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First impressions can influence rater-based judgments but their contribution to rater bias is unclear. Research suggests raters can overcome first impressions in experimental exam contexts with explicit first impressions, but these findings may not generalize to a workplace context with implicit first impressions. The study had two aims. First, to assess if first impressions affect raters' judgments when workplace performance changes. Second, whether explicitly stating these impressions affects subsequent ratings compared to implicitly-formed first impressions. Physician raters viewed six videos where learner performance either changed (Strong to Weak or Weak to Strong) or remained consistent. Raters were assigned two groups. Group one (n = 23, Explicit) made a first impression global rating (FIGR), then scored learners using the Mini-CEX. Group two (n = 22, Implicit) scored learners at the end of the video solely with the Mini-CEX. For the Explicit group, in the Strong to Weak condition, the FIGR (M = 5.94) was higher than the Mini-CEX Global rating (GR) (M = 3.02, p < 0.001). In the Weak to Strong condition, the FIGR (M = 2.44) was lower than the Mini-CEX GR (M = 3.96 p < 0.001). There was no difference between the FIGR and the Mini-CEX GR in the consistent condition (M = 6.61, M = 6.65 respectively, p = 0.84). There were no statistically significant differences in any of the conditions when comparing both groups' Mini-CEX GR. Therefore, raters adjusted their judgments based on the learners' performances. Furthermore, raters who made their first impressions explicit showed similar rater bias to raters who followed a more naturalistic process.

The conducting of universal mental health screening is one widely endorsed practice suitable for use within P-12 school settings to more proactively identify children and young people experiencing or displaying characteristics of a mental health disorder. Absent routine screening, many school-age youth with mental health concerns, especially those of an internalizing nature, may go unidentified and left without timely treatment, support, and services. The current study, which employed survey methodology with principal respondents from four Midwestern states, primarily sought to contribute to and update the literature on the universal mental health screening practice habits of P-12 schools. Most principal respondents reported that their school does not currently conduct universal mental health screening and cited barriers (e.g., money, time, lack of support system in place) to screening commonly documented in prior studies. Many principals reported at least a moderate degree of interest in their school beginning to conduct universal screening in their buildings; however, a similar majority reported little to no knowledge about this important practice. Fortunately, principal respondents were generally interested in and receptive to support from their school psychologist in exploring and eventually implementing the conducting of universal mental health screening in their building. Implications for practice and future research, along with the potential for school psychologist leadership and role expansion, are discussed.

Purpose: Using data from a randomized clinical trial evaluating cognitive behavioral therapy (CBT) for children with autism and co-occurring anxiety, this study examined the relationship between autism features and anxiety symptoms throughout CBT. Methods: Two multilevel mediation analyses were run which examined the mediating role of changes in anxiety for changes in two core features of autism: (a) repetitive and restrictive behaviors (RRBs); and (b) social communication/interaction impairments, between pre- and post-treatment. Results: Indirect effects between time and autism characteristics were significant for both models, indicating that as anxiety changes, so do RRBs and social communication/interaction as the outcomes respectively. Conclusion: Findings suggest a bidirectional relationship between anxiety and autism features. Implications of these findings are discussed.

Abstract Background In this study, we tested whether genotyping both live and dead animals (GSD) realises more genetic gain for post-weaning survival (PWS) in pigs compared to genotyping only live animals (GOS). Methods Stochastic simulation was used to estimate the rate of genetic gain realised by GSD and GOS at a 0.01 rate of pedigree-based inbreeding in three breeding schemes, which differed in PWS (95%, 90% and 50%) and litter size (6 and 10). Pedigree-based selection was conducted as a point of reference. Variance components were estimated and then estimated breeding values (EBV) were obtained in each breeding scheme using a linear or a threshold model. Selection was for a single trait, i.e. PWS with a heritability of 0.02 on the observed scale. The trait was simulated on the underlying scale and was recorded as binary (0/1). Selection candidates were genotyped and phenotyped before selection, with only live candidates eligible for selection. Genotyping strategies differed in the proportion of live and dead animals genotyped, but the phenotypes of all animals were used for predicting EBV of the selection candidates. Results Based on a 0.01 rate of pedigree-based inbreeding, GSD realised 14 to 33% more genetic gain than GOS for all breeding schemes depending on PWS and litter size. GSD increased the prediction accuracy of EBV for PWS by at least 14% compared to GOS. The use of a linear versus a threshold model did not have an impact on genetic gain for PWS regardless of the genotyping strategy and the bias of the EBV did not differ significantly among genotyping strategies. Conclusions Genotyping both dead and live animals was more informative than genotyping only live animals to predict the EBV for PWS of selection candidates, but with marginal increases in genetic gain when the proportion of dead animals genotyped was 60% or greater. Therefore, it would be worthwhile to use genomic information on both live and more than 20% dead animals to compute EBV for the genetic improvement of PWS under the assumption that dead animals reflect increased liability on the underlying scale.

A new species of bumble bee-mimicking brood parasitic bee, Tetralonioidella mimetica Orr & Zhu, sp. nov., is described from China. The systematic placement of this species was initially challenging but was resolved using a combination of phylogenomic and COI barcode analyses, which strongly support the new species as a member of the genus Tetralonioidella Strand. Interestingly, the new species mimics the color pattern of both a bumble bee (Bombus Latreille), and its host Habropoda Smith species, a mimicry format previously unknown for bees. A review of the other Tetralonioidella species revealed three additional bee mimics, including two further likely model-host-brood parasite mimicry complexes. To our knowledge, these represent the first documented three-tiered mimetic systems in bees. Several additional taxonomic actions recently became necessary in these and related taxa: Tetralonioidella meghalayensis Dohling & Dey, 2024 is synonymized syn. nov. with Habropoda radoszkowskii (Dalla Torre, 1896) and Varthemapistra Engel, stat. rev. is again synonymized with Habrophorula Lieftinck. Our results also highlight issues with the generic classification of the tribe Melectini as currently used, as Melecta Latreille was found paraphyletic in relation to the remaining melectine genera. As a first step toward resolving this issue, we return the Melecta subgenus Eupavlovskia Popov, stat. rev. to genus level and discuss the ongoing systematic uncertainties regarding melectine taxonomy.

Abstract Transarterial chemoembolization (TACE) is an image-guided minimally invasive treatment for liver cancer which involves delivery of chemotherapy and embolic material into tumor-supplying arteries to block blood flow to a liver tumor and to deliver chemotherapy directly to the tumor. However, the released drug diffuses only less than a millimeter away from the beads. To enhance the efficacy of TACE, the development of microbubbles electrostatically bound to the surface of drug-eluting beads loaded with different amounts of doxorubicin (0–37.5 mg of Dox/mL of beads) is reported. Up to 400 microbubbles were bound to Dox-loaded beads (70–150 microns). This facilitated ultrasound imaging of the beads and increased the release rate of Dox upon exposure to high intensity focused ultrasound (HIFU). Furthermore, ultrasound exposure (1 MPa peak negative pressure) increased the distance at which Dox could be detected from beads embedded in a tissue-mimicking phantom, compared with a no ultrasound control.

Abstract Intratumoral injections have the potential for enhanced cancer treatment efficacy while reducing costs and systemic exposure. However, intratumoral drug injections can result in substantial off-target leakage and are invisible under standard imaging modalities like ultrasound (US) and x-ray. A thermosensitive poloxamer-based gel for drug delivery was developed that is visible using x-ray imaging (computed tomography (CT), cone beam CT, fluoroscopy), as well as using US by means of integrating perfluorobutane-filled microbubbles (MBs). MBs content was optimized using tissue mimicking phantoms and ex vivo bovine livers. Gel formulations less than 1% MBs provided gel depositions that were clearly identifiable on US and distinguishable from tissue background and with minimal acoustic artifacts. The cross-sectional areas of gel depositions obtained with US and CT imaging were similar in studies using ex vivo bovine liver and postmortem in situ swine liver. The gel formulation enhanced multimodal image-guided navigation, enabling fusion of ultrasound and x-ray/CT imaging, which may enhance targeting, definition of spatial delivery, and overlap of tumor and gel. Although speculative, such a paradigm for intratumoral drug delivery might streamline clinical workflows, reduce radiation exposure by reliance on US, and boost the precision and accuracy of drug delivery targeting during procedures. Imageable gels may also provide enhanced temporal and spatial control of intratumoral conformal drug delivery.

Abstract Test subjects were assessed in a partial gravity environment during parabolic flight while they performed mission-critical activities that challenged their balance and locomotion. These functional activities included rising from a seated position and walking, jumping down, recovering from falls, and maintaining an upright stance. Twelve volunteers were tested during 10 parabolas that produced 0.25×g, 0.5×g, or 0.75×g, and at 1×g during level flight intervals between parabolas. Additionally, 14 other subjects were tested using identical procedures in a 1×g laboratory setting. Partial gravity altered the performance of settling after standing and navigating around obstacles. As gravity levels decreased, the time required to stand up, settle, walk, and negotiate obstacles, and the number of falls increased. Information obtained from these tests will allow space agencies to assess the vestibular, sensorimotor, and cardiovascular risks associated with different levels of partial gravity.

Abstract Powerful associations that link drugs of abuse with cues in the drug-paired environment often serve as prepotent relapse triggers. Drug-associated contexts and cues activate ensembles of nucleus accumbens (NAc) neurons, including D1-class medium spiny neurons (MSNs) that typically promote, and D2-class MSNs that typically oppose, drug seeking. We found that in mice, cocaine conditioning upregulated transiently the activity-regulated transcription factor, Neuronal PAS Domain Protein 4 (NPAS4), in a small subset of NAc neurons. The NPAS4+ NAc ensemble was required for cocaine conditioned place preference. We also observed that NPAS4 functions within NAc D2-, but not D1-, MSNs to support cocaine-context associations and cue-induced cocaine, but not sucrose, seeking. Together, our data show that the NPAS4+ ensemble of NAc neurons is essential for cocaine-context associations in mice, and that NPAS4 itself functions in NAc D2-MSNs to support cocaine-context associations by suppressing drug-induced counteradaptations that oppose relapse-related behaviour.

Heterosexism, the belief that heterosexual identities are superior to homosexual identities, is deeply embedded in educational institutions, including school-based agricultural education (SBAE). Negligible research exists developing impactful practices for queer students in SBAE programs. This study sought to describe the attitudes of post-secondary agricultural education students toward lesbian and gay identities to identify potential barriers to the inclusion of queer students in SBAE. A total of 119 students from 21 higher education institutions across 12 states completed the Multidimensional Scale of Attitudes Toward Lesbians and Gay Men. The questionnaire evaluated attitudes related to rejection of proximity, pathologizing of homosexuality, modern heterosexism, and support. Findings from this study reveal students are relatively supportive of lesbian and gay individuals, but do not challenge heterosexist beliefs. Recommendations include further qualitative and intersectional investigations, greater curricular inclusion of queer experiences, and providing opportunities to challenge homophobic and heterosexist group norms.

This study aimed to describe school-based agricultural education (SBAE) teachers' perceived Pedagogical Content Knowledge (PCK) and individualized professional development needs by licensure type. A series of survey questions were used to describe the sample of SBAE teachers, their PCK, sources of knowledge, and professional development needs. Regardless of licensure type, participants mostly agreed on their sources of knowledge, with teaching experience and previous employment being the top sources of knowledge. However, there were differences in PCK, and professional development needs by licensure type. For example, traditionally certified teachers had higher PCK in Horizon Content Knowledge and Knowledge of Content and Students. In addition, they reported a greater need for professional development in content-specific topics and FFA & SAEs. On the other hand, alternatively certified teachers had higher PCK in Common Content Knowledge and Specialized Content Knowledge. In addition, they reported a greater need for professional development in curriculum development and instructional strategies.

Iraq is a large country in the Middle East region that borders both Turkey and Iran, countries known to host two of the largest bee faunas globally, as expected for a group of insects that favour dry to Mediterranean climates. Despite this huge regional species richness, the bee fauna of Iraq is chronically understudied and poorly known, both in relative and absolute terms. This is true for the hyper-speciose bee genus Andrena, for which only 17 species have been previously published for Iraq. This work is the first modern contribution to the revision of the Andrena fauna of Iraq. Based on new specimen collections in Duhok Governorate (Iraqi Kurdistan) during 2023, a revised total of 59 Andrena species for Iraq (42 species recorded for the first time) is presented, including the description of two new species: Andrena (Aciandrena) duhokensis Wood, sp. nov. and Andrena (Notandrena) baiocchii Wood, sp. nov. The unknown males of A. (Micrandrena) elam Wood, 2022, A. (Micrandrena) obsidiana Wood, 2022, and A. (Notandrena) ayna Wood, 2023 are described. Andrena bakrajoensis Amin & Mawlood, 2019, syn. nov. is synonymised with A. (Holandrena) variabilis Smith, 1853. Additional records are presented from nearby Middle Eastern countries, particularly Lebanon. These results highlight the fundamentally understudied nature of the Iraqi Andrena fauna.

Abstract We present 4k video and whole transcriptome data for seven deep-sea invertebrate animals collected in the Eastern Pacific Ocean during a research expedition onboard the Schmidt Ocean Institute’s R/V Falkor in August of 2021. The animals include one jellyfish (Atolla sp.), three siphonophores (Apolemia sp., Praya sp., and Halistemma sp.), one larvacean (Bathochordaeus mcnutti), one tunicate (Pyrosomatidae sp.), and one ctenophore (Lampocteis sp.). Four of the animals were sequenced with long-read RNA sequencing technology, such that the reads themselves define a reference assembly for those animals. The larvacean tissues were successfully preserved in situ and has paired long-read reference data and short read quantitative transcriptomic data for within-specimen analyses of gene expression. Additionally, for three animals we provide quantitative image data, and a 3D model for one siphonophore. The paired image and transcriptomic data can be used for species identification, species description, and reference genetic data for these deep-sea animals.

The Peak Design Ltd hyperspectral radiometer (HSR1) was tested at the Atmospheric Radiation Measurement (ARM) user facility Southern Great Plains (SGP) site in Lamont, Oklahoma, for 2 months from May to July 2022. The HSR1 is a prototype instrument that measures total (Ftotal) and diffuse (Fdiffuse) spectral irradiance from 360 to 1100 nm with a spectral resolution of 3 nm. The HSR1 spectral irradiance measurements are compared to nearby collocated spectral radiometers, including two multifilter rotating shadowband radiometers (MFRSRs) and the Shortwave Array Spectroradiometer–Hemispheric (SASHe) radiometer. The Ftotal at 500 nm for the HSR1 compared to the MFRSRs has a mean (relative) difference of 0.01 W m−2 nm−1 (1 %–2 %). The HSR1 mean Fdiffuse at 500 nm is smaller than the MFRSRs' by 0.03–0.04 (10 %) W m−2 nm−1. The HSR1 clear-sky aerosol optical depth (AOD) is also retrieved by considering Langley regressions and compared to collocated instruments such as the Cimel sunphotometer (CSPHOT), MFRSRs, and SASHe. The mean HSR1 AOD at 500 nm is larger than the CSPHOT's by 0.010 (8 %) and larger than the MFRSRs' by 0.007–0.017 (6 %–18 %). In general, good agreement between the HSR1 and other instruments is found in terms of the Ftotal, Fdiffuse, and AODs at 500 nm. The HSR1 quantities are also compared at other wavelengths to the collocated instruments. The comparisons are within ∼ 10 % for the Ftotal and Fdiffuse, except for 940 nm, where there is relatively larger disagreement. The AOD comparisons are within ∼ 10 % at 415 and 440 nm; however, a relatively larger disagreement in the AOD comparison is found for higher wavelengths.

Abstract Liver cancer ranks as the fifth leading cause of cancer-related death globally. Direct intratumoral injections of anti-cancer therapeutics may improve therapeutic efficacy and mitigate adverse effects compared to intravenous injections. Some challenges of intratumoral injections are that the liquid drug formulation may not remain localized and have unpredictable volumetric distribution. Thus, drug delivery varies widely, highly-dependent upon technique. An X-ray imageable poloxamer 407 (POL)-based drug delivery gel was developed and characterized, enabling real-time feedback. Utilizing three needle devices, POL or a control iodinated contrast solution were injected into an ex vivo bovine liver. The 3D distribution was assessed with cone beam computed tomography (CBCT). The 3D distribution of POL gels demonstrated localized spherical morphologies regardless of the injection rate. In addition, the gel 3D conformal distribution could be intentionally altered, depending on the injection technique. When doxorubicin (DOX) was loaded into the POL and injected, DOX distribution on optical imaging matched iodine distribution on CBCT suggesting spatial alignment of DOX and iodine localization in tissue. The controllability and localized deposition of this formulation may ultimately reduce the dependence on operator technique, reduce systemic side effects, and facilitate reproducibility across treatments, through more predictable standardized delivery.

Abstract Background Workplace-based assessment (WBA) used in post-graduate medical education relies on physician supervisors’ feedback. However, in a training environment where supervisors are unavailable to assess certain aspects of a resident’s performance, nurses are well-positioned to do so. The Ottawa Resident Observation Form for Nurses (O-RON) was developed to capture nurses’ assessment of trainee performance and results have demonstrated strong evidence for validity in Orthopedic Surgery. However, different clinical settings may impact a tool’s performance. This project studied the use of the O-RON in three different specialties at the University of Ottawa. Methods O-RON forms were distributed on Internal Medicine, General Surgery, and Obstetrical wards at the University of Ottawa over nine months. Validity evidence related to quantitative data was collected. Exit interviews with nurse managers were performed and content was thematically analyzed. Results 179 O-RONs were completed on 30 residents. With four forms per resident, the ORON’s reliability was 0.82. Global judgement response and frequency of concerns was correlated (r = 0.627, P

IntroductionBed rest can be used as a ground-based analog of the body unloading associated with spaceflight. In this study, we determined how strict head-down tilt bed rest affects subjects’ performance of functional tests (sit-to-stand, tandem walk, walk-and-turn, dynamic posturography) that challenge astronauts’ balance control systems immediately after they return from space.MethodsForty-seven participants were assessed before and a few hours after 30 days of 6° head down tilt bed rest at the DLR:envihab facility. During this bed rest study, called SANS-CM, the participants were divided into 4 groups that either a) were positioned in head-down tilt continuously throughout the 30 days; b) sat upright for 6 h a day; c) were exposed to lower body negative pressure (LBNP) for 6 h a day; or d) exercised for 60 min and then wore venous-occlusive cuffs for 6 h a day.ResultsResults showed that strict head-down tilt bed rest caused deficits in performance of functional tasks that were similar to those observed in astronauts after spaceflight. Seated upright posture mitigated these deficits, whereas exercise or LBNP and cuffs partly mitigated them.DiscussionThese data suggest that more direct, active sensorimotor-based countermeasures may be necessary to maintain preflight levels of functional performance after a long period of body unloading.

Abstract Substrate composition has been widely recognised as a primary variable shaping lotic macroinvertebrate communities at the habitat unit level. However, fundamental understanding of how communities inhabiting mineralogical habitats (i.e., gravel, sand and silt) are structured across differing rivers is lacking. Moreover, research largely focusses on gravel beds and fine sediment in general (

India is a large country in Asia, and covers the transition zone between the Palaearctic and Indomalayan biogeographic realms, with influences from both. Present in India are members of the genus Andrena, an enormous bee genus distributed predominantly throughout the Holarctic, with the greatest Indian diversity in the Himalayan region due to its Palaearctic influences. Despite early studies in the late 19th and early 20th centuries, there has been almost no work on this group in India during the past century. A revision of type and non-type museum material combined with new collections has produced a revised total of 36 species of Andrena for India, including 11 species reported for the first time as well as the newly described Andrena (Melandrena) kedarnatha Wood & Gautam sp. nov. (northern India and Nepal) and Andrena (Simandrena) tungnatha Wood & Gautam sp. nov. (northern India). The true holotype of A. (Euandrena) communis Smith, 1879 is definitively located. Andrena burkelii Bingham, 1908 is synonymised with A. (Pallandrena) morosa Cameron, 1897. Lectotypes are designated for A. (Euandrena) murreensis Cockerell, 1923 and A. (incertae sedis) comberima beharica Cockerell, 1920. Further comments are made on the status of Andrena taxa described from India for which type material is and is not currently available. Thirty additional Andrena taxa suggested as present in the Indian fauna are excluded as either erroneous or lacking supporting data. These results illustrate the extent to which study of the Indian Andrena fauna has been confused, and provide a more stable taxonomic base for future studies in this country.

Abstract Background Social and Therapeutic Horticulture (STH) is a process where trained practitioners work with plants and people to improve an individual’s physical and psychological health, communication and thinking skills. Evidence suggests that STH can support individuals with mental ill-health, however, current commissioning of STH within mental health care is limited. This study aimed to understand the barriers to commissioning STH in mental health care and to identify potential solutions to barriers, to support more widespread availability of services. Methods Individuals with a role in mental health care commissioning from across the UK were invited to take part in semi-structured interviews via zoom. Interviews explored factors influencing the mental health services they commission or refer to, their perception of the role of STH in mental health care and the barriers to commissioning STH, together with potential solutions to any barriers identified. Results Commissioners identified a lack of knowledge of STH and evidence of its effectiveness, and a culture which prioritises traditional medical models, as barriers to commissioning. Challenges for STH providers in responding to large-scale commissioning requirements were also highlighted as a barrier. Conclusions To upscale commissioning of STH in mental health care, STH interventions need to be embedded within NHS priorities and information on STH services and their effectiveness needs to be easily accessible to practitioners. The sector should also be supported in working collaboratively to enable commissioning of services at scale.

Abstract White striping (WS) is a myopathy of growing concern to the turkey industry. It is rising in prevalence and has negative consequences for consumer acceptance and the functional properties of turkey meat. The objective of this study was to conduct a genome-wide association study (GWAS) and functional analysis on WS severity. Phenotypic data consisted of white striping scored on turkey breast fillets (N = 8422) by trained observers on a 0–3 scale (none to severe). Of the phenotyped birds, 4667 genotypic records were available using a proprietary 65 K single nucleotide polymorphism (SNP) chip. The SNP effects were estimated using a linear mixed model with a 30-SNP sliding window approach used to express the percentage genetic variance explained. Positional candidate genes were those located within 50 kb of the top 1% of SNP windows explaining the most genetic variance. Of the 95 positional candidate genes, seven were further classified as functional candidate genes because of their association with both a significant gene ontology and molecular function term. The results of the GWAS emphasize the polygenic nature of the trait with no specific genomic region contributing a large portion to the overall genetic variance. Significant pathways relating to growth, muscle development, collagen formation, circulatory system development, cell response to stimulus, and cytokine production were identified. These results help to support published biological associations between WS and hypoxia and oxidative stress and provide information that may be useful for future-omics studies in understanding the biological associations with WS development in turkeys.

Background and objective: Focal therapy (FT) is increasingly recognized as a promising approach for managing localized prostate cancer (PCa), notably reducing treatment-related morbidities. However, post-treatment anatomical changes present significant challenges for surveillance using current imaging techniques. This study aimed to evaluate the inter-reader agreement and efficacy of the Prostate Imaging after Focal Ablation (PI-FAB) scoring system in detecting clinically significant prostate cancer (csPCa) on post-FT multiparametric magnetic resonance imaging (mpMRI). Methods: A retrospective cohort study was conducted involving patients who underwent primary FT for localized csPCa between 2013 and 2023, followed by post-FT mpMRI and a prostate biopsy. Two expert genitourinary radiologists retrospectively evaluated post-FT mpMRI using PI-FAB. The key measures included inter-reader agreement of PI-FAB scores, assessed by quadratic weighted Cohen’s kappa (κ), and the system’s efficacy in predicting in-field recurrence of csPCa, with a PI-FAB score cutoff of 3. Additional diagnostic metrics including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were also evaluated. Key findings and limitations: Scans from 38 patients were analyzed, revealing a moderate level of agreement in PI-FAB scoring (κ = 0.56). Both radiologists achieved sensitivity of 93% in detecting csPCa, although specificity, PPVs, NPVs, and accuracy varied. Conclusions and clinical implications: The PI-FAB scoring system exhibited high sensitivity with moderate inter-reader agreement in detecting in-field recurrence of csPCa. Despite promising results, its low specificity and PPV necessitate further refinement. These findings underscore the need for larger studies to validate the clinical utility of PI-FAB, potentially aiding in standardizing post-treatment surveillance. Patient summary: Focal therapy has emerged as a promising approach for managing localized prostate cancer, but limitations in current imaging techniques present significant challenges for post-treatment surveillance. The Prostate Imaging after Focal Ablation (PI-FAB) scoring system showed high sensitivity for detecting in-field recurrence of clinically significant prostate cancer. However, its low specificity and positive predictive value necessitate further refinement. Larger, more comprehensive studies are needed to fully validate its clinical utility.

Abstract Microgravity alters vestibular signaling and reduces body loading, driving sensory reweighting. The unloading effects can be modelled using head-down tilt bedrest (HDT). Artificial gravity (AG) has been hypothesized to serve as an integrated countermeasure for the declines associated with HDT and spaceflight. Here, we examined the efficacy of 30 min of daily AG to counteract brain and behavior changes from 60 days of HDT. Two groups received 30 min of AG delivered via short-arm centrifuge daily (n = 8 per condition), either in one continuous bout, or in 6 bouts of 5 min. To improve statistical power, we combined these groups (AG; n = 16). Another group served as controls in HDT with no AG (CTRL; n = 8). We examined how HDT and AG affect vestibular processing by collecting fMRI scans during vestibular stimulation. We collected these data prior to, during, and post-HDT. We assessed brain activation initially in 12 regions of interest (ROIs) and then conducted an exploratory whole brain analysis. The AG group showed no changes in activation during vestibular stimulation in a cerebellar ROI, whereas the CTRL group showed decreased activation specific to HDT. Those that received AG and showed little pre- to post-HDT changes in left vestibular cortex activation had better post-HDT balance performance. Whole brain analyses identified increased pre- to during-HDT activation in CTRLs in the right precentral gyrus and right inferior frontal gyrus, whereas AG maintained pre-HDT activation levels. These results indicate that AG could mitigate activation changes in vestibular processing that is associated with better balance performance.

Abstract During long-duration spaceflight, astronauts experience headward fluid shifts and expansion of the cerebral perivascular spaces (PVS). A major limitation to our understanding of the changes in brain structure and physiology induced by spaceflight stems from the logistical difficulties of studying astronauts. The current study aimed to determine whether PVS changes also occur on Earth with the spaceflight analog head-down tilt bed rest (HDBR). We examined how the number and morphology of magnetic resonance imaging-visible PVS (MV-PVS) are affected by HDBR with and without elevated carbon dioxide (CO2). These environments mimic the headward fluid shifts, body unloading, and elevated CO2 observed aboard the International Space Station. Additionally, we sought to understand how changes in MV-PVS are associated with signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), ocular structural alterations that can occur with spaceflight. Participants were separated into two bed rest campaigns: HDBR (60 days) and HDBR + CO2 (30 days with elevated ambient CO2). Both groups completed multiple magnetic resonance image acquisitions before, during, and post-bed rest. We found that at the group level, neither spaceflight analog affected MV-PVS quantity or morphology. However, when taking into account SANS status, persons exhibiting signs of SANS showed little or no MV-PVS changes, whereas their No-SANS counterparts showed MV-PVS morphological changes during the HDBR + CO2 campaign. These findings highlight spaceflight analogs as models for inducing changes in MV-PVS and implicate MV-PVS dynamic compliance as a mechanism underlying SANS. These findings may lead to countermeasures to mitigate health risks associated with human spaceflight.

Abstract Non‐adherence to medication is a major challenge in healthcare that results in worsened treatment outcomes for patients. Reducing the frequency of required administrations could improve adherence but is challenging for topical drug delivery due to the generally short residence time of topical formulations on the skin. In this study, we sought to determine the feasibility of developing a microbiome‐based, long‐acting, topical delivery platform using Bacillus subtilis for drug production and delivery on the skin, which was assessed using green fluorescent protein as a model heterologous protein for delivery. We developed a computational model of bacteria population dynamics on the skin and used its qualitative predictions to guide experimental design choices. Using an ex vivo pig skin model and a human skin tissue culture model, we saw persistence of delivered bacteria for multiple days and observed little evidence of cytotoxicity to human keratinocyte cells in vitro. Finally, using an in vivo mouse model, we found that the delivered bacteria persisted on the skin for at least 1 day during every‐other‐day application and did not appear to present safety concerns. Taken together, our results support the feasibility of using engineered B. subtilis for topical drug delivery.

Implication Statement The development of multiple-choice questions (MCQs) for undergraduate medical education study purposes is resource intensive. Commercially available question banks are typically expensive, only available in English, and may not be aligned with medical school learning objectives. Here, we introduce The Ottawa Question Bank: a student-led, bilingual study resource curated to a Canadian undergraduate medicine curriculum (www.theottawaquestionbank.ca). In total, 205 medical students wrote and edited 4438 original MCQs linked to objectives from the University of Ottawa undergraduate medical education curriculum. The project has received positive feedback from both developers and users. Our experience suggests that involving medical students in MCQ development is feasible and can result in the rapid creation of a low-cost, high-quality study resource curated to a program’s learning objectives. The platform outlined here can be used as a model for other medical schools and professional degree programs to develop their own question banks, including pharmacy, dentistry, nursing, and physiotherapy. Interested programs are encouraged to contact our team for collaborative opportunities.

Summary: Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults. Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%–68.2%), compared with 63.4% in the control group (95% CI 61.8%–65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%–20.7%), compared with 18.8% in the control group (95% CI 17.4%–20.2%) a difference of +0.6 percentage points (95% CI −1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination. Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease. Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.

Abstract Heat-based local ablation techniques are effective treatments for specific oligometastatic and localized cancers and are being studied for their potential to induce immunogenic cell death and augment systemic immune responses to immunotherapies. The diverse technologies associated with thermal therapy have an unmet need for method development to enable device-specific experimentation, optimization, calibration and refinement of the parameter space to optimize therapeutic intent while minimizing side effects or risk to the patient. Quality assurance, training, or comparing thermal dose among different modalities or techniques using animal models is time and resource intensive. Therefore, the application and use of tissue mimicking thermosensitive, thermochromic liquid crystal and thermochromic paint phantom models may reduce costs and hurdles associated with animal use. Further, their homogenous composition may enable more precise assessment of ablative techniques. This review utilized SciFinder, Web of Science, PubMed and EMBASE to systematically evaluate the literature describing the background and applications of thermochromic liquid crystal, thermochromic paint and tissue-mimicking thermochromic phantoms used to characterize the thermal effects of ablation devices with a focus on facilitating their use across the medical device development life cycle. Graphical Abstract

Slope units are terrain partitions bounded by drainage and divide lines. In landslide modeling, including susceptibility modeling and event-specific modeling of landslide occurrence, slope units provide several advantages over gridded units, such as better capturing terrain geometry, improved incorporation of geospatial landslide-occurrence data in different formats (e.g., point and polygon), and better accommodating the varying data accuracy and precision in landslide inventories. However, the use of slope units in regional (> 100 km2) landslide studies remains limited due, in part, to the large computational costs and/or poor reproducibility with current delineation methods. We introduce a computationally efficient algorithm for the parameter-free delineation of slope units that leverages tools from within TauDEM and GRASS, using an R interface. The algorithm uses geomorphic laws to define the appropriate scaling of the slope units representative of hillslope processes, avoiding the often ambiguous determination of slope unit size. We then demonstrate how slope units enable more robust regional-scale landslide susceptibility and event-specific landslide occurrence maps.

Retro-ondontoid pseudotumors represent soft tissue proliferation surrounding the transverse ligament of the atlas, which most commonly results in cervical neck pain or myelopathy due to impingement upon the cervicomedullary junction. The causes of retro-odontoid pseudotumor formation are varied and include metabolic, inflammatory, degenerative, and post-traumatic etiologies. To the best of our knowledge, an abducens nerve palsy as a result of a complex retro-odontoid pseudotumor has never been reported. We discuss a case of a 90-year-old woman who presents with acute lateral gaze palsy with multimodality imaging demonstrating a retro-odontoid pseudotumor with an unusual protrusion which courses superolaterally to the level of the pons and compresses the abducens nerve root entry zone.

Abstract Background Within the Hymenoptera, bees are notable for their relationship with flowering plants, being almost entirely dependent on plant pollen and nectar. Though functionally herbivorous, as a result of their role as pollinators, bees have received comparatively little attention as models for insect herbivory. Bees often display dietary specialization, but quantitative comparison against other herbivorous insects has not previously been conducted. Results In the most comprehensive analysis to date for 860 bee species, dietary specialization amounted to 50.1% of studied species collecting pollen from between 1 and 2 botanical families with a relatively long tail of dietary generalists, with 11.1% of species collecting from more than 10 botanical families. This distribution deviated from the truncated Pareto distribution of dietary breadth seen in other herbivorous insect lineages. However, this deviation was predominantly due to eusocial bee lineages, which show a range of dietary breadths that conformed to a normal distribution, while solitary bees show a typical truncated distribution not strongly different from other herbivorous insects. We hypothesize that the relatively low level of dietary specialization in bees as a whole reflects the relaxation of the constraints typically observed in herbivorous insects with a comparatively reduced importance of plant chemistry and comparatively increased importance of phenology and foraging efficiency. The long flight periods of eusocial bees that are necessary to allow overlapping generations both allows and necessitates the use of multiple flowering resources, whereas solitary bees with short flight periods have more limited access to varied resources within a constrained activity period. Conclusions Collectively, solitary bees show slightly lower specialization compared to other herbivorous insects, possibly due to their balanced relationship with plants, rather than direct antagonism such as seen in the direct consumption of plant tissues. An additional factor may be the mediocre diversity of bees at low latitudes combined with low levels of dietary specialization, whereas these areas typically display a high rate of specialization by herbivorous insects in general. Though the most important factors structuring dietary specialization in bees appear to differ from many other herbivorous insects, solitary bees show a surprisingly similar overall pattern of dietary specialization.

Introduction Psychiatric drugs, including antipsychotics and antidepressants, are widely prescribed, even in young and adolescent populations at early or subthreshold disease stages. However, their impact on brain structure remains elusive. Elucidating the relationship between psychotropic medication and structural brain changes could enhance the understanding of the potential benefits and risks associated with such treatment. Objectives Investigation of the associations between psychiatric drug intake and longitudinal grey matter volume (GMV) changes in a transdiagnostic sample of young individuals at early stages of psychosis or depression using an unbiased data-driven approach. Methods The study sample comprised 247 participants (mean [SD] age = 25.06 [6.13] years, 50.61% male), consisting of young, minimally medicated individuals at clinical high-risk states for psychosis, individuals with recent-onset depression or psychosis, and healthy control individuals. Structural magnetic resonance imaging was used to obtain whole-brain voxel-wise GMV for all participants at two timepoints (mean [SD] time between scans = 11.15 [4.93] months). The multivariate sparse partial least squares (SPLS) algorithm (Monteiro et al. JNMEDT 2016; 271:182-194) was embedded in a nested cross-validation framework to identify parsimonious associations between the cumulative intake of psychiatric drugs, including commonly prescribed antipsychotics and antidepressants, and change in GMV between both timepoints, while additionally factoring in age, sex, and diagnosis. Furthermore, we correlated the retrieved SPLS results to personality domains (NEO-FFI) and childhood trauma (CTQ). Results SPLS analysis revealed significant associations between the antipsychotic classes of benzamides, butyrophenones and thioxanthenes and longitudinal GMV decreases in cortical regions including the insula, posterior superior temporal sulcus as well as cingulate, postcentral, precentral, orbital and frontal gyri (Figure 1A-C). These brain regions corresponded most closely to the dorsal and ventral attention, somatomotor, salience and default network (Figure 1D). Furthermore, the medication signature was negatively associated with the personality domains extraversion, agreeableness and conscientiousness and positively associated with the CTQ domains emotional and physical neglect. Image: Conclusions Psychiatric drug intake over a period of one year was linked to distinct GMV reductions in key cortical hubs. These patterns were already visible in young individuals at early or subthreshold stages of mental illness and were further linked to childhood neglect and personality traits. Hence, a better and more in-depth understanding of the structural brain implications of medicating young and adolescent individuals might lead to more cautious, sustainable and targeted treatment strategies. Disclosure of Interest None Declared

Introduction The clinical high-risk state for psychosis (CHR) is associated with alterations in grey matter volume (GMV) in various regions such as the hippocampus (Vissink et al. BP:GOS 2022; 2(2) 147-152). Within the scope of the North American Prodrome Longitudinal Study (NAPLS-2; Cannon et al. AM J Psychiatry 2016; 173(10), 980-988), a publicly available risk calculator based on clinical variables was developed to assess the likelihood of individuals to transition to psychosis within a 2-year period. Objectives In the current study, we aim to examine the association between GMV and NAPLS-2 risk scores calculated for individuals with CHR and recent-onset depression (ROD), taking a transdiagnostic approach on the transition to psychosis. Methods The sample consisted of 315 CHR (M = 23.85, SD = ± 5.64; female: 164) and 295 ROD (M = 25.11, SD = ± 6.21; female: 144) patients from the multi-site Personalised Prognostic Tools for Early Psychosis Management (PRONIA) Study (Koutsouleris et al. JAMA Psychiatry 2018; 57(11), 1156-1172). Risk scores were calculated using the six clinical and neurocognitive variables included in the NAPLS-2 risk calculator that were significant for predicting psychosis. Further, we derived smoothed GMV maps from T1-weighted structural magnetic resonance imaging using a full width at half maximum kernel size of 8 mm. We employed a multiple regression design in SPM12 to examine associations between risk scores and GMV. On the whole-brain level, we calculated permutation-based threshold-free cluster enhancement (TFCE) contrasts using the TFCE toolbox. Additionally, we calculated t-contrasts within a region-of-interest (ROI) analysis encompassing the hippocampus. All results were thresholded at p < 0.05 with family wise error correction to address multiple comparisons. Results Our analysis revealed that linear GMV increases in the right middle and superior frontal gyrus (kE= 2726 voxels) were significantly associated with higher risk for psychosis transition within two years (see figure 1, highlighted in blue). In the ROI analysis, we found a significant negative linear association between GMV decreases in the left hippocampus (kE = 353 voxels) and higher risk for psychosis transition (see figure 1, highlighted in red). Image: Conclusions GMV reductions in the hippocampus have frequently been observed in CHR and psychosis patients (Vissink et al. BP:GOS 2022; 2(2) 147-152), therefore our results further highlight the crucial role of this region in the progression of the disease. There is limited evidence on GMV increases in CHR patients. However, the GMV increase we found in the frontal pole may reflect compensatory mechanisms of the brain in the development of psychosis. In addition, we were able to provide biological validation of the NAPLS-2 risk calculator and its assessment of risk for transition to psychosis. Disclosure of Interest None Declared

The perceptual and motor coordination problems experienced following return from spaceflight reflect the sensory adaptation to altered gravity. The purpose of this study was to develop a ground-based analog that replicates similar sensorimotor impairment using a standard measures test battery and subjective feedback from experienced crewmembers. This Sensorimotor Disorientation Analog (SDA) included varying levels of sensorimotor disorientation through combined vestibular, visual, and proprioceptive disruptions. The SDA was evaluated on five previously flown astronauts to compare with their postflight experience and functional motor performance immediately (Return (R)+0 days) and +24 h (R+1) after landing. The SDA consisted of galvanic vestibular stimulation (GVS), visual disruption goggles, and a weighted suit to alter proprioceptive feedback and replicate perceived heaviness postflight. Astronauts reported that GVS alone replicated ∼50–90% of their postflight performance with the weighted suit fine-tuning the experience to replicate an additional 10%–40% of their experience. Astronauts did not report feeling that the disruption goggles represented either the visual disruptions or illusory sensations that they experienced, nor did they impact motor performance in postflight tasks similarly. Based on these results, we recommend an SDA including the GVS and the weighted suit. These results provide a more realistic and portable SDA framework to provide transient spaceflight-relevant sensorimotor disruptions for use in countermeasure testing and as a pre-flight training tool.

Background Myocardial infarction secondary to spontaneous coronary artery dissection (SCAD) can be traumatic and potentially trigger posttraumatic stress disorder (PTSD). In a large, multicenter, registry‐based cohort, we documented prevalence of lifetime and past‐month SCAD‐induced PTSD, as well as related treatment seeking, and examined a range of health‐relevant correlates of SCAD‐induced PTSD. Methods and Results Patients with SCAD were enrolled in the iSCAD (International SCAD) Registry. At baseline, site investigators completed medical report forms, and patients reported demographics, medical/SCAD history, psychosocial factors (including SCAD‐induced PTSD symptoms), health behaviors, and health status via online questionnaires. Of 1156 registry patients, 859 patients (93.9% women; mean age, 52.3 years) completed questionnaires querying SCAD‐induced PTSD. Nearly 35% (n=298) of patients met diagnostic criteria for probable SCAD‐induced PTSD in their lifetime, and 6.4% (n=55) met criteria for probable past‐month PTSD. Of 811 patients ever reporting any SCAD‐induced PTSD symptoms, 34.8% indicated seeking treatment for this distress. However, 46.0% of the 298 patients with lifetime probable SCAD‐induced PTSD diagnoses reported never receiving trauma‐related treatment. Younger age at first SCAD, fewer years since SCAD, being single, unemployed status, more lifetime trauma, and history of anxiety were associated with greater past‐month PTSD symptom severity in multivariable regression models. Greater past‐month SCAD‐induced PTSD symptoms were associated with greater past‐week sleep disturbance and worse past‐month disease‐specific health status when adjusting for various risk factors. Conclusions Given the high prevalence of SCAD‐induced PTSD symptoms, efforts to support screening for these symptoms and connecting patients experiencing distress with empirically supported treatments are critical next steps. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04496687.

IntroductionPsychological factors linked to political participation are largely understudied in American Indians. Prior work notes relatively low levels of participation compared to other racial and ethnic groups and suggests that identification with being American Indian is linked to overall levels of civic engagement in part through perceptions of group discrimination.MethodsIn the current work, in a sample of 727 American Indian adults, we created two groups: Group 1 (N = 398) reported perceived discrimination related to race, and Group 2 (N = 329) reported perceived discrimination not related to race or ethnicity. We investigated the relationships between individual experiences of everyday discrimination related to race, levels of political efficacy, and political participation (Group 1), and individual experiences of everyday discrimination not related to race or ethnicity, political efficacy, and political participation (Group 2).ResultsWe found that greater experiences of everyday discrimination related to race was associated with higher levels of political participation through increased levels of internal and collective efficacy. In contrast, greater experiences of everyday discrimination related to race was associated with higher levels of political participation through lower external political efficacy. For Group 2, we found that greater experiences of everyday discrimination not related to race or ethnicity was not directly associated with political participation, but mediation analyses revealed a relationship with lower levels of political participation through decreased internal and collective efficacy. The indirect effect through external political efficacy was not significant.DiscussionGiven low levels of American Indian political participation, political efficacy could be a target for interventions aiming to increase participation in the political system.

Abstract Background Current standard of care for advanced biliary tract cancer (BTC) is gemcitabine, cisplatin plus anti‐PD1/PD‐L1, but response rates are modest. The purpose of this study was to explore the efficacy and safety of durvalumab (anti‐PD‐L1) and tremelimumab (anti‐CTLA‐4), with and without an interventional radiology (IR) procedure in advanced BTC. Methods Eligible patients with advanced BTC who had received or refused at least one prior line of systemic therapy were treated with tremelimumab and durvalumab for four combined doses followed by monthly durvalumab alone with and without an IR procedure until the progression of disease or unacceptable toxicity. Objective response was assessed through CT or MRI by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) every 8 weeks. Adverse events (AEs) were recorded and managed. The primary endpoint was 6‐month progression‐free survival (PFS). Results Twenty‐three patients with advanced BTC were enrolled; 17 patients were assigned to treatment with durvalumab and tremelimumab (Durva/Treme); and 6 patients were treated with the combination of durvalumab, tremelimumab plus IR procedure (Durva/Treme + IR). The best clinical responses in the Durva/Treme arm were partial response (n = 1), stable disease (n = 5), progressive disease (n = 5), and in the Durva/Treme + IR arm: partial response (n = 0), stable disease (n = 3), progressive disease (n = 3). The median PFS was 2.2 months (95% CI: 1.3–3.1 months) in the Durva/Treme arm and 2.9 months (95% CI: 1.9–4.7 months) in the Durva/Treme + IR arm (p = 0.27). The median OS was 5.1 months (95% CI: 2.5–6.9 months) in the Durva/Treme arm and 5.8 months (95% CI: 2.9–40.1 months) in the Durva/Treme + IR arm (p = 0.31). The majority of AEs were grades 1–2. Conclusion Durva/Treme and Durva/Treme + IR showed similar efficacy. With a manageable safety profile. Larger studies are needed to fully characterize the efficacy of Durva/Treme ± IR in advanced BTC.

Abstract Attempts to delineate an immune subtype of schizophrenia have not yet led to the clear identification of potential treatment targets. An unbiased informatic approach at the level of individual immune cytokines and symptoms may reveal organisational structures underlying heterogeneity in schizophrenia, and potential for future therapies. The aim was to determine the network and relative influence of pro- and anti-inflammatory cytokines on depressive, positive, and negative symptoms. We further aimed to determine the effect of exposure to minocycline or placebo for 6 months on cytokine-symptom network connectivity and structure. Network analysis was applied to baseline and 6-month data from the large multi-center BeneMin trial of minocycline (N = 207) in schizophrenia. Pro-inflammatory cytokines IL-6, TNF-α, and IFN-γ had the greatest influence in the inflammatory network and were associated with depressive symptoms and suspiciousness at baseline. At 6 months, the placebo group network connectivity was 57% stronger than the minocycline group, due to significantly greater influence of TNF-α, early wakening, and pathological guilt. IL-6 and its downstream impact on TNF-α, and IFN-γ, could offer novel targets for treatment if offered at the relevant phenotypic profile including those with depression. Future targeted experimental studies of immune-based therapies are now needed.

Long-duration bedrest impairs upright postural and locomotor control, prompting the need for assessment tools to predict the effects of deconditioning on post-bedrest outcome measures. We developed a tilt board mounted vertically with a horizontal air-bearing sled as a potential supine assessment tool for a future bedrest study. The purpose of this pilot study was to examine the association between supine proprioceptive assessments on the tilt board and upright functional mobility. Seventeen healthy participants completed variations of a supine tilt board task and an upright functional mobility task (FMT), which is an established obstacle avoidance course. During the supine tasks, participants lay on the air-bearing sled with axial loading toward the tilt board. Participants tilted the board to capture virtual targets on an overhead monitor during 30 s trials. The tasks included two dynamic tasks (i.e., double-leg stance matching mediolateral tilt targets over ±3° or ±9° ranges) and two static tasks (i.e., single-leg stance maintaining a central target position). The performances during the dynamic tasks were significantly correlated with the FMT time to completion. The dominant-leg static task performance showed a moderate trend with the FMT time to completion. The results indicate that supine proprioceptive assessments may be associated with upright ambulation performance, and thus, support the proposed application in bedrest studies.