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Identity cues appear ubiquitously alongside content in social media today. Some also suggest universal identification, with names and other cues, as a useful deterrent to harmful behaviours online. Unfortunately, we know little about the effects of identity cues on opinions and online behaviours. Here we used a large-scale longitudinal field experiment to estimate the extent to which identity cues affect how people form opinions about and interact with content online. We randomly assigned content produced on a social news aggregation website to 'identified' and 'anonymous' conditions to estimate the causal effect of identity cues on how viewers vote and reply to content. The effects of identity cues were significant and heterogeneous, accounting for between 28% and 61% of the variation in voting associated with commenters' production, reputation and reciprocity. Our results also showed that identity cues cause people to vote on content faster (consistent with heuristic processing) and to vote according to content producers' reputations, production history and reciprocal votes with content viewers. These results provide evidence that rich-get-richer dynamics and inequality in social content evaluation are mediated by identity cues. They also provide insights into the evolution of status in online communities. From a practical perspective, we show via simulation that social platforms may improve content quality by including votes on anonymized content as a ranking signal.

This study provides a new record of nitrogen (N) deposition and ecological response at a remote, high-elevation lake within the ecologically fragile Three River Headwaters Region, northwest China, from the early 20thCentury to the past decade. A multi-proxy investigation of a lake sediment core including analyses of chironomids (non-biting midge), lake sediment geochemistry (δ15N, δ13C, TN, TOC, OC:TN), pollen, non-pollen palynomorphs and 210Pb-dating. Results were compared with regional pollution forcings, including fertiliser application, atmospheric nitrate and dust deposition, and a localised multiscale air quality modelling system for N-deposition. Our data reflect a mesotrophic lake for the majority of the 20th Century with minimal anthropogenic impact. A shift in the lake conditions is evident after 1985 with increased nutrient enrichment. Low δ15N, OC:TN and increasing TN values, together with an increase in chironomid taxa associated with eutrophic conditions and macrophytes are exhibited in the record, particularly since 2002. These changes are consistent with nutrient loading causing a change in trophic status. Redundancy analysis (RDA) and partial RDAs verified TN as an important driver behind the shift in chironomid community composition in recent decades, explaining 22.2% of the variance on its own and 16.9% with other environmental variables partialled out. While temperature change since 1960 was not a primary control on the chironomid community of Lake Bander, a step-change increase in summer temperatures since the 1990s coincided with the disappearance of cold stenotherms from the record and seems to have exacerbated the shift to more productive conditions. This study highlights the reach of airborne N from modern agricultural and industrial activity to remote locations, and demonstrates the utility of palaeolimnological techniques as part of modern ecosystem assessment for conservation.

Individuals from minoritized racial/ethnic groups have higher levels of circulating inflammatory markers. However, the mechanisms underlying these differences remain understudied. The objective of this study was to examine racial/ethnic variations in multiple markers of inflammation and whether impaired sleep contributes to these racial/ethnic differences. Nurses from two regional hospitals in Texas (n = 377; 71.62% White; 6.90% Black; 11.14% Hispanic, 10.34% Asian; mean age = 39.46; 91.78% female) completed seven days of sleep diaries and actigraphy to assess mean and variability in total sleep time (TST) and sleep efficiency (SE). On day 7, blood was drawn to assess 4 inflammatory markers: C-reactive protein (CRP), Interleukin-6 (IL-6), Interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α). Results from regression models showed differences in inflammatory markers by race/ethnicity, adjusting for age and gender. The associations between sleep parameters and inflammatory markers also varied by race/ethnicity. Among White nurses, lower mean and greater variability in actigraphy-determined TST and greater variability in diary-determined TST were associated with higher levels of IL-6. Among Black nurses, lower mean diary-determined SE was associated with higher levels of IL-6 and IL-1β. Among Hispanic nurses, greater diary-determined mean TST was associated with higher CRP. Among Asian nurses, greater intraindividual variability in actigraphy-determined SE was associated with lower CRP. Among nurses, we did not find racial/ethnic disparities in levels of inflammation. However, analyses revealed differential relationships between sleep and inflammatory markers by race/ethnicity. Results highlight the importance of using a within-group approach to understand predictors of inflammatory markers.

Although most pathogens infect the human body via mucosal surfaces, very few injectable vaccines can specifically target immune cells to these tissues where their effector functions would be most desirable. We have previously shown that certain adjuvants can program vaccine-specific helper T cells to migrate to the gut, even when the vaccine is delivered non-mucosally. It is not known whether this is true for antigen-specific B cell responses. Here we show that a single intradermal vaccination with the adjuvant double mutant heat-labile toxin (dmLT) induces a robust endogenous, vaccine-specific, isotype-switched B cell response. When the vaccine was intradermally boosted, we detected non-circulating vaccine-specific B cell responses in the lamina propria of the large intestines, Peyer’s patches, and lungs. When compared to the TLR9 ligand adjuvant CpG, only dmLT was able to drive the establishment of isotype-switched resident B cells in these mucosal tissues, even when the dmLT-adjuvanted vaccine was administered non-mucosally. Further, we found that the transcription factor Batf3 was important for the full germinal center reaction, isotype switching, and Peyer’s patch migration of these B cells. Collectively, these data indicate that specific adjuvants can promote mucosal homing and the establishment of activated, antigen-specific B cells in mucosal tissues, even when these adjuvants are delivered by a non-mucosal route. These findings could fundamentally change the way future vaccines are formulated and delivered.

Background Treatment options for patients with inherited retinal disease are limited, although research into novel therapies is underway. To ensure the success of future clinical trials, appropriate visual function outcome measures that can assess changes resulting from therapeutic interventions are urgently required. Rod-cone degenerations are the most common type of inherited retinal disease. Visual acuity is a standard measure but is typically preserved until late disease stages, frequently making it an unsuitable visual function marker. Alternative measures are required. This study investigates the clinical utility of a range of carefully selected visual function tests and patient reported outcome measures. The aim is to identify suitable outcome measures for future clinical trials that could be considered for regulatory approval. Methods This cross-sectional study involves two participant groups, patients with inherited retinal disease (n = 40) and healthy controls (n = 40). The study has been designed to be flexible and run alongside NHS clinics. The study is split into two parts. Part one includes examining standard visual acuity, low luminance visual acuity, the Moorfields acuity chart visual acuity, mesopic microperimetry and three separate patient reported outcome measures. Part two involves 20 min of dark adaptation followed by two-colour scotopic microperimetry. Repeat testing will be undertaken where possible to enable repeatability analyses. A subset of patients with inherited retinal disease will be invited to participate in a semi-structured interview to gain awareness of participants’ thoughts and feelings around the study and different study tests. Discussion The study highlights a need for reliable and sensitive validated visual function measures that can be used in future clinical trials. This work will build on work from other studies and be used to inform an outcome measure framework for rod-cone degenerations. The study is in keeping with the United Kingdom Department of Health and Social Care research initiatives and strategies for increasing research opportunities for NHS patients as part of their NHS care. Trial registration ISRCTN registry, ISRCTN24016133, Visual Function in Retinal Degeneration, registered on 18th August 2022.

Background While prior work has revealed conditions that foster policymakers’ use of research evidence, few studies have rigorously investigated the effectiveness of theory-based practices. Specifically, policymakers are most apt to use research evidence when it is timely, relevant, brief, and messaged appropriately, as well as when it facilitates interactive engagement. This study sought to experimentally evaluate an enhanced research dissemination intervention, known as the SciComm Optimizer for Policy Engagement (SCOPE), implemented during the COVID-19 pandemic among US state legislators. Methods State legislators assigned to health committees and their staff were randomized to receive the SCOPE intervention. This involved providing academic researchers with a pathway for translating and disseminating research relevant to current legislative priorities via fact sheets emailed directly to officials. The intervention occurred April 2020–March 2021. Research language was measured in state legislators’ social media posts. Results Legislators randomized to receive the intervention, relative to the control group, produced 24% more social media posts containing research language related to COVID-19. Secondary analyses revealed that these findings were driven by two different types of research language. Intervention officials produced 67% more COVID-related social media posts referencing technical language (e.g., statistical methods), as well as 28% more posts that referenced research-based concepts. However, they produced 31% fewer posts that referenced creating or disseminating new knowledge. Conclusions This study suggests that strategic, targeted science communication efforts may have the potential to change state legislators’ public discourse and use of evidence. Strategic science communication efforts are particularly needed in light of the role government officials have played in communicating about the pandemic to the general public.

Fractional flow reserve (FFR) is the current gold standard invasive assessment of coronary artery disease (CAD). FFR reports coronary blood flow (CBF) as a fraction of a hypothetical and unknown normal value. Although used routinely to diagnose CAD and guide treatment, how accurately FFR predicts actual CBF changes remains unknown. In this study, we compared fractional CBF with absolute CBF (aCBF, in ml min−1), measured with a computational method during standard angiography and pressure wire assessment, on 203 diseased arteries (143 patients). We found a substantial correlation between the two measurements (r = 0.89 and Cohen’s kappa = 0.71). Concordance between fractional and absolute CBF reduction was high when FFR was >0.80 (91%) but reduced when FFR was ≤0.80 (81%), 0.70–0.80 (68%) and, particularly, 0.75–0.80 (62%). Discordance was associated with coronary microvascular resistance, vessel diameter and mass of myocardium subtended, all factors to which FFR is agnostic. Assessment of aCBF complements FFR and may be valuable to assess CBF, particularly in cases within the FFR ‘gray zone’.

Objective To examine whether the prevalence of age- and sex-adjusted BMI at, or above, the 85th, 95th and 99.7th percentiles continues to decline in New Zealand preschool children, over time. Methods As part of a national screening programme, 438,972 New Zealand 4-year-old children had their height and weight measured between 2011 and 2019. Age- and sex-adjusted BMI was calculated using WHO Growth Standards and the prevalence of children at, or above, the 85th, 95th, and 99.7th percentiles and at, or below, the 2nd percentile were determined. Log-binomial models were used to estimate linear time trends of ≥85th, ≥95th and ≥99.7th percentiles for the overall sample and separately by sex, deprivation, ethnicity and urban-rural classification. Results The percentage of children at, or above, the 85th, 95th and 99.7th percentile reduced by 4.9% [95% CI: 4.1%, 5.7%], 3.5% [95% CI: 2.9%, 4.1%], and 0.9% [95% CI: 0.7%, 1.2%], respectively, between ‘2011/12’ and ‘2018/19’. There was evidence of a decreasing linear trend (risk reduction, per year) for the percentage of children ≥85th (risk ratio (RR): 0.980 [95% CI: 0.978, 0.982]), ≥95th (RR: 0.966 [95% CI: 0.962, 0.969]) and ≥99.7th (RR: 0.957 [95% CI: 0.950, 0.964]) percentiles. Downward trends were also evident across all socioeconomic indicators (sex, ethnicity, deprivation, and urban-rural classification), for each of the BMI thresholds. Larger absolute decreases were evident for children residing in the most deprived compared with the least deprived areas, at each BMI threshold. There appeared to be no consistent trend for the percentage of children ≤2nd percentile. Conclusions Reassuringly, continued declines of children with age- and sex-adjusted BMI at, or above, the 85th, 95th and 99.7th percentiles are occurring over time, overall and across all sociodemographic indicators, with little evidence for consistent trends in the prevalence of children at, or below, the 2nd percentile.

Background Autism spectrum condition and attention-deficit/hyperactivity disorder (ADHD) are associated with a range of physical health conditions. The aim of this study was to examine the etiological components contributing to co-occurring physical health conditions in autism and ADHD. Methods In this nationwide Child and Adolescent Twin Study in Sweden, we analyzed data from 10,347 twin pairs aged 9 and 12. Clinical diagnoses of autism, ADHD, and physical health conditions were identified through the Swedish National Patient Register. Subclinical phenotypes of autism and ADHD were defined by symptom thresholds on a standardized parent-interview, the Autism–Tics, ADHD, and Other Comorbidities inventory. Associations between physical health conditions and autism/ADHD phenotypes were examined using generalized estimating equations. Bivariate twin models were applied to estimate the extent to which genetic and environmental risk factors accounted for physical health comorbidities. Results Similar patterns of association with physical health conditions were found in clinical and subclinical autism/ADHD, with odds ratios ranging from 1.31 for asthma in subclinical ADHD to 8.03 for epilepsy in clinical autism. The estimated genetic correlation (ra) with epilepsy was 0.50 for clinical autism and 0.35 for subclinical autism. In addition, a modest genetic correlation was estimated between clinical autism and constipation (ra = 0.31), functional diarrhea (ra = 0.27) as well as mixed gastrointestinal disorders (ra = 0.30). Genetic effects contributed 0.86 for mixed gastrointestinal disorders in clinical ADHD (ra = 0.21). Finally, subclinical ADHD shared genetic risk factors with epilepsy, constipation, and mixed gastrointestinal disorders (ra = 0.30, 0.17, and 0.17, respectively). Limitations Importantly, since medical records from primary care were not included in the registry data used, we probably identified only more severe rather than the full range of physical health conditions. Furthermore, it needs to be considered that the higher prevalence of physical health conditions among autistic children and children with ADHD could be associated with the increased number of medical visits. Conclusions Shared genetic effects contribute significantly to autism and ADHD phenotypes with the co-occurring physical health conditions across different organ systems, including epilepsy and gastrointestinal disorders. The shared genetic liability with co-occurring physical health conditions was present across different levels of autism and ADHD symptom severity.

Arginyl-tRNA-protein transferase 1 (ATE1) is a master regulator of protein homeostasis, stress response, cytoskeleton maintenance, and cell migration. The diverse functions of ATE1 arise from its unique enzymatic activity to covalently attach an arginine onto its protein substrates in a tRNA-dependent manner. However, how ATE1 (and other aminoacyl-tRNA transferases) hijacks tRNA from the highly efficient ribosomal protein synthesis pathways and catalyzes the arginylation reaction remains a mystery. Here, we describe the three-dimensional structures of Saccharomyces cerevisiae ATE1 with and without its tRNA cofactor. Importantly, the putative substrate binding domain of ATE1 adopts a previously uncharacterized fold that contains an atypical zinc-binding site critical for ATE1 stability and function. The unique recognition of tRNAArg by ATE1 is coordinated through interactions with the major groove of the acceptor arm of tRNA. Binding of tRNA induces conformational changes in ATE1 that helps explain the mechanism of substrate arginylation.

Accurate segregation of chromosomes is required to maintain genome integrity during cell division. This feat is accomplished by the microtubule-based spindle. To build a spindle rapidly and with high fidelity, cells take advantage of branching microtubule nucleation, which exponentially amplifies microtubules during cell division. Branching microtubule nucleation relies on the hetero-octameric augmin complex, but understanding how augmin promotes branching has been hindered by a lack of structural information about the complex. Here, we report an integrated model of vertebrate augmin, combining cryo-electron microscopy, advanced protein structural prediction, and the visualization of fused bulky tags via negative stain electron microscopy. This strategy allowed us to identify the location and orientation of each subunit within the structure. Evolutionary analysis of augmin’s structure reveals that it is highly conserved across diverse eukaryotes, and that augmin contains a previously-unidentified microtubule binding site. Moreover, we identify homology with the kinetochore-localized NDC80 complex. This new model of the augmin complex provides insight towards the mechanism and evolution of branching microtubule nucleation.

To better understand functional morphological adaptations to high elevation (> 3000 m above sea level) life in both North American and African mountain-associated rodents, we used microCT scanning to acquire 3D images and a 3D morphometric approach to calculate endocranial volumes and skull lengths. This was done on 113 crania of low-elevation and high-elevation populations in species of North American cricetid mice (two Peromyscus species, n = 53), and African murid rodents of two tribes, Otomyini (five species, n = 49) and Praomyini (four species, n = 11). We tested two distinct hypotheses for how endocranial volume might vary in high-elevation populations: the expensive tissue hypothesis, which predicts that brain and endocranial volumes will be reduced to lessen the costs of growing and maintaining a large brain; and the brain-swelling hypothesis, which predicts that endocranial volumes will be increased either as a direct phenotypic effect or as an adaptation to accommodate brain swelling and thus minimize pathological symptoms of altitude sickness. After correcting for general allometric variation in cranial size, we found that in both North American Peromyscus mice and African laminate-toothed (Otomys) rats, highland rodents had smaller endocranial volumes than lower-elevation rodents, consistent with the expensive tissue hypothesis. In the former group, Peromyscus mice, crania were obtained not just from wild-caught mice from high and low elevations but also from those bred in common-garden laboratory conditions from parents caught from either high or low elevations. Our results in these mice showed that brain size responses to elevation might have a strong genetic basis, which counters an opposite but weaker environmental effect on brain volume. These results potentially suggest that selection may act to reduce brain volume across small mammals at high elevations but further experiments are needed to assess the generality of this conclusion and the nature of underlying mechanisms.

Autism is a heritable and common neurodevelopmental condition, with behavioural symptoms typically emerging around age 2 to 3 years. Differences in basic perceptual processes have been documented in autistic children and adults. Specifically, data from many experiments suggest links between autism and alterations in global visual motion processing (i.e., when individual motion information is integrated to perceive an overall coherent pattern). Yet, no study has investigated whether a distinctive organization of global motion processing precede the emergence of autistic symptoms in early childhood. Here, using a validated infant electroencephalography (EEG) experimental paradigm, we first establish the normative activation profiles for global form, global motion, local form, and local motion in the visual cortex based on data from two samples of 5-month-old infants (total n = 473). Further, in a sample of 5-month-olds at elevated likelihood of autism (n = 52), we show that a different topographical organization of global motion processing is associated with autistic symptoms in toddlerhood. These findings advance the understanding of neural organization of infants’ basic visual processing, and its role in the development of autism.

15-prostaglandin dehydrogenase (15-PGDH) is a negative regulator of tissue stem cells that acts via enzymatic activity of oxidizing and degrading PGE2, and related eicosanoids, that support stem cells during tissue repair. Indeed, inhibiting 15-PGDH markedly accelerates tissue repair in multiple organs. Here we have used cryo-electron microscopy to solve the solution structure of native 15-PGDH and of 15-PGDH individually complexed with two distinct chemical inhibitors. These structures identify key 15-PGDH residues that mediate binding to both classes of inhibitors. Moreover, we identify a dynamic 15-PGDH lid domain that closes around the inhibitors, and that is likely fundamental to the physiologic 15-PGDH enzymatic mechanism. We furthermore identify two key residues, F185 and Y217, that act as hinges to regulate lid closing, and which both inhibitors exploit to capture the lid in the closed conformation, thus explaining their sub-nanomolar binding affinities. These findings provide the basis for further development of 15-PGDH targeted drugs as therapeutics for regenerative medicine.

Cassava genetic transformation has mostly been reported for African cassava varieties, but not for Asian varieties. This is the first report of cassava transformation in Asian elite varieties using friable embryogenic calli. Agrobacterium-mediated cassava transformation via friable embryogenic calli (FEC) has enabled the robust production of transgenic cassava. So far, mostly the model cassava variety 60444 and African varieties have been transformed because of their good production and regeneration from embryogenic tissues. It is important to develop transformation methods for elite Asian cassava varieties to meet the changing needs in one of the world's major cassava production areas. However, a suitable transformation method for the Asian elite variety Kasetsart 50 (KU50) has not been developed. Here, we report a transformation method for KU50, the cultivar with the highest planting area in Thailand and Vietnam. In cassava transformation, the preparation of FEC as the target tissue for transgene integration is a key step. FEC induction from KU50 was improved by using media with reduced nutrients and excess vitamin B1, and somatic embryo and plant regeneration optimized by manipulation of naphthalene acetic acid (NAA), and benzylamino purine (BAP). The transformation efficiency for KU50 was 22%, approximately half that of 60444 at 45%. Transcriptome analysis indicated that the expression of genes related to cell-wall loosening was upregulated in FEC from KU50 compared with 60444, indicating that cell-wall production and assembly were disproportionate in the Asian variety. The transformation system for KU50 reported here will contribute to the molecular breeding of cassava plants for Asian farmers using transgenic and genome-editing technologies.

Background Good quality sleep, regular physical activity, and limited time spent sedentary are all considered individually important in promoting good mental health in children. However, few studies have examined the influence of each behaviour simultaneously, using compositional analysis which accounts for the closed nature of the 24-h day. Our aim was to determine how compositional time use in early childhood is prospectively related to mental and psychosocial health at 5 years of age. Methods A total of 392 children wore Actical accelerometers 24-h a day for one week at 2, 3.5 and 5 years of age to examine time in sleep, physical activity, and sedentary behaviour. Psychosocial and mental health were assessed at age 5 using both laboratory based (researcher-assessed) and questionnaire (parental-report) measures. Associations were estimated using regression models with isometric log-ratios of time-use components as predictors. Results Cross-sectionally, 5-year old children who spent 10% (64 min) more time asleep than average had better inhibitory control (standardised mean difference [d]; 0.19; 95% confidence interal [CI]: 0.02, 0.36 for Statue test and d = 0.16; 95% CI: − 0.01, 0.33 for Heads–Toes–Knees–Shoulders task). A greater proportion of time spent active (10%, 31 min) was associated with poorer inhibitory control (d = − 0.07; 95% CI: − 0.13, − 0.02 for Statue test, d = − 0.06; 95% CI: − 0.11, − 0.01 for Heads–Toes–Knees–Shoulders task). By contrast, differences in time-use were not found to be significantly associated with any measure of self-regulation or mental health at 5 years of age, nor were any significant longitudinal relationships apparent. Conclusions We did not find a significant association between 24-h time use in the preschool years and any measure of psychosocial or mental health at 5 years of age, although some relationships with inhibitory control were observed cross-sectionally. Trial registration: ClinicalTrials.gov number NCT00892983, registered 5th May 2009.

Background Multiple clinical trials demonstrate consistent but modest benefit of adjuvant extended endocrine therapy (EET) in HR + breast cancer patients. Predictive biomarkers to identify patients that benefit from EET are critical to balance modest reductions in risk against potential side effects of EET. This study compares the performance of the Breast Cancer Index, BCI (HOXB13/IL17BR, H/I), with expression of estrogen (ER), progesterone (PR), and androgen receptors (AR), and Ki67, for prediction of EET benefit. Methods Node-positive (N+) patients from the Trans-aTTom study with available tissue specimen and BCI results (N = 789) were included. Expression of ER, PR, AR, and Ki67 was assessed by quantitative immunohistochemistry. BCI (H/I) gene expression analysis was conducted by quantitative RT-PCR. Statistical significance of the treatment by biomarker interaction was evaluated by likelihood ratio tests based on multivariate Cox proportional models, adjusting for age, tumor size, grade, and HER2 status. Pearson’s correlation coefficients were calculated to evaluate correlations between BCI (H/I) versus ER, PR, AR, Ki67 and AR/ER ratio. Results EET benefit, measured by the difference in risk of recurrence between patients treated with tamoxifen for 10 versus 5 years, is significantly associated with increasing values of BCI (H/I) (interaction P = 0.01). In contrast, expression of ER (P = 0.83), PR (P = 0.66), AR (P = 0.78), Ki67 (P = 0.87) and AR/ER ratio (P = 0.84) exhibited no significant relationship with EET benefit. BCI (H/I) showed a very weak negative correlation with ER (r = − 0.18), PR (r = − 0.25), and AR (r = − 0.14) expression, but no correlation with either Ki67 (r = 0.04) or AR/ER ratio (r = 0.02). Conclusion These findings are consistent with the growing body of evidence that BCI (H/I) is significantly predictive of response to EET and outcome. Results from this direct comparison demonstrate that expression of ER, PR, AR, Ki67 or AR/ER ratio are not predictive of benefit from EET. BCI (H/I) is the only clinically validated biomarker that predicts EET benefit.

Bats have been proposed as reliable bioindicators for monitoring bioaccumulation of elements and chemicals in natural and transformed ecosystems. Non-invasive methods are becoming more popular as research moves away from destructive methodologies. We present the first concentrations of 23 elements in Mops condylurus and Tadarida aegyptiaca (Molossidae) fur and blood from an opencast diamond mine and reference area using inductively coupled plasma mass spectrometry (ICP-MS). Concentrations of B, K, Rb and Cd in the bats’ fur were significantly higher in the mining footprint compared to the reference area (P < 0.05). Other elements such as Zn and Hg were significantly higher in the blood of bats from the mining footprint than the reference area (P < 0.05), whereas Mn was significantly higher in the blood of bats from the reference area than from the mining footprint (P < 0.05). Sixteen of the 22 elements above the limit of detection, with the exception of Ba, were significantly higher in the fur samples than in the blood due to elements being incorporated over time into the fur as it grows, whereas blood reveals short-term exposure to elements. Concentrations of most of the elements were reasonably low except Al, Fe and Zn. In general, the element concentrations particularly in the fur samples were comparable with other international studies reporting elemental fur concentrations from anthropogenically impacted and natural areas. Fur and blood have the potential to be viable indicators of environmental toxicity, but research is required on toxic thresholds and physiological and ecological unknowns around element concentrations in bat tissues and organs.

α-Sn has been hailed as a single-element topological material with great promise for spintronic applications due to its strong spin–orbit coupling. Epitaxial growth on CdTe is identified as a method to isolate the novel electronic properties of thin film α-Sn, in order to perform transport studies without shunting through other lattice-matched substrates that may be conducting, such as InSb. As opposed to the bulk semimetallic or semiconducting states studied previously on CdTe, thinner films are expected to be topologically insulating. Field-effect gating allows for an in-depth analysis of the carrier distributions involved to determine both the potential and the challenges posed by this material system. We find two-carrier n- and p-type transport, as well as a narrow band gap in the surface state as a result of an annihilation of the Dirac points in the [001] projection. The transport properties are greatly affected by carrier scattering at the heteroepitaxial growth surface, as evidenced by linear magnetoresistance, a high background of carriers, and low mobility. Future studies involving the great promise of topological insulator states of α-Sn grown on electrically insulating CdTe will find such transport measurements invaluable for the creation of topological devices in this material system.

Background Climate change has significant implications for health, yet healthcare provision itself contributes significant greenhouse gas emission. Medical students need to be prepared to address impacts of the changing environment and fulfil a key role in climate mitigation. Here we evaluate the effectiveness of an online module on climate-change and sustainability in clinical practice designed to achieve learning objectives adapted from previously established sustainable healthcare priority learning outcomes. Methods A multi-media, online module was developed, and 3rd and 4th year medical students at Brighton and Sussex Medical School were invited to enrol. Students completed pre- and post-module questionnaires consisting of Likert scale and white space answer questions. Quantitative and qualitative analysis of responses was performed. Results Forty students enrolled and 33 students completed the module (83% completion rate). There was a significant increase in reported understanding of key concepts related to climate change and sustainability in clinical practice (p Conclusion This is the first study to evaluate learner outcomes of an online module in the field of sustainable health and healthcare. Our results suggest that completion of the module was associated with significant improvement in self-assessed knowledge of key concepts in climate health and sustainability. We hope this approach is followed elsewhere to prepare healthcare staff for impacts of climate change and to support improving the environmental sustainability of healthcare delivery. Trial registration Study registered with Brighton and Sussex Medical School Research Governance and Ethics Committee (BSMS RGEC). Reference: ER/BSMS3576/8, Date: 4/3/2020.

Binding of precursor tRNAs (ptRNAs) by bacterial ribonuclease P (RNase P) involves an encounter complex (ES) that isomerizes to a catalytic conformation (ES*). However, the structures of intermediates and the conformational changes that occur during binding are poorly understood. Here, we show that pairing between the 5′ leader and 3′RCCA extending the acceptor stem of ptRNA inhibits ES* formation. Cryo-electron microscopy single particle analysis reveals a dynamic enzyme that becomes ordered upon formation of ES* in which extended acceptor stem pairing is unwound. Comparisons of structures with alternative ptRNAs reveals that once unwinding is completed RNase P primarily uses stacking interactions and shape complementarity to accommodate alternative sequences at its cleavage site. Our study reveals active site interactions and conformational changes that drive molecular recognition by RNase P and lays the foundation for understanding how binding interactions are linked to helix unwinding and catalysis.

The balance wheel hypothesis-a classic tenet of USA state-level policy analysis that suggests state funding for higher education varies in response to macroeconomic cycles-has held up to scrutiny over time. However, new social conditions within the Republican Party, namely growing hostility toward independent institutions, call for a more nuanced understanding of the relationship between state budgets and higher education. Drawing on recent research in political science and political economy, we conceptualize declining state appropriations to higher education in Republican-dominated U.S. states as an instance of democratic backsliding. Using a panel of state-level data we found that political partisanship conditioned state appropriations to higher education during and after the Great Recession. Our finding that the balance wheel operated differently in states with and without unified Republican control not only suggests partisan hostility toward higher education is a potentially worrisome indicator of democratic backsliding, but also the importance of updating models to consider the extent to which they still hold as contexts change over time.

There are sparse hydrogeological data and insufficient hydrogeological knowledge in many areas of the world reliant on groundwater. Nicaragua’s Pacific coast is one such region that is also experiencing water scarcity resulting from increasing demand on groundwater resources and climate change. The primary source of water in the region is the aquifer system associated with the Brito Formation, which is a marine sedimentary stratum of mostly sandstone that blankets 75 km of coastline in southwest Nicaragua. This study focused on the Tola municipality with the objective to advance a conceptual understanding of the hydrogeology and to support sustainable water development. Results demonstrate a heterogeneous aquifer system with regional flow characteristics and other factors that influence groundwater availability and water quality. Primary porosity is low, and secondary porosity is the primary mechanism of aquifer storage and is influenced by geological structure and diagenesis processes. Groundwater recharge is spatially and temporally heterogeneous and direct recharge is low. Infiltration of streamflow and runoff, especially early in the rainy season, is thought to be a large component of groundwater recharge. Climate, flow and recharge dynamics, and low storage capacity make the Brito Formation a sensitive resource and vulnerable to drought, increased abstraction, and climate change. This assessment provides data and insights useful for informing future studies and investments within the region and may be applicable in other Central American and Caribbean nations with coastal sandstone aquifers.

High-purity crystalline solid-state materials play an essential role in various technologies for quantum information processing, from qubits based on spins to topological states. New and improved crystalline materials emerge each year and continue to drive new results in experimental quantum science. This article summarizes the opportunities for a selected class of crystalline materials for qubit technologies based on spins and topological states and the challenges associated with their fabrication. We start by describing semiconductor heterostructures for spin qubits in gate-defined quantum dots and benchmark GaAs, Si, and Ge, the three platforms that demonstrated two-qubit logic. We then examine novel topologically nontrivial materials and structures that might be incorporated into superconducting devices to create topological qubits. We review topological insulator thin films and move onto topological crystalline materials, such as PbSnTe, and its integration with Josephson junctions. We discuss advances in novel and specialized fabrication and characterization techniques to enable these. We conclude by identifying the most promising directions where advances in these material systems will enable progress in qubit technology.

Classical models of voluntary disclosure feature two economic forces: the existence of an adverse selection problem (e.g., a manager possesses some private information) and the cost of ameliorating the problem (e.g., costs associated with disclosure). Traditionally these forces are modelled independently. In this paper, we use a simple model to motivate empirical predictions in a setting where these forces are jointly determined––where greater adverse selection entails greater costs of disclosure. We show that joint determination of these forces generates a pronounced non-linearity in the probability of voluntary disclosure. We find that this non-linearity is empirically descriptive of multiple measures of voluntary disclosure in two distinct empirical settings that are commonly thought to feature both private information and proprietary costs: capital investments and sales to major customers.

The diagnostic experiences of autistic adults in New Zealand have not been investigated and little is known globally about autistic adults’ satisfaction with the autism diagnostic process. This study describes the diagnostic experiences of 70 autistic adults living in New Zealand and explores how these experiences are related to satisfaction during three stages of the diagnostic process. The results show that autistic adults were reasonably satisfied with the early query and diagnostic assessment stages, but were dissatisfied with the post-diagnostic support stage, with significant unmet needs. Dissatisfaction during the post-diagnostic support stage was also related to satisfaction during previous stages and poor coordination of supports. Suggestions are made on how to improve the autism diagnostic pathway for autistic adults in New Zealand.

Visual cultures are being increasingly discussed in the history of science literature, although relatively very little of that work concerns the nuclear age. In addition, within the discrete yet bourgeoning literature on global nuclear art and culture, Oceania is often overlooked despite its central role in the development of the American, British, and French nuclear weapon capabilities, as well as their associated colonial legacies. This article serves to redress both concerns by examining the visual politics of Maralinga in relation to settler-colonial and Aboriginal experiences, vulnerabilities and (re)presentations. I do so by surveying artworks with a connection to the Australian experience of nuclear colonialism and find that the figure of biological life has been conspicuously left absent from contemporary non-Indigenous Australian depictions of British nuclear testing in Australia.

Almond production is a significant horticulture crop for Australia. Serious yield losses can be caused by the fungal disease anthracnose, caused by Colletotrichum species that infect the fruit and leaves. Genomic sequence data for gene extraction, along with multigene phylogenetic analyses and whole genome average nucleotide identity (ANI) analysis were used to determine the phylogeny of Colletotrichum isolates collected from almonds across Australia. Multigene phylogenetic analyses of six gene regions (ITS, tub2, gapdh, chs-1, act and his3) identified C. acutatum sensu stricto, C. fioriniae and C. simmondsii as pathogens of almond. Similar topology was observed using ANI, which provided increased resolution within C. acutatum, with isolates separating largely according to geographic origin. The ANI analysis also supported three separate species with isolates within each species sharing >98.7% ANI (species cut off = 95%), while between species there was

Breast feathers of Neotropic Cormorants (Phalacrocorax brasilianus) from two nesting colonies in Lake Livingston (LALIV) and Richland Creek, Texas, were collected during 2014 and were analyzed for metals and metalloids. Mean concentrations of Al, As, Cr, Cu, Fe, Pb, Sb, and Se were not significantly different in breast feathers of cormorants from the two locations or between sexes. However, mean concentrations of Co, Mn, Ni, and V were significantly greater in feathers of cormorants from Richland Creek than in those from LALIV; and Zn concentrations were greater in cormorants from LALIV than in those from Richland Creek (p

Overall trends of academic staffing in the US have indicated declines in tenure, increased use of contingent faculty, and stratification of teaching and research efforts. However, little is known about academic staffing patterns in professional programs, and little research has been done using program-level data. The purposes of this study were to identify faculty staffing patterns, determine if patterns change over time, and identify predictors of staffing patterns in US-based physical therapy programs. Yearly program-level accreditation data from 2008 to 2017 were analyzed. A finite mixture model analysis identified staffing patterns. Logistic regression analyses were run to predict category membership and observe change over time. Two academic staffing categories emerged: (1) Broad staffing patterns (90.4% of programs) composed of more core faculty on tenure track and who held academic degrees and (2) Flexible programs (9.7% of observations) with higher numbers of core faculty, fewer faculty on tenure track, and fewer faculty with an academic doctoral degree. There was little change over time from one category to another. Programs were more likely to adopt a Flexible pattern when budget and faculty teaching time rose. Membership to one of two staffing models appears to be predicted by institutional reliance on professional programs for revenues. Either programs lower expenses by having tenured faculty balance teaching and research, or they rely on non-tenured faculty positions and higher enrollments.

Implementing statistical training into undergraduate or postgraduate chemistry courses can provide high-impact learning experiences for students. However, the opportunity to reinforce this training with a combined laboratory practical can significantly enhance learning outcomes by providing a practical bolstering of the concepts. This paper outlines a flow chemistry laboratory practical for integrating design of experiments optimisation techniques into an organic chemistry laboratory session in which students construct a simple flow reactor and perform a structured series of experiments followed by computational processing and analysis of the results.

In 2018, the American Society of Clinical Oncology/College of American Pathologists revised the criteria for HER2 immunohistochemistry (IHC) equivocal (2+) classification in their updated guideline. We reviewed invasive breast cancer specimens originally classified as equivocal (2+) under the 2018 guideline that underwent HER2 fluorescence in situ hybridization (FISH) testing from August 2018 to August 2019 at our Canadian reference hospital to investigate cases with ambiguous staining patterns between the 1+ and 2+ definitions. Demographics, pathologic features, and pre-analytic conditions were recorded. The H&E and corresponding HER2 IHC slides were reviewed to confirm tumor type and grade, and classify as HER2 indeterminate, 0, 1+, 2+, or “Intermediate” (staining features between the 1+ and 2+ classifications). FISH testing was performed on 289 cases and 273 met inclusion criteria. The FISH-amplified rate was 12.1%. Upon IHC review, 44.7% (122/273) of cases were reclassified as Intermediate. These cases had incomplete staining with moderate intensity (43/122, 35.3%) and/or

Background Rapid-cycling Brassica napus (B. napus-RC) has potential as a rapid trait testing system for canola (B. napus) because its life cycle is completed within 2 months while canola usually takes 4 months, and it is susceptible to the same range of diseases and abiotic stress as canola. However, a rapid trait testing system for canola requires the development of an efficient transformation and tissue culture system for B. napus-RC. Furthermore, effectiveness of this system needs to be demonstrated by showing that a particular trait can be rapidly introduced into B. napus-RC plants. Results An in-vitro regeneration protocol was developed for B. napus-RC using 4-day-old cotyledons as the explant. High regeneration percentages, exceeding 70%, were achieved when 1-naphthaleneacetic acid (0.10 mg/L), 6-benzylaminopurine (1.0 mg/L), gibberellic acid (0.01 mg/L) and the ethylene antagonist silver nitrate (5 mg/L) were included in the regeneration medium. An average transformation efficiency of 16.4% was obtained using Agrobacterium-mediated transformation of B. napus-RC cotyledons using Agrobacterium strain GV3101 harbouring a plasmid with an NPTII (kanamycin-selectable) marker gene and the Arabidopsis thaliana cDNA encoding ACYL-COA-BINDING PROTEIN6 (AtACBP6). Transgenic B. napus-RC overexpressing AtACBP6 displayed better tolerance to freezing/frost than the wild type, with enhanced recovery from cellular membrane damage at both vegetative and flowering stages. AtACBP6-overexpressing B. napus-RC plants also exhibited lower electrolyte leakage and improved recovery following frost treatment, resulting in higher yields than the wild type. Ovules from transgenic AtACBP6 lines were better protected from frost than those of the wild type, while the developing embryos of frost-treated AtACBP6-overexpressing plants showed less freezing injury than the wild type. Conclusions This study demonstrates that B. napus-RC can be successfully regenerated and transformed from cotyledon explants and has the potential to be an effective trait testing platform for canola. Additionally, AtACBP6 shows potential for enhancing cold tolerance in canola however, larger scale studies will be required to further confirm this outcome.

Montane grasslands and forest-grassland ecotones are unique and dynamic components of many landscapes, but the processes that regulate their dynamics are difficult to observe over ecologically relevant time spans. We aimed to demonstrate the efficacy of using grassland-forest ecotone trees to reconstruct spatial and temporal properties of the historical fire regime in a complex landscape of montane forests and adjacent grasslands. We sampled and crossdated fire-scarred trees along ecotones and compared variations in historical fire occurrence within and among nine adjoining valle basins in a 10,158 ha landscape. We analyzed fire year extensiveness, climate regulation, and the occurrence of consecutive fire years. The resulting tree-ring record covers 1240–2005 AD, with 296 trees recording 125 replicated fire years during the analysis period 1601–1902 AD. Mean fire intervals for all events recorded on two or more trees ranged from 4.7 to 13.6 years in individual valles, and a mean of 2.4 ± 1.7 (SD) years at the landscape scale. Between 1660 and 1902, extensive fires occurring in six or more valles occurred 15 times, on average at ~ 17-year intervals; 29 moderately widespread fires (3–5 valles) occurred during this period, at 8.7 year intervals on average. Widespread events occurred in years with a significantly lower Palmer Drought Severity Index (PDSI) preceded by years of significantly positive PDSI, indicating conditions favorable for fine fuel production. Spatial reconstruction of fire extent revealed multiple occurrences of consecutive-year fires burning non-overlapping areas, associated with persistent low PDSI anomalies preceded by positive conditions in antecedent years. A landscape spatiotemporal approach to reconstructing fire regimes of montane forest-grassland complexes provides a valuable baseline for guiding prescribed and natural fire management at large spatial scales.