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Previously institutionalized adolescents show increased risk for psychopathology, though placement into high-quality foster care can partially mitigate this risk. White matter (WM) structure is associated with early institutional rearing and psychopathology in youth. Here we investigate associations between WM structure and psychopathology in previously institutionalized youth. Adolescent psychopathology data were collected using the MacArthur Health and Behavior Questionnaire. Participants underwent diffusion MRI, and data were processed using fixel-based analyses. General linear models investigated interactions between institutionalization groups and psychopathology on fixel metrics. Supplementary analyses also examined the main effects of psychopathology and institutionalization group on fixel metrics. Ever–Institutionalized children included 41 randomized to foster care (Mage=16.6), and 40 to care-as-usual (Mage=16.7)). In addition, 33 participants without a history of institutionalization were included as a reference group (Mage=16.9). Ever–Institutionalized adolescents displayed altered general psychopathology–fixel associations within the cerebellar peduncles, inferior longitudinal fasciculi, corticospinal tract, and corpus callosum, and altered externalizing–fixel associations within the cingulum and fornix. Our findings indicate brain–behavior associations reported in the literature may not be generalizable to all populations. Previously institutionalized youth may develop differential brain development, which in turn leads to altered neural correlates of psychopathology that are still apparent in adolescence.

Purpose: Patients with conjunctival squamous cell carcinoma that present with persisting disease or recurrence following topical chemotherapy and/or surgery especially when invading the sclera are challenging to treat. Herein, we describe the use of high-dose-rate (HDR), FDA-cleared, yttrium-90 (90Y) plaque brachytherapy for such lesions. Observation: Three cases of invasive conjunctival squamous cell carcinoma that had exhibited a poor response or recurrence following topical chemotherapy and/or surgery are described. As treatment, HDR 90Y beta-radiation was applied to the tumor and margins for a single, continuous duration. In contrast to low-dose-rate (LDR) plaque, HDR 90Y brachytherapy did not require episcleral sutures, amniotic membrane buffering of the cornea, a Gunderson flap, outpatient dwell time, or second surgery. Radiation safety was improved by eliminating LDR-implant related post-operative radiation exposure to health care personnel, the community, family, and pets. Follow-up examination at one month revealed complete tumor resolution in all patients. At last follow-up (8, 11 and 18 months) all patients remained clinically tumor-free as confirmed by slit-lamp biomicroscopy, anterior segment optical coherence tomography, and high-frequency ultrasound imaging. There were no acute complications (e.g., corneal edema, iridocyclitis, scleropathy, keratopathy or cataract). Conclusion and Importance: 90Y brachytherapy demonstrated efficacy as a single-surgery, minimally invasive, outpatient irradiation for squamous carcinoma of the ocular surface. While short-term results were promising, long-term follow-up monitoring for side-effects and recurrence are essential.

Traumatic brain injury (TBI) causes a prolonged inflammatory response in the central nervous system (CNS) driven by microglia. Microglial reactivity is exacerbated by stress, which often provokes sleep disturbances. We have previously shown that sleep fragmentation (SF) stress after experimental TBI increases microglial reactivity and impairs hippocampal function 30 days post-injury (DPI). The neuroimmune response is highly dynamic the first few weeks after TBI, which is also when injury induced sleep-wake deficits are detected. Therefore, we hypothesized that even a few weeks of TBI SF stress would synergize with injury induced sleep-wake deficits to promote neuroinflammation and impair outcome. Here, we investigated the effects of environmental SF in a lateral fluid percussion model of mouse TBI. Half of the mice were undisturbed, and half were exposed to 5 h of SF around the onset of the light cycle, daily, for 14 days. All mice were then undisturbed 15–30 DPI, providing a period for SF stress recovery (SF-R). Mice exposed to SF stress slept more than those in control housing 7–14 DPI and engaged in more total daily sleep bouts during the dark period. However, SF stress did not exacerbate post-TBI sleep deficits. Testing in the Morris water maze revealed sex dependent differences in spatial reference memory 9–14 DPI with males performing worse than females. Post-TBI SF stress suppressed neurogenesis-related gene expression and increased inflammatory signaling in the cortex at 14 DPI. No differences in sleep behavior were detected between groups during the SF stress recovery period 15–30 DPI. Microscopy revealed cortical and hippocampal IBA1 and CD68 percent-area increased in TBI SF-R mice 30 DPI. Additionally, neuroinflammatory gene expression was increased, and synaptogenesis-related gene expression was suppressed in TBI-SF mice 30 DPI. Finally, IPA canonical pathway analysis showed post-TBI SF impaired and delayed activation of synapse-related pathways between 14 and 30 DPI. These data show that transient SF stress after TBI impairs recovery and conveys long-lasting impacts on neuroimmune function independent of continuous sleep deficits. Together, these finding support that even limited exposure to post-TBI SF stress can have lasting impacts on cognitive recovery and regulation of the immune response to trauma.

Summary: Mechanisms by which Porphyromonas gingivalis (P. gingivalis) infection enhances oral tumor growth or resistance to cell death remain elusive. Here, we determined that P. gingivalis infection mediates therapeutic resistance via inhibiting lethal mitophagy in cancer cells and tumors. Mechanistically, P. gingivalis targets the LC3B-ceramide complex by associating with LC3B via bacterial major fimbriae (FimA) protein, preventing ceramide-dependent mitophagy in response to various therapeutic agents. Moreover, ceramide-mediated mitophagy is induced by Annexin A2 (ANXA2)-ceramide association involving the E142 residue of ANXA2. Inhibition of ANXA2-ceramide-LC3B complex formation by wild-type P. gingivalis prevented ceramide-dependent mitophagy. Moreover, a FimA-deletion mutant P. gingivalis variant had no inhibitory effects on ceramide-dependent mitophagy. Further, 16S rRNA sequencing of oral tumors indicated that P. gingivalis infection altered the microbiome of the tumor macroenvironment in response to ceramide analog treatment in mice. Thus, these data provide a mechanism describing the pro-survival roles of P. gingivalis in oral tumors.

Background: Pseudomonas aeruginosa is an opportunistic bacterium that causes serious hospital-acquired infections. To assess the risk of clinically isolated P. aeruginosa to human health, we analyzed the resistance and virulence mechanisms of a collection of clinical isolates. Methods: This was a retrospective study in which P. aeruginosa isolates collected from January 1, 2018 to August 31, 2019 were analyzed using phenotypic and whole-genome sequencing (WGS) methods. The analysis included 48 clinical samples. Median patient age was 54.0 (29.5) years, and 58.3% of patients were women. Data from the microbiology laboratory database were reviewed to identify P. aeruginosa isolates. All unique isolates available for further testing were included, and related clinical data were collected. Infections were defined as hospital acquired if the index culture was obtained at least 48 h after hospitalization. Results: High-risk P. aeruginosa clones, including sequence types (STs) ST235 and ST111, were identified, in addition to 12 new STs. The isolates showed varying degrees of biofilm formation ability when evaluated at room temperature, along with reduced metabolic activity, as measured by metabolic staining, suggesting their ability to evade antimicrobial therapy. Most isolates (77.1%) were multidrug resistant (MDR), with the highest resistance and susceptibility rates to beta-lactams and colistimethate sodium, respectively. Conclusions: The MDR phenotypes of the examined isolates can be explained by the high prevalence of efflux-mediated resistance- and hydrolytic enzyme-encoding genes. These isolates had high cytotoxic potential, as indicated by the detection of toxin production-related genes.

Summary: Metastasis is one of the defining features of pancreatic ductal adenocarcinoma (PDAC) that contributes to poor prognosis. In this study, the palmitoyl transferase ZDHHC20 was identified in an in vivo short hairpin RNA (shRNA) screen as critical for metastatic outgrowth, with no effect on proliferation and migration in vitro or primary PDAC growth in mice. This phenotype is abrogated in immunocompromised animals and animals with depleted natural killer (NK) cells, indicating that ZDHHC20 affects the interaction of tumor cells and the innate immune system. Using a chemical genetics platform for ZDHHC20-specific substrate profiling, a number of substrates of this enzyme were identified. These results describe a role for palmitoylation in enabling distant metastasis that could not have been detected using in vitro screening approaches and identify potential effectors through which ZDHHC20 promotes metastasis of PDAC.

Despite copious data linking brain function with changes to social behavior and mental health, little is known about how puberty relates to brain functioning. We investigated the specificity of brain network connectivity associations with pubertal indices and age to inform neurodevelopmental models of adolescence. We examined how brain network connectivity during a peer evaluation fMRI task related to pubertal hormones (dehydroepiandrosterone and testosterone), pubertal timing and status, and age. Participants were 99 adolescents assigned female at birth aged 9–15 (M = 12.38, SD = 1.81) enriched for the presence of internalizing symptoms. Multivariate analysis revealed that within Salience, between Frontoparietal – Reward and Cinguloopercular – Reward network connectivity were associated with all measures of pubertal development and age. Specifically, Salience connectivity linked with age, pubertal hormones, and status, but not timing. In contrast, Frontoparietal – Reward connectivity was only associated with hormones. Finally, Cinguloopercular – Reward connectivity related to age and pubertal status, but not hormones or timing. These results provide evidence that the salience processing underlying peer evaluation is jointly influenced by various indices of puberty and age, while coordination between cognitive control and reward circuitry is related to pubertal hormones, pubertal status, and age in unique ways.

The mobility of rare earth elements (REE) and arsenic (As) from acid mine drainage (AMD) impacted soil was investigated in a column leaching study. AMD impacted soils from prominent gold and coal mining regions in South Africa were eluted with a 1 µM CaCl2 solution for 14 h and samples were collected at timed intervals corresponding to liquid to solid (L/S) ratios from 0 to 10. The results showed fast initial leaching (L/S

The Prairie region of Canada is an agriculture-intensive area and is strategic to Canada's food security. Moisture deficit due to extreme temperatures leading to high evapotranspiration can have significant impacts on water availability, resulting in poor crop yield. The primary objective of this study is to quantify the spatial structure and dependency of extreme temperatures by employing Max-Stable Process (MSP) modeling on daily annual maximum temperature data spanning 1970–2020. The spatial trend surface of the marginal parameters of the Spatial Generalized Extreme Value (SGEV) shows that geographical coordinates, topography due to the Rocky Mountains, and proximity (Euclidean distance) to Hudson Bay are important covariates in capturing the spatial trend of extreme temperatures. Furthermore, through the SGEV, important products such as the point-wise return periods and levels were derived using the best selected model as determined by Takeuchi's information criteria. The return levels show that the southern portion of the Canadian Prairies shows a consistent increase in extreme temperature for all the return periods. The results show that all the return periods mentioned above have extreme temperatures exceeding 37 °C in the southern portion of the Canadian Prairies. An unconditional simulation using the fitted MSP model provided various realizations of temperature extremes. The results from this study provide important insights into extreme temperatures in this important region, where water resources management is crucial. This study will be beneficial to the hydrologists, water resource specialists, climate change scientists and policy makers involved in the monitoring of extreme events in the Canadian Prairies.

Energy system models are important tools to guide our understanding of current and future carbon dioxide emissions as well as to inform strategies for emissions reduction. These models offer a vital evidence base that increasingly underpins energy and climate policies in many countries. In light of this important role in policy formation, there is growing interest in, and demands for, energy modellers to integrate more diverse perspectives on possible and preferred futures into the modelling process. The main purpose of this is to ensure that the resultant policy decisions are both fairer and better reflect people's concerns and preferences. However, while there has been a focus in the literature on efforts to bring societal dimensions into modelling tools, there remains a limited number of examples of well-structured participatory energy systems modelling processes and no available how-to guidance. This paper addresses this gap by providing good practice guidance for integrating stakeholder and public involvement in energy systems modelling based on the reflections of a diverse range of experts from this emergent field. The framework outlined in this paper offers multiple entry points for modellers to incorporate participatory elements either throughout the process or in individual stages. Recognising the messiness of both fields (energy systems modelling and participatory research), the good practice principles are not comprehensive or set in stone, but rather pose important questions to steer this process. Finally, the reflections on key issues provide a summary of the crucial challenges and important areas for future research in this critical field.

Summary: Background: Deep learning has revolutionized digital pathology, allowing automatic analysis of hematoxylin and eosin (H&E) stained whole slide images (WSIs) for diverse tasks. WSIs are broken into smaller images called tiles, and a neural network encodes each tile. Many recent works use supervised attention-based models to aggregate tile-level features into a slide-level representation, which is then used for downstream analysis. Training supervised attention-based models is computationally intensive, architecture optimization of the attention module is non-trivial, and labeled data are not always available. Therefore, we developed an unsupervised and fast approach called SAMPLER to generate slide-level representations. Methods: Slide-level representations of SAMPLER are generated by encoding the cumulative distribution functions of multiscale tile-level features. To assess effectiveness of SAMPLER, slide-level representations of breast carcinoma (BRCA), non-small cell lung carcinoma (NSCLC), and renal cell carcinoma (RCC) WSIs of The Cancer Genome Atlas (TCGA) were used to train separate classifiers distinguishing tumor subtypes in FFPE and frozen WSIs. In addition, BRCA and NSCLC classifiers were externally validated on frozen WSIs. Moreover, SAMPLER's attention maps identify regions of interest, which were evaluated by a pathologist. To determine time efficiency of SAMPLER, we compared runtime of SAMPLER with two attention-based models. SAMPLER concepts were used to improve the design of a context-aware multi-head attention model (context-MHA). Findings: SAMPLER-based classifiers were comparable to state-of-the-art attention deep learning models to distinguish subtypes of BRCA (AUC = 0.911 ± 0.029), NSCLC (AUC = 0.940 ± 0.018), and RCC (AUC = 0.987 ± 0.006) on FFPE WSIs (internal test sets). However, training SAMLER-based classifiers was >100 times faster. SAMPLER models successfully distinguished tumor subtypes on both internal and external test sets of frozen WSIs. Histopathological review confirmed that SAMPLER-identified high attention tiles contained subtype-specific morphological features. The improved context-MHA distinguished subtypes of BRCA and RCC (BRCA-AUC = 0.921 ± 0.027, RCC-AUC = 0.988 ± 0.010) with increased accuracy on internal test FFPE WSIs. Interpretation: Our unsupervised statistical approach is fast and effective for analyzing WSIs, with greatly improved scalability over attention-based deep learning methods. The high accuracy of SAMPLER-based classifiers and interpretable attention maps suggest that SAMPLER successfully encodes the distinct morphologies within WSIs and will be applicable to general histology image analysis problems. Funding: This study was supported by the National Cancer Institute (Grant No. R01CA230031 and P30CA034196).

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with liver and cardiovascular morbidity and mortality. Recently published NAFLD Quality Standards include 11 key performance indicators (KPIs) of good clinical care. This national study, endorsed by British Association for the Study of the Liver (BASL) and British Society of Gastroenterology (BSG), aimed to benchmark NAFLD care in UK hospitals against these KPIs. Methods: This study included all new patients with NAFLD reviewed in the outpatient clinic in the months of March 2019 and March 2022. Participating UK hospitals self-registered for the study through BASL/BSG. KPI outcomes were compared using Fisher’s exact or Chi-square tests. Results: Data from 776 patients with NAFLD attending 34 hospitals (England [25], Scotland [four], Wales [three], Northern Ireland [two]) were collected. A total of 85.3% of hospitals reported established local liver disease assessment pathways, yet only 27.9% of patients with suspected NAFLD had non-invasive fibrosis assessment documented at the point of referral to secondary care. In secondary care, 79.1% of patients had fibrosis assessment. Assessment of cardiometabolic risk factors including obesity, type 2 diabetes, hypertension, and smoking were conducted in 73.2%, 33.0%, 19.3%, and 54.9% of all patients, respectively. There was limited documentation of diet (35.7%) and exercise advice (55.1%). Excluding those on statins, only 9.1% of patients with NAFLD at increased cardiovascular risk (T2DM and/or QRISK-3 >10%) had documented discussion of statin treatment. Significant KPI improvements from 2019 to 2022 were evident in use of non-invasive fibrosis assessment before secondary care referral, statin recommendations, and diet and exercise recommendations. Conclusions: This national study identified substantial variation in NAFLD management in the UK with clear areas for improvement, particularly fibrosis risk assessment before secondary care referral and management of associated cardiometabolic risk factors. Impact and implications: This study identified significant variation in the management of NAFLD in the UK. Only 27.9% of patients with suspected NAFLD had non-invasive fibrosis assessment performed to identify those at greater risk of advanced liver disease before specialist referral. Greater emphasis is needed on the management of associated cardiometabolic risk factors in individuals with NAFLD. Hospitals with multidisciplinary NAFLD service provision had higher rates of fibrosis evaluation and assessment and management of cardiometabolic risk than hospitals without multidisciplinary services. Further work is needed to align guideline recommendations and real-world practice in NAFLD care.

Background: With notable benefits in reducing length of stay (LOS), this study aimed to quantify the temporal trend and the factors contributing to increased LOS for primary and revision total hip (THA and rTHA) and knee (TKA and rTKA) arthroplasty. The study was carried out for a large population-based cohort over a 20-year period. Methods: This was a retrospective population-based study assessing the LOS for all primary and revision THA and TKA procedures between 2003 and 2022. The primary outcome of interest was LOS. Univariate and multivariate analyses were performed to identify associated variables. Results: For the entire dataset, there were 16,677 primary THAs, 13,018 primary TKAs, 3276 (aseptic) rTHAs, 1445 (aseptic) rTKAs, 820 (septic) rTHAs, and 667 (septic) rTKAs. The median LOS over the 20-year period between 2003 and 2022 demonstrated a steady and continuous decline from a median of 5 days (interquartile range 3-7) in 2003 to 1 day (interquartile range 1-2) in 2022. On multivariate analysis, there were a number of factors associated with increasing LOS: year of procedure (P < .0001), procedure type (P < .0001), age (P < .0001), and American Society of Anesthesiologists class (P < .0001). On multivariate analysis, body mass index was not associated with increased LOS (P = .5631). Conclusions: There was a downward trend in LOS for all types of primary and revision THA and TKA. The factors contributing most to a reduction in LOS include the year the procedure was performed, primary THA procedures, aseptic (vs periprosthetic joint infection) revision procedures, younger age, and lower American Society of Anesthesiologists classes.

Background: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. Methods: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. Results: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. Conclusion: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.

Approximately 70% of Earth’s surface is impacted by human land-use. While numerous studies have demonstrated that species richness is higher in primary (undisturbed) forest than in secondary forest or agriculture sites, some studies fail to detect differences in species richness across land-use type. Recent work suggests that individual-level changes such as body size or body condition can occur more rapidly than population- or community-level processes, such as abundance and species richness, respectively. Thus, body size and condition may be more sensitive measures of environmental changes. We examined body size, body condition, abundance, and species richness of anurans in primary forest, secondary forest, and agriculture in Sabah, Malaysian Borneo, to determine whether individual-, population-, and community-level measures show similar sensitivities to land-use type. We found that observed anuran species richness and estimated population size are lower in agriculture than in primary or secondary forest, as were body size (SVL), mass, and body condition of female Meristogenys orphnocnemis. Further, anuran body condition (all species pooled) was higher in primary forest than agriculture or secondary forest, and size (SVL), mass, and body condition of male M. orphnocnemis were higher in primary forest than in agriculture or secondary forest areas. Collectively, our data demonstrate that primary forests are the best habitat for anurans in Sabah, and that individual-level processes such as size, mass, and body condition, show larger differences across land-use type than population- (abundance) or community-level processes (species richness). These data highlight the importance of primary forest for preserving anuran biodiversity in Borneo.

Background: Delays in starting postoperative radiotherapy (PORT) have been established as negative predictors for clinical outcomes in head and neck squamous cell carcinomas (HNSCC). Our study aimed to examine the effect of delays during PORT, and the impact of national holidays in Canada, a publicly funded system, on oncologic outcomes such as Overall Survival (OS) and Local Recurrence (LR). Methods: The provincial cancer registry was queried to obtain demographic, pathologic, and outcomes data from cancer patients treated for all squamous cell carcinomas of the head and neck region treated between January 1, 2007 and November 30, 2019. All extracted information was cross-referenced and supplemented by chart review of patient electronic medical records. Extracted data were analyzed for OS and LR, in the context of Canadian national holidays causing delays during PORT. Results: 1433 patients treated for HNSCCs were identified, of whom 338 were treated curatively with surgery followed by PORT. 68.6% of patients experienced at least one day of interruption during treatments due to holidays. LR was 15.4% and OS was 59.6% at 5 years. Treatment interruptions by holidays were predictive of local recurrence (HR, 2.38; 95% CI 1.17–4.83; p = 0.017). Patients that developed early recurrence prior to PORT had very poor oncologic outcomes. Conclusion: Our findings were consistent with previously published studies in limiting the interval between surgery and PORT. We identified the novel finding of paired holidays as a significant predictor in determining LR, suggesting the importance of modifying RT delivery schedules and timing.

Summary: In the brain, the complement system plays a crucial role in the immune response and in synaptic elimination during normal development and disease. Here, we sought to identify pathways that modulate the production of complement component 4 (C4), recently associated with an increased risk of schizophrenia. To design a disease-relevant assay, we first developed a rapid and robust 3D protocol capable of producing large numbers of astrocytes from pluripotent cells. Transcriptional profiling of these astrocytes confirmed the homogeneity of this population of dorsal fetal-like astrocytes. Using a novel ELISA-based small-molecule screen, we identified epigenetic regulators, as well as inhibitors of intracellular signaling pathways, able to modulate C4 secretion from astrocytes. We then built a connectivity map to predict and validate additional key regulatory pathways, including one involving c-Jun-kinase. This work provides a foundation for developing therapies for CNS diseases involving the complement cascade.

The mobilisation of potentially harmful chemical constituents in wildfire ash can be a major consequence of wildfires, posing widespread societal risks. Knowledge of wildfire ash chemical composition is crucial to anticipate and mitigate these risks.Here we present a comprehensive dataset on the chemical characteristics of a wide range of wildfire ashes (42 types and a total of 148 samples) from wildfires across the globe and examine their potential societal and environmental implications. An extensive review of studies analysing chemical composition in ash was also performed to complement and compare our ash dataset.Most ashes in our dataset had an alkaline reaction (mean pH 8.8, ranging between 6 and 11.2). Important constituents of wildfire ash were organic carbon (mean: 204 g kg−1), calcium, aluminium, and iron (mean: 47.9, 17.9 and 17.1 g kg−1). Mean nitrogen and phosphorus ranged between 1 and 25 g kg−1, and between 0.2 and 9.9 g kg−1, respectively. The largest concentrations of metals of concern for human and ecosystem health were observed for manganese (mean: 1488 mg kg−1; three ecosystems > 1000 mg kg−1), zinc (mean: 181 mg kg−1; two ecosystems > 500 mg kg−1) and lead (mean: 66.9 mg kg−1; two ecosystems > 200 mg kg−1). Burn severity and sampling timing were key factors influencing ash chemical characteristics like pH, carbon and nitrogen concentrations. The highest readily dissolvable fractions (as a % of ash dry weight) in water were observed for sodium (18 %) and magnesium (11.4 %). Although concentrations of elements of concern were very close to, or exceeded international contamination standards in some ashes, the actual effect of ash will depend on factors like ash loads and the dilution into environmental matrices such as water, soil and sediment. Our approach can serve as an initial methodological standardisation of wildfire ash sampling and chemical analysis protocols.

Background Serosurveillance can be used to investigate the extent and distribution of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within a population. Characterisation of humoral immune responses gives insight into whether immunity is infection- or vaccine-derived.Methods A longitudinal study of health care workers (HCWs) in Dili, Timor-Leste, was conducted during vaccine rollout (ChAdOx1) and a concurrent SARS-CoV-2 outbreak.Results A total of 324 HCWs were included at baseline (April-May 2021). Out of those, 32 (9.9%) were seropositive for anti-nucleocapsid protein (anti-N) IgG antibodies, indicating a significant sub-clinical infection among HCWs early in the local outbreak. Follow-up was conducted in 157 (48.5%) participants (July-September 2021), by which time there had been high uptake of vaccination (91.7%), and 86.0% were seropositive for anti-spike protein antibodies. Acquisition of anti-N antibodies was observed in partially vaccinated HCWs (30/76, 39.5%), indicating some post-dose-1 infections.Discussion Serosurveillance of HCWs may provide early warning of SARS-CoV-2 outbreaks and should be considered in non-endemic settings, particularly where there is limited availability/uptake of testing for acute infection. Characterisation of humoral immune responses may be used to assess vaccine impact and coverage. Such studies should be considered in national and international efforts to investigate and mitigate against future emerging pathogens.

Intro: The World Health Organisation recommends that healthcare workers (HCWs) are immune to measles and rubella, and those at risk of blood exposure are offered hepatitis B vaccine. There have been no studies of vaccine- preventable disease (VPD) seroprevalence among HCWs in Timor-Leste and there is no formal program for occupational assessment or provision of vaccinations. Methods: A cross sectional study was undertaken to determine seroprevalence of hepatitis B, measles and rubella among HCWs in Dili, Timor-Leste. All patient- facing employees at three healthcare institutions during April-June 2021 were invited to participate. Epidemiological data was collected by interview- questionnaire and a serum sample was collected by phlebotomy and analysed at the National Health Laboratory. Participants were contacted to discuss results. Vaccines were provided to seronegative individuals and those with active hepatitis B infection were referred for further assessment and management in hepatology clinic. Findings: Three-hundred-and-twenty-four HCWs were included (representing 51.3% of all eligible HCWs registered as working at the three participating institutions). Sixteen (4.9%) had active hepatitis B infection, 121 (37.3%) had evidence of previous (cleared) hepatitis B infection, 134 (41.4%) were hepatitis B naïve, and 53 (16.4%) had been vaccinated. Two-hundred-and-sixty-seven (82.4%) and 306 (94.4%) individuals exhibited antibodies to measles and rubella, respectively. At the time of writing 97/134 (72.4%) of elligible participants had recieved one or more dose of hepatitis B vaccine and 36/57 (56.8%) of elligible participants had recieved one or more dose of measles- rubella vaccine. Conclusion: This study identified significant immunity gaps and a high burden of hepatitis B infection among HCWs in Dili Municipality, Timor-Leste. HCWs and patients may be at risk. Routine occupational assessment and targeted vaccination of this group would be beneficial. This study forms a template for a national guideline.

Summary: Bromodomain-containing protein 8 (BRD8) is a subunit of the NuA4/TIP60-histone acetyltransferase complex. Although BRD8 has been considered to act as a co-activator of the complex, its biological role remains to be elucidated. Here, we uncovered that BRD8 accumulates in colorectal cancer cells through the inhibition of ubiquitin-dependent protein degradation by the interaction with MRG domain binding protein. Transcriptome analysis coupled with genome-wide mapping of BRD8-binding sites disclosed that BRD8 transactivates a set of genes independently of TIP60, and that BRD8 regulates the expression of multiple subunits of the pre-replicative complex in concert with the activator protein-1. Depletion of BRD8 induced cell-cycle arrest at the G1 phase and suppressed cell proliferation. We have also shown that the bromodomain of BRD8 is indispensable for not only the interaction with histone H4 or transcriptional regulation but also its own protein stability. These findings highlight the importance of bromodomain as a therapeutic target.

Extensions of the Standard Model have been attempted from the bottom up and from the top down, yet there remains a largely unexplored middle ground. In this paper, using the Mathematica package LieART, we exhaustively enumerate embeddings of the Standard Model within the class of theories with bifundamental fermions in product gauge group SU(a)×SU(b)×SU(c) with no more generators than E6, while achieving SM family unification rather than replication. We incorporate simple phenomenological constraints and find 151 unique models, including 9 that have only vector-like particle content beyond-the-Standard Model (BSM) particles, which we conjecture belong to 5 infinite families of such models. We describe the potentially most viable models: namely, the 9 with strictly vector-like BSM content along with the 29 models we found with no more than 30 additional BSM chiral particles. These include models with fractional electric charge color singlets, and hence magnetic monopoles with multiple Dirac charge. This latter collection of models predicts chiral particles with masses near the electroweak scale accessible to current and future collider experiments.

Earlier pubertal development appears to be one pathway through which childhood trauma contributes to psychopathology in adolescence. Puberty-related changes in neural networks involved in emotion processing, namely the amygdala-medial prefrontal (mPFC) circuit, may be a potential mechanism linking trauma and adolescent psychopathology. Our participants were 227 youth between 10 and 13 years of age who completed assessments of threat and deprivation-related experiences of adversity, pubertal stage, and internalizing and externalizing symptoms. A subset (n = 149) also underwent a functional MRI scan while passively viewing fearful and calm faces. Potential mechanisms linking childhood trauma with psychopathology, encompassing earlier pubertal timing and neural response to aversive stimuli were explored. Earlier pubertal development was associated with childhood trauma as well as increased externalizing symptoms in boys only. Earlier pubertal timing in males and females was negatively associated with activation in bilateral amygdala, hippocampal, and fusiform regions when comparing fearful and calm faces. However, amygdala-mPFC connectivity showed no association with pubertal timing or psychopathology symptoms. These findings do not support accelerated amygdala-mPFC development as a mechanism linking childhood trauma and psychopathology, but instead provide support for the role of pubertal development in normative decreases in limbic activation across development.

The dimensional model of adversity proposes that experiences of threat and deprivation have distinct neurodevelopmental consequences. We examined these dimensions, separately and jointly, with brain structure in a sample of 149 youth aged 8–17—half recruited based on exposure to threat-related experiences. We predicted that greater threat would be uniquely associated with reduced cortical thickness and surface area in brain regions associated with salience processing including ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), and insula, and that deprivation experiences would be uniquely associated with reductions in cortical thickness and surface area in frontoparietal areas associated with cognitive control. As predicted, greater threat was associated with thinner cortex in a network including areas involved in salience processing (anterior insula, vmPFC), and smaller amygdala volume (particularly in younger participants), after controlling for deprivation. Contrary to our hypotheses, threat was also associated with thinning in the frontoparietal control network. However, these associations were reduced following control for deprivation. No associations were found between deprivation and brain structure. This examination of deprivation and threat concurrently in the same sample provided further evidence that threat-related experiences influence the structure of the developing brain independent of deprivation.

Background and objectives: Diabetes is an increasing public health concern worldwide. The impact of extreme heat exposure on diabetes healthcare utilization such as diabetes-related hospital admissions and emergency department (ED) visits was understudied although extreme temperature exposure was linked with diabetes mortality. In addition, very few systematic reviews have been conducted in this field. This review aims to systematically evaluate the currently available evidence on the association between extreme ambient heat exposure and hospital admissions/ED visits for diabetes and the vulnerable population to heat extremes. Methods: A systematic literature review was conducted by using the keywords/terms “ambient temperature or heatwave or heat wave or extreme temperature or high temperature effect” and “diabetes morbidity or diabetes hospital admissions or diabetes emergency room visits” for available publications until August 2022. The heat exposure was categorized into four groups using difference definitions. The outcomes were diabetes-related hospital admissions/ED visits. A meta-analysis was performed to estimate the pooled effects of relative risk (RR)/odds ratio (OR) and 95% confidence intervals (CI) for each of the associations of interest. Results: Eighteen articles were selected from forty full-text, English written papers based on the inclusion and exclusion criteria. The overall pooled effect of excessive heat on diabetes, across all groups, was 1.045 (95% CI: 1.024-1.066). The pooled effects for each exposure group were significant/borderline significant. Additionally, the pooled effect of the RR/OR was 1.100 (95% CI: 1.067-1.135) among adults aged 65 years or older. The most controlled confounders were air pollutants. The commonly listed limitation in those studies was misclassification of exposure. Conclusions: The body of evidence supports that ambient extreme heat exposure is associated with diabetes-related hospital admissions/ED visits. Additionally, adults 65 years of age or older with diabetes are vulnerable to heat extremes. Future studies should consider controlling for various biases and confounders.

Background: Although power outage (PO) is one of the most important consequences of increasing weather extremes and the health impact of POs has been reported previously, studies on the neighborhood environment underlying the population vulnerability in such situations are limited. This study aimed to identify dominant neighborhood environmental predictors which modified the impact of POs on multiple health outcomes in New York State. Methods: We applied a two-stage approach. In the first stage, we used time series analysis to determine the impact of POs (versus non-PO periods) on multiple health outcomes in each power operating division in New York State, 2001-2013. In the second stage, we classified divisions as risk-elevated and non-elevated, then developed predictive models for the elevation status based on 36 neighborhood environmental factors using random forest and gradient boosted trees. Results: Consistent across different outcomes, we found predictors representing greater urbanization, particularly, the proportion of residents having access to public transportation (importance ranging from 4.9–15.6%), population density (3.3–16.1%), per capita income (2.3–10.7%), and the density of public infrastructure (0.8–8.5%), were associated with a higher possibility of risk elevation following power outages. Additionally, the percent of minority (-6.3–27.9%) and those with limited English (2.2–8.1%), the percent of sandy soil (6.5–11.8%), and average soil temperature (3.0–15.7%) were also dominant predictors for multiple outcomes. Spatial hotspots of vulnerability generally were located surrounding New York City and in the northwest, the pattern of which was consistent with socioeconomic status. Conclusion: Population vulnerability during power outages was dominated by neighborhood environmental factors representing greater urbanization.

Objective: Zinc transporter 8 (ZnT8) is a major humoral target in human type 1 diabetes (T1D). Polymorphic variants of Slc30A8, which encodes ZnT8, are also associated with protection from type 2 diabetes (T2D). The current study examined whether ZnT8 might play a role beyond simply being a target of autoimmunity in the pathophysiology of T1D. Methods: The phenotypes of NOD mice with complete or partial global loss of ZnT8 were determined using a combination of disease incidence, histological, transcriptomic, and metabolic analyses. Results: Unexpectedly, while complete loss of ZnT8 accelerated spontaneous T1D, heterozygosity was partially protective. In vivo and in vitro studies of ZnT8 deficient NOD.SCID mice suggested that the accelerated disease was due to more rampant autoimmunity. Conversely, beta cells in heterozygous animals uniquely displayed increased mitochondrial fitness under mild proinflammatory conditions. Conclusions: In pancreatic beta cells and immune cell populations, Zn2+ plays a key role as a regulator of redox signaling and as an independent secondary messenger. Importantly, Zn2+ also plays a major role in maintaining mitochondrial homeostasis. Our results suggest that regulating mitochondrial fitness by altering intra-islet zinc homeostasis may provide a novel mechanism to modulate T1D pathophysiology.

Myriad findings connect stress and inflammation to mood disorders. Social defeat in mice promotes the convergence of neuronal, central inflammatory (microglia), and peripheral immune (monocytes) pathways causing anxiety, social avoidance, and “stress-sensitization.” Stress-sensitization results in augmented inflammation and the recurrence of anxiety after re-exposure to social stress. Different cell compartments, including neurons, may be uniquely sensitized by social defeat-induced interleukin-1 (IL-1) signaling. Therefore, the aim of this study was to determine if glutamatergic neuronal IL-1 receptor signaling was essential in promoting stress-sensitization after social defeat. Here, wild-type (IL-1R1+/+) mice and mice with IL-1 receptor-1 deleted selectively in glutamatergic neurons (Vglut2-IL-1R1−/−) were stress-sensitized by social defeat (6-cycles) and then exposed to acute defeat (1-cycle) at day 30. Acute defeat-induced neuronal activation (ΔFosB and phospo-CREB) in the hippocampus of stress-sensitized mice was dependent on neuronal IL-1R1. Moreover, acute defeat-induced social withdrawal and working memory impairment in stress-sensitized mice were also dependent on neuronal IL-1R1. To address region and time dependency, an AAV2-IL-1 receptor antagonist construct was administered into the hippocampus after sensitization, but prior to acute defeat at day 30. Although stress-sensitized mice had increased hippocampal pCREB and decreased working memory after stress re-exposure, these events were not influenced by AAV2-IL-1 receptor antagonist. Hippocampal ΔFosB induction and corresponding social withdrawal in stress-sensitized mice after stress re-exposure were prevented by the AAV2-IL-1 receptor antagonist. Collectively, IL-1 signaling in glutamatergic neurons of the hippocampus was essential in neuronal-sensitization after social defeat and the recall of social withdrawal.

Even when subjects are at rest, it is thought that brain activity is organized into distinct brain states during which reproducible patterns are observable. Yet, it is unclear how to define or distinguish different brain states. A potential source of brain state variation is arousal, which may play a role in modulating functional interactions between brain regions. Here, we use simultaneous resting state functional magnetic resonance imaging (fMRI) and pupillometry to study the impact of arousal levels indexed by pupil area on the integration of large-scale brain networks. We employ a novel sparse dictionary learning-based method to identify hub regions participating in between-network integration stratified by arousal, by measuring k-hubness, the number (k) of functionally overlapping networks in each brain region. We show evidence of a brain-wide decrease in between-network integration and inter-subject variability at low relative to high arousal, with differences emerging across regions of the frontoparietal, default mode, motor, limbic, and cerebellum networks. State-dependent changes in k-hubness relate to the actual patterns of network integration within these hubs, suggesting a brain state transition from high to low arousal characterized by global synchronization and reduced network overlaps. We demonstrate that arousal is not limited to specific brain areas known to be directly associated with arousal regulation, but instead has a brain-wide impact that involves high-level between-network communications. Lastly, we show a systematic change in pairwise fMRI signal correlation structures in the arousal state-stratified data, and demonstrate that the choice of global signal regression could result in different conclusions in conventional graph theoretical analysis and in the analysis of k-hubness when studying arousal modulations. Together, our results suggest the presence of global and local effects of pupil-linked arousal modulations on resting state brain functional connectivity.

Eutrophication has been a prevalent problem in South African water bodies for many decades, resulting in algal blooms and growth of invasive alien aquatic weeds such as water hyacinth. It was brought under control in the 1990′s, but in recent years this problem has been exacerbated by increasing incidences of untreated sewage entering the river systems, along with other anthropogenic nutrient sources. This study investigated the potential for water hyacinth to be used as a phytoremediation tool to reduce the eutrophic state of Hartbeespoort Dam, and to determine if the water quality, aside from the nutrient concentrations, affects the rate of removal of nutrients by water hyacinth. Water hyacinth plants were grown in both water from the Hartbeespoort Dam and Hoagland Solution to test the effect of growth medium ‘purity’ on hyacinth growth. Another set of vessels containing Hartbeespoort Dam water only, without a hyacinth plant, was used to observe the remediation potential of the plant and its effectiveness at suppressing algal growth. The results show that one plant can absorb up to 7,38 mg of Phosphates and 27 mg of Nitrates within 11 days. Water hyacinth can reduce the nutrient concentration of 3 L of Hartbeespoort Dam water from 0,65 mg/L phosphates to 0,04 mg/L phosphate and from 4,1 mg/L nitrates to 0,5 mg/L nitrates in 4 days. These results suggest that water hyacinth can be employed as a phytoremediation tool to mitigate eutrophication in open water bodies and may have the potential to reduce Microcystis blooms.

The out-of-phase rainfall and temperature and deep root system make the sequential connection between past rainfall events, soil water storage, and forest growth response complicated and temporally extended in asynchronous climates with Mediterranean-type settings. Unfortunately, these location-specific deep-soil water stores are rarely measured due to logistic and financial constraints, especially in the forest. Therefore, at a large spatio-temporal scale, forest growth relationship to growth drivers is still unknown in these ecosystems, limiting our knowledge to understand the functioning of these forests and their links with hydrological processes. Although process-based water balance models can analyze vegetation growth response to the input climate forcing, they rely upon some significant assumptions regarding plants access to deep soil water storage. Thus, this study aims to understand how the out-of-phase rainfall events affect the current ecosystem growth response, represented by the observed Normalized Difference Vegetation Index (NDVI), across the landscape. We have used an empirical approach on long term observed data without any assumption on access to deep-soil water stores. We estimated time lags between forest growth and rainfall events using a lagged correlation analysis applied to monthly anomalies of NDVI and rainfall against their climatological averages over 2002–2018. The study found that the forests in asynchronous climates exhibit unexpectedly long (10–25 months) memory to rain, and this memory has a systematic pattern across the landscape, which we contend has highlighted three things: 1) the forest in the middle aridity (∼3–4.5) range are relatively more sensitive to changes in the short-term rainfall than the forest in lower (5) aridity regions, could be due to rapid depletion of relatively small soil water storage in between the storms, 2) the variable memory of forest to rain across the landscape can be an indicator of soil depth/rooting depth, and 3) the variable sized location specific antecedent rainfall windows can explain significant variability in forest growth status in asynchronous climates, thus these rainfall windows can be employed to forecast forest growth with a lead time (>4 months).

The design an effective treatment processes for the remediation of acid mine drainage (AMD) requires an understanding of the composition of the AMD water. The pH and elemental composition of AMD waters are site specific and are dependent on the regional geology, and environmental factors. To establish the chemical and physical characteristics of two AMD sites located in the Mpumalanga coal mining region, South Africa, samples were taken between February 2018 to April 2019. These data were compared against regulatory legislation, and the potential health effects of exposure indicated. Strong correlations were noted between parameters and statistical evaluation demonstrated that electrical conductivity (EC) could be a useful correlative for prediction of total acidity, dissolved iron, and sulfur concentrations in acidic AMD waters. From these findings, empirical correlations were used to derive regression equations which were used to derive the EC values corresponding to the respective water quality limits for total dissolved solids (TDS), dissolved iron, and sulfur to provide a rapid method for testing compliance. Given the site specificity of AMD composition, this approach is intended as a proof of concept for the development of a methodology for adaption at other AMD sites. The regression equations should not be considered as universal to all AMD sites and EC should also not be used as a replacement for more complete chemical analysis.

Photocatalytic reduction of carbon dioxide (CO2) into value-added carbon products is a promising strategy for dealing with carbon emission. Selected metal–organic frameworks (MOFs) have been shown promise in photocatalytic CO2 reduction owing to their photochemical activity and structural modularity. Here, we take advantage of displaceable nonstructural ligands on the nodes of a pyrene-based MOF, NU-1000, to graft a molecular catalyst, tetra(4-carboxyphenyl) porphyrin iron (III) chloride (Fe-TCPP). The pyrene linkers in the MOF absorb photons and transfer electrons to the porphyrin catalyst, resulting in a self-contained photocatalyst. The obtained Fe-TCPP@NU-1000 heterogeneous catalysts exhibit activity for CO2 photoreduction under illumination at 390 nm, with a TON for CO of 22 in 2 h. Molecular hydrogen is co-evolved. Leaching of the grafted catalyst from the MOF ultimately limits performance.

The role of growth hormone (GH) in chondrosteans is poorly understood, particularly with regard to its effects on growth. In this study, we examined the influence of exogenous GH on growth performance and body composition in juvenile Siberian sturgeon (Acipenser baerii). Fish with initial weight of 80.2 ± 0.1 g (mean ± S.E) were injected once every 10 days with either purified ovine GH (oGH) at 1, 2, 4, and 8 μg oGH/g body weight (BW) or with saline over a 50-day period. Treatment with the highest dose of oGH significantly enhanced growth performance (final body weight and length, body weight increase and specific growth rate, SGR). Notably, 8 μg oGH/g BW increased body weight by 33% and SGRw by 141% compared to control fish. GH-stimulated (8 μg oGH/g BW) growth was accompanied by increased crude protein content; however, oGH treatment did not affect levels of total protein, total lipid, cholesterol, triglyceride, or glucose in plasma. oGH decreased plasma levels of thyroxine (at 4 μg oGH/g BW), but had no significant effect on plasma levels of triiodothyronine or cortisol compared to controls. These findings indicate that 8 μg oGH/g BW enhances somatic growth and synthesis of body protein in juvenile Siberian sturgeon and demonstrate the feasibility of exogenous oGH treatment in conservation and aquaculture programs for this ancient species.

Background/objective: Measures of oxygen uptake efficiency (OUE) have been used to evaluate cardiorespiratory fitness (CRF) in adolescents unable to perform maximal exercise. The oxygen uptake efficiency slope (OUES) and oxygen uptake efficiency plateau (OUEP) have been proposed as surrogates for maximal oxygen consumption (V̇O2max). We assessed the validity of the OUES and OUEP as predictors of V̇O2max in healthy male adolescents. Methods: Sixty-three healthy male adolescents aged 15.40 ± 0.34 years underwent an incremental treadmill test to determine V̇O2max, OUES and OUEP. OUE throughout the test was assessed by dividing each V̇O2 value by the corresponding minute ventilation (V̇E) value. OUEP was determined as the 90 s average highest consecutive values for OUE. OUES was determined using data up to the ventilatory threshold (VT) by calculating the slope of the linear relation between V̇O2 and the logarithm of V̇E. Results: Limits of agreement for V̇O2max predicted by OUES (±13.3 mL kg−1.min−1) and OUEP (±16.7 mL kg−1.min−1) relative to V̇O2max were wide and a magnitude bias was found for OUES and OUEP as predictors of V̇O2max (p

A diverse range of molecules with anticancer, antiviral, and antibiotic activities has been identified and isolated from algal species. Such metabolites could address unmet clinical needs and be used to fight human diseases. Further, the natural compounds derived from algae present several advantages in terms of sustainable supply, low cytotoxicity and low cost. Seaweeds represent one of the richest known sources of natural antivirals, as well as a significant source of other bioactive compounds. Increasing evidence has demonstrated that algae comprise a vast untapped reservoir of pharmaceutical potential with many underexplored species and underexploited drug candidates, which may be derived from these ‘plants of the sea’.In recent decades, new therapeutic lead compounds including polysaccharides, lectins, terpenes, alkaloids, carotenoids, and sterols, with a broad spectrum of antiviral activities, have been isolated from marine macro- and micro-algae. The current high volume of research studies exploring the antiviral potency of seaweeds epitomises the increased interest in this field. This review focuses on bioactive marine macromolecules with antiviral activities which may serve as a starting point for enhanced knowledge and a stimulus for wider research in this field. The review also seeks to improve the understanding of the antiviral mechanisms and complex structures of algal-derived macromolecules. Since the purification of such structurally complex and frequently heterogeneous extracts and molecular classes remain fraught with difficulty, efforts to decipher the structure and composition of these macromolecules would offer enhanced possibilities for future scientific and pharmaceutical advances.

Virtual patient assessment will inevitably require smartphone technology to remotely measure knee range of motion. We conducted an experiment to analyze the impact of observer position relative to the flexed knee on the perceived angle measured using an electronic application (Dr. Goniometer) for iPhone. Two observers measured the apparent knee flexion angle from 7 different positions at 3 different heights relative to the center of the knee joint. Intraclass correlations were calculated to evaluate the intraobserver and interobserver variability using two-way mixed-effects models. The intraclass correlation for interobserver variability was excellent at 0.804 (95% confidence interval 0.663-0.889). When the observer was greater than 15° from the knee perpendicular, the true angle of knee flexion (90°) was not observed in any of the measurements. This was the case when observed from both proximal (range 95°-121°) and distal (range 92°-108°) directions. Ideally the camera lens should be perpendicular to the long axis of the lower limb in the proximal-distal direction and at the same height. However, if the camera lens is within 15° of the perpendicular, then at 90° of true flexion, the perceived angle will not be greater than 95° in 94% of cases.

Purpose: Our purpose was to review the preliminary outcomes of patients with uveal melanoma treated with iodine-125 plaques using a novel treatment planning approach. Methods and Materials: This was a single institution, retrospective review of patients treated with iodine-125 brachytherapy for uveal melanoma from November 2016 to February 2019. We used 3-dimensional treatment planning with the Eye Physics Plaque Simulator to ensure that a minimum of 63 Gy covered a 2-mm circumferential tumor margin and the apex height of the tumor over 94 hours. Primary endpoints were local failure, systemic metastasis, final visual acuity (VA), and radiation retinopathy. Associations between primary endpoints and tumor characteristics/radiation dose were performed using univariate analysis. Results: Sixty-nine patients were included in the analysis. Mean largest basal diameter was 11.67 mm (range, 6-18; median, 12), and the average tumor thickness to the inner sclera was 3.18 mm (range, 0.5-9.3; median, 2.8). Molecular testing that was successfully performed in 59 patients revealed that 27% (16 of 59) had class 2 gene expression profile designation. Average follow-up posttreatment was 28.3 months (range, 4-46; median, 29), with 6% (4 of 69) developing local failure and 6% (4 of 69) developing metastasis over this duration. Average final VA (0.57 logMAR [Snellen 20/74]; range, 0-2.9; median, 0.3) was decreased from baseline (0.34 logMAR [Snellen 20/44]; range, 0-2.3; median, 0.1), and 48% (33 of 69) developed radiation retinopathy. Fifty percent of patients had a final VA 20/40 or better and 22% had a final VA 20/200 or worse. Conclusions: In patients with uveal melanoma, preliminary results with brachytherapy using Eye Physics plaques with a treatment plan that delivers 63 Gy to a 2-mm circumferential tumor margin and the tumor apex suggest effective disease control and favorable VA outcomes.

Objectives: To understand the interpersonal and communication behaviors that are perceived positively by patients in a video encounter and whether patient-centered relationships can be established virtually. Patients and Methods: A qualitative analysis of patient visit feedback was performed to build consensus around exemplary interpersonal and communication practices during a virtual urgent care visit. Voluntarily submitted patient comments associated with a 5-star review after a visit were randomly selected from more than 49,000 comments in an 11-month period, from January 1, 2016, through November 30, 2016. Researchers used a consensus-based, widely used health care communications framework as a sensitizing scaffold to develop a preliminary set of codes. Results: More than 30% of the comments coded were classified as Building Rapport. The next most frequently assigned code was Shares Information/Provides Guidance. Among codable comments, the third most frequently assigned code was Elicits Information. Provided Treatment accounted for only 2% of comments. Conclusion: These results suggest that patients who are satisfied with telemedicine encounters appreciate their relational experiences with the clinician and overall user experience, including access and convenience. Highly satisfied patients who interacted with providers on this platform commented on key aspects of medical communication, particularly skills that demonstrate patient-centered relationship building. This supports the notion that clinician-patient relationships can be established in a video-first model, without a previous in-person encounter, and that positive ratings do not seem to be focused solely on prescription receipt.

Medicinal plants have been used for a very long time to improve human health; they are gaining increasing popularity globally as drugs, complementary and alternative medicines, food supplements, cosmetics and, more surprisingly, as medical devices. The complexity of herbs and extracts, supplied to such a wide range of markets and in different requlatory environments, raises major quality issues, increasing the need for appropriate analytical methods for their identification and standardization, but also for the detection of adulterants and contaminants. Customs laboratories are often confronted with herbal samples which pose a range of challenges, ranging from quality issues to safety and even legal issues. Selecting a relevant analytical method, from the many available (microscopy, spectrometry, spectroscopy, chromatography…), is a crucial point that mainly depends on the set analytical goals. This review aims to detail such analytical goals and their complexity to propose a selection of analytical methods likely fit for each purpose. Major limiting factors, such as herbal product naming, sampling and sample preparation are also discussed.

Summary: Cells maintain their volume through fine intracellular osmolarity regulation. Osmotic challenges drive fluid into or out of cells causing swelling or shrinkage, respectively. The dynamics of cell volume changes depending on the rheology of the cellular constituents and on how fast the fluid permeates through the membrane and cytoplasm. We investigated whether and how poroelasticity can describe volume dynamics in response to osmotic shocks. We exposed cells to osmotic perturbations and used defocusing epifluorescence microscopy on membrane-attached fluorescent nanospheres to track volume dynamics with high spatiotemporal resolution. We found that a poroelastic model that considers both geometrical and pressurization rates captures fluid-cytoskeleton interactions, which are rate-limiting factors in controlling volume changes at short timescales. Linking cellular responses to osmotic shocks and cell mechanics through poroelasticity can predict the cell state in health, disease, or in response to novel therapeutics.

Air pollution is estimated to cause 7 million annual deaths globally. Our aim was to determine if dietary propolis consumption could prevent the immune and functional damage in a mouse model of acute urban dust exposure. Female C57BL/6J mice were challenged three times with intranasal urban dust over seven days which significantly increased proinflammatory cytokines and immune cells in the lung 24 h post final challenge. Dietary New Zealand propolis (2%) with gamma cyclodextrin supplementation reduced urban dust-induced lung TNFα, IL-4, and IL-6 cytokine production; but did not alter immune cell infiltration into the lung, or lung function outcomes. This suggests that daily consumption of 8% propolis with gamma cyclodextrin supplemented food was sufficient to reduce urban dust pollution-induced proinflammatory cytokine production but was not sufficient to prevent immune cell recruitment into the lung or lung function decline in a murine model of lung inflammation.

Summary: We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.

Background: Cross-sectional studies have found that individuals with posttraumatic stress disorder (PTSD) exhibit deficits in autonomic functioning. While PTSD rates are twice as high in women compared to men, sex differences in autonomic functioning are relatively unknown among trauma-exposed populations. The current study used a prospective design to examine sex differences in posttraumatic autonomic functioning. Methods: 192 participants were recruited from emergency departments following trauma exposure (Mean age = 35.88, 68.2% female). Skin conductance was measured in the emergency department; fear conditioning was completed two weeks later and included measures of blood pressure (BP), heart rate (HR), and high frequency heart rate variability (HF-HRV). PTSD symptoms were assessed 8 weeks after trauma. Results: 2-week systolic BP was significantly higher in men, while 2-week HR was significantly higher in women, and a sex by PTSD interaction suggested that women who developed PTSD demonstrated the highest HR levels. Two-week HF-HRV was significantly lower in women, and a sex by PTSD interaction suggested that women with PTSD demonstrated the lowest HF-HRV levels. Skin conductance response in the emergency department was associated with 2-week HR and HF-HRV only among women who developed PTSD. Conclusions: Our results indicate that there are notable sex differences in autonomic functioning among trauma-exposed individuals. Differences in sympathetic biomarkers (BP and HR) may have implications for cardiovascular disease risk given that sympathetic arousal is a mechanism implicated in this risk among PTSD populations. Future research examining differential pathways between PTSD and cardiovascular risk among men versus women is warranted.

Aim and Objective: Explore the views and experiences of quality of care provided during a first postnatal visit from the perspectives of mothers and public health nurses. Background: Quality of nursing care is high on the policy agenda internationally, especially in the year of Nurse and Midwife. Public health nurses are acknowledged nationally and globally as essential health professionals supporting infants and parents. The first postnatal visit provided by the public health nurse is a complex intervention for mothers incorporating physical, social, educational and emotional support, and we know little about the quality of care provided. International evidence suggests a lack of consensus in setting priorities for this crucial visit. Design: Exploratory, qualitative design, utilising focus groups and interviews and analysed using thematic analysis. Setting/Participants: Nineteen public health nurses from all four health service regions and five mothers from one health service region were interviewed to explore the quality of care provided during first postnatal visits. Methods: Adopting qualitative data collection methods for the study; five individual semi-structured interviews with mothers ascertained their experiences of care. Further, four focus groups with public health nurses explored their understanding of the quality of care provided to mothers. The data collection period was August 2015 to January 2016. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. Results: Mothers and public health nurses identified that public health nurses were crucial for providing support during the first postnatal visit as mothers required care and advice around physical, psychological and social wellbeing for themselves and their new infant. Discordant experiences of quality care and lack of standardisation of care practices emerged. Nurses identified relationship building, empowerment and health promotion as pivotal to the public health nurses' role. Mothers acknowledged the supportive and practical aspects of the care provided. Conclusion: This is the first Irish study combining nurses and mothers experiences, identifying care provided at the first postnatal visit, presenting the quality of care experienced. This visit is vital for relationship-building and empowering mothers' child-care and self-care abilities. The findings provide an insight into how quality of care is perceived by public health nurses and mothers. Experiences facilitate reflection and the development of quality improvements to ensure mothers and infants are adequately supported during the first postnatal visit.