal of more explicitly addressing DOE's mission needs regarding impacts to the US energy sector facing Earth system changes. The NARRM features finer horizontal resolution grids centered over NA, consisting of 25→100 km atmosphere and land, 0.125° river routing model, and 14→60 km ocean and sea ice. By design, the computational cost of NARRM is ∼3x of the uniform low-resolution (LR) model at 100 km but only ∼10–20 % of a globally uniform high-resolution model at 25 km. A novel hybrid timestep strategy for the atmosphere is key for NARRM to achieve improved climate simulation fidelity within the high-resolution patch without sacrificing the overall global performance. The global climate, including climatology, time series, sensitivity, and feedback, is confirmed to be largely identical between NARRM and LR as quantified with typical climate metrics. Over the refined NA area, NARRM is generally superior to LR, including for precipitation and clouds over the contiguous US (CONUS), summertime marine stratocumulus clouds off the coast of California, liquid and ice phase clouds near the North polar region, extratropical cyclones, and spatial variability in land hydrological processes. The improvements over land are related to the better resolved topography in NARRM, whereas those over ocean are attributable to the improved air-sea interactions with finer grids for both atmosphere and ocean/sea ice. Some features appear insensitive to the resolution change analyzed here, for instance the diurnal propagation of organized mesoscale convective systems over CONUS, and the warm-season land-atmosphere coupling at the Southern Great Plains. In summary, our study presents a realistically efficient approach to leverage the RRM framework for a standard Earth system model release and high-resolution climate production simulations.

Public health emergencies like SARS, MERS, and COVID-19 have prioritized surveillance of zoonotic coronaviruses, resulting in extensive genomic characterization of coronavirus diversity in bats. Sequencing viral genomes directly from animal specimens remains a laboratory challenge, however, and most bat coronaviruses have been characterized solely by PCR amplification of small regions from the best-conserved gene. This has resulted in limited phylogenetic resolution and left viral genetic factors relevant to threat assessment undescribed. In this study, we evaluated whether a technique called hybridization probe capture can achieve more extensive genome recovery from surveillance specimens. Using a custom panel of 20,000 probes, we captured and sequenced coronavirus genomic material in 21 swab specimens collected from bats in the Democratic Republic of the Congo. For 15 of these specimens, probe capture recovered more genome sequence than had been previously generated with standard amplicon sequencing protocols, providing a median 6.1-fold improvement (ranging up to 69.1-fold). Probe capture data also identified five novel alpha- and betacoronaviruses in these specimens, and their full genomes were recovered with additional deep sequencing. Based on these experiences, we discuss how probe capture could be effectively operationalized alongside other sequencing technologies for high-throughput, genomics-based discovery and surveillance of bat coronaviruses.

Wetland drainage has been pervasive in the North American Prairie Pothole Region. There is strong evidence that this drainage increases the hydrological connectivity of previously isolated wetlands and, in turn, runoff response to snowmelt and rainfall. It can be hard to disentangle the role of climate from the influence of wetland drainage in observed records. In this study, a basin-classification-based virtual modelling approach is described that can isolate these effects on runoff regimes. The basin class which was examined, entitled Pothole Till, extends throughout much of Canada's portion of the Prairie Pothole Region. Three knowledge gaps were addressed. First, it was determined that the spatial pattern in which wetlands are drained has little influence on how much the runoff regime was altered. Second, no threshold could be identified below which wetland drainage has no effect on the runoff regime, with drainage thresholds as low as 10 % in the area being evaluated. Third, wetter regions were less sensitive to drainage as they tend to be better hydrologically connected, even in the absence of drainage. Low flows were the least affected by drainage. Conversely, during extremely wet years, runoff depths could double as the result of complete wetland removal. Simulated median annual runoff depths were the most responsive, potentially tripling under typical conditions with high degrees of wetland drainage. As storage capacity is removed from the landscape through wetland drainage, the size of the storage deficit of median years begins to decrease and to converge on those of the extreme wet years. Model simulations of flood frequency suggest that, because of these changes in antecedent conditions, precipitation that once could generate a median event with wetland drainage can generate what would have been a maximum event without wetland drainage. The advantage of the basin-classification-based virtual modelling approach employed here is that it simulated a long period that included a wide variety of precipitation and antecedent storage conditions across a diversity of wetland complexes. This has allowed seemingly disparate results of past research to be put into context and finds that conflicting results are often only because of differences in spatial scale and temporal scope of investigation. A conceptual framework is provided that shows, in general, how annual runoff in different climatic and drainage situations will likely respond to wetland drainage in the Prairie Pothole Region.

Extensive wetland drainage has occurred across the Canadian Prairies, and drainage activities are ongoing in many areas (Dahl 1990; Watmough and Schmoll 2007; Bartzen et al. 2010; Dahl 2014; Prairi...

The design of electrode interfaces to achieve efficient electron transfer to biomolecules is important in many bioelectrochemical processes. Within the field of biohybrid solar energy conversion, constructing multilayered Photosystem I (PSI) protein films that maintain good electronic connection to an underlying electrode has been a major challenge. Previous shortcomings include low loadings, long deposition times, and poor connection between PSI and conducting polymers within composite films. Here, we show that PSI protein complexes can be deposited into monolayers within a 30 min timespan by leveraging the electrostatic interactions between the protein complex and the poly(3,4-ethylenedioxythiophene)-polystyrenesulfonate (PEDOT:PSS) polymer. Further, we follow a layer-by-layer (LBL) deposition procedure to produce up to 9-layer pairs of PSI and PEDOT:PSS with highly reproducible layer thicknesses as well as distinct changes in surface composition. When tested in an electrochemical cell employing ubiquinone-0 as a mediator, the photocurrent performance of the LBL films increased linearly by 83 ± 6 nA/cm2 per PSI layer up to 6-layer pairs. The 6-layer pair samples yielded a photocurrent of 414 ± 13 nA/cm2, after which the achieved photocurrent diminished with additional layer pairs. The turnover number (TN) of the PSI-PEDOT:PSS LBL assemblies also greatly exceeds that of drop-casted PSI multilayer films, highlighting that the rate of electron collection is improved through the systematic deposition of the protein complexes and conducting polymer. The capability to deposit high loadings of PSI between PEDOT:PSS layers, while retaining connection to the underlying electrode, shows the value in using LBL assembly to produce PSI and PEDOT:PSS bioelectrodes for photoelectrochemical energy harvesting applications.

Introduction Randomised controlled trials have shown that steroids reduce the risk of dying in patients with severe Coronavirus disease 2019 (COVID-19), whilst many real-world studies have failed to replicate this result. We aim to investigate real-world effectiveness of steroids in severe COVID-19. Methods Clinical, demographic, and viral genome data extracted from electronic patient record (EPR) was analysed from all SARS-CoV-2 RNA positive patients admitted with severe COVID-19, defined by hypoxia at presentation, between March 13th 2020 and May 27th 2021. Steroid treatment was measured by the number of prescription-days with dexamethasone, hydrocortisone, prednisolone or methylprednisolone. The association between steroid > 3 days treatment and disease outcome was explored using multivariable cox proportional hazards models with adjustment for confounders (including age, gender, ethnicity, co-morbidities and SARS-CoV-2 variant). The outcome was in-hospital mortality. Results 1100 severe COVID-19 cases were identified having crude hospital mortality of 15.3%. 793/1100 (72.1%) individuals were treated with steroids and 513/1100 (46.6%) received steroid ≤ 3 days. From the multivariate model, steroid > 3 days was associated with decreased hazard of in-hospital mortality (HR: 0.47 (95% CI: 0.31–0.72)). Conclusion The protective effect of steroid treatment for severe COVID-19 reported in randomised clinical trials was replicated in this retrospective study of a large real-world cohort.

Funding: This work was supported by grants from the National Institutes of Health R01AI091595, R01AI120810, R01AI050529, and P30AI045008 (B.H.H.); R01HL139337 (M.T.D.), the National Geographic Society (E.J.S.), the International Primatological Society (E.J.S.), and the American Society of Primatologists (E.J.S.), as well as fellowships from Harvard University (E.J.S.) and the National Science Foundation (E.J.S.). Chimpanzees (Pan troglodytes) harbor rich assemblages of malaria parasites, including three species closely related to P. falciparum (sub-genus Laverania), the most malignant human malaria parasite. Here, we characterize the ecology and epidemiology of malaria infection in wild chimpanzee reservoirs. We used molecular assays to screen chimpanzee fecal samples, collected longitudinally and cross-sectionally from wild populations, for malaria parasite mitochondrial DNA. We found that chimpanzee malaria parasitism has an early age of onset and varies seasonally in prevalence. A subset of samples revealed Hepatocystis mitochondrial DNA, with phylogenetic analyses suggesting that Hepatocystis appears to cross species barriers more easily than Laverania. Longitudinal and cross-sectional sampling independently support the hypothesis that mean ambient temperature drives spatiotemporal variation in chimpanzee Laverania infection. Infection probability peaked at ~24.5 °C, consistent with the empirical transmission optimum of P. falciparum in humans. Forest cover was also positively correlated with spatial variation in Laverania prevalence, consistent with the observation that forest-dwelling Anophelines are the primary vectors. Extrapolating these relationships across equatorial Africa, we map spatiotemporal variation in the suitability of chimpanzee habitat for Laverania transmission, offering a hypothetical baseline indicator of human exposure risk. Publisher PDF