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Learning Assistants (LAs) are undergraduates who work in active-learning classrooms with students facilitating discussions and encouraging deeper thinking, while also receiving pedagogical training. We describe how we built an LA program at a regional comprehensive university starting as a grassroots STEM initiative to recruit teachers, and expanding into a campus-wide multi-disciplinary program focusing on student success in a variety of general education courses. Additionally, in the 2020-2021 academic year, we conducted a formative assessment to further understand the program's impact. Our findings revealed strong alignment among students, faculty, and LAs regarding the LA's role in student learning. Qualitative themes from student surveys and faculty expectations resonated with LAs' weekly field note reflections. One surprising discovery was the consensus that LAs provided substantial support beyond the classroom. This suggests that LAs play a multifaceted role in enhancing student success, extending their influence beyond facilitating in-class discussions.

Abstract The subsurface oceans of Enceladus and Europa are thought to be some of the best candidate environments for finding life beyond Earth. Realistically, the first missions aimed at searching for life on these worlds will likely be restricted to the shallow subsurface. Here, we investigated whether indicators of life, or biosignatures, deposited near the surface could persist long enough to be detected, given that the extremely harsh conditions there would tend to degrade them. We exposed Bacillus subtilis spores to Ocean World surface conditions and used electron microscopy combined with spectroscopic approaches to assess the preservation potential of structural and morphological biosignatures derived from spores. Our results show that spore structure is highly resilient in the face of extreme conditions long after they have been inactivated, suggesting that methods targeting cell morphology would be valuable components in a suite of life detection strategies used in future missions to Ocean Worlds.

Abstract Introduction Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain condition creating a wide range of urologic and pain symptoms. There is currently limited evidence to understand the mechanisms of IC/BPS. There have been recent studies suggesting that altered function in brain motor areas, particularly the supplementary motor cortex (SMA), relates to altered bladder sensorimotor control and may play an important role in IC/BPS. This study aims to provide evidence that non-invasive stimulation targeting the motor cortex may help reduce IC/BPS pain, as well as better understand the neural mechanism by which this stimulation targets neuromuscular dysfunction. This study is a two-group quadruple-blinded randomized controlled trial (RCT) of active vs. sham repetitive transmagnetic stimulation (rTMS). In addition, our study will also include functional magnetic resonance imaging (fMRI), pelvic floor electromyography (EMG), pelvic exam, and outcome measures and questionnaires to further study outcomes. Ethics and dissemination All aspects of the study were approved by the Institutional Review Board of the University of Southern California (protocol HS-20–01021). All participants provided informed consent by the research coordinator/assistants. The results will be submitted for publication in peer-reviewed journals and disseminated at scientific conferences. Trial registration ClinicalTrials.gov NCT04734847. Registered on February 1, 2021.

Abstract Background Sexual differentiation of the brain occurs in all major vertebrate lineages but is not well understood at a molecular and cellular level. Unlike most vertebrates, sex-changing fishes have the remarkable ability to change reproductive sex during adulthood in response to social stimuli, offering a unique opportunity to understand mechanisms by which the nervous system can initiate and coordinate sexual differentiation. Methods This study explores sexual differentiation of the forebrain using single nucleus RNA-sequencing in the anemonefish Amphiprion ocellaris, producing the first cellular atlas of a sex-changing brain. Results We uncover extensive sex differences in cell type-specific gene expression, relative proportions of cells, baseline neuronal excitation, and predicted inter-neuronal communication. Additionally, we identify the cholecystokinin, galanin, and estrogen systems as central molecular axes of sexual differentiation. Supported by these findings, we propose a model of sexual differentiation in the conserved vertebrate social decision-making network spanning multiple subtypes of neurons and glia, including neuronal subpopulations within the preoptic area that are positioned to regulate gonadal differentiation. Conclusions This work deepens our understanding of sexual differentiation in the vertebrate brain and defines a rich suite of molecular and cellular pathways that differentiate during adult sex change in anemonefish.

Abstract Respirovirus 3 is a leading cause of severe acute respiratory infections in vulnerable human populations. Entry into host cells is facilitated by the attachment glycoprotein and the fusion glycoprotein (F). Because of its crucial role, F represents an attractive therapeutic target. Here, we identify 13 F-directed heavy-chain-only antibody fragments that neutralize recombinant respirovirus 3. High-resolution cryo-EM structures of antibody fragments bound to the prefusion conformation of F reveal three distinct, previously uncharacterized epitopes. All three antibody fragments bind quaternary epitopes on F, suggesting mechanisms for neutralization that may include stabilization of the prefusion conformation. Studies in cotton rats demonstrate the prophylactic efficacy of these antibody fragments in reducing viral load in the lungs and nasal passages. These data highlight the potential of heavy-chain-only antibody fragments as effective interventions against respirovirus 3 infection and identify neutralizing epitopes that can be targeted for therapeutic development.

Abstract The Paramyxoviridae family encompasses medically significant RNA viruses, including human respiroviruses 1 and 3 (RV1, RV3), and zoonotic pathogens like Nipah virus (NiV). RV3, previously known as parainfluenza type 3, for which no vaccines or antivirals have been approved, causes respiratory tract infections in vulnerable populations. The RV3 fusion (F) protein is inherently metastable and will likely require prefusion (preF) stabilization for vaccine effectiveness. Here we used structure-based design to stabilize regions involved in structural transformation to generate a preF protein vaccine antigen with high expression and stability, and which, by stabilizing the coiled-coil stem region, does not require a heterologous trimerization domain. The preF candidate induces strong neutralizing antibody responses in both female naïve and pre-exposed mice and provides protection in a cotton rat challenge model (female). Despite the evolutionary distance of paramyxovirus F proteins, their structural transformation and local regions of instability are conserved, which allows successful transfer of stabilizing substitutions to the distant preF proteins of RV1 and NiV. This work presents a successful vaccine antigen design for RV3 and provides a toolbox for future paramyxovirus vaccine design and pandemic preparedness.

Abstract The telencephalon has undergone remarkable diversification and expansion throughout vertebrate evolution, exhibiting striking variations in structural and functional complexity. Nevertheless, fundamental features are shared across vertebrate taxa, such as the presence of distinct regions including the pallium, subpallium, and olfactory structures. Teleost fishes have a uniquely “everted” telencephalon, which has confounded comparisons of their brain regions to other vertebrates. Here we combine spatial transcriptomics and single nucleus RNA-sequencing to generate a spatially-resolved transcriptional atlas of the Mchenga conophorus cichlid fish telencephalon. We then compare cell-types and anatomical regions in the cichlid telencephalon with those in amphibians, reptiles, birds, and mammals. We uncover striking transcriptional similarities between cell-types in the fish telencephalon and subpallial, hippocampal, and cortical cell-types in tetrapods, and find support for partial eversion of the teleost telencephalon. Ultimately, our work lends new insights into the organization and evolution of conserved cell-types and regions in the vertebrate forebrain.

Mesophotic Coral Ecosystems (MCEs) represent unique ecological habitats that range from 30 to 150 m deep, harbouring phylogenetically distinct species and offering refuge for many taxa during times of environmental stress. Yet owing to inaccessibility of ecosystems at these depths, most MCEs remain unexplored, with quantifications of ecological communities in these habitats lacking across many regions. Here, using open- and closed-circuit technical diving, we quantified benthic and fish community composition at four mesophotic reef sites (45 m depth) in Grand Cayman. We show significant differences in benthic community composition over a small spatial scale driven by disparate coverage of sponges, crustose coralline algae, and sand/rubble, yet consistent patterns of macroalgal dominance representing >50% coverage at each site and low hard coral cover at an average of 2.4%. Reef fish species richness, biomass, and density was consistent across sites, however the relative contribution of individual species to community composition differed significantly. Macrocarnivores were found to be the dominant contributors to biomass, with invertivores the most speciose, and omnivores and planktivores at the highest densities, consistent with previous descriptions of mesophotic fish assemblages in other regions. Similarly, the low hard coral cover and high macroalgae and sponge cover of the benthic communities also appear ecologically similar to several described mesophotic reefs yet is not uniform across the Caribbean. The ecological organisation of Grand Cayman’s MCEs may result from a variety of factors such as isolation from other major land masses, geology, local geography, and anthropogenic activity at both the local and global scale and highlight the importance of continued exploration and documentation of MCE communities.

IntroductionWomen are at a higher risk of developing Alzheimer’s disease (AD), and the decline in estrogens post-menopause is thought of as a factor increasing this risk. Estradiol (E2) is important in supporting cholinergic neuronal integrity, and cholinergic functioning may be negatively impacted following the loss of E2 post-menopause. The use of exogenous E2 has been observed to enhance cholinergically mediated cognitive performance in healthy post-menopausal women, which indicates a potentially protective mechanism. However, E2 is often co-administered with progestin or progesterone to prevent endometrial proliferation. Progesterone/progestins have previously been shown to have a detrimental effect on E2-mediated biological and cognitive effects mediated by cholinergic systems in preclinical models, therefore the present study aimed to assess whether progesterone would modify the effect of E2 to influence cognition during cholinergic blockade.MethodsTwenty participants completed 3-months of oral E2 treatment with micronized progesterone (mPRO) or with placebo (PLC) in a repeated-measures within-subjects crossover design, in which they also completed five anticholinergic challenge days per hormone treatment condition. During the challenge participants were administered low or high doses of the nicotinic cholinergic antagonist mecamylamine, the muscarinic cholinergic antagonist scopolamine, or placebo. Following drug administration participants performed cognitive tests sensitive to cholinergic tone, assessing attention, episodic memory, and working memory.ResultsSignificant decrements were found on some tasks when participants were taking E2+mPRO compared to E2 alone. Specifically, under more challenging task conditions and larger anticholinergic doses, participants showed poorer performance on the Critical Flicker Fusion task and the Stroop test and responded more conservatively on the N-back working memory task. Other tasks showed no differences between treatments under cholinergic blockade.DiscussionThe findings show that mPRO when taken in concert with E2, was detrimental to effortful cognitive performance, in the presence of cholinergic blockade. These results are important for assessing the impact of combined postmenopausal hormone treatment on cognitive performance that is dependent on cholinergic functioning after menopause.

Coral reef ecosystems are facing severe degradation due to anthropogenic activities at both local and global scales. In response, extensive restoration efforts are underway, aiming to bolster coral cover and enhance reef fish communities to foster facilitation between fish and corals. This reciprocal relationship is anticipated to improve overall restoration efficacy and enhance coral reef resilience in the face of global warming. Here, we investigate the impact of coral restoration using out-planted Acropora cervicornis colonies attached to raised domes on the associated fish community on the isolated, well-protected reef of Little Cayman Island in the Central Caribbean. Surveys were conducted immediately preceding out-planting, five days later, and 85 days later to capture temporal changes in the fish community. After 85 days of out-planting, there were no changes in fish biomass, abundance, or species richness for the entire fish community. This pattern was consistent for selected fish functional groups. Additionally, no significant differences were observed in the fish community before outplanting, five days after out-planting, or 85 days after out-planting of restoration domes. Our results underscore the limited impact of coral restoration for influencing fish communities in the isolated and highly protected reef of Little Cayman over an 85-day period. Consequently, our findings have implications for using coral restoration as a mechanism to enhance fish populations, particularly in marginally disturbed regions where structural complexity has not been lost. Future restoration programs should therefore incorporate local knowledge of environmental history and restoration needs along with an increased data-driven understanding of the intricate interaction between fish and coral populations to be successful.

Abstract In March 2020, the world went into lockdown to curb the spread of the novel coronavirus (SARS-CoV-2), with immediate impacts on wildlife across ecosystems. The strict 2-year long lockdown in Grand Cayman provided an unprecedented opportunity to assess how the ‘human confinement experiment’ influenced the community composition of reef fish. Using a suite of multivariate statistics, our findings revealed a stark increase in reef fish biomass during the 2 years of lockdown, especially among herbivores, including parrotfish, with drastic increases in juvenile parrotfishes identified. Additionally, when comparing baseline data of the community from 2018 to the 2 years during lockdown, over a three-fold significant increase in mean reef fish biomass was observed, with a clear shift in community composition. Our findings provide unique insights into the resilience of reef fish communities when local anthropogenic stressors are removed for an unprecedented length of time. Given the functional role of herbivores including parrotfish, our results suggest that reductions in human water-based activities have positive implications for coral reef ecosystems and should be considered in future management strategies.

Peripheral nerve regeneration fails following more severe injuries where the gap between nerve stumps is too large. Nerve guidance conduits (NGCs) can be implanted to connect the nerve stumps and provide a regenerative microenvironment. This study shows that poly(glycerol sebacate)-methacrylate (PGS-M), a photocurable and biodegradable elastomer, can be used to fabricate porous NGCs. Further, novel developments in emulsion templating techniques are used to generate composite structures and their mechanical properties are investigated. The most appropriate composite for nerve tissue repair had a compressive and tensile Young’s modulus of 0.168 MPa and 0.694 MPa respectively, much closer to that of native nerve tissue than previously used polymers. SEM images revealed high porosity/interconnectivity of NGCs, important for the diffusion of nutrients to further aid nerve regeneration. FITC-Dextran (150 kDa) effectively diffused through conduit walls. Histological analysis demonstrated the small pore size successfully prevented infiltration of fibroblasts. In vitro studies indicated that the NGCs were cytocompatible. Ex vivo analysis showed that neurons of embryonic chick dorsal root ganglia grew on the surface of the conduits, and Schwann cells migrated effectively along the lumen. This study demonstrates a novel way of fabricating porous scaffolds and demonstrates their potential for the treatment of PNI.

Abstract Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results in irreversible vision loss due to the mammalian central nervous system’s limited regenerative capacity. RGC repopulation is a promising therapeutic approach to reverse vision loss from optic neuropathies if the newly introduced neurons can reestablish functional retinal and thalamic circuits. In theory, RGCs might be repopulated through the transplantation of stem cell-derived neurons or via the induction of endogenous transdifferentiation. The RGC Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) Consortium was established to address the challenges associated with the therapeutic repair of the visual pathway in optic neuropathy. In 2022, the RReSTORe Consortium initiated ongoing international collaborative discussions to advance the RGC repopulation field and has identified five critical areas of focus: (1) RGC development and differentiation, (2) Transplantation methods and models, (3) RGC survival, maturation, and host interactions, (4) Inner retinal wiring, and (5) Eye-to-brain connectivity. Here, we discuss the most pertinent questions and challenges that exist on the path to clinical translation and suggest experimental directions to propel this work going forward. Using these five subtopic discussion groups (SDGs) as a framework, we suggest multidisciplinary approaches to restore the diseased visual pathway by leveraging groundbreaking insights from developmental neuroscience, stem cell biology, molecular biology, optical imaging, animal models of optic neuropathy, immunology & immunotolerance, neuropathology & neuroprotection, materials science & biomedical engineering, and regenerative neuroscience. While significant hurdles remain, the RReSTORe Consortium’s efforts provide a comprehensive roadmap for advancing the RGC repopulation field and hold potential for transformative progress in restoring vision in patients suffering from optic neuropathies.

Throughout the isolation process, human islets are subjected to destruction of the islet basement membrane (BM) and reduced oxygen supply. Reconstruction of the BM represents an option to improve islet function and survival post-transplant and may particularly be relevant for islet encapsulation devices and scaffolds. In the present study, we assessed whether Perlecan, used alone or combined with the BM proteins (BMPs) Collagen-IV and Laminin-521, has the ability to protect isolated human islets from hypoxia-induced damage. Islets isolated from the pancreas of seven different organ donors were cultured for 4–5 days at 2% oxygen in plain CMRL (sham-treated controls) or in CMRL supplemented with BMPs used either alone or in combination. Postculture, islets were characterized regarding survival, in vitro function and production of chemokines and reactive oxygen species (ROS). Individually added BMPs significantly doubled islet survival and increased in vitro function. Combining BMPs did not provide a synergistic effect. Among the tested BMPs, Perlecan demonstrated the significantly strongest inhibitory effect on chemokine and ROS production when compared with sham-treatment (p < 0.001). Perlecan may be useful to improve islet survival prior to and after transplantation. Its anti-inflammatory potency should be considered to optimise encapsulation and scaffolds to protect isolated human islets post-transplant.

Abstract Social behaviors are diverse in nature, but it is unclear how conserved genes, brain regions, and cell populations generate this diversity. Here we investigate bower-building, a recently-evolved social behavior in cichlid fishes. We use single nucleus RNA-sequencing in 38 individuals to show signatures of recent behavior in specific neuronal populations, and building-associated rebalancing of neuronal proportions in the putative homolog of the hippocampal formation. Using comparative genomics across 27 species, we trace bower-associated genome evolution to a subpopulation of glia lining the dorsal telencephalon. We show evidence that building-associated neural activity and a departure from quiescence in this glial subpopulation together regulate hippocampal-like neuronal rebalancing. Our work links behavior-associated genomic variation to specific brain cell types and their functions, and suggests a social behavior has evolved through changes in glia.

Purpose: The Retinal Ganglion Cell (RGC) Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) consortium was founded in 2021 to help address the numerous scientific and clinical obstacles that impede development of vision-restorative treatments for patients with optic neuropathies. The goals of the RReSTORe consortium are: (1) to define and prioritize the most critical challenges and questions related to RGC regeneration; (2) to brainstorm innovative tools and experimental approaches to meet these challenges; and (3) to foster opportunities for collaborative scientific research among diverse investigators. Design and Participants: The RReSTORe consortium currently includes > 220 members spanning all career stages worldwide and is directed by an organizing committee comprised of 15 leading scientists and physician-scientists of diverse backgrounds. Methods: Herein, we describe the structure and organization of the RReSTORe consortium, its activities to date, and the perceived impact that the consortium has had on the field based on a survey of participants. Results: In addition to helping propel the field of regenerative medicine as applied to optic neuropathies, the RReSTORe consortium serves as a framework for developing large collaborative groups aimed at tackling audacious goals that may be expanded beyond ophthalmology and vision science. Conclusions: The development of innovative interventions capable of restoring vision for patients suffering from optic neuropathy would be transformative for the ophthalmology field, and may set the stage for functional restoration in other central nervous system disorders. By coordinating large-scale, international collaborations among scientists with diverse and complementary expertise, we are confident that the RReSTORe consortium will help to accelerate the field toward clinical translation. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Nemertean worms contain toxins that are used to paralyze their prey and to deter potential predators. Hoplonemerteans often contain pyridyl alkaloids like anabaseine that act through nicotinic acetylcholine receptors and crustacean chemoreceptors. The chemical reactivity of anabaseine, the first nemertean alkaloid to be identified, has been exploited to make drug candidates selective for alpha7 subtype nAChRs. GTS-21, a drug candidate based on the anabaseine scaffold, has pro-cognitive and anti-inflammatory actions in animal models. The circumpolar chevron hoplonemertean Amphiporus angulatus contains a multitude of pyridyl compounds with neurotoxic, anti-feeding, and anti-fouling activities. Here, we report the isolation and structural identification of five new compounds, doubling the number of pyridyl alkaloids known to occur in this species. One compound is an isomer of the tobacco alkaloid anatabine, another is a unique dihydroisoquinoline, and three are analogs of the tetrapyridyl nemertelline. The structural characteristics of these ten compounds suggest several possible pathways for their biosynthesis.

Abstract The impact of ischaemia can severely damage procured donor organs for transplantation. The pancreas, and pancreatic islets in particular, is one of the most sensitive tissues towards hypoxia. The present study was aimed to assess the effect of hypoxic preconditioning (HP) performed ex-vivo in islets isolated from heart-beating donor (HBD) and non heart-beating donor (NHBD) rats. After HP purified islets were cultured for 24 h in hypoxia followed by islet characterisation. Post-culture islet yields were significantly lower in sham-treated NHBD than in HBD. This difference was reduced when NHBD islets were preconditioned. Similar results were observed regarding viability, apoptosis and in vitro function. Reactive oxygen species generation after hypoxic culture was significantly enhanced in sham-treated NHBD than in HBD islets. Again, this difference could be diminished through HP. qRT-PCR revealed that HP decreases pro-apoptotic genes but increases HIF-1 and VEGF. However, the extent of reduction and augmentation was always substantially higher in preconditioned NHBD than in HBD islets. Our findings indicate a lower benefit of HBD islets from HP than NHBD islets. The ischaemic preconditioning paradox suggests that HP should be primarily applied to islets from marginal donors. This observation needs evaluation in human islets.

Upernavik Isstrøm, a marine glacier undergoing rapid retreat, is simulated by forcing a numerical model with ocean-driven melt. A review of processes driving retreat led us to hypothesize that a glacier undergoing rapid retreat may be less sensitive to perturbations in the balance of forces than a glacier that is undergoing moderate changes or a glacier in steady state. Numerical experiments suggest this is not the case, and that a system in rapid retreat is as sensitive to basal traction perturbations as a system that is near to steady state. This result is important when considering other glacier systems experiencing marine-forced retreat. While the ice–ocean interface is of primary importance, additional perturbations from meltwater-forced decoupling of the glacier from its bed continue to feature in glacier dynamics.

Objective To compare outcomes following Ahmed-FP7 (AGI-FP7), Baerveldt-250mm2 (BGI-250), or Baerveldt-350mm2 (BGI-350) implantation.Methods and analysis Retrospective cohort study comprising 800 eyes from 800 individuals who underwent surgery 1 January 2016–31 December 2020 at a tertiary-care institution. Data were extracted from standardised fields in the electronic health record. Primary outcome was failure (defined as intraocular pressure (IOP) ≤5 mm Hg or >18 mm Hg or reduction

Examining reflected light from exoplanets aids in our understanding of the scattering properties of their atmospheres and will be a primary task of future flagship space- and ground-based telescopes. We introduce an enhanced capability of Planetary Intensity Code for Atmospheric Scattering Observations ( PICASO ), an open-source radiative transfer model used for exoplanet and brown dwarf atmospheres, to produce reflected light phase curves from three-dimensional atmospheric models. Since PICASO is coupled to the cloud code Virga , we produce phase curves for different cloud condensate species and varying sedimentation efficiencies ( f _sed ) and apply this new functionality to Kepler-7b, a hot Jupiter with phase curve measurements dominated by reflected starlight. We model three different cloud scenarios for Kepler-7b: MgSiO _3 clouds only, Mg _2 SiO _4 clouds only, and Mg _2 SiO _4 , Al _2 O _3 , and TiO _2 clouds. All our Virga models reproduce the cloudy region west of the substellar point expected from previous studies, as well as clouds at high latitudes and near the eastern limb, which are primarily composed of magnesium silicates. Al _2 O _3 and TiO _2 clouds dominate near the substellar point. We then compare our modeled reflected light phase curves to Kepler observations and find that models with all three cloud condensate species and low sedimentation efficiencies (0.03–0.1) match best, though our reflected light phase curves show intensities approximately one-third of those observed by Kepler. We conclude that a better understanding of zonal transport, cloud radiative feedback, and particle scattering properties is needed to further explain the differences between the modeled and observed reflected light fluxes.

Salt clouds are predicted to be common on warm exoplanets, but their optical properties are uncertain. The Exoplanet Cloud Ensemble Scattering System (ExCESS), a new apparatus to measure the scattering intensity and degree of linear polarization for an ensemble of particles, is introduced here and used to study the light scattering properties of KCl cloud analogs. ExCESS illuminates particles with a polarized laser beam (532 nm) and uses a photomultiplier tube detector to sweep the plane of illumination. Scattering measurements for KCl particles were collected for three size distributions representative of modeled clouds for the warm exoplanet GJ 1214b. Our measurements show that Lorenz–Mie calculations, commonly used to estimate the light scattering properties of assumedly spherical cloud particles, offer an inaccurate depiction of cubic and cuboid KCl particles. All of our measurements indicate that Lorenz–Mie scattering overestimates the backscattering intensity of our cloud analogs and incorrectly predicts the scattering at mid-phase angles (∼90°) and the preferential polarization state of KCl scattered light. Our results align with the general scattering properties of nonspherical particles and underscore the importance of further understanding the effects that such particles will have on radiative transfer models of exoplanet atmospheres and reflected light observations of exoplanets by the upcoming Nancy Grace Roman Space Telescope and Habitable Worlds Observatory.

Evidence-based supported employment has become a core community mental health service in much of the U.S. Although a national learning community has facilitated progress in about half of the states, other states have tried to implement evidence-based supported employment on their own. Many studies have examined site-level factors influencing implementation of supported employment, but few have focused on the role of state agency policies and actions. This study examined four states that have not joined the learning community, comparing two that have implemented with success (adopting states) and two that have faced challenges (non-adopting states). This comparative case study approach compared barriers, facilitators, and strategies in two states adopting IPS to two states that did not. The authors examined quantitative data from public records and conducted content analysis of qualitative and quantitative data from key informant interviews. The two non-adopting states lacked model clarity, funding, focus on people with serious mental illness, and collaboration between state mental health and vocational rehabilitation agencies. The two successful states experienced similar barriers but overcame them following lawsuit settlements that required implementation of evidence-based supported employment. Key strategies for successful implementation were funding, fidelity monitoring, technical assistance, and collaboration between state mental health and vocational rehabilitation agencies. With legal settlements serving as the catalyst, states facing challenges to implementing evidence-based supported employment can achieve success using standard implementation strategies to fund and ensure the quality of services.

The geometry and thermal structure of western Greenland ice sheet are known to have undergone relatively substantial change over the Holocene. Evolution of the frozen and melted fractions of the bed associated with the ice-sheet retreat over this time frame remains unclear. We address this question using a thermo-mechanically coupled flowline model to simulate a 11 ka period of ice-sheet retreat in west central Greenland. Results indicate an episode of ~100 km of terminus retreat corresponded to ~16 km of upstream frozen/melted basal boundary migration. The majority of migration of the frozen area is associated with the enhancement of the frictional and strain heating fields, which are accentuated toward the retreating ice margin. The thermally active bedrock layer acts as a heat sink, tending to slow contraction of frozen-bed conditions. Since the bedrock heat flux in our region is relatively low compared to other regions of the ice sheet, the frozen region is relatively greater and therefore more susceptible to marginward changes in the frictional and strain heating fields. Migration of melted regions thus depends on both geometric changes and the antecedent thermal state of the bedrock and ice, both of which vary considerably around the ice sheet.

Abstract Background The rising temperature of the oceans has been identified as the primary driver of mass coral reef declines via coral bleaching (expulsion of photosynthetic endosymbionts). Marine protected areas (MPAs) have been implemented throughout the oceans with the aim of mitigating the impact of local stressors, enhancing fish biomass, and sustaining biodiversity overall. In coral reef regions specifically, protection from local stressors and the enhanced ecosystem function contributed by MPAs are expected to increase coral resistance to global-scale stressors such as marine heatwaves. However, MPAs still suffer from limitations in design, or fail to be adequately enforced, potentially reducing their intended efficacy. Here, we address the hypothesis that the local-scale benefits resulting from MPAs moderate coral bleaching under global warming related stress. Results Bayesian analyses reveal that bleaching is expected to occur in both larger and older MPAs when corals are under thermal stress from marine heatwaves (quantified as Degree Heating Weeks, DHW), but this is partially moderated in comparison to the effects of DHW alone. Further analyses failed to identify differences in bleaching prevalence in MPAs relative to non-MPAs for coral reefs experiencing different levels of thermal stress. Finally, no difference in temperatures where bleaching occurs between MPA and non-MPA sites was found. Conclusions Our findings suggest that bleaching is likely to occur under global warming regardless of protected status. Thus, while protected areas have key roles for maintaining ecosystem function and local livelihoods, combatting the source of global warming remains the best way to prevent the decline of coral reefs via coral bleaching.

Abstract Background Medical school curricular hours dedicated to ophthalmology are low and declining. Extracurricular ophthalmology activities, such as participation in community vision screenings, may serve an important adjunctive role in medical school curricula. The Johns Hopkins University (JHU) Vision Screening In Our Neighborhoods (ViSION) Program is an example of a voluntary medical student-directed community service-learning program. Methods We used a mixed-methods cross-sectional approach, including an online survey and semi-structured interviews. JHU School of Medicine students enrolled in MD or MD/PhD programs during the 2019–2020 academic year were surveyed regarding demographics, career and service interests, involvement in ophthalmology-related activities, and confidence in their ophthalmology-related skills. Survey responses were compared between ViSION volunteers and non-volunteers using Fisher’s exact chi-square tests. Semi-structured interviews were conducted via webconference with 8 prior or current ViSION volunteers and responses analyzed using inductive thematic analysis. Data were collected when ViSION volunteers were in variable stages of their medical education and involvement with the ViSION program. Results A total of 118 medical students were included, representing an overall response rate of 24.6% of JHU medical students. ViSION volunteers reported greater involvement in ophthalmology-related research (42% vs. 4%, p

Terrestrial LiDAR scans (TLS) offer a rich data source for high-fidelity vegetation characterization, addressing the limitations of traditional fuel sampling methods by capturing spatially explicit distributions that have a significant impact on fire behavior. However, large volumes of complex, high resolution data are difficult to use directly in wildland fire models. In this study, we introduce a novel method that employs a voxelization technique to convert high-resolution TLS data into fine-grained reference voxels, which are subsequently aggregated into lower-fidelity fuel cells for integration into physics-based fire models. This methodology aims to transform the complexity of TLS data into a format amenable for integration into wildland fire models, while retaining essential information about the spatial distribution of vegetation. We evaluate our approach by comparing a range of aggregate geometries in simulated burns to laboratory measurements. The results show insensitivity to fuel cell geometry at fine resolutions (2–8 cm), but we observe deviations in model behavior at the coarsest resolutions considered (16 cm). Our findings highlight the importance of capturing the fine scale spatial continuity present in heterogeneous tree canopies in order to accurately simulate fire behavior in coupled fire-atmosphere models. To the best of our knowledge, this is the first study to examine the use of TLS data to inform fuel inputs to a physics based model at a laboratory scale.

Breastfeeding is often considered principally a biological issue but success is impacted by the socio-ecological environment of the lactating parent. Identifying current attitudes towards breastfeeding is essential in the effort toward normalizing breastfeeding in communities, including university campuses. The study explored campus community knowledge, awareness, and attitudes about breastfeeding, including available resources and applicable laws on two university campuses in the southern United States. This cross-sectional, self-reporting study utilized the Iowa Infant Feeding Attitude Scale and an adaptation of the Breastfeeding Behavior Questionnaire to survey a convenience sample. Results revealed decreased awareness of protective laws, availability of private lactation space, and insufficient public appreciation of breastfeeding's unique advantages to both lactating parent and infant as barriers to breastfeeding. These findings will help develop additional breastfeeding strategies to improve university campus community breastfeeding initiatives.

Summary: Tight glycemic control (TGC), the cornerstone of diabetic management, reduces the incidence and progression of diabetic microvascular disease. However, TGC can also lead to transient episodes of hypoglycemia, which have been associated with adverse outcomes in patients with diabetes. Here, we demonstrate that low glucose levels result in hypoxia-inducible factor (HIF)-1-dependent expression of the glucose transporter, Glut1, in retinal cells. Enhanced nuclear accumulation of HIF-1α was independent of its canonical post-translational stabilization but instead dependent on stimulation of its translation and nuclear localization. In the presence of hypoxia, this physiologic response to low glucose resulted in a marked increase in the secretion of the HIF-dependent vasoactive mediators that promote diabetic retinopathy. Our results provide a molecular explanation for how early glucose control, as well as glycemic variability (i.e., oscillating serum glucose levels), contributes to diabetic eye disease. These observations have important implications for optimizing glucose management in patients with diabetes.

Purpose: To describe twelve cases in which home intraocular pressure (IOP) monitoring complimented clinical decision-making in glaucoma management. Observations: Home IOP monitoring elucidated peaks and amplitudes of variation that were not captured by in-clinic IOP measurements during the pre- or post-interventional period. Conclusions & Importance: Home monitoring can establish pre-treatment IOP patterns that are not evident during in-clinic measurements. Home monitoring can also demonstrate response to treatment more quickly than in-clinic monitoring, and provide more information about nyctohemoral fluctuations than is ascertained by in-clinic tonometry.

Objective To establish short-term and medium-term complications 1-year postdiagnosis, of acute pancreatitis (AP) in children aged 0–14 years.Design One-year follow-up of a prospective monthly surveillance of new cases of AP in children under 15 years through the British Paediatric Surveillance Unit (BPSU) from April 2013 to April 2014.Setting A monthly surveillance of >3700 consultant paediatricians and paediatric surgeons in the UK and Ireland using the BPSU.Patients Children aged 0–14 years with a new diagnosis of AP.Main outcome measures The outcomes following AP, including the incidence of complications and comorbidity at diagnosis and at 1 year.Results Of the 94 new confirmed cases of AP identified in the UK during the study period, 90 cases (96%) were included in the 1-year follow-up. 30 patients (32%) developed further episode(s) of AP. Over one-fifth of patients developed one or more major complication. At initial admission, the most common of these was pancreatic necrosis (n=8, 9%), followed by respiratory failure (n=7, 7%). Reported complications by 1 year were pseudocyst formation (n=9, 10%), diabetes requiring insulin therapy (n=4, 4%) and maldigestion (n=1, 1%). At 1-year postdiagnosis, only 59% of children made a full recovery with no acute or chronic complications or recurrent episodes of AP. Two patients died, indicating a case fatality of ~2.0%.Conclusions AP in childhood is associated with significant short-term and medium-term complications and comorbidities including risk of recurrence in approximately a third of cases.

We report silicon nanowire (SiNW) growth with a novel Cu-In bimetallic catalyst using a plasma-enhanced chemical vapor deposition (PECVD) method. We study the structure of the catalyst nanoparticles (NPs) throughout a two-step process that includes a hydrogen plasma pre-treatment at 200 °C and the SiNW growth itself in a hydrogen-silane plasma at 420 °C. We show that the H2-plasma induces a coalescence of the Cu-rich cores of as-deposited thermally evaporated NPs that does not occur when the same annealing is applied without plasma. The SiNW growth process at 420 °C induces a phase transformation of the catalyst cores to Cu7In3; while a hydrogen plasma treatment at 420 °C without silane can lead to the formation of the Cu11In9 phase. In situ transmission electron microscopy experiments show that the SiNWs synthesis with Cu-In bimetallic catalyst NPs follows an essentially vapor-solid–solid process. By adjusting the catalyst composition, we manage to obtain small-diameter SiNWs—below 10 nm—among which we observe the metastable hexagonal diamond phase of Si, which is predicted to have a direct bandgap.

2-, 4-, 5-, and 6-hydroxynicotinic acids were crystallized in a pH-dependent manner using only water as the preferred solvent. The crystallization outcome was quite diverse: individual crystals of different sizes and shapes, microcrystalline powders, crystalline aggregates, and almost amorphous solids. Such a variety of solid forms demonstrates the relevance of pH control during crystallization processes.

Abstract Lake Malawi cichlid fishes exhibit extensive divergence in form and function built from a relatively small number of genetic changes. We compared the genomes of rock- and sand-dwelling species and asked which genetic variants differed among the groups. We found that 96% of differentiated variants reside in non-coding sequence but these non-coding diverged variants are evolutionarily conserved. Genome regions near differentiated variants are enriched for craniofacial, neural and behavioral categories. Following leads from genome sequence, we used rock- vs. sand-species and their hybrids to (i) delineate the push–pull roles of BMP signaling and irx1b in the specification of forebrain territories during gastrulation and (ii) reveal striking context-dependent brain gene expression during adult social behavior. Our results demonstrate how divergent genome sequences can predict differences in key evolutionary traits. We highlight the promise of evolutionary reverse genetics—the inference of phenotypic divergence from unbiased genome sequencing and then empirical validation in natural populations.

Summary: Retinal ganglion cell (RGC) transplantation has the potential to restore vision in optic neuropathy, but donor neuron survival and retinal integration remain challenging. Here, we present a protocol for ex vivo human RGC transplantation on flatmounted murine organotypic retinal explants, providing a robust platform for studying donor RGC survival, dendritic stratification, topographic distribution, donor-host interactions, and pro-engraftment strategies. The protocol includes microscopy-based analyses to evaluate donor cell engraftment and can be adapted to various donor cell types or culture systems.For complete details on the use and execution of this protocol, please refer to Zhang et al. (2021a, 2021b).

Purpose: Suprachoroidal intraocular foreign bodies (IOFBs) are an exceedingly rare manifestation of ocular trauma. Here we present a unique case of a metallic wire tracking from the cornea through the suprachoroidal space, and remarkably sparing the retina and lens. The patient attained an excellent visual outcome after management of resultant cyclodialysis cleft. Observations: A 34-year-old male experienced a penetrating IOFB while operating a rotary wire brush. He presented to the emergency department where posterior involvement of the IOFB was confirmed on CT scan. He underwent emergent pars plana vitrectomy, during which the IOFB was found to be located underneath intact retina and choroid on scleral depression. The wire was removed through the entry wound, which was self-sealing. At follow up, intraocular pressure was 3 mmHg with findings of hypotony. A cyclodialysis cleft was confirmed with ultrasound biomicroscopy. Cycloplegic and photocoagulation treatments were attempted, but ultimately direct cyclopexy was performed to successfully repair the cleft. One year after the initial incident, visual acuity is 20/25 and IOP is 17 mmHg. Conclusion and importance: Cyclodialysis cleft is a rare sequela of penetrating ocular injury. Clinicians should consider the presence of a cyclodialysis cleft in the setting of postoperative hypotony and confirm either with gonioscopy or other anterior segment imaging methods. Despite failure of conservative therapies, our patient had an excellent visual outcome following surgical closure of the cleft.

Abstract Recent work has shown that certain deformations of the scalar potential in Jackiw-Teitelboim gravity can be written as double-scaled matrix models. However, some of the deformations exhibit an apparent breakdown of unitarity in the form of a negative spectral density at disc order. We show here that the source of the problem is the presence of a multi-valued solution of the leading order matrix model string equation. While for a class of deformations we fix the problem by identifying a first order phase transition, for others we show that the theory is both perturbatively and non-perturbatively inconsistent. Aspects of the phase structure of the deformations are mapped out, using methods known to supply a non-perturbative definition of undeformed JT gravity. Some features are in qualitative agreement with a semi-classical analysis of the phase structure of two-dimensional black holes in these deformed theories.

Abstract Age-related macular degeneration (AMD) is the primary cause of blindness in adults over 60 years of age, and clinical trials are currently assessing the therapeutic potential of retinal pigmented epithelial (RPE) cell monolayers on implantable scaffolds to treat this disease. However, challenges related to the culture, long-term storage, and long-distance transport of such implants currently limit the widespread use of adherent RPE cells as therapeutics. Here we report a xeno-free protocol to cryopreserve a confluent monolayer of clinical-grade, human embryonic stem cell-derived RPE cells on a parylene scaffold (REPS) that yields viable, polarized, and functional RPE cells post-thaw. Thawed cells exhibit ≥ 95% viability, have morphology, pigmentation, and gene expression characteristic of mature RPE cells, and secrete the neuroprotective protein, pigment epithelium-derived factor (PEDF). Stability under liquid nitrogen (LN2) storage has been confirmed through one year. REPS were administered immediately post-thaw into the subretinal space of a mammalian model, the Royal College of Surgeons (RCS)/nude rat. Implanted REPS were assessed at 30, 60, and 90 days post-implantation, and thawed cells demonstrate survival as an intact monolayer on the parylene scaffold. Furthermore, immunoreactivity for the maturation marker, RPE65, significantly increased over the post-implantation period in vivo, and cells demonstrated functional attributes similar to non-cryopreserved controls. The capacity to cryopreserve adherent cellular therapeutics permits extended storage and stable transport to surgical sites, enabling broad distribution for the treatment of prevalent diseases such as AMD.

Abstract In the wild, behaviors are often expressed over long time periods in complex and dynamic environments, and many behaviors include direct interaction with the environment itself. However, measuring behavior in naturalistic settings is difficult, and this has limited progress in understanding the mechanisms underlying many naturally evolved behaviors that are critical for survival and reproduction. Here we describe an automated system for measuring long-term bower construction behaviors in Lake Malawi cichlid fishes, in which males use their mouths to sculpt sand into large species-specific structures for courtship and mating. We integrate two orthogonal methods, depth sensing and action recognition, to simultaneously track the developing bower structure and the thousands of individual sand manipulation behaviors performed throughout construction. By registering these two data streams, we show that behaviors can be topographically mapped onto a dynamic 3D sand surface through time. The system runs reliably in multiple species, across many aquariums simultaneously, and for up to weeks at a time. Using this system, we show strong differences in construction behavior and bower form that reflect species differences in nature, and we gain new insights into spatial, temporal, social dimensions of bower construction, feeding, and quivering behaviors. Taken together, our work highlights how low-cost tools can automatically quantify behavior in naturalistic and social environments over long timescales in the lab.

Intracellular generation of gold nanoparticles has drawn attention but toxic effects have limited potential applications. Here, the authors report on the delivery of ionic gold with PEG resulting in faster synthesis and reduced toxicity due to lower concentrations of ionic gold required and explore potential applications.

Retinal vein occlusion can cause blindness, and features neuronal dysfunction, inflammation and breakdown of vascular integrity. Here the authors report a non-apoptotic role of endothelial caspase-9 in regulating blood-retina barrier integrity and neuronal survival, which can be therapeutically targeted in a mouse model of retinal vein occlusion.

Aquaporin 4 is absent from astrocytes in the rodent optic nerve head, despite high expression in the retina and myelinated optic nerve. The purpose of this study was to quantify regional aquaporin channel expression in astrocytes of the porcine and human mouse optic nerve (ON). Ocular tissue sections were immunolabeled for aquaporins 1(AQP1), 4(AQP4), and 9(AQP9), myelin basic protein (MBP), glial fibrillary acidic protein (GFAP) and alpha-dystroglycan (αDG) for their presence in retina, lamina, myelin transition zone (MTZ, region just posterior to lamina) and myelinated ON (MON). Semi- quantification of AQP4 labeling & real-time quantitative PCR (qPCR) data were analyzed in retina and ON tissue. Porcine and control human eyes had abundant AQP4 in Müller cells, retinal astrocytes, and myelinated ON (MON), but minimal expression in the lamina cribrosa. AQP1 and AQP9 were present in retina, but not in the lamina. Immunolabeling of GFAP and αDG was similar in lamina, myelin transition zone (MTZ) and MON regions. Semi-quantitative AQP4 labeling was at background level in lamina, increasing in the MTZ, and highest in the MON (lamina vs MTZ, MON; p≤0.05, p≤0.01, respectively). Expression of AQP4 mRNA was minimal in lamina and substantial in MTZ and MON, while GFAP mRNA expression was uniform among the lamina, MTZ, and MON regions. Western blot assay showed AQP4 protein expression in the MON samples, but none was detected in the lamina tissue. The minimal presence of AQP4 in the lamina is a specific regional phenotype of astrocytes in the mammalian optic nerve head.