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Styrene, benzene, toluene, ethylbenzene, and xylenes (SBTEX) are established neurotoxicants. SBTEX contains hazardous air pollutants (HAPs) that are released from the petrochemical industry, combustion process, transport emission, and solvent usage sources. Although several SBTEX toxic assessment studies have been conducted, they have mainly relied on ambient measurements to estimate exposure and limit their scope to specific locations and observational periods. To overcome these spatiotemporal limitations, an air quality modeling system over the US Gulf region was created, predicting the spatially and temporally enhanced SBTEX modeling concentrations from May to September 2012. Due to the incompleteness of SBTEX in the official US Environmental Protection Agency (EPA) National Emission Inventory (NEI), the Hazardous Air Pollutions Imputation (HAPI) program was used to identify and estimate the missing HAP emissions. The improved emission data were processed to generate the chemically speciated hourly gridded emission inputs for the Comprehensive Air Quality Model with Extensions (CAMx) chemical transport model to simulate the SBTEX concentrations over the Gulf modeling region. SBTEX pollutants were modeled using the Reactive Tracer feature in CAMx that accounts for their chemical and physical processes in the atmosphere. The data show that the major SBTEX emissions in this region are contributed by mobile emissions (45 %), wildfire (30 %), and industry (26 %). Most SBTEX emissions are emitted during daytime hours (local time 14:00–17:00), and the emission rate in the model domain is about 20–40 t h−1, which is about 4 times higher than that in the nighttime (local time 24:00–04:00, about 4–10 t h−1). High concentrations of SBTEX (above 1 ppb) occurred near the cities close to the I-10 interstate highway (Houston, Beaumont, Lake Charles, Lafayette, Baton Rouge, New Orleans, and Mobile) and other metropolitan cities (Shreveport and Dallas). High styrene concentrations were co-located with industrial sources, which contribute the most to the styrene emissions. The HAPI program successfully estimated missing emissions of styrene from the chemical industry. The change increased total styrene emissions by 22 %, resulting in maximum ambient concentrations increasing from 0.035 to 1.75 ppb across the model domain. The predicted SBTEX concentrations with imputed emissions present good agreement with observational data, with a correlation coefficient (R) of 0.75 (0.46 to 0.77 for individual SBTEX species) and a normalized mean bias (NMB) of −5.6 % (−24.9 % to 32.1 % for the individual SBTEX species), suggesting their value for supporting any SBTEX-related human health studies in the Gulf region. The SBTEX data were published at Zenodo (https://doi.org/10.5281/zenodo.7967541) (Wang et al., 2023), and the HAPI tool was also published at Zenodo (https://doi.org/10.5281/zenodo.7987106) (Wang and Baek, 2023).

Abstract Despite recent advances in cryo-electron microscopy and artificial intelligence-based model predictions, a significant fraction of structure determinations by macromolecular crystallography still requires experimental phasing, usually by means of single-wavelength anomalous diffraction (SAD) techniques. Most synchrotron beamlines provide highly brilliant beams of X-rays of between 0.7 and 2 Å wavelength. Use of longer wavelengths to access the absorption edges of biologically important lighter atoms such as calcium, potassium, chlorine, sulfur and phosphorus for native-SAD phasing is attractive but technically highly challenging. The long-wavelength beamline I23 at Diamond Light Source overcomes these limitations and extends the accessible wavelength range to λ = 5.9 Å. Here we report 22 macromolecular structures solved in this extended wavelength range, using anomalous scattering from a range of elements which demonstrate the routine feasibility of lighter atom phasing. We suggest that, in light of its advantages, long-wavelength crystallography is a compelling option for experimental phasing.

Winter represents a stressful period for many organisms, and terrestrial insects are particularly susceptible to adverse thermal conditions. However, exposure to thermal stress and its effects on insect survival and performance can be modulated by various external factors. In forest systems, the overwintering microsite, stand structure, and regional climatic conditions may play a role in overwintering survival and performance at the individual microsite, local stand, and landscape level, respectively. To better understand the effects of these potential influences, rarely examined simultaneously, we deployed wild and lab-reared diapausing spruce budworm in a series of field experiments established across a range of spatial scales.Overwintering survival was higher on black spruce than balsam fir, likely owing to differences in substrate structure (and hence microsite quality/availability) between these two hosts. At the stand level, neither tree species nor age had an impact on insect survival; however, we observed a positive carryover effect of overwintering in a black spruce stand, enhancing performance in post-diapause development, possibly owing to buffering against warm spells during winter. Lastly, despite exposure to a broad range of winter temperatures across an extensive latitudinal gradient, overwintering survival was high (>80%) and did not vary at the landscape level.Our results indicate that insect overwintering was influenced by environmental factors at multiple spatial scales. Interestingly, despite it being considered a poor host for larval feeding, overwintering on black spruce clearly benefited spruce budworm survival and post-diapause performance. Secondly, microsite and stand-level factors had a greater impact than did regional climate variation. Collectively, these findings highlight the importance of finer-scale environmental factors on larval overwintering at both the lethal and sub-lethal level, with implications for basic and applied ecology of this iconic forest insect pest.

The waters of Aotearoa New Zealand span over 4.2 million km2 of the South Pacific Ocean and harbour a rich diversity of seafloor-associated taxa. Due to the immensity and remoteness of the area, there are significant gaps in the availability of data that can be used to quantify and map the distribution of seafloor and demersal biodiversity, limiting effective management. In this study, we describe the development and accessibility of an online atlas of seabed biodiversity that aims to fill these gaps. Species distribution models were developed for 579 taxa across four taxonomic groups: demersal fish, reef fish, subtidal invertebrates and macroalgae. Spatial layers for taxa distribution based on habitat suitability were statistically validated and then, as a further check, evaluated by taxonomic experts to provide measures of confidence to guide the future use of these layers. Spatially explicit uncertainty (SD) layers were also developed for each taxon distribution. We generated layer-specific metadata, including statistical and expert evaluation scores, which were uploaded alongside the accompanying spatial layers to the open access database Zenodo. This database provides the most comprehensive source of information on the distribution of seafloor taxa for Aotearoa New Zealand and is thus a valuable resource for managers, researchers and the public that will guide the management and conservation of seafloor communities. The atlas of seabed biodiversity for Aotearoa New Zealand is freely accessible via the open-access database Zenodo under https://doi.org/10.5281/zenodo.7083642 (Stephenson et al., 2022).

Marguerite McDonald,1 Susan B Janik,2 Frank W Bowden,3 Amit Chokshi,4 Michael A Singer,5 Sean Tighe,6,7 Olivia G Mead,6 Seema Nanda,8 Mujtaba A Qazi,9 Damon Dierker,10 Adam T Shupe,11 Brittany J McMurren12 1Ophthalmic Consultants of Long Island, Lynbrook, NY, USA; 2Solinsky Eye Care, Kensington, CT, USA; 3Bowden Eye & Associates, Jacksonville, FL, USA; 4Florida Eye Specialists, Jacksonville, FL, USA; 5Medical Center Ophthalmology Associates, San Antonio, TX, USA; 6BioTissue Holdings, Inc, Miami, FL, USA; 7Florida International University Herbert Wertheim College of Medicine, Miami, FL, USA; 8Nanda Dry Eye & Vision Institute, Houston, TX, USA; 9Pepose Vision Institute, Chesterfield, MO, USA; 10Eye Surgeons of Indiana, Indianapolis, IN, USA; 11Royo Eye Care, Marysville, CA, USA; 12Werner Optometry, San Diego, CA, USACorrespondence: Sean Tighe, 7300 Corporate Center Drive, Suite 700, Miami, FL, 33126, USA, Email stighe@biotissue.comBackground: While sutureless, cryopreserved amniotic membrane (cAM) has been shown to significantly improve signs and symptoms of dry eye disease (DED), no studies have assessed the association of cAM treatment duration to the differential response in clinical outcomes.Methods: A multi-center, retrospective study was conducted on patients with moderate-to-severe DED who were treated with self-retained cAM (Prokera® Slim) for 2 to 7 days. The primary outcome measure was DEWS severity score assessed at 1 week, 1 month, and 3 months. Secondary outcome measures included ocular discomfort, visual symptoms, corneal staining, and visual acuity.Results: A total of 89 eyes (77 patients) with moderate-to-severe DED (DEWS severity 3.24 ± 0.56) received treatment with self-retained cAM for 2 days (n = 10), 3 days (n = 15), 4 days (n = 12), 5 days (n = 19), 6 days (n = 6), or 7 days (n = 27). DEWS scores significantly improved at 1 week, 1 month, and 3 months for all treatment duration groups, with no significant difference observed between groups at any timepoint. In addition to an improvement in DEWS severity scores, those receiving cAM treatment for 2 days demonstrated a significant improvement in corneal staining, visual symptoms, and ocular discomfort at 1 week, 1 month, and 3 months.Conclusion: This retrospective study suggests that a single placement of self-retained cAM for 2 days can significantly improve signs and symptoms of DED with a lasting benefit observed for up to 3 months.Keywords: amniotic membrane, cryopreserved, dry eye, ocular surface, Prokera

Abstract Anisotropic and efficient transport of ions under external stimuli governs the operation and failure mechanisms of energy-conversion systems and microelectronics devices. However, fundamental understanding of ion hopping processes is impeded by the lack of atomically precise materials and probes that allow for the monitoring and control at the appropriate time- and length- scales. In this work, using in-situ transmission electron microscopy, we directly show that oxygen ion migration in vacancy ordered, semiconducting SrFeO2.5 epitaxial thin films can be guided to proceed through two distinctly different diffusion pathways, each resulting in different polymorphs of SrFeO2.75 with different ground electronic properties before reaching a fully oxidized, metallic SrFeO3 phase. The diffusion steps and reaction intermediates are revealed by means of ab-initio calculations. The principles of controlling oxygen diffusion pathways and reaction intermediates demonstrated here may advance the rational design of structurally ordered oxides for tailored applications and provide insights for developing devices with multiple states of regulation.

Abstract The zoonotic Rift Valley fever virus (RVFV) can cause severe disease in humans and has pandemic potential, yet no approved vaccine or therapy exists. Here we describe a dual-mechanism human monoclonal antibody (mAb) combination against RVFV that is effective at minimal doses in a lethal mouse model of infection. We structurally analyze and characterize the binding mode of a prototypical potent Gn domain-A-binding antibody that blocks attachment and of an antibody that inhibits infection by abrogating the fusion process as previously determined. Surprisingly, the Gn domain-A antibody does not directly block RVFV Gn interaction with the host receptor low density lipoprotein receptor-related protein 1 (LRP1) as determined by a competitive assay. This study identifies a rationally designed combination of human mAbs deserving of future investigation for use in humans against RVFV infection. Using a two-pronged mechanistic approach, we demonstrate the potent efficacy of a rationally designed combination mAb therapeutic.

Abstract Background The benefit of physical activity (PA) for increasing longevity is well-established, however, the impact of diurnal timing of PA on mortality remains poorly understood. We aimed to derive circadian PA patterns and investigate their associations with all-cause mortality. Methods We used 24 h PA time series from 96,351 UK Biobank participants aged between 42 and 79 years at accelerometry in 2013–2015. Functional principal component analysis (fPCA) was applied to obtain circadian PA patterns. Using multivariable Cox proportional hazard models, we related the loading scores of these fPCs to estimate risk of mortality. Results During 6.9 years of follow-up, 2,850 deaths occurred. Four distinct fPCs accounted for 96% of the variation of the accelerometry data. Using a loading score of zero (i.e., average overall PA during the day) as the reference, a fPC1 score of + 2 (high overall PA) was inversely associated with mortality (Hazard ratio, HR = 0.91; 95% CI: 0.84–0.99), whereas a score of -2 (low overall PA) was associated with higher mortality (1.69; 95% CI: 1.57–1.81; p for non-linearity

Abstract Background Major depressive disorder (MDD) has a significant impact on global burden of disease. Complications in clinical management can occur when response to pharmacological modalities is considered inadequate and symptoms persist (treatment-resistant depression (TRD)). We aim to investigate inflammation, proxied by C-reactive protein (CRP) levels, and body mass index (BMI) as putative causal risk factors for depression and subsequent treatment resistance, leveraging genetic information to avoid confounding via Mendelian randomisation (MR). Methods We used the European UK Biobank subcohort ( $$n=451,025$$ n = 451 , 025 ), the mental health questionnaire (MHQ) and clinical records. For treatment resistance, a previously curated phenotype based on general practitioner (GP) records and prescription data was employed. We applied univariable and multivariable MR models to genetically predict the exposures and assess their causal contribution to a range of depression outcomes. We used a range of univariable, multivariable and mediation MR models techniques to address our research question with maximum rigour. In addition, we developed a novel statistical procedure to apply pleiotropy-robust multivariable MR to one sample data and employed a Bayesian bootstrap procedure to accurately quantify estimate uncertainty in mediation analysis which outperforms standard approaches in sparse binary outcomes. Given the flexibility of the one-sample design, we evaluated age and sex as moderators of the effects. Results In univariable MR models, genetically predicted BMI was positively associated with depression outcomes, including MDD ( $$\beta$$ β ( $$95\%$$ 95 % CI): 0.133(0.072, 0.205)) and TRD (0.347(0.002, 0.682)), with a larger magnitude in females and with age acting as a moderator of the effect of BMI on severity of depression (0.22(0.050, 0.389)). Multivariable MR analyses suggested an independent causal effect of BMI on TRD not through CRP (0.395(0.004, 0.732)). Our mediation analyses suggested that the effect of CRP on severity of depression was partly mediated by BMI. Individuals with TRD ( $$n=2199$$ n = 2199 ) observationally had higher CRP and BMI compared with individuals with MDD alone and healthy controls. Discussion Our work supports the assertion that BMI exerts a causal effect on a range of clinical and questionnaire-based depression phenotypes, with the effect being stronger in females and in younger individuals. We show that this effect is independent of inflammation proxied by CRP levels as the effects of CRP do not persist when jointly estimated with BMI. This is consistent with previous evidence suggesting that overweight contributed to depression even in the absence of any metabolic consequences. It appears that BMI exerts an effect on TRD that persists when we account for BMI influencing MDD.

Background Brief intervention services provide rapid, mobile and flexible short-term delivery of interventions to resolve mental health crises. These interventions may provide an alternative pathway to the emergency department or in-patient psychiatric services for children and young people (CYP), presenting with an acute mental health condition. Aims To synthesise evidence on the effectiveness of brief interventions in improving mental health outcomes for CYP (0–17 years) presenting with an acute mental health condition. Method A systematic literature search was conducted, and the studies’ methodological quality was assessed. Five databases were searched for peer-reviewed articles between January 2000 and September 2022. Results We synthesised 30 articles on the effectiveness of brief interventions in the form of (a) crisis intervention, (b) integrated services, (c) group therapies, (d) individualised therapy, (e) parent–child dyadic therapy, (f) general services, (g) pharmacotherapy, (h) assessment services, (i) safety and risk planning and (j) in-hospital treatment, to improve outcomes for CYP with an acute mental health condition. Among included studies, one study was rated as providing a high level of evidence based on the National Health and Medical Research Council levels of evidence hierarchy scale, which was a crisis intervention showing a reduction in length of stay and return emergency department visits. Other studies, of moderate-quality evidence, described multimodal brief interventions that suggested beneficial effects. Conclusions This review provides evidence to substantiate the benefits of brief interventions, in different settings, to reduce the burden of in-patient hospital and readmission rates to the emergency department.

Abstract A controlled growth of two‐dimensional (2D) π‐conjugated metal‐organic frameworks (MOFs) on solid substrates can open exciting opportunities for the application of 2D MOFs as optoelectronic devices. Some factors like solvent composition and type of substrates are known to influence the properties of solution‐processed 2D MOF crystals; however, a mechanistic understanding of how interactions between solvent, substrate, and precursors affect heterogeneous nucleation has been limited. Here, it is reported that the structure of Ni‐catecholate (Ni‐CAT‐1) MOFs at a solid–liquid interface is controlled by solvent–substrate and solvent–MOF precursor interactions. Specifically, the structure of the MOF film can be controlled by varying the affinity of the solvent to the substrate. As a fraction of N,N‐dimethylformamide (DMF) in a binary solvent mixture of water and DMF increases, the arrangement of Ni‐CAT‐1 crystals varies from vertically aligned nanorods to the graphite substrate to less ordered nanorods with the lower initial nucleation number density of Ni‐CAT‐1 crystals on the surface.

Abstract Introduction The current study examined the contributions of comprehensive neuropsychological assessment and volumetric assessment of selected mesial temporal subregions on structural magnetic resonance imaging (MRI) to identify patients with amnestic mild cognitive impairment (aMCI) and mild probable Alzheimer's disease (AD) dementia in a memory clinic cohort. Methods Comprehensive neuropsychological assessment and automated entorhinal, transentorhinal, and hippocampal volume measurements were conducted in 40 healthy controls, 38 patients with subjective memory symptoms, 16 patients with aMCI, 16 patients with mild probable AD dementia. Multinomial logistic regression was used to compare the neuropsychological and MRI measures. Results Combining the neuropsychological and MRI measures improved group membership prediction over the MRI measures alone but did not improve group membership prediction over the neuropsychological measures alone. Conclusion Comprehensive neuropsychological assessment was an important tool to evaluate cognitive impairment. The mesial temporal volumetric MRI measures contributed no diagnostic value over and above the determinations made through neuropsychological assessment.

Abstract Population declines of vultures of the genus Gyps in the Indian Subcontinent in the 1990s and 2000s were among the most rapid global population declines recorded for any bird species. Multiple lines of evidence identified veterinary treatment of cattle with the non‐steroidal anti‐inflammatory drug (NSAID) diclofenac as the principal cause of the vulture population crash. Diclofenac causes kidney failure and death within a few days of a vulture scavenging the carcass of a recently treated cow. Despite coordinated regulatory action by governments to ban veterinary diclofenac in South Asia, enforcement has been incomplete in many areas. Progress in preventing the veterinary use of other NSAIDs now also known to be vulture‐toxic has been slow. A mosaic of inconsistent licensing processes currently exists across South Asian vulture range states, leading to issues with successful policy implementation, legitimacy and effectiveness. At present, mandatory safety testing to ensure NSAIDs already in use or proposed for use are vulture‐safe is not part of drug licensing procedures in any vulture range state. In 2021, Bangladesh became the first country to ban a vulture‐toxic NSAID, in addition to diclofenac, by banning veterinary use of ketoprofen. In 2023, India became the second country to take this step when the government announced a ban on veterinary aceclofenac and ketoprofen. This government action in India may have been triggered by a recent legal challenge. Despite its veterinary use now being banned in South Asian and the Middle Eastern countries, diclofenac has been authorised for sale since 2013 as a veterinary drug in Spain, even though Spain holds 90% of the vulture population of Europe. The European Commission's decision to leave the authorisation of this drug to Member States is at odds with a central pillar of environmental law in the European Union (EU): the precautionary principle. Furthermore, this approach is not consistent with the stringent standards and burden of proof applied to the licensing of EU plant protection products. Solution. A solution to this lack of protection of Gyps vulture populations is for regulatory regimes for veterinary NSAIDs to be augmented.

BackgroundLong term intervention services have proven to be effective in improving mental health (MH) outcomes and the quality of life for children and young people (CYP).AimTo synthesize evidence on the effectiveness of long-term interventions in improving MH outcomes for CYP, 0-17 years, presenting with MH conditions.MethodsA systematic search was carried out and the methodological quality of included long term MH intervention studies were assessed. Six databases were searched for peer-reviewed articles between January 2000 and September 2022.ResultsWe found 30 studies that reported on the effectiveness of a range of long-term MH interventions in the form of (i) group therapy, (ii) multisystemic behavior therapy, (iii) general services, (iv) integrated services, (v) psychotherapy, (vi) intensive intervention services, (vii) comprehensive collaborative care, (viii) parent training, and (ix) home outreach service. Among the included studies, seven were rated as high level of evidence based on the National Health and Medical Research Council (NHMRC) levels of evidence hierarchy scale and seven were of moderate quality evidence. Others were rated as lower-quality evidence. Among the studies providing high quality evidence, most were reported for group therapy, general services, and psychotherapy studies demonstrating beneficial effects.ConclusionThis systematic review provides evidence to demonstrate the benefits of a range of long-term interventions, in a range of settings, can be effective in improving MH outcomes for CYP and their families.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022323324.

The applicability of electrical impedance tomography (EIT) in birds is unknown. This study aimed to evaluate the use of EIT in anaesthetised chickens in four recumbency positions. Four adult Hyline chickens were anaesthetised with isoflurane in oxygen, and intubated endotracheally for computed tomography (CT). A rubber belt was placed around the coelom caudal to the shoulder joint. A chicken-specific finite element (FE) model, which is essential to generate anatomically accurate functional EIT images for analysis, was constructed based on the CT images obtained at the belt level. Ten additional chickens were anaesthetised with the same protocol. An EIT electrode belt was placed at the same location. The chickens were breathing spontaneously and positioned in dorsal, ventral, right and left lateral recumbency in a randomised order. For each recumbency, raw EIT data were collected over 2 min after 13 min of stabilisation. The data were reconstructed into functional EIT images. EIT variables including tidal impedance variation (TIV), centre of ventilation right to left (CoVRL) and ventral to dorsal (CoVVD), right to left (RL) ratio, impedance change (ΔZ) and eight regional impedance changes including the dorsal, central-dorsal, central-ventral and ventral regions of the right and left regions were analysed. Four breathing patterns (BrP) were observed and categorised based on the expiratory curve. A linear mixed model was used to compare EIT variables between recumbencies. Fisher's exact test was used to compare the frequencies of breathing patterns for each recumbency. The ΔZ observed was synchronous to ventilation, and represented tidal volume of the cranial air sacs as confirmed by CT. Significant differences were found in CoVVD and regional impedance changes between dorsal and ventral recumbencies (P < 0.05), and in CoVRL, RL ratio and regional impedance changes between right and left recumbencies (P < 0.05), which suggested a tendency for the distribution of ventilation to shift towards non-dependent air sacs. No differences were found for TIV and respiratory rate between recumbencies. Recumbency had a significant effect on the frequencies of each of the four BrPs (P = 0.001). EIT can monitor the magnitude and distribution of ventilation of the cranial air sacs in different recumbencies in anaesthetised chickens.

ABSTRACTPredators play a central role in shaping community structure, function, and stability. The degree to which bacteriophage predators (viruses that infect bacteria) evolve to be specialists with a single bacterial prey species versus generalists able to consume multiple types of prey has implications for their effect on microbial communities. The presence and abundance of multiple bacterial prey types can alter selection for phage generalists, but less is known about how interactions between prey shape predator specificity in microbial systems. Using a phenomenological mathematical model of phage and bacterial populations, we find that the dominant phage strategy depends on prey ecology. Given a fitness cost for generalism, generalist predators maintain an advantage when prey species compete, while specialists dominate when prey are obligately engaged in cross-feeding interactions. We test these predictions in a synthetic microbial community with interacting strains of Escherichia coli and Salmonella enterica by competing a generalist T5-like phage able to infect both prey against P22vir, an S. enterica-specific phage. Our experimental data conform to our modeling expectations when prey species are competing or obligately mutualistic, although our results suggest that the in vitro cost of generalism is caused by a combination of biological mechanisms not anticipated in our model. Our work demonstrates that interactions between bacteria play a role in shaping ecological selection on predator specificity in obligately lytic bacteriophages and emphasizes the diversity of ways in which fitness trade-offs can manifest.IMPORTANCEThere is significant natural diversity in how many different types of bacteria a bacteriophage can infect, but the mechanisms driving this diversity are unclear. This study uses a combination of mathematical modeling and an in vitro system consisting of Escherichia coli, Salmonella enterica, a T5-like generalist phage, and the specialist phage P22vir to highlight the connection between bacteriophage specificity and interactions between their potential microbial prey. Mathematical modeling suggests that competing bacteria tend to favor generalist bacteriophage, while bacteria that benefit each other tend to favor specialist bacteriophage. Experimental results support this general finding. The experiments also show that the optimal phage strategy is impacted by phage degradation and bacterial physiology. These findings enhance our understanding of how complex microbial communities shape selection on bacteriophage specificity, which may improve our ability to use phage to manage antibiotic-resistant microbial infections.