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Trends in International Mathematics and Science Study (TIMSS) 2019 data revealed that Grade 8 science teachers in several Asian countries (Chinese Taipei, Hong Kong SAR, Japan, and South Korea) reported lower job satisfaction levels than the international average. For example, while Japanese Grade 8 students ranked among the highest in science achievement on the TIMSS 2019, their science teachers reported the lowest job satisfaction composite scale score compared to the other 63 participating countries. Using teacher questionnaire data from TIMSS 2019, we utilized correlation analysis and multiple linear regression to uncover the answers to this research question: Which factors contribute to Japanese Grade 8 science teachers’ job satisfaction? The results from the analysis indicate that working in a safe and orderly school environment was the strongest predictor of Japanese Grade 8 science teacher job satisfaction. The number of working hours, amount of perceived pressure exerted by their students’ parents, participation in professional development focused on science curriculum, and adopting a constructivist orientation to science teaching were the other significant factors that predicted job satisfaction. Findings from this study have implications for Japanese educational policy stakeholders, school administrators, mentor teachers, science department leadership, and those invested in science teachers’ professional development.

Abstract Heterocyclic rings are important structural scaffolds encountered in both natural and synthetic compounds, and their biological activity often depends on these motifs. They are predominantly accessible via cycloaddition reactions, realized by either thermal, photochemical, or catalytic means. Various starting materials are utilized for this purpose, and, among them, diazo compounds are often encountered, especially vinyldiazo compounds that give access to donor-acceptor cyclopropenes which engage in [2+n] cycloaddition reactions. Herein, we describe the development of photochemical processes that produce diverse heterocyclic scaffolds from multisubstituted oximidovinyldiazo compounds. High chemoselectivity, good functional group tolerance, and excellent scalability characterize this methodology, thus predisposing it for broader applications. Experimental and computational studies reveal that under light irradiation these diazo reagents selectively transform into cyclopropenes which engage in cycloaddition reactions with various dipoles, while under thermal conditions the formation of pyrazole from vinyldiazo compounds is favored.

Abstract T cells recirculate through tissues and lymphatic organs to scan for their cognate antigen. Radiation therapy provides site-specific cytotoxicity to kill cancer cells but also has the potential to eliminate the tumor-specific T cells in field. To dynamically study the effect of radiation on CD8 T cell recirculation, we used the Kaede mouse model to photoconvert tumor-infiltrating cells and monitor their movement out of the field of radiation. We demonstrate that radiation results in loss of CD8 T cell recirculation from the tumor to the lymph node and to distant sites. Using scRNASeq, we see decreased proliferating CD8 T cells in the tumor following radiation therapy resulting in a proportional enrichment in exhausted phenotypes. By contrast, 5 days following radiation increased recirculation of T cells from the tumor to the tumor draining lymph node corresponds with increased immunosurveillance of the treated tumor. These data demonstrate that tumor radiation therapy transiently impairs systemic T cell recirculation from the treatment site to the draining lymph node and distant untreated tumors. This may inform timing therapies to improve systemic T cell-mediated tumor immunity.

Abstract Physical activity has been found to alter sleep architecture, but these effects have been studied predominantly in the laboratory and the generalizability of these findings to naturalistic environments and longer time intervals, as well as their psychological effects, have not been evaluated. Recent technological advancements in wearable devices have made it possible to capture detailed measures of sleep outside the lab, including timing of specific sleep stages. In the current study, we utilized photoplethysmography coupled with accelerometers and smartphone ambulatory assessment to collect daily measurements of sleep, physical activity and mood in a sample of N = 82 over multi-month data collection intervals. We found a robust inverse relationship between sedentary behavior and physical activity and sleep architecture: both low-intensity and moderate-to-vigorous physical activity were associated with increased NREM sleep and decreased REM sleep, as well as a longer REM latency, while higher levels of sedentary behavior showed the opposite pattern. A decreased REM/NREM ratio and increased REM latency were in turn associated with improved wellbeing, including increased energy, reduced stress and enhanced perceived restfulness of sleep. Our results suggest that physical activity and sleep account for unique variance in a person’s mood, suggesting that these effects are at least partially independent.

A long-standing challenge in the study of RNA structure-function dynamics using fluorescence-based methods has been the precise attachment of fluorophores to structured RNA molecules. Despite significant advancements in the field, existing techniques have limitations, especially for 3ʹ end labeling of long, structured RNAs. In response to this challenge, we developed a chemo-enzymatic method that uses Klenow DNA polymerase to label RNAs. In this method: • Klenow DNA polymerase adds an amino-modified nucleotide to the 3ʹ end of the RNA, guided by the DNA oligonucleotide template. • An NHS-ester dye is then conjugated to the amino-modified RNA, forming a covalent amide bond. • For highly structured RNAs, DNA oligonucleotides complementary to the RNA disrupt pre-existing intramolecular RNA structures.This methodological advancement enables site-specific incorporation of a single modified nucleotide at the 3′ terminus of various RNA substrates, irrespective of their length or secondary structure. The user-friendly nature of the technique, with minimal modifications required for different RNA targets, makes it readily adaptable by a broad range of researchers. This approach has the potential to significantly improve the development of functionalized RNA for various applications.

Digitals twins, used to represent dynamic environments, require accurate tracking of human movement to enhance their real-world application. This paper contributes to the field by systematically evaluating and comparing pre-existing tracking methods to identify strengths, weaknesses and practical applications within digital twin frameworks. The purpose of this study is to assess the efficacy of existing human movement tracking techniques for digital twins in real world environments, with the goal of improving spatial analysis and interaction within these virtual modes. We compare three approaches using indoor-mounted lidar sensors: (1) a frame-by-frame method deep learning model with convolutional neural networks (CNNs), (2) custom algorithms developed using OpenCV, and (3) the off-the-shelf lidar perception software package Percept version 1.6.3. Of these, the deep learning method performed best (F1 = 0.88), followed by Percept (F1 = 0.61), and finally the custom algorithms using OpenCV (F1 = 0.58). Each method had particular strengths and weaknesses, with OpenCV-based approaches that use frame comparison vulnerable to signal instability that is manifested as “flickering” in the dataset. Subsequent analysis of the spatial distribution of error revealed that both the custom algorithms and Percept took longer to acquire an identification, resulting in increased error near doorways. Percept software excelled in scenarios involving stationary individuals. These findings highlight the importance of selecting appropriate tracking methods for specific use. Future work will focus on model optimization, alternative data logging techniques, and innovative approaches to mitigate computational challenges, paving the way for more sophisticated and accessible spatial analysis tools. Integrating complementary sensor types and strategies, such as radar, audio levels, indoor positioning systems (IPSs), and wi-fi data, could further improve detection accuracy and validation while maintaining privacy.

Here we update U.S. West Coast Biologically Important Areas (BIAs) that were published in 2015 using new data and approaches. Additionally, BIAs were delineated for two species that were not delineated in the 2015 BIAs: fin whales and Southern Resident killer whales (SRKW). While harbor porpoise BIAs remained the same, substantial changes were made for other species including identifying both larger overall areas (parent BIAs) and smaller core areas (child BIAs). For blue, fin, and humpback whales we identified, delineated, and scored BIAs using the overlap between the distribution and relative density from three data sources, leveraging the strengths and weaknesses of these approaches: 1) habitat density models based on Southwest Fisheries Science Center (SWFSC) line-transect data from systematic ship surveys conducted through 2018, 2) satellite tag data from deployments conducted by three research groups, and 3) sightings of feeding behavior from non-systematic effort mostly associated with small-boat surveys for photo-identification conducted by Cascadia Research Collective. While the previous BIAs were based solely on a more subjective assignment from only the small boat sightings, here we incorporate the other two data sources and use a more rigorous, quantitative approach to identify higher density areas and integrate the data types. This resulted in larger, better-supported, objective BIAs compared to the previous effort. Our methods are also more consistent with the delineation of BIAs in other regions. For SRKWs, the parent BIA was based on a modification of the Critical Habitat boundaries defined by the National Oceanographic and Atmospheric Administration (NOAA) and the Department of Fisheries and Oceans (DFO) Canada; a core BIA highlighting areas of intensified use was identified using both NOAA’s Critical Habitat and kernel density analyses of satellite tag data. Gray whale BIAs were re-evaluated for the migratory corridor of Eastern North Pacific gray whales, for Pacific Coast Feeding Group feeding areas, and for gray whales that feed regularly in Puget Sound.

Summary: Cross-cultural studies of the meaning of facial expressions have largely focused on judgments of small sets of stereotypical images by small numbers of people. Here, we used large-scale data collection and machine learning to map what facial expressions convey in six countries. Using a mimicry paradigm, 5,833 participants formed facial expressions found in 4,659 naturalistic images, resulting in 423,193 participant-generated facial expressions. In their own language, participants also rated each expression in terms of 48 emotions and mental states. A deep neural network tasked with predicting the culture-specific meanings people attributed to facial movements while ignoring physical appearance and context discovered 28 distinct dimensions of facial expression, with 21 dimensions showing strong evidence of universality and the remainder showing varying degrees of cultural specificity. These results capture the underlying dimensions of the meanings of facial expressions within and across cultures in unprecedented detail.

Abstract Successful outcomes of outpatient substance use disorder treatment result from many factors for clients—including intersections between individual characteristics, choices made, and social determinants. However, prioritizing which of these and in what combination, to address and provide support for remains an open and complex question. Therefore, we ask: What factors are associated with outpatient substance use disorder clients remaining in treatment for > 90 days and successfully completing treatment? To answer this question, we apply a virtual twins machine learning (ML) model to de-identified data for a census of clients who received outpatient substance use disorder treatment services from 2018 to 2021 from one treatment program in the Southeast U.S. We find that primary predictors of outcome success are: (1) attending self-help groups while in treatment, and (2) setting goals for treatment. Secondary predictors are: (1) being linked to a primary care provider (PCP) during treatment, (2) being linked to supplemental nutrition assistance program (SNAP), and (3) attending 6 or more self-help group sessions during treatment. These findings can help treatment programs guide client choice making and help set priorities for social determinant support. Further, the ML method applied can explain intersections between individual and social predictors, as well as outcome heterogeneity associated with subgroup differences.

Abstract Tropical peatlands are carbon-dense ecosystems because they accumulate partially-decomposed plant material. A substantial fraction of this organic matter may derive from fine root production (FRP). However, few FRP estimates exist for tropical peatlands, with none from the world’s largest peatland complex in the central Congo Basin. Here we report on FRP using repeat photographs of roots from in situ transparent tubes (minirhizotrons), measured to 1 m depth over three one-month periods (spanning dry to wet seasons), in a palm-dominated peat swamp forest, a hardwood-dominated peat swamp forest, and a terra firme forest. We find FRP of 2.6 ± 0.3 Mg C ha−1 yr−1, 1.9 ± 0.5 Mg C ha−1 yr−1, and 1.7 ± 0.1 Mg C ha−1 yr−1 in the three ecosystem types respectively (mean ± standard error; no significant ecosystem type differences). These estimates fall within the published FRP range worldwide. Furthermore, our hardwood peat swamp estimate is similar to the only other FRP study in tropical peatlands, also hardwood-dominated, from Micronesia. We also found that FRP decreased with depth and was the highest during the dry season. Overall, we show that minirhizotrons can be used as a low-disturbance method to estimate FRP in tropical forests and peatlands.

Abstract Samuraciclib is a selective oral CDK7-inhibitor. A multi-modular, open-label Phase I study to evaluate safety and tolerability of samuraciclib in patients with advanced malignancies was designed (ClinicalTrials.gov: NCT03363893). Here we report results from dose escalation and 2 expansion cohorts: Module 1A dose escalation with paired biopsy cohort in advanced solid tumor patients, Module 1B-1 triple negative breast cancer (TNBC) monotherapy expansion, and Module 2A fulvestrant combination in HR+/HER2− breast cancer patients post-CDK4/6-inhibitor. Core study primary endpoints are safety and tolerability, and secondary endpoints are pharmacokinetics (PK), pharmacodynamic (PD) activity, and anti-tumor activity. Common adverse events are low grade nausea, vomiting, and diarrhea. Maximum tolerated dose is 360 mg once daily. PK demonstrates dose proportionality (120 mg-480 mg), a half-life of approximately 75 hours, and no fulvestrant interaction. In dose escalation, one partial response (PR) is identified with disease control rate of 53% (19/36) and reduction of phosphorylated RNA polymerase II, a substrate of CDK7, in circulating lymphocytes and tumor tissue. In TNBC expansion, one PR (duration 337 days) and clinical benefit rate at 24 weeks (CBR) of 20.0% (4/20) is achieved. In combination with fulvestrant, 3 patients achieve PR with CBR 36.0% (9/25); in patients without detectable TP53-mutation CBR is 47.4% (9/19). In this study, samuraciclib exhibits tolerable safety and PK is supportive of once-daily oral administration. Clinical activity in TNBC and HR+/HER2-breast cancer post-CDK4/6-inhibitor settings warrants further evaluation.

Published associations between combined oral contraceptive use and uterine fibroid development have lacked prospective imaging with ultrasound to distinguish between incident and prevalent fibroids. The Study of Environment, Lifestyle, and Fibroids prospectively followed fibroid-free, African-American women (the group with the highest disease burden in the U.S.) to identify incident cases. We examined associations between combined oral contraceptive use and the 40-month cumulative risk of fibroids. History of hormonal contraceptive use was collected via telephone interview at enrollment. Fibroid identification was performed using transvaginal ultrasonography at enrollment, and at 20 and 40-months of follow-up. Inverse probability weights for exposures and censoring were used to construct weighted risk ratios (wRR) and weighted risk different (wRD) estimators which control for differences in fibroid risk factors between exposure groups. In addition, unweighted fully adjusted log-binomial regression models (aRR) were run for comparison. Of the 1,308 participants in the analysis sample, 70% had used combined oral contraceptives and 17% developed fibroids by 40 months. We observed an inverse association between ever use of combined oral contraceptives and cumulative fibroid incidence (wRR: 0.78; 95% Confidence Interval (CI): 0.60, 1.00; wRD: -0.05, 95% CI: -0.11, 0; aRR: 0.76, 95% CI: 0.60, 0.98). Fibroid incidence was greater in participants who started using combined oral contraceptives after age 17 years than among younger initiators, though the restriction to ever-users made this estimate less precise (wRR: 1.25; 95% CI: 0.89, 1.76; wRD: 0.04, 95% CI: -0.02, 0.10). No consistent patterns of fibroid incidence were seen among ever-users for duration of, or years since, last combined oral contraceptives use.

ObjectiveTo assess whether case finding for depression among people aged 65 and above improves mental health.DesignOpportunistic evaluation using a regression discontinuity analysis with data from a randomised controlled trial.SettingThe REFORM trial, a falls prevention study that recruited patients from NHS podiatry clinics.Participants1010 community-dwelling adults over the age of 65 with at least one risk factor for falling (recent previous fall or fear of falling).InterventionLetter sent to patient's General Practitioner if they scored 10 points or above on the 15-item Geriatric Depression Scale (GDS-15) informing them of the patient's risk of depression.Main outcome measureGDS-15 score six months after initial completion of GDS-15.Results895 (88.6%) of the 1010 participants randomised into REFORM had a valid baseline and six-month GDS-15 score and were included in this study. The mean GDS-15 baseline score was 3.5 (SD 3.0, median 3.0, range 0-15); 639 (71.4%) scored 0-4, 204 (22.8%) scored 5-9 indicating mild depression, and 52 (5.8%) scored 10 or higher indicating severe depression. At six months follow-up, those scoring 10 points or higher at baseline had, on average, a reduction of 1.08 points on the GDS-15 scale (95% confidence interval -1.83 to -0.33, p = 0.005) compared to those scoring less than 10, using the simplest linear regression model.ConclusionCase finding of depression in podiatry patients based on a GDS-15 score of 10 or more followed by a letter to their General Practitioner significantly reduced depression severity. Whether this applies to all older patients in primary care is unknown. Further research is required to confirm these findings. Regression discontinuity analyses could be prespecified and embedded within other existing research studies.

Small, island-associated populations of cetaceans have evolved around numerous oceanic islands, likely due to habitat discontinuities between nearshore and offshore waters. However, little is known about the ecology and structure of cetacean populations around the Mariana Islands, a remote archipelago in the western Pacific Ocean. We present sighting, photo-identification, and genetic data collected during twelve years of surveys around these islands that reveal the existence of a small, island-associated population of bottlenose dolphins. Nearly half of the photo-identified individuals were encountered in more than one year. Both haplotypic and nuclear genetic diversity among sampled individuals was low (haplotypic diversity = 0.701, nuclear heterozygosity = 0.658), suggesting low abundance. We used mark-recapture analysis of photo-identification data to estimate yearly abundance in the southern portion of the population’s range from 2011 to 2018. Each abundance estimate was less than 54 individuals, with each upper 95% confidence interval below 100. Additional survey effort is necessary to generate a full population abundance estimate. We found extensive introgression of Fraser’s dolphin DNA into both the mitochondrial and nuclear genomes of the population, suggesting at least two hybridization events more than two generations in the past. The Mariana Islands are used extensively by the U.S. military for land and sea training operations. Thus, this unique bottlenose dolphin population likely faces high exposure to multiple threats.

Abstract Each year, bovine respiratory disease (BRD) results in significant economic loss in the cattle sector, and novel metabolic profiling for early diagnosis represents a promising tool for developing effective measures for disease management. Here, 1H-nuclear magnetic resonance (1H-NMR) spectra were used to characterize metabolites from blood plasma collected from male dairy calves (n = 10) intentionally infected with two of the main BRD causal agents, bovine respiratory syncytial virus (BRSV) and Mannheimia haemolytica (MH), to generate a well-defined metabolomic profile under controlled conditions. In response to infection, 46 metabolites (BRSV = 32, MH = 33) changed in concentration compared to the uninfected state. Fuel substrates and products exhibited a particularly strong effect, reflecting imbalances that occur during the immune response. Furthermore, 1H-NMR spectra from samples from the uninfected and infected stages were discriminated with an accuracy, sensitivity, and specificity ≥ 95% using chemometrics to model the changes associated with disease, suggesting that metabolic profiles can be used for further development, understanding, and validation of novel diagnostic tools.

Abstract Mosquitoes are important vectors for human and animal diseases. Genetic markers, like the mitochondrial COI gene, can facilitate the taxonomic classification of disease vectors, vector-borne disease surveillance, and prevention. Within the control region (CR) of the mitochondrial genome, there exists a highly variable and poorly studied non-coding AT-rich area that contains the origin of replication. Although the CR hypervariable region has been used for species differentiation of some animals, few studies have investigated the mosquito CR. In this study, we analyze the mosquito mitogenome CR sequences from 125 species and 17 genera. We discovered four conserved motifs located 80 to 230 bp upstream of the 12S rRNA gene. Two of these motifs were found within all 392 Anopheles (An.) CR sequences while the other two motifs were identified in all 37 Culex (Cx.) CR sequences. However, only 3 of the 304 non-Culicidae Dipteran mitogenome CR sequences contained these motifs. Interestingly, the short motif found in all 37 Culex sequences had poly-A and poly-T stretch of similar length that is predicted to form a stable hairpin. We show that supervised learning using the frequency chaos game representation of the CR can be used to differentiate mosquito genera from their dipteran relatives.

Abstract The simian parasite Plasmodium knowlesi is the predominant species causing human malaria infection, including hospitalisations for severe disease and death, in Malaysian Borneo. By contrast, there have been only a few case reports of knowlesi malaria from Indonesian Borneo. This situation seems paradoxical since both regions share the same natural macaque hosts and Anopheles mosquito vectors, and therefore have a similar epidemiologically estimated risk of infection. To determine whether there is a true cross-border disparity in P. knowlesi prevalence, we conducted a community-based malaria screening study using PCR in Kapuas Hulu District, West Kalimantan. Blood samples were taken between April and September 2019 from 1000 people aged 6 months to 85 years attending health care facilities at 27 study sites within or close to jungle areas. There were 16 Plasmodium positive samples by PCR, five human malarias (two Plasmodium vivax, two Plasmodium ovale and one Plasmodium malariae) and 11 in which no species could be definitively identified. These data suggest that, if present, simian malarias including P. knowlesi are rare in the Kapuas Hulu District of West Kalimantan, Indonesian Borneo compared to geographically adjacent areas of Malaysian Borneo. The reason for this discrepancy, if confirmed in other epidemiologically similar regions of Indonesian Borneo, warrants further studies targeting possible cross-border differences in human activities in forested areas, together with more detailed surveys to complement the limited data relating to monkey hosts and Anopheles mosquito vectors in Indonesian Borneo.

Abstract Multiple preclinical studies have shown improved outcomes when radiation therapy is combined with immune modulating antibodies. However, to date, many of these promising results have failed to translate to successful clinical studies. This led us to explore additional checkpoint and co-stimulatory pathways that may be regulated by radiation therapy. Here, we demonstrate that radiation increases the expression of inducible T cell co-stimulator (ICOS) on both CD4 and CD8 T cells in the blood following treatment. Moreover, when we combined a novel ICOS agonist antibody with radiation we observed durable cures across multiple tumor models and mouse strains. Depletion studies revealed that CD8 T cells were ultimately required for treatment efficacy, but CD4 T cells and NK cells also partially contributed to tumor control. Phenotypic analysis showed that the combination therapy diminished the increased infiltration of regulatory T cells into the tumor that typically occurs following radiation alone. Finally, we demonstrate in a poorly immunogenic pancreatic tumor model which is resistant to combined radiation and anti-PD1 checkpoint blockade that the addition of this novel ICOS agonist antibody to the treatment regimen results in tumor control. These findings identify ICOS as part of a T cell pathway that is modulated by radiation and targeting this pathway with a novel ICOS antibody results in durable tumor control in preclinical models.

FGFR-1 upregulation has been associated with endocrine therapy resistance in breast cancer patients. Here the authors report the results of a phase IIa study to assess the safety and efficacy of AZD454, an inhibitor of FGFR-1, 2 and 3 receptor tyrosine kinases, in combination with anastrozole or letrozole, in estrogen receptor positive breast cancer patients.

Abstract Biogenic reefs have been hotspots of biodiversity and evolutionary novelty throughout the Phanerozoic. The largest reef systems in Earth’s history occurred in the Devonian period, but collapsed during the Late Devonian Mass Extinction. However, the consequences for the functional diversity of Palaeozoic reefs have received little attention. Here, we examine changes in the functional diversity of tabulate coral assemblages over a 35 million year period from the middle Devonian to the Carboniferous, straddling the multiphase extinction event to identify the causes and ecological consequences of the extinction for tabulate corals. By examining five key morphological traits, we show a divergent response of taxonomic and functional diversity to the mass extinction: taxonomic richness peaked during the Givetian (~ 388–383 Ma) and coincided with peak reef building, but functional diversity was only moderate because many species had very similar trait combinations. The collapse of taxonomic diversity and reef building in the late Devonian had minimal impact on functional richness of coral assemblages. However, non-random shifts towards species with larger corallites and lower colony integration suggest a shift from photosymbiotic to asymbiotic taxa associated over the study period. Our results suggest that the collapse of the huge Devonian reef systems was correlated with a breakdown of photosymbiosis and extinction of photosymbiotic tabulate coral taxa. Despite the appearance of new tabulate coral species over the next 35 million years, the extinction of taxa with photosymbiotic traits had long-lasting consequences for reef building and, by extension, shallow marine ecosystems in the Palaeozoic.

BackgroundAcquired zoonotic infections with Pasteurella bacterial species have a wide clinical spectrum of disease from invasive infections to localised bite-wound infections.MethodsThis study reviewed the spectrum of the demographic, clinical, temporal, and microbiological trends of laboratory confirmed Pasteurella species infections presenting to a single-centre tropical tertiary hospital over a twenty-year period.Results195 episodes from 190 patients were included. 51.3% patients were female, and 20.5% Aboriginal or Torres Strait Islander peoples. Crude incidence of Pasteurella spp. infections increased from 1.5 per 100,000 population in 2000, to 11.4 per 100,000 population in 2021. There were 22 (11.3%) bloodstream infections, 22 (11.3%) invasive, 34 (17.4%) deep local, 98 (50.2%) superficial infections, and 19 (9.7%) other or unknown. Adults over 65 years of age accounted for the majority of bacteraemias (63.7%). More severe infections, including bacteraemia, invasive and deep local infections, were more common in lower limb infections and in those with underlying comorbidities. Animal contact with cats was more common in bloodstream infections (36.4%), but dog bites more common in invasive, deep local and superficial infections. 30-day all-cause mortality was low at 1.0%. Pasteurella multocida was most commonly identified (61.1%), but P. canis, P. dagmatis, and other Pasteurella infections were also noted. 67.7% of specimens were polymicrobial, with other significant organisms being Staphylococcus aureus, Streptococcus pyogenes, Group G Streptococcus and Pseudomonas aeruginosa.ConclusionPasteurella species remain clinically important pathogens, with the ability to cause severe and invasive infections with associated morbidity. Presentations to hospital are becoming more common, and the polymicrobial nature of bites wounds has implications for empiric antibiotic guidelines.

Background Acquired zoonotic infections with Pasteurella bacterial species have a wide clinical spectrum of disease from invasive infections to localised bite-wound infections. Methods This study reviewed the spectrum of the demographic, clinical, temporal, and microbiological trends of laboratory confirmed Pasteurella species infections presenting to a single-centre tropical tertiary hospital over a twenty-year period. Results 195 episodes from 190 patients were included. 51.3% patients were female, and 20.5% Aboriginal or Torres Strait Islander peoples. Crude incidence of Pasteurella spp. infections increased from 1.5 per 100,000 population in 2000, to 11.4 per 100,000 population in 2021. There were 22 (11.3%) bloodstream infections, 22 (11.3%) invasive, 34 (17.4%) deep local, 98 (50.2%) superficial infections, and 19 (9.7%) other or unknown. Adults over 65 years of age accounted for the majority of bacteraemias (63.7%). More severe infections, including bacteraemia, invasive and deep local infections, were more common in lower limb infections and in those with underlying comorbidities. Animal contact with cats was more common in bloodstream infections (36.4%), but dog bites more common in invasive, deep local and superficial infections. 30-day all-cause mortality was low at 1.0%. Pasteurella multocida was most commonly identified (61.1%), but P. canis, P. dagmatis, and other Pasteurella infections were also noted. 67.7% of specimens were polymicrobial, with other significant organisms being Staphylococcus aureus, Streptococcus pyogenes, Group G Streptococcus and Pseudomonas aeruginosa. Conclusion Pasteurella species remain clinically important pathogens, with the ability to cause severe and invasive infections with associated morbidity. Presentations to hospital are becoming more common, and the polymicrobial nature of bites wounds has implications for empiric antibiotic guidelines.

In this assessment we incorporated published and unpublished information to delineate and score Biologically Important Areas (BIAs) for cetaceans in the Hawaiʻi region following standardized criteria. Twenty-six cetacean species have been documented in Hawaiʻi. Eleven odontocete species have distinct small populations resident to one or more island areas: rough-toothed dolphins, pantropical spotted dolphins, common bottlenose dolphins, spinner dolphins, short-finned pilot whales, false killer whales, pygmy killer whales, melon-headed whales, Blainville’s beaked whales, Cuvier’s beaked whales, and dwarf sperm whales. Eight species of mysticetes have been documented, although their occurrence and behavior are poorly understood, with the exception of breeding humpback whales and, more recently, common minke whales. Thirty-five BIAs were delineated or revised from the initial 2015 effort: 33 for small and resident odontocete populations and two for humpback whale reproductive areas. Hierarchical BIAs reflecting core areas of use or population-specific ranges were delineated for nine species. Reproductive watch list areas were designated for common minke whales in the main Hawaiian Islands (MHI) and humpback whales in the Northwestern Hawaiian Islands (NWHI); these areas did not meet the criteria for a BIA due to limited supporting information. All but three BIAs were in the MHI, reflecting the disparities in research effort between this region and the NWHI. Spatial extents of BIA boundaries ranged from 457 km2 to 138,001 km2 (median = 8,299 km2). Scores (range: 1-3) for Data Support and Boundary Certainty were moderate to high (mean = 2.40 and 2.43, respectively), while Intensity and Importance scores were slightly lower (mean = 1.94 and 1.89, respectively). Many of the Hawaiʻi species have been extensively studied over several decades; accordingly, this region ranks among the highest in terms of Data Support relative to other regions. BIAs presented here describe known ranges of small resident populations, intensities of use, and uncertainties in important areas for cetaceans in Hawaiʻi based on the best available data, and have also revealed knowledge gaps to guide future research efforts.

Morphological characters play an important role in species descriptions and are essential for a better understanding of the function, evolution and plasticity of an organism’s shape. However, in complex-shaped organisms lacking characteristic features that can be used as landmarks, quantifying morphological traits, assessing their intra- and interspecific variation, and subsequently delineating phenotypically distinct groups continue to be problematic. For such organisms, three-dimensional morphological analysis might be a promising approach to differentiate morphogroups and potentially aid the delineation of species boundaries, though identifying informative features remains a challenge. Here, we assessed the potential of 3D-based quantitative morphology to delineate a priori and/or to discriminate a posteriori morphogroups of complex-shaped and taxonomically challenging organisms, such as corals from the morphologically diverse genus Acropora. Using three closely related coral taxa previously delimited using other lines of evidence, we extracted a set of variables derived from triangulated polygon meshes and medial axis skeletons of the 3D models. From the resulting data set, univariate and multivariate analyses of 3D-based variables quantifying overall shape including curvature, branching, and complexity were conducted. Finally, informative feature selection was performed to assess the discriminative power of the selected variables. Results revealed significant interspecific differences in the means of a set of 3D-based variables, highlighting potentially informative characters that provide sufficient resolution to discriminate morphogroups congruent with independent species identification based on other lines of evidence. A combination of representative features, remarkably represented by curvature, yielded measures that assisted in differentiating closely related species despite the overall morphospaces overlap. This study shows that a well-justified combination of 3D-based variables can aid species discrimination in complex-shaped organisms such as corals and that feature screening and selection is useful for achieving sufficient resolution to validate species boundaries. Yet, the significant discriminative power displayed by curvature-related variables and their potential link to functional significance need to be explored further. Integrating informative morphological features with other independent lines of evidence appears therefore a promising way to advance not only taxonomy but also our understanding of morphological variation in complex-shaped organisms.

Polarized light-based navigation in insects is facilitated by a polarization-sensitive part of the eye, the dorsal rim area (DRA). Existing methods to study the anatomy of the DRA are destructive and time-consuming. We presented a novel method for DRA localization, dissection, and measurement using 3D volumetric images from X-ray micro-computed tomography in combination with 2D photographs. Applying the method on size-polymorphic buff-tailed bumblebees, Bombus terrestris, we found that the DRA was easily obtainable from photographs of the dorsal eye region. Allometric analysis of the DRA in relation to body size in B. terrestris showed that it increased with the body size but not at the same rate. By localizing the DRA of individual bumblebees, we could also perform individual-level descriptions and inter-individual comparisons between the ommatidial structures (lens, crystalline cones, rhabdoms) of three different eye regions (DRA, non-DRA, proximate to DRA). One feature distinct to the bumblebee DRA was the smaller dimension of the crystalline cones in comparison to other regions of the eye. Using our novel methodology, we provide the first individual-level description of DRA ommatidial features and a comparison of how the DRA varies with body size in bumblebees.

R loops are formed when single-stranded RNA anneals to one strand of DNA, forming three-stranded structures containing DNA-RNA hybrids and the displaced non-template single-stranded DNA. Here the authors reveal that the DNA:RNA helicase UPF1 plays a role in promoting R loops formation at telomeric double strand breaks to stimulate DNA resection and repair.

Abstract The carbon (C) accumulation histories of peatlands are of great interest to scientists, land users and policy makers. Because peatlands contain more than 500 billion tonnes of C, an understanding of the fate of this dynamic store, when subjected to the pressures of land use or climate change, is an important part of climate-change mitigation strategies. Information from peat cores is often used to recreate a peatland’s C accumulation history from recent decades to past millennia, so that comparisons between past and current rates can be made. However, these present day observations of peatlands’ past C accumulation rates (known as the apparent rate of C accumulation - aCAR) are usually different from the actual uptake or loss of C that occurred at the time (the true C balance). Here we use a simple peatland model and a more detailed ecosystem model to illustrate why aCAR should not be used to compare past and current C accumulation rates. Instead, we propose that data from peat cores are used with existing or new C balance models to produce reliable estimates of how peatland C function has changed over time.

Abstract Traumatic brain injury (TBI) is of significant concern in the realm of high impact contact sports, including mixed martial arts (MMA). Extracellular vesicles (EVs) travel between the brain and oral cavity and may be isolated from salivary samples as a noninvasive biomarker of TBI. Salivary EVs may highlight acute neurocognitive or neuropathological changes, which may be particularly useful as a biomarker in high impact sports. Pre and post-fight samples of saliva were isolated from 8 MMA fighters and 7 from controls. Real-time PCR of salivary EVs was done using the TaqMan Human Inflammatory array. Gene expression profiles were compared pre-fight to post-fight as well as pre-fight to controls. Largest signals were noted for fighters sustaining a loss by technical knockout (higher impact mechanism of injury) or a full match culminating in referee decision (longer length of fight), while smaller signals were noted for fighters winning by joint or choke submission (lower impact mechanism as well as less time). A correlation was observed between absolute gene information signals and fight related markers of head injury severity. Gene expression was also significantly different in MMA fighters pre-fight compared to controls. Our findings suggest that salivary EVs as a potential biomarker in the acute period following head injury to identify injury severity and can help elucidate pathophysiological processes involved in TBI.

Lignin conversion to higher value products is essential to the economic viability of lignocellulosic biorefineries. Here, the authors demonstrate the bioconversion of alkali pretreated lignin to itaconic acid by dynamic two stage fermentation using a signal-amplified nitrogen-limitation biosensor.

Circulating tumour DNA can provide useful information on disease burden. Here, the authors analysed circulating tumour DNA from 800 patients from a breast cancer clinical trial and investigate the subclonal nature of the disease, and identify DNA mutations associated with resistance and poor survival.

Diffuse intrinsic pontine glioma (DIPG) carries an extremely poor prognosis, with 2-year survival rates of 2 = 0.568, p = 0.005 *; R2 = 0.605, p = 0.0002 *). Critically, neither of these parameters represent limitations to the implantation of a device within the dimensions of those currently available. Our findings confirm that the anatomy present within this age group is amenable to the placement of a 2 × 1 cm electrode array in 94% of patients examined. Our work serves to demonstrate the feasibility of implantable transclival devices for the provision of TTFs as a novel adjunctive therapy for DIPG.

Measurement(s) Point in Time Date and Time Data Type • Spawning Technology Type(s) Observation • digital curation Sample Characteristic - Organism Scleractinia Sample Characteristic - Environment ocean Sample Characteristic - Location Pacific Ocean • Indian Ocean region Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13100552

Laser wakefield accelerators are compact sources of ultra-relativistic electrons which are highly sensitive to many control parameters. Here the authors present an automated machine learning based method for the efficient multi-dimensional optimization of these plasma-based particle accelerators.

Abstract Prostate cancer accounts for approximately 13.5% of all newly diagnosed male cancer cases. Significant clinical burdens remain in terms of ineffective prognostication, with overtreatment of insignificant disease. Additionally, the pathobiology underlying disease heterogeneity remains poorly understood. As the role of cancer stem cells in the perpetuation of aggressive carcinoma is being substantiated by experimental evidence, it is crucially important to understand the molecular mechanisms, which regulate key features of cancer stem cells. We investigated two methods for in vitro cultivation of putative prostate cancer stem cells based on ‘high-salt agar’ and ‘monoclonal cultivation’. Data demonstrated ‘monoclonal cultivation’ as the superior method. We demonstrated that ‘holoclones’ expressed canonical stem markers, retained the exclusive ability to generate poorly differentiated tumours in NOD/SCID mice and possessed a unique mRNA-miRNA gene signature. miRNA:Target interactions analysis visualised potentially critical regulatory networks, which are dysregulated in prostate cancer holoclones. The characterisation of this tumorigenic population lays the groundwork for this model to be used in the identification of proteomic or small non-coding RNA therapeutic targets for the eradication of this critical cellular population. This is significant, as it provides a potential route to limit development of aggressive disease and thus improve survival rates.

BackgroundPhysical activity (PA) has many health benefits, but motherhood is often associated with reduced PA. Considering that ages and number of children may be associated with maternal PA, and that PA patterns may change as children transition to formal schooling, we aimed to investigate the associations between ages and number of children and device-measured maternal PA.MethodsCross-sectional analyses were conducted using data from 848 mothers from the Southampton Women's Survey at two different timepoints. Two-level random intercept linear models were used to investigate associations between ages (≤4y(ears) ("younger"), school-aged, both age groups) and number (1, 2, ≥3) of children, and their interaction, and accelerometer-assessed minutes of maternal moderate or vigorous PA (log-transformed MVPA) and light, moderate or vigorous PA (LMVPA).ResultsWomen with any school-aged children engaged in more MVPA than those with only ≤4y (e.g. % difference in minutes of MVPA [95% confidence interval]: 46.9% [22.0;77.0] for mothers with only school-aged vs only ≤4y). Mothers with multiple children did less MVPA than those with 1 child (e.g. 12.5% [-1.1;24.3] less MVPA for those with 2 children). For mothers with multiple children, those with any school-aged children did less LMVPA than those with only ≤4y (e.g. amongst mothers with 2 children, those with only school-aged children did 34.0 [3.9;64.1] mins/day less LMVPA). For mothers with any ≤4y, those with more children did more LMVPA (e.g. amongst mothers with only ≤4y, those with 2 children did 42.6 [16.4;68.8] mins/day more LMVPA than those with 1 child).ConclusionsMothers with multiple children and only children aged ≤4y did less MVPA. Considering that many of these women also did more LMVPA than mothers with fewer or older children, interventions and policies are needed to increase their opportunities for higher intensity PA to maximise health benefits.Trial registrationClinicalTrials.gov Identifier: NCT04715945.

BackgroundRobot-mediated interventions show promise in supporting the development of children on the autism spectrum.ObjectivesIn this systematic review and meta-analysis, we summarize key features of available evidence on robot-interventions for children and young people on the autism spectrum aged up to 18 years old, as well as consider their efficacy for specific domains of learning.Data sourcesPubMed, Scopus, EBSCOhost, Google Scholar, Cochrane Library, ACM Digital Library, and IEEE Xplore. Grey literature was also searched using PsycExtra, OpenGrey, British Library EThOS, and the British Library Catalogue. Databases were searched from inception until April (6th) 2021.Synthesis methodsSearches undertaken across seven databases yielded 2145 articles. Forty studies met our review inclusion criteria of which 17 were randomized control trials. The methodological quality of studies was conducted with the Quality Assessment Tool for Quantitative Studies. A narrative synthesis summarised the findings. A meta-analysis was conducted with 12 RCTs.ResultsMost interventions used humanoid (67%) robotic platforms, were predominantly based in clinics (37%) followed home, schools and laboratory (17% respectively) environments and targeted at improving social and communication skills (77%). Focusing on the most common outcomes, a random effects meta-analysis of RCTs showed that robot-mediated interventions significantly improved social functioning (g = 0.35 [95%CI 0.09 to 0.61; k = 7). By contrast, robots did not improve emotional (g = 0.63 [95%CI -1.43 to 2.69]; k = 2) or motor outcomes (g = -0.10 [95%CI -1.08 to 0.89]; k = 3), but the numbers of trials were very small. Meta-regression revealed that age accounted for almost one-third of the variance in effect sizes, with greater benefits being found in younger children.ConclusionsOverall, our findings support the use of robot-mediated interventions for autistic children and youth, and we propose several recommendations for future research to aid learning and enhance implementation in everyday settings.Prospero registrationOur methods were preregistered in the PROSPERO database (CRD42019148981).

Passive acoustic monitoring (PAM) has proven a powerful tool for the study of marine mammals, allowing for documentation of biologically relevant factors such as movement patterns or animal behaviors while remaining largely non-invasive and cost effective. From 2008–2019, a set of PAM recordings covering the frequency band of most toothed whale (odontocete) echolocation clicks were collected at sites off the islands of Hawaiʻi, Kauaʻi, and Pearl and Hermes Reef. However, due to the size of this dataset and the complexity of species-level acoustic classification, multi-year, multi-species analyses had not yet been completed. This study shows how a machine learning toolkit can effectively mitigate this problem by detecting and classifying echolocation clicks using a combination of unsupervised clustering methods and human-mediated analyses. Using these methods, it was possible to distill ten unique echolocation click ‘types’ attributable to regional odontocetes at the genus or species level. In one case, auxiliary sightings and recordings were used to attribute a new click type to the rough-toothed dolphin, Steno bredanensis. Types defined by clustering were then used as input classes in a neural-network based classifier, which was trained, tested, and evaluated on 5-minute binned data segments. Network precision was variable, with lower precision occurring most notably for false killer whales, Pseudorca crassidens, across all sites (35–76%). However, accuracy and recall were high (>96% and >75%, respectively) in all cases except for one type of short-finned pilot whale, Globicephala macrorhynchus, call class at Kauaʻi and Pearl and Hermes Reef (recall >66%). These results emphasize the utility of machine learning in analysis of large PAM datasets. The classifier and timeseries developed here will facilitate further analyses of spatiotemporal patterns of included toothed whales. Broader application of these methods may improve the efficiency of global multi-species PAM data processing for echolocation clicks, which is needed as these datasets continue to grow.

For the first time, dolphins wearing video cameras were observed capturing and eating live native fish. While freely swimming in San Diego Bay, one dolphin caught 69 resident fish, 64 demersal, 5 near surface, while the other caught 40, 36 demersal and 4 near the surface. Two other dolphins were observed capturing 135 live native fish in a sea water pool. Two additional dolphins were observed feeding opportunistically during open water sessions in the Pacific Ocean. Notably, one of these dolphins was observed to consume 8 yellow-bellied sea snakes (Hydrophis platurus). Searching dolphins clicked at intervals of 20 to 50 ms. On approaching prey, click intervals shorten into a terminal buzz and then a squeal. Squeals were bursts of clicks that varied in duration, peak frequency, and amplitude. Squeals continued as the dolphin seized, manipulated and swallowed the prey. If fish escaped, the dolphin continued the chase and sonar clicks were heard less often than the continuous terminal buzz and squeal. During captures, the dolphins' lips flared to reveal nearly all of the teeth. The throat expanded outward. Fish continued escape swimming even as they entered the dolphins' mouth, yet the dolphin appeared to suck the fish right down.

We present a method for performing efficient barycentric interpolation for large grain boundary octonion point sets which reside on the surface of a hypersphere. This method includes removal of degenerate dimensions via singular value decomposition (SVD) transformations and linear projections, determination of intersecting facets via nearest neighbor (NN) searches, and interpolation. This method is useful for hyperspherical point sets for applications such as grain boundaries structure-property models, robotics, and specialized neural networks. We provide a case study of the method applied to the 7-sphere. We provide 1-sphere and 2-sphere visualizations to illustrate important aspects of these dimension reduction and interpolation methods. A MATLAB implementation is available at github.com/sgbaird-5dof/interp. • Barycentric interpolation is combined with hypersphere facet intersections, dimensionality reduction, and linear projections to reduce computational complexity without loss of information • A max nearest neighbor threshold is used in conjunction with facet intersection determination to reduce computational runtime.

Differences in organ scaling among individuals may play an important role in determining behavioural variation. In social insects, there are well-documented intraspecific differences in colony behaviour, but the extent that organ scaling differs within and between colonies remains unclear. Using 12 different colonies of the bumblebee Bombus terrestris, we aim to address this knowledge gap by measuring the scaling relationships between three different organs (compound eyes, wings and antennae) and body size in workers. Though colonies were exposed to different rearing temperatures, this environmental variability did not explain the differences of the scaling relationships. Two colonies had differences in wing versus antenna slopes, three colonies showed differences in wing versus eye slopes and a single colony has differences between eye versus antenna slopes. There are also differences in antennae scaling slopes between three different colonies, and we present evidence for putative trade-offs in morphological investment. We discuss the utility of having variable scaling among colonies and the implication for understanding variability in colony fitness and behaviour.

PurposeThe COVID-19 pandemic and associated risk-mitigation strategies have altered the social contexts in which adolescents in low- and middle-income countries live. Little is known, however, about the impacts of the pandemic on displaced populations, and how those impacts differ by gender and life stage. We investigate the extent to which the pandemic has compounded pre-existing social inequalities among adolescents in Jordan, and the role support structures play in promoting resilience.MethodsOur analysis leverages longitudinal quantitative survey data and in-depth qualitative interviews, collected before and after the onset of COVID-19, with over 3,000 Syrian refugees, stateless Palestinians and vulnerable Jordanians, living in camps, host communities and informal tented settlements. We utilize mixed-methods analysis combining multivariate regression with deductive qualitative tools to evaluate pandemic impacts and associated policy responses on adolescent wellbeing and mental health, at three and nine months after the pandemic onset. We also explore the role of support systems at individual, household, community, and policy levels.FindingsWe find the pandemic has resulted in severe economic and service disruptions with far-reaching and heterogenous effects on adolescent wellbeing. Nine months into the pandemic, 19.3% of adolescents in the sample presented with symptoms of moderate-to severe depression, with small signs of improvement (3.2 percentage points [pp], pConclusionsPre-existing social inequalities among refugee adolescents affected by forced displacement have been compounded during the COVID-19 pandemic, with related disruptions to services and social networks. To achieve Sustainable Development Goal targets to support healthy and empowered development in adolescence and early adulthood requires interventions that target the urgent needs of the most vulnerable adolescents while addressing population-level root causes and determinants of psychosocial wellbeing and resilience for all adolescent girls and boys.

BackgroundBreastfeeding is critical to health outcomes, particularly in low-resource settings where there is little access to clean water. For infants in their first twelve months of life, the delivery of medications is challenging, and use of oral syringes to deliver liquid formulations can pose both practical and emotional challenges.ObjectiveTo explore the potential to deliver medicine to infants via a solid formulation during breastfeeding.MethodsSingle center feasibility study within a tertiary level neonatal unit in the UK, involving twenty-six breastfeeding mother-infant dyads. A solid formulation of Vitamin B12 was delivered to infants during breastfeeding. Outcomes included the quantitative change in serum vitamin B12 and assessment of maternal expectations and experiences.ResultsDelivery of Vitamin B12 through a solid formulation that dissolved in human milk did not impair breastfeeding, and Vitamin B12 levels rose in all infants from a mean baseline (range) 533 pg/mL (236-925 pg/mL) to 1871 pg/mL (610-4981 pg/mL) at 6-8 hours post-delivery. Mothers described the surprising ease of 'drug' delivery, with 85% reporting a preference over the use of syringes.ConclusionsSolid drug formulations can be delivered during breastfeeding and were preferred by mothers over the delivery of liquid formulations via a syringe.

Passive acoustic monitoring (PAM) has proven a powerful tool for the study of marine mammals, allowing for documentation of biologically relevant factors such as movement patterns or animal behaviors while remaining largely non-invasive and cost effective. From 2008-2019, a set of PAM recordings covering the frequency band of most toothed whale (odontocete) echolocation clicks were collected at sites off the islands of Hawai'i, Kaua'i, and Pearl and Hermes Reef. However, due to the size of this dataset and the complexity of species-level acoustic classification, multi-year, multi-species analyses had not yet been completed. This study shows how a machine learning toolkit can effectively mitigate this problem by detecting and classifying echolocation clicks using a combination of unsupervised clustering methods and human-mediated analyses. Using these methods, it was possible to distill ten unique echolocation click 'types' attributable to regional odontocetes at the genus or species level. In one case, auxiliary sightings and recordings were used to attribute a new click type to the rough-toothed dolphin, Steno bredanensis. Types defined by clustering were then used as input classes in a neural-network based classifier, which was trained, tested, and evaluated on 5-minute binned data segments. Network precision was variable, with lower precision occurring most notably for false killer whales, Pseudorca crassidens, across all sites (35-76%). However, accuracy and recall were high (>96% and >75%, respectively) in all cases except for one type of short-finned pilot whale, Globicephala macrorhynchus, call class at Kaua'i and Pearl and Hermes Reef (recall >66%). These results emphasize the utility of machine learning in analysis of large PAM datasets. The classifier and timeseries developed here will facilitate further analyses of spatiotemporal patterns of included toothed whales. Broader application of these methods may improve the efficiency of global multi-species PAM data processing for echolocation clicks, which is needed as these datasets continue to grow.

The objective of this work is to examine disparities in the completion of substance use disorder treatment in the U.S. Our data is from the Treatment Episode Dataset Discharge (TEDS-D) datasets from the U.S. Substance Abuse and Mental Health Services Administration (SAMHSA) for 2017-2019. We apply a two-stage virtual twins model (random forest + decision tree) where, in the first stage (random forest), we determine differences in treatment completion probability associated with race/ethnicity, income source, no co-occurrence of mental health disorders, gender (biological), no health insurance, veteran status, age, and primary substance (alcohol or opioid). In the second stage (decision tree), we identify subgroups associated with probability differences, where such subgroups are more or less likely to complete treatment. We find the subgroups most likely to complete substance use disorder treatment, when the subgroup represents more than 1% of the sample, are those with no mental health condition co-occurrence (4.8% more likely when discharged from an ambulatory outpatient treatment program, representing 62% of the sample; and 10% more likely for one of the more specifically defined subgroups representing 10% of the sample), an income source of job-related wages/salary (4.3% more likely when not having used in the 30 days primary to discharge and when primary substance is not alcohol only, representing 28% of the sample), and white non-Hispanics (2.7% more likely when discharged from residential long-term treatment, representing 9% of the sample). Important implications are that: 1) those without a co-occurring mental health condition are the most likely to complete treatment, 2) those with job related wages or income are more likely to complete treatment, and 3) racial/ethnicity disparities persist in favor of white non-Hispanic individuals seeking to complete treatment. Thus, additional resources may be needed to combat such disparities.

IntroductionDepression is a leading mental health problem worldwide. People with long-term conditions are at increased risk of experiencing depression. The COVID-19 pandemic led to strict social restrictions being imposed across the UK population. Social isolation can have negative consequences on the physical and mental wellbeing of older adults. In the Behavioural Activation in Social IsoLation (BASIL+) trial we will test whether a brief psychological intervention (based on Behavioural Activation), delivered remotely, can mitigate depression and loneliness in older adults with long-term conditions during isolation.MethodsWe will conduct a two-arm, parallel-group, randomised controlled trial across several research sites, to evaluate the clinical and cost-effectiveness of the BASIL+ intervention. Participants will be recruited via participating general practices across England and Wales. Participants must be aged ≥65 with two or more long-term conditions, or a condition that may indicate they are within a 'clinically extremely vulnerable' group in relation to COVID-19, and have scored ≥5 on the Patient Health Questionnaire (PHQ9), to be eligible for inclusion. Randomisation will be 1:1, stratified by research site. Intervention participants will receive up to eight intervention sessions delivered remotely by trained BASIL+ Support Workers and supported by a self-help booklet. Control participants will receive usual care, with additional signposting to reputable sources of self-help and information, including advice on keeping mentally and physically well. A qualitative process evaluation will also be undertaken to explore the acceptability of the BASIL+ intervention, as well as barriers and enablers to integrating the intervention into participants' existing health and care support, and the impact of the intervention on participants' mood and general wellbeing in the context of the COVID-19 restrictions. Semi-structured interviews will be conducted with intervention participants, participant's caregivers/supportive others and BASIL+ Support Workers. Outcome data will be collected at one, three, and 12 months post-randomisation. Clinical and cost-effectiveness will be evaluated. The primary outcome is depressive symptoms at the three-month follow up, measured by the PHQ9. Secondary outcomes include loneliness, social isolation, anxiety, quality of life, and a bespoke health services use questionnaire.DiscussionThis study is the first large-scale trial evaluating a brief Behavioural Activation intervention in this population, and builds upon the results of a successful external pilot trial.Trial registrationClinicalTrials.Gov identifier ISRCTN63034289, registered on 5th February 2021.

The type-section of the Blackwater Draw Formation (BDF) consists of a series of five paleosol horizons developed on eolian deposits and an overlying surficial soil. Previous work has shown that magnetic properties (e.g., χ, ARM, and IRM) as a function of depth in this type-section, display both magnetically enhanced and magnetically depleted signals for different paleosols. To better understand the magnetic mineralogy responsible for these varying responses, various rock-magnetic experiments, scanning electron microscopy, and Mössbauer spectroscopy were conducted on representative samples from the six soil units which constitute the BDF type-section. Our results show that sub-micron hematite [with a minor contribution from single-domain sized hematite (Hc = ∼500 mT) dominates all the soils in terms of weight percent concentration. Whereas, low coercivity (Hc = ∼35 mT or less) magnetite/maghemitized-magnetite grains, largely in the PSD state (Mr/Ms=∼0.14 +/– 0.03588, Hcr/Hc=∼2.68 +/– 0.298789), dominate the magnetic signal. Magnetically depleted soils show a relatively higher proportion of goethite, while magnetically enhanced soils show an increased contribution from SP/SSD magnetite/maghemite phases.By combining our data-set with geochemically-derived climofunctions, we have correlated the magnetically preserved, depleted, and enhanced sections of the type-section to three distinct environmental phases (I-III). The basal sediments of Phase I displays relatively homogenous (neither enhanced nor depleted) magnetic properties due to relatively arid conditions and minimal alteration of southerly derive eolian sands. Conversely, Phase II-III represents a change in weathering intensities and provenance, resulting in a mix of southerly derived sands and northerly derived silts. Phase II, experienced greater precipitation levels, resulting in the dissolution of Fe-oxide phases and thus magnetic depletion. The uppermost Phase III experienced intermediate precipitation intensities resulting in magnetic enhancement.Using previously published age models we tentatively interpret these changing environmental conditions to be influenced by the Middle-Pleistocene Transition (1.2-0.7 Ma), where the Earth’s climatic cycles shifted from a ∼41 kyr to ∼100 kyr cycles. However, ambiguities persist due to uncertainties in the currently published age model. Due to the complexity of the magnetic signal, we recommend future studies utilize a holistic approach, incorporating rock-magnetic, geochemical, and microscopy observations for more accurate reconstruction of regional paleoenvironments.